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Aminoglycoside antibiotics target an internal RNA loop within the bacterial ribosomal decoding site. Here, we described the synthesis and SAR of novel 3,5-diamino-piperidine derivatives as aminoglycoside mimetics, and show they act as inhibitors of bacterial translation and growth.

Structure-activity relationships of the 3,5-diamino-piperidinyl triazine series, a novel class of bacterial translation inhibitors, are described. Optimization was focused on the triazine C-4 position in which aromatic substituents that contained electron-withdrawing groups led to potent inhibitors. The initial lack of antibacterial activity was correlated with poor cellular penetration. Whole cell antibacterial activity was achieved by linking additional aromatic moieties at the triazine C-4 position.

We introduce a novel approach in EEG data sonification for process monitoring and exploratory as well as comparative data analysis. The approach uses an excitory/articulatory speech model and a particularly selected parameter mapping to obtain auditory gestalts (or auditory objects) that correspond to features in the multivariate signals. The sonification is adaptable to patient-specific data patterns, so that only characteristic deviations from background behavior (pathologic features) are involved in the sonification rendering. Thus the approach combines data mining techniques and case-dependent sonification design to give an application-specific solution with high potential for clinical use. We explain the sonification technique in detail and present sound examples from clinical data sets.

In this paper we develop a sonification model following the Model-based Sonification approach that allows to scan high-dimensional data distributions by means of a physical object in the hand of the user. In the sonification model, the user is immersed in a 3D space of invisible but acoustically active objects which can be excited by him. Tangible computing allows to identify the excitation object (e.g. a geometric surface) with a physical object used as controller, and thus creates a strong metaphor for understanding and relating feedback sounds in response to the user's own activity, position and orientation. We explain the technique and our current implementation in detail and give examples at hand of synthetic and real-world data sets.

We determined small-angle neutron-scattering (SANS) curves of isolated GroEL ( R G = (6.20 ± 0.04) nm) and GroES ( R G = (3.07 ± 0.01) nm) and showed that the obtained structural information is compatible with the data from X-ray crystallography. Our neutron scattering investigations, along with molecular modeling, allowed us to propose the probable location of residues that were previously not resolved in the crystallographic structure. Significant differences between isolated GroEL and GroES compared to the components in complex were revealed by the scattering curves. The center-to-center distance between GroEL and GroES in the complex ( R G = (6.35 ± 0.02) nm and (2.99 ± 0.02) nm, respectively) was determined ( d = 8.6 nm).

several other RNA motifs form well-defined complexes with individual aminoglycosides, which makes these antibiotics excellent model ligands for the study of RNA recognition. The target “promiscuity” of the aminoglycosides has been attributed to two major factors: 1) their highly charged nature, which is responsible for their eletrostatically driven RNA-binding mode and 2) their conformational adaptability. Although rotation around the glycosidic bonds that link the saccharide building blocks is restricted, the remaining limited flexibility explains some adaptability toward diverse RNA targets. This restricted conformational flexibility attenuates the contribution of charged interactions between RNA and the aminoglycosides, resulting in the formation of welldefined drug complexes that are distinct from nonspecific interactions of nucleic acids with flexible polyamines such as spermidine. The term structural electrostatic complementarity has been coined for this promiscuous yet target-specific binding of aminoglycosides to RNA. Aminoglycosides derived from 4,5-disubstituted 2-deoxystreptamine (2-DOS, ring I), including neomycin (1a) and paromomycin (1b), bind to a variety of RNA sequences. Examination of structurally characterized aminoglycoside complexes reveals that the relative orientation of rings I and II is very similar, whereas the conformation around the linkages to rings III and IV is significantly variable depending on the RNA target. The apparent rigidity of the ring I/II system underlines the importance of this module for RNA recognition, attested by the fact that the 2-DOS and ring II moieties participate in key interactions that are responsible for target binding in decoding-site complexes with aminoglycosides. Whereas higher thermal factors of rings III and IV in the crystal structure of paromomycin might suggest that these sugars generally contribute less to target-specific interactions, the results presented herein suggest that the affinity of neomycin for the cognate decoding-site RNA and thus the antibacterial activity of this compound depend on an exquisitely balanced interplay of all four rings. Previous investigations of aminoglycoside mimetics derived from neamine and paromamine, both of which lack rings III and IV, confirm the key role that the ring I/II core plays in decoding-site binding. In the crystal structure of the related aminoglycoside paromomycin (1b) complexed with bacterial decoding-site RNA, the distance between the 2’-amino group of ring II and the 5’’-C atom of ring III is 3.7 =, which suggests that cross-linking these positions may yield an aminoglycoside that retains the decoding-site-bound conformation of the parent drug. To support this hypothesis, we determined the X-ray crystal structures of neomycin (1a), among the most potent aminoglycoside antibiotics of therapeutic relevance, and its conformationally restricted analogue 2 bound to a decoding-site oligonucleotide (Figure 1a). Herein, we analyze the structural characteristics of both RNA–small-molecule complexes and discuss the structural basis of aminoglycoside ligand affinity along with general implications on the understanding of RNA recognition. For the synthesis of restricted neomycin 2 we devised an intramolecular and regioselective cyclization strategy of an unprotected 5’’-activated neomycin intermediate under highdilution conditions that exploits the proximity of the 2’-amino and 5’’-hydroxymethyl groups (Scheme 1). The sulfonateactivated intermediate was obtained after Boc protection of the amino groups of neomycin, reaction of the primary alcohol at the 5’’ position with 2,4,6-triisopropylbenzene sulfonyl chloride, and cleavage of the Boc protecting [*] F. Zhao, Dr. K. F. Blount, Prof. Dr. Y. Tor, Dr. T. Hermann Department of Chemistry and Biochemistry University of California, San Diego La Jolla, CA 92093 (USA) Fax: (+1)858-534-0202 E-mail: tch@chem.ucsd.edu

