bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Basis of Src Tyrosine Kinase Inhibition with a New Class of Potent and Selective Trisubstituted Purine‐based Compounds
Authors: Dalgarno David , Stehle Thilo , Narula Surinder , Schelling Pierre , Rose van Schravendijk Marie , Adams Susan , Andrade Lawrence , Keats Jeff , Ram Mary , Jin Lei , Grossman Trudy , MacNeil Ian , Metcalf Chester , Shakespeare William , Wang Yihan , Keenan Terry , Sundaramoorthi Raji , Bohacek Regine , Weigele Manfred , Sawyer Tomi
Published: December 2005

The tyrosine kinase pp60src (Src) is the prototypical member of a family of proteins that participate in a broad array of cellular signal transduction processes, including cell growth, differentiation, survival, adhesion, and migration. Abnormal Src family kinase (SFK) signaling has been linked to several disease states, including osteoporosis and cancer metastases. Src has thus emerged as a molecular target for the discovery of small‐molecule inhibitors that regulate Src kinase activity by binding to the ATP pocket within the catalytic domain. Here, we present crystal structures of the kinase domain of Src in complex with two purine‐based inhibitors: AP23451, a small‐molecule inhibitor designed to inhibit Src‐dependent bone resorption, and AP23464, a small‐molecule inhibitor designed to inhibit the Src‐dependent metastatic spread of cancer. In each case, a trisubstituted purine template core was elaborated using structure‐based drug design to yield a potent Src kinase inhibitor. These structures represent early examples of high affinity purine‐based Src family kinase–inhibitor complexes, and they provide a detailed view of the specific protein–ligand interactions that lead to potent inhibition of Src. In particular, the 3‐hydroxyphenethyl N9 substituent of AP23464 forms unique interactions with the protein that are critical to the picomolar affinity of this compound for Src. The comparison of these new structures with two relevant kinase–inhibitor complexes provides a structural basis for the observed kinase inhibitory selectivity. Further comparisons reveal a concerted induced‐fit movement between the N‐ and C‐terminal lobes of the kinase that correlates with the affinity of the ligand. Binding of the most potent inhibitor, AP23464, results in the largest induced‐fit movement, which can be directly linked to interactions of the hydrophenethyl N9 substituent with a region at the interface between the two lobes. A less pronounced induced‐fit movement is also observed in the Src–AP23451 complex. These new structures illustrate how the combination of structural, computational, and medicinal chemistry can be used to rationalize the process of developing high affinity, selective tyrosine kinase inhibitors as potential therapeutic agents.
Use of an Induced Fit Receptor Structure in Virtual Screening
Authors: Sherman Woody , Beard Hege S. , Farid Ramy
Published: December 2005

Structured‐based drug design has traditionally relied on a single receptor structure as a target for docking and screening studies. However, it has become increasingly clear that in many cases where protein flexibility is an issue, it is critical to accurately model ligand‐induced receptor movement in order to obtain high enrichment factors. We present a novel protein‐ligand docking method that accounts for both ligand and receptor flexibility and accurately predicts the conformation of protein‐ligand binding complexes. This method can generate viable receptor ensembles that can be used in virtual database screens.
Comment on "How Science Survived: Medieval Manuscripts' `Demography' and Classic Texts' Extinction"
Authors: Declercq Georges
Published: December 2005

Exciting though it may seem, the mathematical model developed by Cisne (Reports, 25 February 2005, p. 1305) to analyze the transmission of texts and manuscripts from Antiquity and the Middle Ages does not hold up to scrutiny. It seriously underestimates the losses, thus leading to conclusions that are unwarranted.
Snapshot of Activated G Proteins at the Membrane: The Gα
q
-GRK2-Gßγ Complex
Authors: Tesmer Valerie M. , Kawano Takeharu , Shankaranarayanan Aruna , Kozasa Tohru , Tesmer John J. G.
Published: December 2005

G protein–coupled receptor kinase 2 (GRK2) plays a key role in the desensitization of G protein–coupled receptor signaling by phosphorylating activated heptahelical receptors and by sequestering heterotrimeric G proteins. We report the atomic structure of GRK2 in complex with Gα
q
and Gβγ, in which the activated Gα subunit of G
q
is fully dissociated from Gβγ and dramatically reoriented from its position in the inactive Gαβγ heterotrimer. Gα
q
forms an effector-like interaction with the GRK2 regulator of G protein signaling (RGS) homology domain that is distinct from and does not overlap with that used to bind RGS proteins such as RGS4.
Transcriptome Analysis of
Paracoccidioides brasiliensis
Cells Undergoing Mycelium-to-Yeast Transition
Authors: Nunes Luiz R. , Costa de Oliveira Regina , Leite Daniela Batista , da Silva Vivian Schmidt , dos Reis Marques Everaldo , da Silva Ferreira Márcia Eliana , Ribeiro Diógenes Custódio Duarte , de Souza Bernardes Luciano Ângelo , Goldman Maria Helena S. , Puccia Rosana , Travassos Luiz R. , Batista Wagner L. , Nóbrega Marina Pasetto , Nobrega Francisco G. , Yang Ding-Yah , de Bragança Pereira Carlos A. , Goldman Gustavo H.
Published: December 2005

