bluuebunny/crossref_metadata_2025 huggingface dataset:
Airborne minerals and related aerosol particles: Effects on climate and the environment
Authors: Buseck Peter R. , Pósfai Mihály
Published: July 2002

Aerosol particles are ubiquitous in the troposphere and exert an important influence on global climate and the environment. They affect climate through scattering, transmission, and absorption of radiation as well as by acting as nuclei for cloud formation. A significant fraction of the aerosol particle burden consists of minerals, and most of the remainder— whether natural or anthropogenic—consists of materials that can be studied by the same methods as are used for fine-grained minerals. Our emphasis is on the study and character of the individual particles. Sulfate particles are the main cooling agents among aerosols; we found that in the remote oceanic atmosphere a significant fraction is aggregated with soot, a material that can diminish the cooling effect of sulfate. Our results suggest oxidization of SO2may have occurred on soot surfaces, implying that even in the remote marine troposphere soot provided nuclei for heterogeneous sulfate formation. Sea salt is the dominant aerosol species (by mass) above the oceans. In addition to being important light scatterers and contributors to cloud condensation nuclei, sea-salt particles also provide large surface areas for heterogeneous atmospheric reactions. Minerals comprise the dominant mass fraction of the atmospheric aerosol burden. As all geologists know, they are a highly heterogeneous mixture. However, among atmospheric scientists they are commonly treated as a fairly uniform group, and one whose interaction with radiation is widely assumed to be unpredictable. Given their abundances, large total surface areas, and reactivities, their role in influencing climate will require increased attention as climate models are refined.
The chimeric eukaryote: Origin of the nucleus from the karyomastigont in amitochondriate protists
Authors: Margulis Lynn , Dolan Michael F. , Guerrero Ricardo
Published: July 2002

We present a testable model for the origin of the nucleus, the
membrane-bounded organelle that defines eukaryotes. A chimeric cell
evolved via symbiogenesis by syntrophic merger between an
archaebacterium and a eubacterium. The archaebacterium, a
thermoacidophil resembling extant
Thermoplasma
,
generated hydrogen sulfide to protect the eubacterium, a heterotrophic
swimmer comparable to
Spirochaeta
or
Hollandina
that oxidized sulfide to sulfur. Selection
pressure for speed swimming and oxygen avoidance led to an ancient
analogue of the extant cosmopolitan bacterial consortium
“Thiodendron latens.” By eubacterial-archaebacterial genetic
integration, the chimera, an amitochondriate heterotroph, evolved. This
“earliest branching protist” that formed by permanent DNA
recombination generated the nucleus as a component of the
karyomastigont, an intracellular complex that assured genetic
continuity of the former symbionts. The karyomastigont organellar
system, common in extant amitochondriate protists as well as in
presumed mitochondriate ancestors, minimally consists of a single
nucleus, a single kinetosome and their protein connector. As
predecessor of standard mitosis, the karyomastigont preceded free
(unattached) nuclei. The nucleus evolved in karyomastigont ancestors by
detachment at least five times (archamoebae, calonymphids, chlorophyte
green algae, ciliates, foraminifera). This specific model of syntrophic
chimeric fusion can be proved by sequence comparison of functional
domains of motility proteins isolated from candidate taxa.
Reciprocity and Change within the Affective Family Environment in Early Adolescence
Authors: Stemmler Mark , Petersen Anne C.
Published: July 2002

This study examined: (1) the extent and change of affective relationships between young adolescents and their parents over a two-year period; and (2) the amount of reciprocity or concordance of family feelings. Relationship patterns were examined longitudinally from the child’s sixth to eighth grade in school (Petersen, 1984). Mothers, fathers, and adolescents completed the Lowman Inventory of Family Feelings (LIFF; Lowman, 1974, 1980). The results are based on a longitudinal sample of 54 complete triads and between 128 and 284 dyads depending on measurement point and informant. Family feelings were positive overall, but declined by eighth grade. Here, no differences in results depending on the gender of the adolescent or the parent were detected. Nonreciprocity of family feelings was only present in sixth grade but not in eighth grade. At sixth grade, boys especially, shared less positive family feelings. Results indicate the importance of studying the quality and change of parent-offspring relationships across adolescence.
The Assessment of Local Tolerance, Acute Toxicity, and DNA Biodistribution Following Particle-Mediated Delivery of a DNA Vaccine to Minipigs
Authors: Pilling Andrew M. , Harman Risa M. , Jones Stewart A. , Mccormack Nicola A.M. , Lavender Debbie , Haworth Richard
Published: July 2002

Particle-mediated DNA delivery was used to administer a DNA vaccine against Hepatitis B to minipigs. The study represented one arm of the safety evaluation program for this product and was designed to assess local tolerance, acute toxicity, and biodistribution of the DNA plasmid. The vaccine was given to 4 groups of minipigs that were sacrificed at 2, 28, 56, or 141 days after treatment. The procedure was well tolerated with mild local skin reactions at 2 days postdosing and no evidence of systemic toxicity. By 28 days the skin lesions had regressed apart from a low grade perivascular mononuclear cell infiltrate in the upper dermis, together with a small number of phagocytosed gold particles. This infiltrate persisted up to 141 days. The expressed HBsAg was detected by immunohistochemistry in keratinocytes (usually in association with an intranuclear gold particle) at 2 days but not at later time points. Polymerase chain reaction (PCR) was used to assay treatment sites and selected internal organs to evaluate biodistribution and persistence of the DNA plasmid. At 2 days the plasmid was detected in the treatment sites and also in the inguinal lymph nodes. At day 57 it was present in the treatment sites only and by day 141 appeared to have cleared. The results from this study demonstrate that particle-mediated gene delivery was well tolerated in the minipig. The biodistribution and persistence of the plasmid was within acceptabl e limits for this type of vaccine. As the minipig is regarded as a good model for humans these data support the concept that particle-mediated DNA delivery will be safe in human clinical applications.
Periosteal Hyperostosis (Exostosis) in DBA/1 Male Mice
Authors: Schuh Joann C.L. , Hall Randy , Lambert Dina , Harrington Kim , Mohler Ken , Barone Dauphine
Published: July 2002