The lack of high RNA target selectivity displayed by aminoglycoside antibiotics results from both their electrostatically driven binding mode and their conformational adaptability. The inherent flexibility around their glycosidic bonds allows them to easily assume a variety of conformations, permitting them to structurally adapt to diverse RNA targets. This structural promiscuity results in the formation of aminoglycoside complexes with diverse RNA targets in which the antibiotics assume distinct conformations. Such differences suggest that covalently linking individual rings in an aminoglycoside could reduce its available conformations, thereby altering target selectivity. To explore this possibility, conformationally constrained neomycin and paromomycin analogues designed to mimic the A-site bound aminoglycoside structure have been synthesized and their affinities to the TAR and A-site, two therapeutically relevant RNA targets, have been evaluated. As per design, this constraint has minimal deleterious effect on binding to the A-site. Surprisingly, however, preorganizing these neomycin-class antibiotics into a TAR-disfavored structure has no deleterious effect on binding to this HIV-1 RNA sequence. We rationalize these observations by suggesting that the A-site and HIV TAR possess inherently different selectivities toward aminoglycosides. The inherent plasticity of the TAR RNA, coupled to the remaining flexibility within the conformationally constrained analogues, makes this RNA site an accommodating target for such polycationic ligands. In contrast, the deeply encapsulating A-site is a more discriminating RNA target. These observations suggest that future design of novel target selective RNA-based therapeutics will have to consider the inherent "structural" selectivity of the RNA target and not only the selectivity patterns displayed by the low molecular weight ligands.

This paper introduces Crystallization Sonification , a sonification model for exploratory analysis of high-dimensional datasets. The model is designed to provide information about the intrinsic data dimensionality (which is a local feature) and the global data dimensionality, as well as the transitions between a local and global view on a dataset. Furthermore the sound allows to display the clustering in high-dimensional datasets. The model defines a crystal growth process in the high-dimensional data-space which starts at a user selected “condensation nucleus” and incrementally includes neighboring data according to some growth criterion. The sound summarizes the temporal evolution of this crystal growth process. For introducing the model, a simple growth law is used. Other growth laws which are used in the context of hierarchical clustering are also suited and their application in crystallization sonification offers new ways to inspect the results of data clustering as an alternative to dendrogram plots. In this paper, the sonification model is described and example sonifications are presented for some synthetic high-dimensional datasets.

We study cross-correlations in irregularly spiking systems. A single system displays spiking sequences that resemble a stochastic (Poisson) process. Linear coupling between two systems leaves the inter-spike interval distribution qualitatively unchanged but induces cross-correlations between the units. For strong coupling this leads to synchronization as expected but for weak coupling, both a good statistic and sonification reveal the presence of ``motifs'', preferred short firing sequences which are due to the deterministic spiking mechanism. We argue that the use of sonification for time series analysis is superior in the case where intrinsic non-stationarity of an experiment cannot be ruled out.