Paracoccidioides brasiliensis
is a thermodimorphic fungus associated with paracoccidioidomycosis (PCM), a systemic mycosis prevalent in South America. In humans, infection starts by inhalation of fungal propagules, which reach the pulmonary epithelium and transform into the yeast parasitic form. Thus, the mycelium-to-yeast transition is of particular interest because conversion to yeast is essential for infection. We have used a
P. brasiliensis
biochip carrying sequences of 4,692 genes from this fungus to monitor gene expression at several time points of the mycelium-to-yeast morphological shift (from 5 to 120 h). The results revealed a total of 2,583 genes that displayed statistically significant modulation in at least one experimental time point. Among the identified gene homologues, some encoded enzymes involved in amino acid catabolism, signal transduction, protein synthesis, cell wall metabolism, genome structure, oxidative stress response, growth control, and development. The expression pattern of 20 genes was independently verified by real-time reverse transcription-PCR, revealing a high degree of correlation between the data obtained with the two methodologies. One gene, encoding 4-hydroxyl-phenyl pyruvate dioxygenase (4-HPPD), was highly overexpressed during the mycelium-to-yeast differentiation, and the use of NTBC [2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione], a specific inhibitor of 4-HPPD activity, as well as that of NTBC derivatives, was able to inhibit growth and differentiation of the pathogenic yeast phase of the fungus in vitro. These data set the stage for further studies involving NTBC and its derivatives as new chemotherapeutic agents against PCM and confirm the potential of array-based approaches to identify new targets for the development of alternative treatments against pathogenic microorganisms.
Genetic and Molecular Analysis of Phytochromes from the Filamentous FungusNeurospora crassa
Authors: Froehlich Allan C. , Noh Bosl , Vierstra Richard D. , Loros Jennifer , Dunlap Jay C.
Published: December 2005

Phytochromes (Phys) comprise a superfamily of red-/far-red-light-sensing proteins. Whereas higher-plant Phys that control numerous growth and developmental processes have been well described, the biochemical characteristics and functions of the microbial forms are largely unknown. Here, we describe analyses of the expression, regulation, and activities of two Phys in the filamentous fungusNeurospora crassa. In addition to containing the signature N-terminal domain predicted to covalently associate with a bilin chromophore, PHY-1 and PHY-2 contain C-terminal histidine kinase and response regulator motifs, implying that they function as hybrid two-component sensor kinases activated by light. A bacterially expressed N-terminal fragment of PHY-2 covalently bound either biliverdin or phycocyanobilin in vitro, with the resulting holoprotein displaying red-/far-red-light photochromic absorption spectra and a photocycle in vitro. cDNA analysis ofphy-1andphy-2revealed two splice isoforms for each gene. The levels of thephytranscripts are not regulated by light, but the abundance of thephy-1mRNAs is under the control of the circadian clock. Phosphorylated and unphosphorylated forms of PHY-1 were detected; both species were found exclusively in the cytoplasm, with their relative abundances unaffected by light. Strains containing deletions ofphy-1andphy-2, either singly or in tandem, were not compromised in any known photoresponses inNeurospora, leaving their function(s) unclear.
Identification and Characterization of Cor33p, a Novel Protein Implicated in Tolerance towards Oxidative Stress inCandida albicans
Authors: Sohn K. , Roehm M. , Urban C. , Saunders N. , Rothenstein D. , Lottspeich F. , Schröppel K. , Brunner H. , Rupp S.
Published: December 2005

We applied two-dimensional gel electrophoresis to identify downstream effectors ofCPH1andEFG1under hypha-inducing conditions inCandida albicans. Among the proteins that were expressed in wild-type cells but were strongly downregulated in acph1Δ/efg1Δ double mutant in α-minimal essential medium at 37°C, we could identify not-yet-characterized proteins, including Cor33-1p and Cor33-2p. The two proteins are almost identical (97% identity) and represent products of allelic isoforms of the same gene. Cor33p is highly similar to Cip1p fromCandidasp. but lacks any significant homology to proteins fromSaccharomyces cerevisiae. Strikingly, both proteins share homology with phenylcoumaran benzylic ether reductases and isoflavone reductases from plants. For other hypha-inducing media, like yeast-peptone-dextrose (YPD) plus serum at 37°C, we could not detect any transcription forCOR33in wild-type cells, indicating that Cor33p is not hypha specific. In contrast, we found a strong induction forCOR33when cells were treated with 5 mM hydrogen peroxide. However, under oxidative conditions, transcription ofCOR33was not dependent onEFG1, indicating that other regulatory factors are involved. In fact, upregulation depends onCAP1at least, as transcript levels were clearly reduced in a Δcap1mutant strain under oxidative conditions. Unlike in wild-type cells, transcription ofCOR33in atsa1Δ mutant can be induced by treatment with 0.1 mM hydrogen peroxide. This suggests a functional link betweenCOR33and thiol-specific antioxidant-like proteins that are important in the oxidative-stress response in yeasts. Concordantly,cor33Δ deletion mutants show retarded growth on YPD plates supplemented with hydrogen peroxide, indicating thatCOR33in general is implicated in conferring tolerance toward oxidative stress onCandida albicans.
A Novel, Highly Selective Inhibitor of Pestivirus Replication That Targets the Viral RNA-Dependent RNA Polymerase
Authors: Paeshuyse Jan , Leyssen Pieter , Mabery Eric , Boddeker Nina , Vrancken Robert , Froeyen Matheus , Ansari Israrul H. , Dutartre Hélène , Rozenski Jef , Gil Laura H. V. G. , Letellier Carine , Lanford Robert , Canard Bruno , Koenen Frank , Kerkhofs Pierre , Donis Ruben O. , Herdewijn Piet , Watson Julia , De Clercq Erik , Puerstinger Gerhard , Neyts Johan
Published: December 2005