Periosteal hyperostosis (exostosis) was identified in 5.9% (11/188) of DBA/1 male mice 10—14 weeks old used for collagen-induced arthritis (CIA) efficacy testing of immunomodulatory biologics. Mice with and without CIA in the affected limb, and also control and treated groups, were involved, with bilateral lesions in one mouse. Hyperostosis was characterized by circumferential and raised masses of variable location, length, and laterality, generally external to but occasionally breaching the periosteum of the metatarsals, metacarpals, tibia, femur, and humerus. Proportionally, the hyperostotic foci consisted of cancellous and woven bone, followed by osteoid, cartilage, and fibrous connective tissue and rarely infl ammatory cells. A displaced, presumably pathological fracture with callus formation was a concurrent lesion in only one case. Tartrate-resistant acid phosphatase-positive cells were frequent at bony interfaces, indicating an active resorptive process. Periosteal hyperostosi s is an incidental and potentially common finding in DBA/1 mice. Underreporting may occur due to the male bias in disease expression of this CIA model, sampling bias (generally paws only), tissue obliteration in the presence of CIA, and lack of comprehensive historical data on the background and aging lesions in this strain of mouse. Identification of such confounding bony lesions is important to the interpretation of efficacy studies, and suggests the need to further examine the biology of bone development in this strain of mouse.
Equilibrium and Disequilibrium Dynamics in the 1930s
Authors: Zappia Carlo
Published: July 2002

Notwithstanding considerable efforts by at least two generations of economic theorists, the state of art of general equilibrium theory in the Arrow-Debreu framework is still extremely unsatisfactory, especially with respect to the treatment of the time dimension. Indeed, it is now taken for granted even among general equilibrium theorists that, to play a significant role, equilibrium analysis must account for individual agents' expectations about the uncertain future, and that the Arrow-Debreu procedure of collapsing the entire decision process at an initial date is to be interpreted, at most, as a counterfactual argument, the main message of the Arrow-Debreu approach being that “one cannot argue that markets co-ordinate activity if there are many of them missing” (Hahn 1995, p. 12).
Relationship between HIV‐1 viral load and continued drug use in untreated infected injection drug users
Authors: CARRIERI MARIA PATRIZIA , TAMALET CATHERINE , VLAHOV DAVID , YAHI NOUARA , CHESNEY MARGARET , MOATTI JEAN PAUL
Published: July 2002

The role of continued drug use in development of AIDS has been investigated, using mainly CD4+ cells as outcome variable. The objective of this study was to verify whether continued drug use can influence HIV‐1 plasma viral load.We used cross‐sectional enrolment data of the HIV‐infected IDUs cohort study Manif 2000 (October 1995‐October 1996), recruiting patients in hospital departments of Marseilles, Nice and Paris suburbs. To minimize biases due to differential access to health care, only patients receiving outpatient care for at least 2 years but with no antiretroviral treatment were selected for analysis (n = 108). Available information regarding clinical and laboratory information from medical records and clinical examination as well as drug use and HIV‐related risk practices were obtained by a face‐to‐face and a self‐administered questionnaire. Patients denying recent heroin injection were cross‐validated by a serological assay to detect morphine. Forty‐two patients (39%) reported recent heroin injection; among those denying recent use (n=66), eight (positive for serum morphine assay) were re‐classified as IDUs. A difference of 0.35 log in viral load was observed between active and ex‐IDUs which increases (0.6 log, p=0.03) in those who have been using drugs for 10 years or more.This result persisted when adjusted for CD4+ counts, clinical stage or years since diagnosis. Continued drug use may have a significant but limited impact on HIV viral load only in patients with a longer history of drug use. Consequences of persisting drug use on long‐term progression to AIDS has to be investigated further.
Tyrosine Phosphorylation and Src Family Kinases Control Keratinocyte Cell–Cell Adhesion
Authors: Calautti Enzo , Cabodi Sara , Stein Paul L. , Hatzfeld Mechthild , Kedersha Nancy , Paolo Dotto G.
Published: July 2002