The bacterial ribosome is the primary target for many classes of antibiotics including the aminoglycosides, tetracyclins, macrolides, and oxazolidinones, all of which interact predominantly with ribosomal RNA (rRNA), thereby interfering with cellular protein synthesis. 2] These antibiotics bind selectively to RNA sites that harbor unique sequence signatures that distinguish bacterial from eukaryotic targets. The aminoglycoside antibiotics of the related neomycin B and paromomycin classes, for example, induce translational miscoding by recognizing specifically the bacterial 16S rRNA at the decoding site, which differs by two bases from the eukaryotic sequence (Figure 1). In contrast, the aminoglycoside hygromycin B binds to a site that is conserved among bacteria and eukaryotes, inhibiting protein synthesis indiscriminately in organisms from both lineages. Consequently, hygromycin B, which blocks ribosomal translocation without causing significant miscoding, is toxic to eukaryotes and thus not used in anti-infective therapy. The binding sites of paromomycin and hygromycin B are located immediately adjacent to each other, within helix 44 of 16S rRNA, which plays a key role for mRNA decoding and has been implicated in movements during translocation. X-ray crystallographic studies on the whole ribosomal 30S subunit, individual domains of rRNA, and antibiotic complexes thereof have revealed three-dimensional structures of paromomycin and hygromycin B in complex with their RNA targets. 8,11] Comparison of the individual aminoglycoside complexes shows that the binding sites of paromomycin and hygromycin B are partially overlapping at the position of the U1406·U1495 base pair (Figure 1b, c). Mutations at these residues conferring resistance to either aminoglycoside, in agreement with the structural data, have been described. In this report, we outline an approach to develop novel lead structures based on aminoglycoside-hybrid ligands that were conceived to bridge between the paromomycin and hygromycin B binding sites in helix 44 of bacterial rRNA and thereby potentially interfere with ribosomal function. To obtain such bridging RNA binders, we designed compounds that combined the neamine core moiety of neomycin B, which is known to confer bacterial decoding-site-specific RNA binding, along with substituents at the 1and 6-positions of the 2-deoxystreptamine (2-DOS) ring, which were chosen to project into the hygromycin B binding site (Figure 1c). In the superimposition of the rRNA complexes of paromomycin and hygromycin B, the aminoglycosides overlap at the 2-DOS moieties, which adopt almost identical orientations, shifted by approximately 3 along the RNA helix. Ramakrishnan and co-workers have noted that this displacement corresponds exactly to the distance between neighboring residues in the RNA helix. This observation, along with the wide conservation of the 2-DOS moiety among natural aminoglycosides, emphasizes the role of the 2DOS ring system as a privileged scaffold for RNA recognition. Structural studies on aminoglycoside–RNA complexes have revealed that the 1and 3-amino groups of 2-DOS are predominantly involved in RNA base recognition. The hydroxy groups in the 4-, 5-, and 6-positions are often linked to additional sugar moieties. Many aminoglycosides of the potent neomycin and kanamycin classes of antibiotics carry a glucosamine-based substituent at the 4-position. The minimal aminoglycoside core structure of neamine, consisting of 2-DOS, linked at the 4-position to 2,6-diaminoglucose (Figure 1), interferes with protein synthesis at nanomolar concentration and shows moderate antibacterial potency (Table 1). Removal of the 5-hydroxy group leads to enhanced activity of the resulting 5-deoxyneamine against aminoglycoside-resistant bacteria (Table 1). Since the 2,5-dideoxystreptamine (2,5-dDOS) core of 5-deoxyneamine is readily available, we used it as a starting material for the synthesis of the novel RNA binders described herein (Figure 1d). [a] Dr. D. Vourloumis, G. C. Winters, Dr. K. B. Simonsen, M. Takahashi, Dr. B. K. Ayida Department of Medicinal Chemistry, Anadys Pharmaceuticals, Inc. 3115 Merryfield Row, San Diego, CA 92121 (USA) Fax: (+1)858-527-1540 E-mail : dvourloumis@anadyspharma.com [b] S. Shandrick, Dr. Q. Zhao, Dr. Q. Han, Dr. T. Hermann Department of Structural Chemistry, Anadys Pharmaceuticals, Inc. 3115 Merryfield Row, San Diego, CA 92121 (USA) Fax: (+1)858-527-1540 E-mail : thermann@anadyspharma.com Supporting information for this article is available on the WWW under http://www.chembiochem.org or from the author.