We
report on the highly potent and selective antipestivirus activity of
5-[(4-bromophenyl)methyl]-2-phenyl-5
H
-imidazo[4,5-c]pyridine
(BPIP). The 50% effective concentration (EC
50
) for
inhibition of bovine viral diarrhea virus (BVDV)-induced cytopathic
effect formation was 0.04 ± 0.01 μM. Comparable
reduction of viral RNA synthesis (EC
50
= 0.12±
0.02 μM) and production of infectious virus
(EC
50
= 0.074 ± 0.003 μM) were
observed. The selectivity index (ratio of 50% cytostatic
concentration/EC
50
) of BPIP was ∼2,000. BPIP was
inactive against the hepatitis C virus subgenomic replicon and yellow
fever virus but demonstrated weak activity against GB
virus. Drug-resistant mutants were at least 300-fold less
susceptible to BPIP than wild-type virus; showed cross-resistance to
N
-propyl-
N
-[2-(2
H
-1,2,4-triazino[5,6-b]indol-3-ylthio)ethyl]-1-propanamine
(VP32947), and carried the F224S mutation in the viral RNA-dependent
RNA polymerase (RdRp). When the F224S mutation was introduced into an
infectious clone, the drug-resistant phenotype was obtained. BPIP did
not inhibit the in vitro activity of recombinant BVDV RdRp, but did
inhibit the activity of replication complexes (RCs). Computational
docking revealed that F224 is located at the top of the finger domain
of the polymerase. Docking of BPIP in the crystal structure of the BVDV
RdRp revealed aromatic ring stacking, some hydrophobic contacts, and a
hydrogen bond. Since two structurally unrelated compounds, i.e., BPIP
and VP32947, target the same region of the BVDV RdRp, this position may
be expected to be critical in the functioning of the polymerase or
assembly of the RC. The potential of BPIP for the treatment of
pestivirus and hepacivirus infections is
discussed.
VP2 Cleavage and the Leucine Ring at the Base of the Fivefold Cylinder Control pH-Dependent Externalization of both the VP1 N Terminus and the Genome of Minute Virus of Mice
Authors: Farr Glen A. , Cotmore Susan F. , Tattersall Peter
Published: December 2005

Cylindrical projections surrounding the fivefold-symmetry axes in minute virus of mice (MVM) harbor central pores that penetrate through the virion shell. In newly released DNA-containing particles, these pores contain residues 28 to 38 belonging to a single copy of VP2, disposed so that its extreme N-terminal domain projects outside the particle. Virions are metastable, initially sequestering internally the N termini of all copies of the minor capsid protein, VP1, that is essential for entry. This VP1 domain can be externalized in vitro in response to limited heating, and we show here that the efficiency of this transition is greatly enhanced by proteolysis of VP2 N termini to yield VP3. This step also renders the VP1 rearrangement pH dependent, indicating that VP2 cleavage is a maturation step required to prime subsequent emergence of the VP1 “entry” domain. The tightest constriction within the cylinder is created by VP2 leucine 172, the five symmetry-related copies of which form a portal that resembles an iris diaphragm across the base of the pore. In MVMp, threonine substitution at this position, L172T, yields infectious particles following transfection at 37°C, but these can initiate infection only at 32°C, and this process can be blocked by exposing virions to a cellular factor(s) at 37°C during the first 8 h after entry. At 32°C, the mutant particle is highly infectious, and it remains stable prior to VP2 cleavage or following cleavage at pH 5.5 or below. However, upon exposure to neutral pH following VP2 cleavage, its VP1-specific sequences and genome are extruded even at room temperature, underscoring the significance of the VP2 cleavage step for MVM particle dynamics.
Identification and Characterization of a
Penaeus monodon
Lymphoid Cell-Expressed Receptor for the Yellow Head Virus
Authors: Assavalapsakul Wanchai , Smith Duncan R. , Panyim Sakol
Published: December 2005

The yellow head virus is a positive-sense, single-stranded RNA virus that causes significant mortality in farmed penaeid shrimp. This study sought to isolate and characterize the receptor protein used by the virus to gain entry into
Penaeus monodon
Oka (lymphoid) organ cells, a primary target of yellow head virus infections. Virus overlay protein binding assay on Oka organ membrane preparations identified a 65-kDa protein, and antibodies raised against this protein inhibited virus entry in primary Oka cell cultures by approximately 80%. N-terminal sequence analysis of the 65-kDa protein generated a 17-amino acid peptide fragment which was used to design degenerate primers that amplified a 1.5-kbp product from Oka organ total RNA, which was cloned and sequenced. Northern analysis and PCR were used to confirm a single RNA transcript that was expressed in most tissues. Subsequently, the mature cDNA was recloned and the expressed protein shown to cross-react with the antibody raised against the original virus binding band. Down regulation of the message through double-stranded RNA-mediated RNA interference silencing resulted in the complete inhibition of virus entry. While the identity of the clone remains unknown, it nevertheless represents the first invertebrate
Nidovirus
receptor isolated to date.
Alternative Sigma Factors and Their Roles in Bacterial Virulence
Authors: Kazmierczak Mark J. , Wiedmann Martin , Boor Kathryn J.
Published: December 2005