In their progression from the basal to upper differentiated layers of the epidermis, keratinocytes undergo significant structural changes, including establishment of close intercellular contacts. An important but so far unexplored question is how these early structural events are related to the biochemical pathways that trigger differentiation. We show here that β-catenin, γ-catenin/plakoglobin, and p120-Cas are all significantly tyrosine phosphorylated in primary mouse keratinocytes induced to differentiate by calcium, with a time course similar to that of cell junction formation. Together with these changes, there is an increased association of α-catenin and p120-Cas with E-cadherin, which is prevented by tyrosine kinase inhibition. Treatment of E-cadherin complexes with tyrosine-specific phosphatase reveals that the strength of α-catenin association is directly dependent on tyrosine phosphorylation. In parallel with the biochemical effects, tyrosine kinase inhibition suppresses formation of cell adhesive structures, and causes a significant reduction in adhesive strength of differentiating keratinocytes. The Fyn tyrosine kinase colocalizes with E-cadherin at the cell membrane in calcium-treated keratinocytes. Consistent with an involvement of this kinase, fyn-deficient keratinocytes have strongly decreased tyrosine phosphorylation levels of β- and γ-catenins and p120-Cas, and structural and functional abnormalities in cell adhesion similar to those caused by tyrosine kinase inhibitors. Whereas skin of fyn−/− mice appears normal, skin of mice with a disruption in both the fyn and src genes shows intrinsically reduced tyrosine phosphorylation of β-catenin, strongly decreased p120-Cas levels, and important structural changes consistent with impaired keratinocyte cell adhesion. Thus, unlike what has been proposed for oncogene-transformed or mitogenically stimulated cells, in differentiating keratinocytes tyrosine phosphorylation plays a positive role in control of cell adhesion, and this regulatory function appears to be important both in vitro and in vivo.
Antiviral Protection and Germinal Center Formation, But Impaired B Cell Memory in the Absence of CD19
Authors: Fehr Thomas , Rickert Robert C. , Odermatt Bernhard , Roes Jürgen , Rajewsky Klaus , Hengartner Hans , Zinkernagel Rolf M.
Published: July 2002

Coligation of CD19, a molecule expressed during all stages of B cell development except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a factor of 100. The cytoplasmic tail of CD19 contains nine tyrosine residues as possible phosphorylation sites and is postulated to function as the signal transducing element for complement receptor (CR)2. Generation and analysis of CD19 gene–targeted mice revealed that T cell–dependent (TD) antibody responses to proteinaceous antigens were impaired, whereas those to T cell–independent (TI) type 2 antigens were normal or even augmented. These results are compatible with earlier complement depletion studies and the postulated function of CD19. To analyze the role of CD19 in antiviral antibody responses, we immunized CD19−/− mice with viral antigens of TI-1, TI-2, and TD type. The effect of CD19 on TI responses was more dependent on antigen dose and replicative capacity than on antigen type. CR blocking experiments confirmed the role of CD19 as B cell signal transducer for complement. In contrast to immunization with protein antigens, infection of CD19−/− mice with replicating virus led to generation of specific germinal centers, which persisted for >100 d, whereas maintenance of memory antibody titers as well as circulating memory B cells was fully dependent on CD19. Thus, our study confirms a costimulatory role of CD19 on B cells under limiting antigen conditions and indicates an important role for B cell memory.
The Complete Nucleotide Sequence of the Human Immunoglobulin Heavy Chain Variable Region Locus
Authors: Matsuda Fumihiko , Ishii Kazuo , Bourvagnet Patrice , Kuma Kei-ichi , Hayashida Hidenori , Miyata Takashi , Honjo Tasuku
Published: July 2002

The complete nucleotide sequence of the 957-kb DNA of the human immunoglobulin heavy chain variable (VH) region locus was determined and 43 novel VH segments were identified. The region contains 123 VH segments classifiable into seven different families, of which 79 are pseudogenes. Of the 44 VH segments with an open reading frame, 39 are expressed as heavy chain proteins and 1 as mRNA, while the remaining 4 are not found in immunoglobulin cDNAs. Combinatorial diversity of VH region was calculated to be ∼6,000. Conservation of the promoter and recombination signal sequences was observed to be higher in functional VH segments than in pseudogenes. Phylogenetic analysis of 114 VH segments clearly showed clustering of the VH segments of each family. However, an independent branch in the tree contained a single VH, V4-44.1P, sharing similar levels of homology to human VH families and to those of other vertebrates. Comparison between different copies of homologous units that appear repeatedly across the locus clearly demonstrates that dynamic DNA reorganization of the locus took place at least eight times between 133 and 10 million years ago. One nonimmunoglobulin gene of unknown function was identified in the intergenic region.
Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Engagement Delivers an Inhibitory Signal through the Membrane-Proximal Region in the Absence of the Tyrosine Motif in the Cytoplasmic Tail
Authors: Nakaseko Chiaki , Miyatake Shoichiro , Iida Tomohiko , Hara Satoru , Abe Ryo , Ohno Hiroshi , Saito Takashi
Published: July 2002

Cytotoxic T lymphocyte antigen 4 (CTLA-4) is a T cell costimulation receptor that delivers inhibitory signals upon activation. Although the tyrosine-based motif (165YVKM) within its cytoplasmic tail has been shown to associate in vitro with Src homology 2 domain–containing tyrosine phosphatase (SHP-2) and phosphatidylinositol 3 kinase upon phosphorylation, the mechanism of negative signaling remains unclear. Here, we report a new mechanism of negative signaling based on the analysis of murine T cell clones transfected with various mutants of CTLA-4. Upon T cell activation by cross-linking with anti-CD3 and anti-CD28 antibodies, CTLA-4 engagement inhibited both proliferation and interleukin 2 production in tyrosine mutants as well as in wild-type CTLA-4 transfectants. Furthermore, the mutant CTLA-4 lacking most of the cytoplasmic region strongly suppressed interleukin 2 production as well. These data suggest that negative signals by CTLA-4 could be mediated through the membrane-proximal region of CTLA-4 but not through the YVKM motif and that the association of CTLA-4 with SHP-2 is not required for CTLA-4–mediated suppression of T cell activation.
Generation of Interferon α–Producing Predendritic Cell (Pre-Dc)2 from Human Cd34+ Hematopoietic Stem Cells
Authors: Blom Bianca , Ho Stephen , Antonenko Svetlana , Liu Yong-Jun
Published: July 2002