Summary: Alteration of the mouse genome through ho-mologous recombination in embryonic stem (ES) cells isthe most accurate and versatile way to dissect genefunction in a vertebrate model. Most often, a selectablemarker is used to create a knockout allele by replacingan essential part of the gene. However, knockout strat-egies are limited because the mutation is present con-stitutively. Conditional approaches based on the Cre- loxP site-specific recombination (SSR) system addressthis limitation; however, it requires that all parts of thetargeted gene remain in ES cells. Here we report suc-cess with a “knockout-first” strategy that ablates genefunction by insertion of RNA processing signals withoutdeletion of any of the target gene. Incorporation of site-specific recombination target sites creates a multipur-pose allele for both knockout and conditional applica-tions. genesis 38:151–158, 2004. © 2004 Wiley-Liss, Inc. Key words: knockout, conditional, mutagenosis, reporter,mouse Gene function analysis via homologous recombination inmouse ES cells plays a central role in the biologicalsciences. In its most straightforward application, homol-ogous recombination is used to delete essential parts ofa gene to establish a knockout allele. Knockouts arepowerful because the consequences of complete loss offunction are established. However, knockouts only re-port the first role of a gene in development. Becausemany knockouts are developmentally lethal, analysis ofgene function later in development or in the adult isprecluded. To circumvent this limitation, strategies forconditional mutagenesis using Cre/loxP site-specific re-combination have been developed (Gu

Long-chain fatty acids (LCFAs) represent key metabolites for energy generation and storage. Transport and metabolism of LCFA are believed to be regulated by membrane-associated proteins that bind and transport LCFA. Identifying the postulated fatty acid transporters is of considerable interest since altered fatty acid uptake has been implicated in disease such as insulin resistance and obesity. Recently, a family of membrane associated proteins, termed fatty acid transport proteins (FATPs), have been described that enhance uptake of LCFAs. Until today, six members of this family, designated FATP1-6, have been characterized. This review will focus on FATP structure, expression patterns, regulation, mechanism of transport and clinical implications.

Die Erfindung betrifft ein Verfahren zur Steuerung eines auditiven Spiels, wobei die Bewegungen eines Spielobjekts in Echtzeit vorgegeben und klanglich wiedergegeben werden, dadurch gekennzeichnet, dass nach Beginn eines Bewegungsereignisses stets ein Bewegungszustand des Spielobjekts in einem dreidimensionalen Raum einerseits und stets ein Bewegungszustand eines menschlichen Nutzerobjekts im dreidimensionalen Raum andererseits ermittelt werden, dass stets der Bewegungszustand des Spielobjekts und der Bewegungszustand des Nutzerobjekts verglichen wird und in Abhängigkeit vom Vergleichsergebnis ein akustisches Bewegungszustandssignal an den Nutzer ausgegeben wird.

This paper argues for a special focus on the use of dynamic human interaction to explore datasets while they are being transformed into sound. We describe why this is a special case of both human computer interaction (HCI) techniques and sonification methods. Humans are adapted for interacting with their physical environment and making continuous use of all their senses. When this exploratory interaction is applied to a dataset (by continuously controlling its transformation into sound) new insights are gained into the data's macro and micro-structure, which are not obvious in a visual rendering. This paper reviews the importance of interaction in sonification, describes how a certain quality of interaction is required, provides examples of the techniques being applied interactively, and outlines a plan of future work to develop interaction techniques to aid sonification.

We use sonification of temporal information extracted from scalp EEG to characterize the dynamic properties of rhythms in certain frequency bands. Sonification proves particularly useful in the simultaneous monitoring of several EEG channels. Our results suggest sonification as an important tool in the analysis of multivariate data with subtle correlation differences.