Sigma factors provide promoter recognition specificity to RNA polymerase holoenzyme, contribute to DNA strand separation, and then dissociate from the core enzyme following transcription initiation. As the regulon of a single sigma factor can be composed of hundreds of genes, sigma factors can provide effective mechanisms for simultaneously regulating expression of large numbers of prokaryotic genes. One newly emerging field is identification of the specific roles of alternative sigma factors in regulating expression of virulence genes and virulence-associated genes in bacterial pathogens. Virulence genes encode proteins whose functions are essential for the bacterium to effectively establish an infection in a host organism. In contrast, virulence-associated genes can contribute to bacterial survival in the environment and therefore may enhance the capacity of the bacterium to spread to new individuals or to survive passage through a host organism. As alternative sigma factors have been shown to regulate expression of both virulence and virulence-associated genes, these proteins can contribute both directly and indirectly to bacterial virulence. Sigma factors are classified into two structurally unrelated families, the σ
70
and the σ
54
families. The σ
70
family includes primary sigma factors (e.g.,
Bacillus subtilis
σ
A
) as well as related alternative sigma factors; σ
54
forms a distinct subfamily of sigma factors referred to as σ
N
in almost all species for which these proteins have been characterized to date. We present several examples of alternative sigma factors that have been shown to contribute to virulence in at least one organism. For each sigma factor, when applicable, examples are drawn from multiple species.
Bacterial Cell Wall Synthesis: New Insights from Localization Studies
Authors: Scheffers Dirk-Jan , Pinho Mariana G.
Published: December 2005

In order to maintain shape and withstand intracellular pressure, most bacteria are surrounded by a cell wall that consists mainly of the cross-linked polymer peptidoglycan (PG). The importance of PG for the maintenance of bacterial cell shape is underscored by the fact that, for various bacteria, several mutations affecting PG synthesis are associated with cell shape defects. In recent years, the application of fluorescence microscopy to the field of PG synthesis has led to an enormous increase in data on the relationship between cell wall synthesis and bacterial cell shape. First, a novel staining method enabled the visualization of PG precursor incorporation in live cells. Second, penicillin-binding proteins (PBPs), which mediate the final stages of PG synthesis, have been localized in various model organisms by means of immunofluorescence microscopy or green fluorescent protein fusions. In this review, we integrate the knowledge on the last stages of PG synthesis obtained in previous studies with the new data available on localization of PG synthesis and PBPs, in both rod-shaped and coccoid cells. We discuss a model in which, at least for a subset of PBPs, the presence of substrate is a major factor in determining PBP localization.
ELECTRONIC STRUCTURE FOR THE TWO-BAND HUBBARD MODEL OF THE LADDER α′-NaV2O5 COMPOUND
Authors: KOVAČEVIĆ Ž. Lj. , VUKAJLOVIĆ F. R.
Published: December 2005

An effective Hubbard model for one-particle d-like states and two-particle singlet states is derived in order to describe the low-energy electronic spectrum in ladder α′- NaV 2 O 5 compound. The energy shifts and the renormalized hopping parameters for the considered electronic states are calculated on the basis of the projection technique for the two-time matrix Green's function in terms of Hubbard operators.
GIANT MAGNETOIMPEDANCE EFFECT IN MULTILAYERED STRUCTURE (FM/SiO2)3/Ag/(SiO2/FM)3FILMS
Authors: CHEN WEI-PING , XIAO SHU-QIN , WANG WEN-JING , YUAN HUI-MIN , LIU YI-HUA
Published: December 2005

Giant magnetoimpedance (GMI) and giant magnetoreactance (GMX) effects in multilayered structure ( FM/SiO2)3/ Ag /( SiO2/ FM )3( FM ≡ Fe71.5Cu1Cr2.5V4Si12B9) films have been studied. The multilayered films were deposited by radio frequency sputtering under a constant magnetic field of 900 Oe applied in the plane of the sample perpendicular to its long side (transverse direction) and then annealed under different temperatures. The maximum GMI ratio of 122% was obtained at the frequency of 4.6 MHz. The maximum value of GMX ratio and the sensitivity of GMX ratio, 2578% and 129%/Oe, were obtained in a longitudinal field case at the frequency of 1 MHz, respectively. These superior properties are related to the special structure of the multilayered films and the transverse magnetic field used in the deposition process.
ISOTOPE EFFECTS OF Mn AND O IN COLOSSAL MAGNETORESISTIVE MANGANITES
Authors: KOO JE HUAN , CHO GUANGSUP
Published: December 2005

We investigate theoretically manganese oxides where the colossal magnetoresistance (CMR) is observed. We obtain the Curie temperature Tc using a Kondo lattice model for paramagetic to ferromagnetic transition. We also acquire the charge-ordered transition temperature TCO applying spin-Peierls transition. We calculate the isotope exponents of Mn ion and O ion such as αc for Tc and αCO for TCO. Calculated αc of O ion is less than 0.9 and αCO is ~-(0.1~0.9).
QUICK SYNTHESIS OF CARBON NITRIDE FILMS BY NEW DC HOLLOW CATHODE PLASMA SPUTTERING DEPOSITION TECHNIQUE
Authors: YANG P. , FENG X. P. , SHI Y. C. , YAN Y. H. , ZHANG J.
Published: December 2005

High N content of carbon nitride films are quickly deposited onto Si (100) substrates at room temperature by using DC hollow cathode plasma sputtering deposition technique. The deposition rate is up to 283 nm/min at the bias voltage of 400 V. The properties of the films are characterized by using XPS, Raman (scattering) and Fourier transformation infrared (FTIR) spectroscopy. Experiments results provide direct evidences that the structures of CN films can be controlled by regulating bias voltages. The maximum sp3 C – N concentration up to 0.73 is obtained. Raman data is used to confirm XPS results. FTIR of the films clearly show C – N and C = N components (1000–1800 cm-1) together with a tiny peak C ≡ N (2181 cm-1). By reducing particle energy and substrate temperature, we have succeeded in suppressing the mechanisms of losing N -contain species during deposition, and achieved a large amount of sp3 bonds of CN films.
STABILITY OF BLOCH OSCILLATIONS IN TWO COUPLED BOSE–EINSTEIN CONDENSATES
Authors: RANJAN VIKASH , BHATTACHERJEE ARANYA B. , MOHAN MAN
Published: December 2005