Upon viral stimulation, the natural interferon (IFN)-α/β–producing cells (IPCs; also known as pre-dendritic cells (DCs 2) in human blood and peripheral lymphoid tissues rapidly produce huge amounts of IFN-α/β. After performing this innate antiviral immune response, IPCs can differentiate into DCs and strongly stimulate T cell–mediated adaptive immune responses. Using four-color immunofluorescence flow cytometry, we have mapped the developmental pathway of pre-DC2/IPCs from CD34+ hematopoietic stem cells in human fetal liver, bone marrow, and cord blood. At least four developmental stages were identified, including CD34++CD45RA− early progenitor cells, CD34++CD45RA+ late progenitor cells, CD34+CD45RA++CD4+interleukin (IL)-3Rα++ pro-DC2, and CD34−CD45RA++ CD4+IL-3Rα++ pre-DC2/IPCs. Pro-DC2s have already acquired the capacity to produce large amounts of IFN-α/β upon viral stimulation and to differentiate into DCs in culture with IL-3 and CD40 ligand. CD34++CD45RA− early progenitor cells did not have the capacity to produce large amounts of IFN-α/β in response to viral stimulation; however, they can be induced to undergo proliferation and differentiation into IPCs/pre-DC2 in culture with FLT3 ligand.
Human Monocyte–Derived Dendritic Cells Induce Naive T Cell Differentiation into T Helper Cell Type 2 (Th2) or Th1/Th2 Effectors
Authors: Tanaka Hiroyuki , Demeure Christian E. , Rubio Manuel , Delespesse Guy , Sarfati Marika
Published: July 2002

The subset of dendritic cells (DCs) and the nature of the signal inducing DC maturation determine the capacity of DCs to generate polarized immune responses. In this study, we show that the ability of human monocyte-derived DCs (myeloid DC1) to promote T helper type 1 (Th1) or Th2 differentiation was also found to be critically dependent on stimulator/responder ratio. At a low ratio (1:300), mature DCs that have been differentiated after inflammatory (Staphylococcus aureus Cowan 1 or lipopolysaccharide) or T cell–dependent (CD40 ligand) stimulation induced naive T cells to become Th2 (interleukin [IL]-4+, IL-5+, interferon γ) effectors. Th2 differentiation was dependent on B7–CD28 costimulation and enhanced by OX40–OX40 ligand interactions. However, high DC/T cell ratio (1:4) favored a mixed Th1/Th2 cell development. Thus, the fact that the same DC lineage stimulates polarized Th1 or Th2 responses may be relevant since it allows the antigen-presenting cells to initiate an appropriate response for the signal received at the peripheral sites. Controlling the number and the rate of DC migration to the T cell areas in lymphoid tissues may be important for the therapeutic use of DCs.
Cyclic Nucleotide–Gated Channels Colocalize with Adenylyl Cyclase in Regions of Restricted Camp Diffusion
Authors: Rich Thomas C. , Fagan Kent A. , Nakata Hiroko , Schaack Jerome , Cooper Dermot M.F. , Karpen Jeffrey W.
Published: July 2002

Cyclic AMP is a ubiquitous second messenger that coordinates diverse cellular functions. Current methods for measuring cAMP lack both temporal and spatial resolution, leading to the pervasive notion that, unlike Ca2+, cAMP signals are simple and contain little information. Here we show the development of adenovirus-expressed cyclic nucleotide–gated channels as sensors for cAMP. Homomultimeric channels composed of the olfactory α subunit responded rapidly to jumps in cAMP concentration, and their cAMP sensitivity was measured to calibrate the sensor for intracellular measurements. We used these channels to detect cAMP, produced by either heterologously expressed or endogenous adenylyl cyclase, in both single cells and cell populations. After forskolin stimulation, the endogenous adenylyl cyclase in C6-2B glioma cells produced high concentrations of cAMP near the channels, yet the global cAMP concentration remained low. We found that rapid exchange of the bulk cytoplasm in whole-cell patch clamp experiments did not prevent the buildup of significant levels of cAMP near the channels in human embryonic kidney 293 (HEK-293) cells expressing an exogenous adenylyl cyclase. These results can be explained quantitatively by a cell compartment model in which cyclic nucleotide–gated channels colocalize with adenylyl cyclase in microdomains, and diffusion of cAMP between these domains and the bulk cytosol is significantly hindered. In agreement with the model, we measured a slow rate of cAMP diffusion from the whole-cell patch pipette to the channels (90% exchange in 194 s, compared with 22–56 s for substances that monitor exchange with the cytosol). Without a microdomain and restricted diffusional access to the cytosol, we are unable to account for all of the results. It is worth noting that in models of unrestricted diffusion, even in extreme proximity to adenylyl cyclase, cAMP does not reach high enough concentrations to substantially activate PKA or cyclic nucleotide–gated channels, unless the entire cell fills with cAMP. Thus, the microdomains should facilitate rapid and efficient activation of both PKA and cyclic nucleotide–gated channels, and allow for local feedback control of adenylyl cyclase. Localized cAMP signals should also facilitate the differential regulation of cellular targets.
Complex Brjuno functions
Authors: Marmi Stefano , Moussa Pierre , Yoccoz Jean-Christophe
Published: July 2002