This paper argues for a special focus on the use of dynamic human interaction to explore datasets while they are being transformed into sound. We describe why this is a special case of both human computer interaction (HCI) techniques and sonification methods. Humans are adapted for interacting with their physical environment and making continuous use of all their senses. When this exploratory interaction is applied to a dataset (by continuously controlling its transformation into sound) new insights are gained into the data's macro and micro-structure, which are not obvious in a visual rendering. This paper defines the sub-topic of Interactive Sonification, explains how a certain quality of interaction is required, overviews current sonification techniques, provides examples of the techniques being applied interactively, and outlines a research agenda for this topic.

In this paper we present an approach to track a moving body in a sequence of camera images by model adaptation. The parameters of a stick figure model are varied by using a stochastic search algorithm. The similarity of rendered model images and camera images of the user are used as quality measure. A refinement of the algorithm is introduced by using combined stereo views and relevance maps to infer responsible joint angles from the difference of successive input images. Finally, the successful application of various versions of the algorithm on sequences of synthetic images is demonstrated.

This paper presents the gesture desk, a new platform for a human-computer interface at a regular computer workplace. It extends classical input devices like keyboard and mouse by arm and hand gestures, without the need to use any inconvenient accessories like data gloves or markers. A central element is a “gesture box” containing two infrared cameras and a color camera which is positioned under a glass desk. Arm and hand motions are tracked in three dimensions. A synchronizer board has been developed to provide an active glare-free IR-illumination for robust body and hand tracking. As a first application, we demonstrate interactive real-time browsing and querying of auditory self-organizing maps (AuSOMs). An AuSOM is a combined visual and auditory presentation of high-dimensional data sets. Moving the hand above the desk surface allows to select neurons on the map and to manipulate how they contribute to data sonification. Each neuron is associated with a prototype vector in high-dimensional space, so that a set of 2D-topologically ordered feature maps is queried simultaneously. The level of detail is selected by hand altitude over the table surface, allowing to emphasize or deemphasize neurons on the map.

Three complementary methods are used to analyze the dynamics of multivariate EEG data obtained from a human listening to a piece of music. The analysis yields parameters for a data sonification that conserves temporal and frequency relationships as well as wave intensities of the data. Multiple events taking place on different time scales are combined to a polyrhythmic display in real time.

As has been outlined in the accompanying report, synthetic aminoglycoside mimetics constitute lead compounds for the development of novel antibiotics that might achieve antibacterial potency comparable to the natural aminoglycosides without being compromised by bacterial resistance mechanisms specific to the chemical constitution of these natural compounds. Threedimensional structures of the bacterial decoding-site RNA complexed with aminoglycosides 3] have guided our efforts for rational, structure-based design of readily accessible aminoglycoside mimetics (Figure 1). In this report, we outline a novel approach to linking the 6 aminoglucosamine moiety, conserved among many potent natural aminoglycosides, to conformationally restricted 3-(aminomethyl)piperidine scaffolds that mimic the unique spatial arrangement of functional groups in 2-deoxystreptamine (2DOS) required for the recognition of the decoding-site RNA target (Figure 1c ± e). The exocyclic bis-equatorial 1,3-diamine motif of 2-DOS is incorporated into the cyclic piperidine scaffold, which was designed by molecular modeling based on the crystal structure of paromomycin bound to the bacterial decoding site (Figure 1). Three different substitution patterns have been used to generate eight piperidine derivatives of glucosamine (see Table 1), among them the representative hydroxymethyl compound 1 (Figure 1c). The 5-hydroxymethyl substituent in the piperidine glycoside 1 was designed to mimic the 4-hydroxy group of paromamine (Figure 1d), which forms a key interaction with a tightly bound water molecule at the deepgroove edge of the U1406 U1495 base pair in the decoding-site target (Figure 1e). Several other piperidine glycosides were synthesized to explore alternative substitution patterns of the 3-(aminomethyl)piperidine scaffold (see Table 1).

Functional RNAs such as ribosomal RNA and structured domains of mRNA are targets for small molecule ligands that can act as modulators of the RNA biological activity. Natural ligands for RNA display a bewildering structural and chemical complexity that has yet to be matched by synthetic RNA binders. Comparison of natural and artificial ligands for RNA may help to direct future approaches to design and synthesize potent novel scaffolds for specific recognition of RNA targets.