We investigate analytically the stability of Bloch waves at the boundary of the first Brillouin zone in two coupled Bose–Einstein condensates confined in an optical lattice. Contrary to the single component case, we find here two critical density regimes which determine the stability of the Bloch waves. Breakdown of Bloch oscillations appear when n1/n2NC2, here NC1 and NC2 are some critical values of n1/n2. There is an intermediate regime between NC1 and NC2 where the Bloch oscillations are stable and the condensates behave like single particles.
DYNAMICS OF A DELAYED EPIDEMIOLOGICAL MODEL WITH NONLINEAR INCIDENCE: THE ROLE OF INFECTED INCIDENCE FRACTION
Authors: MUKHOPADHYAY B. , BHATTACHARYYA R.
Published: December 2005

We present and analyze an epidemiological model containing Susceptible (S(t)) and Infected (I(t)) populations. The incidence rate is assumed to be nonlinear in the infected fraction (Ip(t)) as well as the susceptible fraction (Sq(t)). The dynamical behavior of the system is investigated from the point of view of stability and bifurcation. To model the recovery time of infected populations, a recovery delay, both in distributed and discrete form is introduced. In all the cases, it is shown that the infected incidence fraction p plays a vital role in controlling the dynamical behavior of the system. Numerical simulations are performed to justify the analytical findings.
POPULATION DYNAMICS OF TRANSPOSABLE ELEMENTS: COPY NUMBER REGULATION AND SPECIES INVASION REQUIREMENTS
Authors: STRUCHINER CLAUDIO J. , KIDWELL MARGARET G. , RIBEIRO JOSÉ M. C.
Published: December 2005

A deterministic population dynamics model of the spread of transposable elements (TE) in sexually reproducing populations is presented. The population is modeled by a three-parameter equation describing host reproductive capacity, population size and the strength of the density dependence, while TE dynamics were modeled based also on three parameters, the maximum ability of the element to copy itself in the absence of regulation (T0), the regulatory effect of copy number decreasing transposition (C0.5), and the deleterious effect of each new transposition on host fitness (d). The mechanism of transposition control is therefore a function of the number of new TE copies. Our results indicate that non-regulated elements cannot fix in host populations, and that prediction of stable copy number following successful invasion is mainly a function of the combination of T0and C0.5values. Fitness reduction does not affect the final copy number after successful invasion of the element. Fitness reduction, however, will affect the surface of the {T0× C0.5} parameter space leading to successful invasion of the TE. Invasion of host populations by eight or more individuals containing elements with appropriate parameters will lead to successful element fixation at any size of the host population. Host population extinction due to the invasion of TE's is observed in a small area of the {T0× C0.5} parameter space. These results are qualitatively preserved under alternative choices for the shape of the functions defining regulation of transposition and distinct sets of parameters determining host population dynamics.
ESTIMATING THE COMPLEXITY OF HEART RATE FLUCTUATIONS — AN APPROACH BASED ON COMPRESSION ENTROPY
Authors: BAUMERT MATHIAS , BAIER VICO , VOSS ANDREAS , BRECHTEL LARS , HAUEISEN JENS
Published: December 2005

Heart rate exhibits spontaneous fluctuations that are mainly modulated by control loops within the autonomic nervous system. Assessing the dynamics of heart rate fluctuations can provide valuable information about regulatory processes and patho-physiological behavior. In this paper heart rate fluctuations and its entropy are assessed using an algorithmic information theoretic concept applying a data compressor. First, the beat-to-beat fluctuations of heart rate are binary coded for decreases and increases, respectively. Subsequently, those symbol sequences are compressed using the LZ77 algorithm. The ratio of the length of the compressed sequences to the original length is used as an estimate of entropy. We investigated the compressibility of heart rate fluctuations in athletes before, during, and after a training camp. Heart rate time series were obtained from ECGs recorded over 30 minutes under supine resting conditions. We found a significant entropy reduction during the training camp, reflecting the effects of physical fatigue. In conclusion, the compression entropy seems to be a suitable approach to assess the complexity of heart rate fluctuations.
STUDY OF THE PRINCIPLES OF INNOVATION FOR THE BOP CONSUMER — THE CASE OF A RURAL WATER FILTER
Authors: PRASAD V. C. S. , GANVIR VIVEK
Published: December 2005

It is now well known that the principles of innovation for the Bottom of the Pyramid (BOP) markets are different from those of the top of the pyramid. This paper discusses these principles taking the example of the development of a rural domestic water filter in India. Work related to two principles are highlighted, viz, product development based on deep understanding of functionality and price — performance focus. The former was achieved through the development of a realistic specification for the bacterial (Coliform) trapping level of filtered water by using DMAIC (Define, Measure, Analyze, Improve and Control) methodology. When the filters made by the villagers from the resulting process is introduced in a small village in India, significant reduction in the number of cases due to water-borne diseases is reported. The resulting reduction in medical costs is shown to far outweigh the initial and subsequent maintenance costs of the filter. A simple entrepreneurship model is outlined showing a win-win situation for the rural consumer as well as the rural entrepreneur.
SIMILARITY-BASED REASONING USING PROVERBS IN MANAGING TECHNOLOGICAL INNOVATIONS FOR SMALL MANUFACTURERS
Authors: ORDOOBADI SHARON , XUE YAN , SHANTEAU JAMES
Published: December 2005