The Brjuno function arises naturally in the study of analytic small divisors problems in one dimension. It belongs to

BMO

(

T

1

)

\hbox {BMO}({\mathbb {T}}^{1})

and it is stable under Hölder perturbations. It is related to the size of Siegel disks by various rigorous and conjectural results. In this work we show how to extend the Brjuno function to a holomorphic function on

H

/

Z

{\mathbb {H}}/{\mathbb {Z}}

, the complex Brjuno function. This has an explicit expression in terms of a series of transformed dilogarithms under the action of the modular group. The extension is obtained using a complex analogue of the continued fraction expansion of a real number. Since our method is based on the use of hyperfunctions, it applies to less regular functions than the Brjuno function and it is quite general. We prove that the harmonic conjugate of the Brjuno function is bounded. Its trace on

R

/

Z

{\mathbb {R}}/{\mathbb {Z}}

is continuous at all irrational points and has a jump of

π

/

q

\pi /q

at each rational point

p

/

q
∈

Q

p/q\in {\mathbb {Q}}

.
Properties of convergence groups and spaces
Authors: Freden Eric
Published: July 2002

This paper discusses algebraic and topological conditions that are consequences of a convergence group action.
BioABACUS: a database of abbreviations and acronyms in biotechnology and computer science.
Authors: Rimer M , O'Connell M
Published: July 2002

SUMMARY: BioABACUS (Biotechnology AB breviation and A cronym U ncovering Service) a new, searchable, cross-referenced, database of abbreviations and acronyms in biotechnology and computer science is described. AVAILABILITY: BioABACUS is accessible over the World Wide Web at http://www.nmsu.edu/molbio/bioABACUShome.htm. CONTACT: mrimer@nmsu.edu,moconnel@nmsu.edu
STRIRED: graphical analysis of string repeats.
Authors: Iazzetti G , Chiusano M L , Calogero R A
Published: July 2002

SUMMARY: STRIRED is a toolkit to generate a graphical picture of the distribution of 4- to 6-mer repeats in a set of user-defined nucleic acid sequences. AVAILABILITY: The STRIRED package can be downloaded as self-extracting archive (strired.exe) by anonymous FTP from biol.dgbm.unina.it (143.225.252.1), in the directory /software/win95/STRIRED. CONTACT: calogero@biol.dgbm.unina. it.
DIAMOD: display and modeling of DNA bending.
Authors: Dlakic M , Harrington R E
Published: July 2002

MOTIVATION: DIAMOD (Displayandmodeling ofDNA) was created as a user-friendly software for exploring and better understanding DNA structural variations, particularly DNA bending. It was intended to be as open as possible so that any of the existing or future predictive models can be used with it. RESULTS: DIAMOD features graphic display and interactive manipulation of DNA molecules on the screen. Since it works with di-, tri- or tetranucleotide models supplied as external files of angular parameters, it was recently used to evaluate critically all available predictive models for DNA bending. The program has a unique option to insert bends at defined positions in DNA sequence independently of the currently used model, which enables the simulation of both intrinsic and protein-induced kinking. Finally, many output file formats facilitate the sharing of data with other programs and the creation of visually pleasing images. AVAILABILITY: The program is available on request to academic users free of charge. It will be distributed via the WWW (http://www-personal.umich.edu/ mensur/software.html). Users with no network access can get a copy directly from the author. CONTACT: mensur@umich.edu
Optimization of ribosomal RNA profile alignments.
Authors: O'Brien E A , Notredame C , Higgins D G
Published: July 2002

MOTIVATION: Large alignments of ribosomal RNA sequences are maintained at various sites. New sequences are added to these alignments using a combination of manual and automatic methods. We examine the use of profile alignment methods for rRNA alignment and try to optimize the choice of parameters and sequence weights. RESULTS: Using a large alignment of eukaryotic SSU rRNA sequences as a test case, we empirically compared the performance of various sequence weighting schemes over a range of gap penalties. We developed a new weighting scheme which gives most weight to the sequences in the profile that are most similar to the new sequence. We show that it gives the most accurate alignments when combined with a more traditional sequence weighting scheme. AVAILABILITY: The source code of all software is freely available by anonymous ftp from chah.ucc.ie in the directory /home/ftp/pub/emmet,in the compressed file PRNAA.tar: CONTACT: emmet@chah.ucc.ie, des@chah.ucc.ie
The new Virgil database: a service of rich links.
Authors: Achard F , Cussat-Blanc C , Viara E , Barillot E
Published: July 2002

MOTIVATION: Links between biological objects are frequently used by researchers in biology. However, many of the links found in public databases are insufficiently documented and difficult to retrieve. Virgil introduces the idea of a rich link, i.e. the link itself and the related pieces of information. Virgil was developed to collect, manage and distribute such links. RESULTS: At the moment, Virgil is a prototype database that contains rich links between GDB genes and Genbank sequences. The Virgil data model is rich enough to describe comprehensively a link between two biological objects. Two different means to access the information were developed: a schema-driven Web interface and a CORBA server. AVAILABILITY: http://www.infobiogen. fr/services/virgil/home.html CONTACT: Frederic.Achard@infobiogen.fr
Molecules to maps: tools for visualization and interaction in support of computational biology.
Authors: Kraemer E T , Ferrin T E
Published: July 2002