In this study, the phosphoproteome of Corynebacterium glutamicum, an industrially important soil bacterium of the Corynebacterium/Mycobacterium/Nocardia (CMN) group of Gram-positive bacteria, was investigated by two different detection methods: first, by in vivo radio-labeling using [(33)P]-phosphoric acid with subsequent autoradiography and second, by immunostaining with phosphoamino acid-specific monoclonal antibodies. After two-dimensional gel electrophoresis (2-DE), around 60 [(33)P]-labeled protein spots were visualized and around 90 antibody-decorated protein spots detected; 31 of the protein spots were detected with both methods. By peptide mass fingerprinting, 41 different proteins were identified, namely 5-enolpyruvylshikimate 3-phosphate synthase, aconitase, acyl-CoA carboxylase, acyl-CoA synthetase, ATP (synthase alpha- and beta-chain), carbamoyl-phosphate synthase, citrate synthase, cysteine synthase, DnaK, the elongation factors G, P, Ts and Tu, enolase, fructose bisphosphate aldolase, fumarase, Gap dehydrogenase, glutamine synthetase I, glycine hydroxymethyltransferase, GroEL2, GTPase, heat-inducible transcriptional repressor DnaJ2, inorganic pyrophosphatase, isocitrate dehydrogenase, ketol-acid reductoisomerase, lactate dehydrogenase, leucine-tRNA ligase, lipoamide dehydrogenase, methionine synthase, O-acetylhomoserine sulfhydrylase, pyruvate carboxylase, pyruvate kinase, pyruvate oxidase, ribosomal protein S1, RNA polymerase (beta-subunit), succinyl-CoA:CoA transferase, transketolase and UDP-N-acetylmuramoyl-L-alanine ligase, besides a hypothetical 35k protein and a hypothetical glucose kinase. Both detection techniques were used to create a phosphoproteome map. Additionally, the influence of nitrogen deprivation on the phosphoproteome of C. glutamicum was investigated.

Natural aminoglycoside antibiotics recognize an internal loop of bacterial ribosomal-decoding-site RNA by binding to the deep groove of the RNA structure. We have designed, synthesized, and tested RNA-targeted paromamine derivatives that exploit additional interactions on the shallow groove face of the decoding-site RNA. An in vitro transcription-translation assay of a series of 6'-derivatives showed the 6'-position to be very sensitive to substitution. This result suggests that the group at the 6'-position plays a pivotal role in RNA target recognition.

This paper reports on a pilot project between our research department and and a local radio station, investigating the use of sonification to render and present auditory weather forecasts. The sonifications include auditory markers for certain relevant time points, expected weather events like thunder, snow or fog and several auditory streams to summarize the temporal weather changes during the day. To our knowledge, this is the first utilization of sonification in a regular radio program. We introduce the sonification concept and present our design of the sonification which is oriented at combined perceptional salience and emotional truthfulness. Sound examples are given for typical weather situations in Germany and several prototypical weather conditions which tune to be connected with emotional value. We will report first experiences with this pilot project and feedback of the audience on ICAD since broadcast started in February 2003.

The role of static structure and conformational flexibility in the recognition of RNA targets by small molecule ligands is discussed with emphasis on the natural aminoglycoside antibiotics and their promiscuity in RNA target binding. A brief overview is given of previous efforts to design simplified aminoglycoside derivatives targeted at the bacterial decoding site RNA.

We present a high-resolution reference map for soluble proteins obtained from Corynebacterium glutamicum cells grown in glucose minimal medium. The analysis window covers the pl range from 4-6 and the molecular mass range from 5-100 kDa. Using overlapping narrow immobilized pH gradients for isoelectric focusing, 970 protein spots were detected after second-dimensional separation on SDS-polyacrylamide gels and colloidal Coomassie-staining. By tryptic peptide mass fingerprinting 169 protein spots were identified, representing 152 different proteins including many enzymes involved in central metabolism (18), amino acid biosynthesis (24) and nucleotide biosynthesis (11). Thirty-five of the identified proteins have no known function. A comparison of the observed and the expected physicochemical properties of the identified proteins indicated that nine proteins were covalently modified, since variants with apparently identical molecular mass, but differing pl were detected. The N-termini of eight proteins were determined by post-source decay (PSD) analysis of selected peptides. In addition to the soluble proteins, a map of the membrane-bound proteins within the pl range 4-7 is presented, which contains 660 protein spots, 22 of which were identified, representing 13 different proteins.