After conducting many interviews with managers and owners of small manufacturing companies regarding their approach to technological innovation, it became clear that in most cases there was no shortage of new ideas that could lead to innovation. However, whether any of these ideas were pursued often depended on the intuition of an individual; often the owner. It seems, independent of the physical nature of activities, some individuals have this intuition and some do not. The concept and methodology discussed in this paper is an attempt to transfer the intuition from those who have it to another person who does not. Since innovation, by nature, is something new and probably in a unique domain, many well known approaches such as case base reasoning or even TRIZ are not quite sufficient for this transfer as they rely mainly on the physical similarities of cases. The technique used here is a specially designed Similarity-Based Reasoning which extracts and characterizes the intuitive aspects that go into attempting and succeeding in technological innovations. A main component of the tool is a collection of scenarios provided by a number of small manufacturers about their experiences, in pursuing technological innovations. These scenarios are built into "cases" stored in a case base. Proverbs are used to extract the abstract concepts behind cases and code them such that they could be retrieved by the decision maker when dealing with an innovation process that "in abstract concept", is similar to someone else's past experience. The significance of this approach is that cases used in guiding the decision maker do not necessarily need to have physical similarities to the problem in hand as long as they are similar in concept.
VALUE ADDITION TO TECHNOLOGY ORGANIZATIONS: THE SIX-DIMENSIONAL OPPORTUNITIES
Authors: CHANG C. M.
Published: December 2005

The dawn of the new millennium is uniquely characterized by the rapid advancement in technologies and tectonic change in global markets. This paper enumerates on opportunities for engineers to add value to technology organizations, such as e-transformation, web-based tools, product development, innovations, and management of global supply chains. These opportunities entail challenges in six dimensions, namely inside, outside, present, future, local and global; they are linkable to stakeholders' value. Engineering managers need to emulate specific personal strategies in order to seize these value-addition opportunities and convert them into business profitability for their technology organizations.
DEVELOPING CAPACITY AND INFORMATION TOOLS FOR VEHICLE EMISSIONS POLICY IN NEW ZEALAND
Authors: PENNY GUY
Published: December 2005

Worldwide, the increasing deterioration in urban air quality due to vehicle emissions has created the need for greater capacity in air quality management and more comprehensive knowledge about the sources and spatial and temporal distribution of vehicle emissions, without which impact studies and subsequent mitigation policy cannot be formulated. To investigate this proposition and assist with the design/development of new air quality information tools for this evolving context, this research examines the generation and use of air quality information in New Zealand, through two case studies. The first case study examines NZTER, a tool used for generating 'vehicle fleet emission rates information' used in a number of different models for air quality assessment and transport policy. The second case examines the early stages of the development and operationalisation of an integrated environmental management tool, the VFEM-w, which hopes to quantify/model the type, source and pathways of airborne pollutants entering the urban stormwater water system. While the NZTER is uncomplicated, it is inefficient and produces information of insufficient quality in the current policy-making context. The VFEM-w case illustrates the challenges of attempting to embed a conceptually and technically complex model in an existing cultural, technical and political setting. Recommendations for the use and development of air quality information tools are made and closing comments consider the issue of information quality in sustainable management.
Development of High Electron Mobility Transistor
Authors: Mimura Takashi
Published: December 2005

The development of the high electron mobility transistor (HEMT) provides a good illustration of the way a new device emerges and evolves toward commercialization. This article will focus on these events that the author feels might be of interest to young researchers. Recent progress and future trends in HEMT technology are also described.
Gap States Induced by Local Oxidation of Silicon in Iron-Contaminated p on p+ Epitaxial Silicon Wafers
Authors: Horikawa Mitsuhiro
Published: December 2005

Heavily doped areas and lattice strains in device structures can provide effective traps for metals and compete with intentionally introduced gettering sites for impurities. In this study, the effect of device structures on Fe gettering by p+ substrates was investigated by reverse current measurements and deep level transient spectroscopy (DLTS) of n+–p junction diodes. A significant improvement in the gettering efficiency was achieved by optimizing the cooling rate in annealing. DLTS detected the gap states, which act as minority carrier traps, in the wafers without optimization of annealing conditions. The gap states correlated to the perimeter length of n+–p junctions, which were defined by local oxidation of silicon (LOCOS). The leakage current and the density of gap states were greatly reduced by optimizating the cooling rate. We suggest that the Fe atoms gettered by lattice strain due to LOCOS generate the gap states, and that these gap states are the origin of excess leakage current.
Analysis of Photoelectrochemical Processes in α-SiC Substrates with Atomically Flat Surfaces
Authors: Mikami Hidenori , Hatayama Tomoaki , Yano Hiroshi , Uraoka Yukiharu , Fuyuki Takashi
Published: December 2005

The etching of α(4H,6H)–SiC{0001} substrates by a photoelectrochemical method using HF (0.015–4.5 wt %) and HF+HNO3 (0.006–1.2 wt %) electrolytes was studied. The dependences of etching rate on polytype, polarity, and pH were measured. In the case of the HF electrolyte, an etching rate of 15–27 nm/min was achieved over a pH range from 0.5 to 4.5 under a photocurrent density of 1 mA/cm2. By optimizing etching conditions, the surface roughness of the Si face could be improved to 0.9 nm (4H) and 0.4 nm (6H) compared with the initial surface roughnesses of 4H (8.9 nm) and 6H–SiC (6.5 nm). In the case of the HF+HNO3 electrolyte, a thin oxide film 2–3 µm thick was formed after 60 min. The oxidized layer was two orders of magnitude thicker than that obtained using the thermal method. The pH of the electrolyte decreased after the electrochemical process, indicating an increase in the concentration of H+ ions. Therefore, holes and H2O have a strong influence on the rate of oxidation reactions in electrochemical methods. Electrochemical etching proceeds by the competitive processes of formation and removal of oxide films.
Reduction in Dislocation Density of Spherical Silicon Solar Cells Fabricated by Decompression Dropping Method
Authors: Okamoto Chikao , Tsujiya Kaoru , Minemoto Takashi , Murozono Mikio , Takakura Hideyuki , Hamakawa Yoshihiro
Published: December 2005