The volume of data produced by genome projects, X-ray crystallography, NMR spectroscopy, and electron and confocal microscopy present the bioinformatics community with new challenges for analyzing, understanding, and exchanging this data. At the 1998 Pacific Symposium on Biocomputing, a track entitled 'Molecules to Maps: Tools for Visualization and Interaction in Computational Biology' provided tool developers and users with the opportunity to discuss advances in tools and techniques to assist scientists in evaluating, absorbing, navigating, and correlating this sea of information, through visualization and user interaction. In this paper we present these advances and discuss some of the challenges that remain to be solved.
Genetic Simulation Library.
Authors: Conery J , Lynch M
Published: July 2002

SUMMARY: The Genetic Simulation Library (GSL) is a set of C++ programs and classes that can be used in individual-based simulation models of plant and animal populations. The classes in this library build representations of genes for a wide variety of different types of organisms, from asexually reproducing single-cell organisms to chromosome-structured sexually reproducing species. AVAILABILITY: http://www.csi.uoregon.edu/projects/genetics/GSL . Free for non-commercial applications; others should contact the author.
bioWidgets: data interaction components for genomics.
Authors: Fischer S , Crabtree J , Brunk B , Gibson M , Overton G C
Published: July 2002

MOTIVATION: The presentation of genomics data in a perspicuous visual format is critical for its rapid interpretation and validation. Relatively few public database developers have the resources to implement sophisticated front-end user interfaces themselves. Accordingly, these developers would benefit from a reusable toolkit of user interface and data visualization components. RESULTS: We have designed the bioWidget toolkit as a set of JavaBean components. It includes a wide array of user interface components and defines an architecture for assembling applications. The toolkit is founded on established software engineering design patterns and principles, including componentry, Model-View-Controller, factored models and schema neutrality. As a proof of concept, we have used the bioWidget toolkit to create three extendible applications: AnnotView, BlastView and AlignView.
DINAMO: interactive protein alignment and model building.
Authors: Bentz J , Baucom A , Hansen M , Gregoret L
Published: July 2002

MOTIVATION: To facilitate the process of structure prediction by both comparative modeling and fold recognition, we describe DINAMO, an interactive protein alignment building and model evaluation tool that dynamically couples a multiple sequence alignment editor to a molecular graphics display. DINAMO allows the user to optimize the alignment and model to satisfy the known heuristics of protein structure by means of a set of analysis tools. The analysis tools return information to both the alignment editor and graphics model in the form of visual cues (color, shape), allowing for rapid evaluation. Several analysis tools may be employed, including residue conservation, residue properties (charge, hydrophobicity, volume), residue environmental preference, and secondary structure propensity. RESULTS: We demonstrate DINAMO by building a model for submission in the 3rd annual Critical Assessment of Techniques for Protein Structure Prediction (CASP3) contest. AVAILABILITY: DINAMO is freely available as a local application or Web-based Java applet at http://tito.ucsc.edu/dinamo
The early days of bioinformatics publishing
Authors: Roberts Richard J.
Published: July 2002

A brief history of the early days of publishing in the bioinformatics field is presented.

Contact: roberts@neb.com
Self-organization and competition in the immune response to
cancer invasion: a phase-orientated computational model of
oncogenesis
Authors: Adrian Oprisan Sorinel , Ardelean Aurel , Frangopol Petre T.
Published: July 2002

Motivation: Recent studies indicate that fractal dimensions can uncover aspects of cellular dynamics prior to pathological manifestation. In this respect we are interested in building a computational model of oncogenesis able to generate patterns with the same fractal dimension spectrum as the in vivo tumor.

Results: A new theoretical model incorporating a systemic view of oncogenesis in a computational model was proposed. The tumor growth is viewed as competition for resources between the two self-organizing subsystems: the neoplastic and the immune. Numerical simulations revealed that tumor escape can be uncovered in some earlier stage of the immune-system–tumor interaction using multifractal measures. The described computational model is able to simulate also the case of immune, surgical, chemical and radiotherapeutical treatment, as well as their effects.

Availability: The software used is available on request from the authors.

Contact: Sorinel Oprisan, University of New Orleans, Department of Psychology, New Orleans, LA 70148, USA. soprisan@uno.edu
HELM: searching for helix motifs within protein sequences
Authors: Facchiano Angelo M.
Published: July 2002

Summary: HELM is a web tool designed to automate the analysis of protein sequences searching for alpha helix motifs. This analysis can be useful in protein engineering studies, aimed at the identification of regions to be modified in order to obtain more suitable features of local and/or global stability.