Spherical Si solar cells were fabricated based on polycrystalline Si spheres with a diameter of 1 mm produced by a dropping method. To decrease the cooling rates of Si spheres by decreasing the convection heat transfer to ambient, the Si spheres were dropped in a free-fall tower at a pressure of 0.2 atm. The conversion efficiency of low-pressure spherical Si solar cells was higher than that of normal-pressure spherical Si solar cells. Both Si spheres were polycrystals that consisting of crystal grains of about 200 µm. The distribution between electric active defects and the crystal quality were characterized by electron beam induced current (EBIC) measurements and transmission electron microscopy (TEM). By EBIC measurements, the low-pressure spherical Si solar cells were clearly observed to have the lower recombination sinks than the normal-pressure spherical Si solar cells. By TEM, the dislocation density in the low-pressure spherical Si solar cells was observed to be more reduced than that in the normal-pressure spherical Si solar cells. The dislocation density in the low-pressure Si spheres decreased because the reduction in the stress generated in the crystal grain.
Thickness Dependence of Strain Field Distribution in SiGe Relaxed Buffer Layers
Authors: Sawano Kentarou , Usami Noritaka , Arimoto Keisuke , Nakagawa Kiyokazu , Shiraki Yasuhiro
Published: December 2005

The buffer thickness dependence of strain field distribution was investigated in SiGe heterostructures by micro-Raman spectroscopy. Crosshatch-like strain fluctuations were clearly observed in strained-Si and SiGe buffer layers, and the fluctuation wavelength was found to increase almost linearly with increasing buffer thickness. It was also found that SiGe homoepitaxial growth on planarized SiGe buffer layers gave rise to crosshatch roughness on the surface with almost the same morphology as the strain distribution, indicating that the strain fluctuation caused the roughness formation associated with growth kinetics. The strain fluctuation still remained on the buffer layer thicker than 7 µm, which should be taken into consideration for device applications.
Crystal Structure of Thermoelectric Compound [Bi1.79Sr1.98Oy]0.63[RhO2]
Authors: Yubuta Kunio , Okada Satoshi , Miyazaki Yuzuru , Terasaki Ichiro , Kajitani Tsuyoshi
Published: December 2005

We have studied the crystal structure of the misfit-layered crystal Bi1.91Sr2Rh1.77O
x
by electron diffraction and high-resolution electron microscopy. This compound consists of two interpenetrating subsystems of a RhO2 sheet and a distorted four-layered rock-salt-type (Bi,Sr)O block. Both subsystems have common a-axes, c-axes, and β-angles with a=5.28 Å, c=29.77 Å, and β=93.7°. On the other hand, the crystal structure is incommensurated parallel to the b-axis, b
1=3.07 Å for the RhO2 sheet and b
2=4.88 Å for the (Bi,Sr)O block. The axis ratio, b
1/b
2∼0.63, characterizes the structural analogue as [Bi1.79Sr1.98O
y
]0.63[RhO2]. This compound has two modulation vectors, q1=a*+0.63b1
* and q2=0.17b1
*+c*, and the superspace group is assigned as the C
c(1β0,0µ1) type from electron diffraction patterns. High-resolution images taken with the incident electron beam parallel to the a- and c-axes clearly exhibit modulated displacive as well as compositional atomic arrangements. A tentative structure model has been proposed, and the calculated image reproduces observed characteristic features reasonably well.
Effects of Ge Doping on Micromorphology of MnSi in MnSi∼1.7 and on Their Thermoelectric Transport Properties
Authors: Aoyama Ikuto , Fedorov Mikhail I. , Zaitsev Vladimir K. , Solomkin Fedor Yu. , Eremin Ivan S. , Samunin Aleksandr Yu. , Mukoujima Mika , Sano Seijiro , Tsuji Toshihide
Published: December 2005

MnSi layers in Ge-doped MnSi∼1.7 increased with increasing Ge content up to x=0.00133, began to break at x=0.00265 and finally disappeared at x=0.00530. An experimental equation for the growth of MnSi was proposed for the interval between the MnSi layers and amount of doped Ge content. The crystallinity of Ge-doped MnSi∼1.7 increased initially with increasing doped Ge content and saturated at high Ge content. Thermoelectric transport properties along the c-axis of Ge-doped MnSi∼1.7 were measured as a function of Ge content at room temperature. Electrical conductivity and thermoelectric power of Ge-doped MnSi∼1.7 were compared to those of Al-doped MnSi∼1.7 in our previous work. A maximum in the electrical conductivity and a minimum in the thermoelectric power of Ge-doped MnSi∼1.7 were observed at x=0.00133, reflecting a change in hole density which was influenced by the volume ratio of MnSi. Hole mobility depended on the existence of MnSi layers and/or of interfaces between MnSi∼1.7 and MnSi and on the crystallinity of MnSi∼1.7. The thermal conductivity of Ge-doped MnSi∼1.7 had a maximum at x=0.00053. The increase in thermal conductivity at low Ge doping can be explained by the increase in the amount of MnSi segregated in doped MnSi∼1.7, while the decrease at high Ge content was caused by the increase in phonon scattering of Ge. A maximum figure of merit of Ge-doped MnSi∼1.7 was obtained at x=0.00974, reflecting a maximum power factor.
Design Methodology for Ti:LiNbO3 Waveguides
Authors: Almeida José Manuel M. M. de , Leite António Manuel P. P.
Published: December 2005

The purpose of this work was to develop a design methodology for the fabrication of waveguides in LiNbO3 operating in the single-mode regime at several wavelengths, with specific characteristics required to optimize integrated devices. To achieve this, it is necessary to obtain the relations between the optical characteristics of the waveguides and their respective fabrication conditions, and to introduce models of the waveguide formation process. The relations between fabrication conditions and optical characteristics of planar waveguides realized by titanium in-diffusion are documented extensively in the literature. However, reports on the characterization of waveguide fabrication processes, performed in a systematic way, could not be found, resulting in the need to combine information from several sources. Discrepancies among results from different researches are evident, resulting from different experimental methodologies and calibrations of equipment. Therefore, aiming at extracting a consistent data set, optical characterization techniques for the refractive index profile were employed to study series of samples.
Proton Transport and Microstructure Properties in Superlattice Thin Films Fabricated by Pulsed Laser Deposition
Authors: Kuwata Naoaki , Sata Noriko , Tsurui Takao , Yugami Hiroo
Published: December 2005

Superlattice thin films of the perovskite-type oxide proton conductor SrZr0.95Y0.05O3/SrTiO3 was fabricated by pulsed laser deposition. Their structural and proton transport properties were reported. X-ray diffraction analysis and selected area electron diffraction revealed that the thin films were epitaxially grown on MgO(001) substrate. High-density edge dislocations and a columnar structure were observed in the films by high-resolution electron microscopy. The in-plane electrical conductivity of the thin films was determined by impedance spectroscopy. The contribution of proton transport to the total conductivity of the films was confirmed by H2O/D2O exchange measurement. The conductivity of superlattice films was increased by introducing heterointerfaces. The high activation energy (E
a=1.0 eV) was explained by the grain-boundary effect of the columnar structure in the films.
High-Luminous-Efficiency AC-Plasma Display Panel Using Separate Discharge Mode in Tiled Sustain Electrode Structure
Authors: Lee Seong Eui , Lee Ho Nyeon , Oh Tae Sik , Kim Young Mo , Kang Sung Kee , Park Do Young , Kim Yong Seog
Published: December 2005

The discharge characteristics of high-efficiency AC-plasma display panels (PDPs) using a separate discharge mode were investigated using both numerical simulation and experiments. New types of segmented sustain electrodes have been proposed in order to increase the luminous efficiency with low power consumption and without major changes in the manufacturing process. We have obtained the higher efficiency with a wider separation between the left-side and right-side discharges in a cell. This effect can be explained in that a wider gap between the tiles is beneficial because the discharge remains confined to the walls, thus efficiently exploiting the phosphor on the walls. The discharge images of an intensified charge-coupled device (ICCD) camera in a tiled sustain electrode structure support these results.
Dependences of Plasma Parameters on Dilution Gas Content in Inductively Coupled C2F6/Ar and C2F6/O2 Discharges
Authors: Kimura Takashi , Noto Masahisa
Published: December 2005

Electron energy probability functions (EEPFs) are investigated in inductive C2F6/Ar and C2F6/O2 discharges. The structure of the EEPFs changes from bi-Maxwellian to Druyvesteyn-like distributions through a Maxwellian one with increasing Ar content, whereas the EEPFs form the bi-Maxwellian structure at any oxygen content except for pure oxygen. Dependences of both the fluorine atom density measured by actinometry and the relative variation of CF2 density determined from an optical emission at 251.9 nm on the dilution gas content are also investigated. The densities of F and CF2 are independent of the Ar content, while they depend strongly on the oxygen content.
Experimental Studies of Transverse and Longitudinal Beam Dynamics in Photoinjector
Authors: Yang Jinfeng , Kondoh Takafumi , Yoshida Youichi , Tagawa Seiichi
Published: December 2005

Both the transverse and longitudinal beam dynamics in a photoinjector were investigated experimentally for high-brightness electron beam generation. The transverse emittance growth and the energy spread, both due to the rf and the space-charge effects in the rf gun, were investigated with the laser injection phase. A 31.7 MeV electron beam at 1.0 nC with a normalized rms transverse emittance of 3.2±0.2 mm·mrad, an rms bunch length of 1.8±0.2 ps, and an rms relative energy spread of 0.04±0.01% was obtained in the photoinjector with a 5 ps (full width at half maximum; FWHM) laser. The phase compression in the bunch length was observed in the rf gun. A sub-picosecond electron bunch was observed experimentally in the rf gun at the low injection phase, such as 0.7±0.2 ps at 15° and 0.5±0.1 ps at 10°. The dependences of the transverse emittance, the bunch length and the energy spread on the rf phase of a booster linear accelerator (linac) downstream of the rf gun were investigated experimentally.
In Vitro Study on Assessment of Blood Coagulation and Clot Formation Using Doppler Ultrasound
Authors: Huang Chih-Chung , Wang Shyh-Hau , Tsui Po-Hsiang
Published: December 2005

A 10 MHz pulsed Doppler ultrasound was applied to measure both Doppler power and Doppler velocity from stirred porcine blood of various hematocrits for assessing variations in blood properties during blood coagulation and clot formation. For each measurement, blood was recalcified by adding calcium chloride solution. Results obtained from original blood at hematocrits of 25, 35, 45, and 55% showed that the mean Doppler power and Doppler velocity were respectively equal to 40.2, 38.5, 38.1, and 37.6 dB, and 24.6, 21.4, 20.0, and 19.6 cm/s. The variations in blood properties during blood coagulation caused Doppler power and velocity to fluctuate markedly. As the clot was formed, Doppler power was increased by approximately 5.5 dB and velocity was decreased to approximately 5.2 cm/s. These studies validated the suggestion that Doppler ultrasound is a feasible and sensitive means to quantify blood properties during blood coagulation and clot formation.