Availability: The tool is available to academic and commercial institutions at the URL http://crisceb.area.na.cnr.it/angelo/PROTEIN_TOOLS/HELM/

Contact: angelo@crisceb.area.na.cnr.it
The development of the external features of the platypus (
Ornithorhynchus anatinus
)
Authors: Manger Paul R. , Hall Leslie S. , Pettigrew John D.
Published: July 2002

The present study describes the post–hatching development of the external features of the platypus. Specimens range in age from the day of hatching through to six months old, and provide the first comprehensive view of the developmental sequence of these features. Various features, those specific to the platypus, those specific to monotremes and those shared with marsupials and eutherians, are described. Features specific to the platypus, including the bill and webbing of the forefeet, are seen to develop precociously. Many features show similarities to marsupials, although marsupials show differential development both in timing and in morphology. The developmental progression is related to the age, in days, although the exact age of the specimens is unclear, and relies on ages given to the specimens at the time of collection, sometimes as long as 70 years ago. Despite this, the progression of development of these features suggests that the ageing given is relatively accurate.
The reverse transcriptase model of somatic hypermutation
Authors: Steele Edward J. , Blanden Robert V.
Published: July 2002

The evidence supporting the reverse transcriptase model of somatic hypermutation is critically reviewed. The model provides a coherent explanation for many apparently unrelated findings. We also show that the somatic hypermutation pattern in the humanBCL–6gene can be interpreted in terms of the reverse transcriptase model and the notion of feedback of somatically mutated sequences to the germline over evolutionary time.
Near-field scanning in the time domain on a spherical surface— A formulation using the free-space Green’s function
Authors: Koc Sencer , Civi O. Aydin , Buyukdura O. Merih
Published: July 2002

Two formulations for determining the characteristics of an unknown source of acoustic waves using the measurement of its field at its near zone are presented. The measurement in both cases is to be performed on a spherical scan surface which encapsulates the source. The first is for an ideal probe which measures the field at its location. The knowledge of the field is sufficient; its normal derivative is not required. In the second formulation a realistic probe is considered. This time it is required only that the probe has an axially symmetric receiving characteristic. With this formulation, the time functions which characterize the source are found using only the signal at the output of the probe. Both formulations are such that they are not specific to the scan surface radius. Furthermore, they are entirely in the time domain, requiring no inverse Fourier transformations left to be performed.
Acoustic scattering of a plane wave by two spherical elastic shells above the coincidence frequency
Authors: Huang H. , Gaunaurd G. C.
Published: July 2002

The acoustic scattering by two fluid-filled spherical elastic shells in close proximity to each other and insonified by plane waves at arbitrary angles of incidence is analyzed exactly in the frequency range that includes the midfrequency or coincidence enhancement region of the backscattered echoes. The incident and scattered wave fields are expanded in terms of the classical modal series and the addition theorem for the spherical wave functions is used to determine the exact expression for the sound fields scattered by each spherical elastic shell in the presence of the other, referred to coordinate systems at the centers of either spherical shell. The solution to the scattering problem is found by simultaneously solving the Helmholtz equations governing the wave motion in the fluid medium in which the two shells are submerged as well as in the fluid media contained in the shells, together with the two sets of equations of motion of the two elastic shells obtained from the complete three-dimensional elasticity theory after satisfying the boundary conditions at all fluid-shell interfaces as well as the far-field radiation condition. Again, the numerical computation of the scattered pressure wave involves the solution of a truncated ill-conditioned complex matrix system the size of which depends on how many terms of the modal series are required for convergence. This in turn depends on the value of the frequency, and on the proximity of the two spherical elastic shells. The ill-conditioned matrix equation is solved using the Gauss–Seidel iteration method. Backscattered and bistatic echoes from two identical spherical elastic shells are extensively calculated. The result also exhibits the large enhancement present in the backscattered echoes for the endfire situation after the midfrequency or coincidence enhancement has taken place. This can be attributed to the effects of focusing by the front elastic shell and to the reflection and refocusing by the back elastic shell of the a0 Lamb wave reradiation in the observer’s direction.
Short pulse acoustic excitation of microbubbles
Authors: Pace Nicholas G. , Cowley Alastair , Campbell A. M.
Published: July 2002

When a bubble is excited at or near its natural frequency it is a very effective scatterer and absorber of sound. In fact at resonance, scattering and absorption cross sections are of the order of 1000 times greater than the geometric cross section for typical marine microbubbles. As with any resonant system, a bubble takes a finite, albeit short time to ring up to steady-state oscillation and continues to oscillate for a finite time after the driving force ceases. A number of studies have been carried out to attempt to describe how acoustic absorption and backscatter depend on the duration of the driving force. Most notable of these are the backscatter measurements for short pulses in near surface sea water [Akulichev et al., Sov. Phys. Acoust. 23(3), 177–180 (1986)] and the forward transmission laboratory measurements for short pulse lengths at 120 kHz [H. R. Suiter, J. Acoust. Soc. Am. 91, 1383–1387 (1992)]. Akulichev observed a decrease in acoustic backscatter for short pulses at three discrete frequencies, whereas Suiter found no corresponding enhancement in forward transmission. This paper details a comprehensive study which measured acoustic attenuation through a well defined bubble cloud over the frequency range 20–200 kHz and for pulse lengths from 20 cycles down to a single cycle using a parametric transmitter. The experiment simulated the conditions for which a decrease in attenuation with decreasing pulse length might have been expected. No effect was observed for two different but well-defined bubble distributions.
Speech intelligibility enhancement using hearing-aid array processing
Authors: Saunders Gabrielle H. , Kates James M.
Published: July 2002

Microphone arrays can improve speech recognition in noise for hearing-impaired listeners by suppressing interference coming from other than the desired signal direction. In a previous paper [J. M. Kates and M. R. Weiss, J. Acoust. Soc. Am. 99, 3138–3148 (1996)], several array-processing techniques were evaluated in two rooms using the AI-weighted array gain as the performance metric. The array consisted of five omnidirectional microphones having uniform 2.5-cm spacing, oriented in the endfire direction. In this paper, the speech intelligibility for two of the array processing techniques, delay-and-sum beamforming and superdirective processing, is evaluated for a group of hearing-impaired subjects. Speech intelligibility was measured using the speech reception threshold (SRT) for spondees and speech intelligibility rating (SIR) for sentence materials. The array performance is compared with that for a single omnidirectional microphone and a single directional microphone having a cardioid response pattern. The SRT and SIR results show that the superdirective array processing was the most effective, followed by the cardioid microphone, the array using delay-and-sum beamforming, and the single omnidirectional microphone. The relative processing ratings do not appear to be strongly affected by the size of the room, and the SRT values determined using isolated spondees are similar to the SIR values produced from continuous discourse.
Comparison of monaural (CMR) and binaural (BMLD) masking release
Authors: van de Par Steven , Kohlrausch Armin
Published: July 2002

Release of masking for a sinusoidal signal of 5 kHz masked by a 25-Hz-wide noise band centered around 5 kHz was measured. The masking release was provided by a second noise band that was comodulated with the on-frequency masker band. For CMR configurations the second noise band was centered at 3 kHz and presented to the ipsi-lateral or to the contra-lateral ear. For BMLD configurations the second band was centered at 5 kHz and presented to the contra-lateral ear. In another condition the second noise band also contained the signal presented with such a phase that maximal differences in the envelope resulted. For both the CMR and the BMLD paradigm, the masking release for the latter condition was larger than for the former condition. To assess further the similarity between monaural and binaural masking release, a sinusoidal masker and either a noise or a sinusoidal signal were used. The data indicate that, at high frequencies, envelope correlation may be a valuable cue for CMR as well as for the BMLD.
Measurements of high-frequency acoustic scattering from seabed vegetation
Authors: Lyons Anthony P. , Pouliquen Eric
Published: July 2002

Knowledge of the acoustic properties of seabed vegetation is required for accurate seafloor characterization in many shallow-water sites. As the study and modeling of acoustic scattering from seabed vegetation have been very limited to date, characteristics such as the dependence of scattering strength on grazing angle or frequency are still largely unknown. In order to quantify these properties, acoustic scattering experiments were conducted in beds of Posidonia Oceanica at several sites near the islands of Elba and Sardinia, Italy and in Saros Bay, Turkey with side-scan, single beam, and parametric transducers. Normal incidence broadband measurements were made at both the primary (40 kHz) and secondary (8 kHz) frequencies of a parametric sonar. Oblique incidence measurements were made with linear sources at frequencies from 29 to 385 kHz and with coverage over a large range of grazing angles. Results of these measurements are presented in terms of scattering strength versus grazing angle as well as scattered amplitude statistics. The mean scattering strength of the posidonia beds was found to be quite high (≊−22 dB) and also to be fairly constant over most of the range of grazing angles, indicative of a volume scattering mechanism. Ultimately this effort will aid in the development of theoretical models of acoustic backscatter in seagrass covered sites.
Conformation transition and behavior of the ultrasonic attenuation in cyclohexanol and aqueous solution of cyclohexanol
Authors: Mirzaev S. Z. , Khabibullaev P. K. , Saidov A. A. , Kononenko V. S. , Shinder I. I.
Published: July 2002

Experimental results for the absorption of ultrasonic waves in pure cyclohexanol and aqueous solution of cyclohexanol in the frequency range 0.06–150 MHz and at temperatures 30, 40, 50, and 60 °C are reported. The ultrasonic relaxation spectra of pure cyclohexanol investigated show two relaxation processes in contrast to those aqueous solutions of cyclohexanol, which indicate a single relaxation process. One relaxation process is located in the frequency range 0.01–1 MHz and the second in the range 0.8–10 GHz. The process with the lower relaxation frequency has been assigned to the “chair”–“chair” molecular conformations.
Frequency relationships for ultrasonic activation of free microbubbles, encapsulated microbubbles, and gas-filled micropores
Authors: Miller Douglas L.
Published: July 2002

The ultrasonic activation of free microbubbles, encapsulated microbubbles, and gas-filled micropores was explored using available linear theory. Encapsulated microbubbles, used in contrast agents for diagnostic ultrasound, have relatively high resonance frequencies and damping. At 2 MHz the resonance radii are 1.75 μm for free microbubbles, 4.0 μm for encapsulated microbubbles, and 1.84 μm for gas-filled micropores. Higher-pressure amplitudes are needed to elicit equivalent subharmonic, fundamental, or second-harmonic responses from the encapsulated microbubbles, and this behavior increases for higher frequencies. If an encapsulated microbubble becomes destabilized during exposure, the resulting liberated microbubble would be about twice the linear resonance size, which would be likely to produce subharmonic signals. Scattered signals used for medical imaging purposes may be indicative of bioeffects potential: The second harmonic signal is proportional to local shear stress for a microbubble on a boundary, and a strong subharmonic signal may imply destabilization and nucleation of free-microbubble cavitation activity. The potential for bioeffects from contrast agent gas bodies decreases rapidly with increasing frequency. This information should be valuable for understanding of the etiology of bioeffects related to contrast agents and for developing exposure indices and risk management strategies for their use in diagnostic ultrasound.