This paper presents a new interface for controlling sonification models. A haptic controller interface is developed which allows both to manipulate a sonification model, e.g. by interacting with it and to provide a haptic data representation. A variety of input types are supported with a hand-sized interface, including shaking, squeezing, hammering, moving, rotating and accelerating. The paper presents details on the interface under development and demonstrates application of the device for controlling a sonification model. For this purpose, the Data-Solid Sonification Model is introduced, which provides an acoustic representation of the local neighborhood relations in high-dimensional datasets for binary classification problems. The model is parameterized by a reduced data representation obtained from a growing neural gas network. Sound examples are given to demonstrate the device and the sonification model.

This paper introduces Crystallization Sonification, a sonification model for exploratory analysis of high-dimensional datasets. The model is designed to provide information about the intrinsic data dimensionality (which is a local feature) and the global data dimensionality, as well as the transitions between a local and global view on a dataset. Furthermore the sound allows to display the clustering in high-dimensional datasets. The model defines a crystal growth process in the high-dimensional data-space which starts at a user selected “condensation nucleus” and incrementally includes neighboring data according to some growth criterion. The sound summarizes the temporal evolution of this crystal growth process. For introducing the model, a simple growth law is used. Other growth laws which are used in the context of hierarchical clustering are also suited and their application in crystallization sonification offers new ways to inspect the results of data clustering as an alternative to dendrogram plots. In this paper, the sonification model is described and example sonifications are presented for some synthetic high-dimensional datasets.

Sonification is a rather new technique in human-computer interaction which addresses auditory perception. In contrast to speech interfaces, sonification uses non-verbal sounds to present information. The most common sonification technique is parameter mapping where for each data point a sonic event is generated whose acoustic attributes are determined from data values by a mapping function. For acoustic data exploration, this mapping must be adjusted or manipulated by the user. We propose the use of hand postures as a particularly natural and intuitive means of parameter manipulation for this data exploration task. As a demonstration prototype we developed a hand posture recognition system for gestural controlling of sound. The presented implementation applies artificial neural networks for the identification of continuous hand postures from camera images and uses a real-time sound synthesis engine. In this paper, we present our system and first applications of the gestural control of sounds. Techniques to apply gestures to control sonification are proposed and sound examples are given.

We consider the combined use of visualization and sound for uncovering important structure in high-dimensional data. Our approach is based on Markov chain Monte Carlo (McMC) simulations. McMC is a popular computational tool for making analytical inferences from complex, high-dimensional probability densities. Given a particular target density p, we simulate a Markov chain that has p as its stationary distribution. We propose a new tool for exploratory data analysis based on an audio representation of McMC output. Several audio streams provide us with information about both the behavior of the Markov chain as well as characteristics of the target density p. We apply this method to the task of identifying structures in high-dimensional data sets by taking p to be a nonparametric density estimate. In this paper, we present a detailed description of our sonification design and illustrate its performance on test cases consisting of both synthetic and real-world data sets. Sound examples are also given.

Markov chain Monte Carlo (McMC) simulation is a popular computational tool for making inferences from complex, high-dimensional probability densities. Given a particular target density , the idea behind this technique is to simulate a Markov chain that has as its stationary distribution. To be successful, the chain needs to be run long enough so that the distribution of the current draw is close to the target density. Unfortunately, very few diagnostic tools exist to monitor characteristics of the chain. In this paper, we present a new approach to render sonifications of McMC simulations. The proposed method consists of several auditory streams which provide information about the behavior of the Markov chain. In particular, we focus on uncovering modes in the target density function. In addition to monitoring, we have found our sonification to be an effective means for understanding the structure of high-dimensional densities. We have also applied our method to the exploratory analysis of high-dimensional data sets. In this case, we take as our target a non-parametric density estimate obtained from the data. In this paper, we present a detailed description of our sonification design and illustrate its performance on test cases consisting of both synthetic and real-world data sets. Sound examples are also given.

Die Gestaltung sozio-technischer Systeme wird durch die Modellierungsmethode SeeMe unterstutzt (Herrmann & Loser 1999). Diagramme auch in anderen Notationen konnen in realen Anwendungen schnell sehr komplex und umfassend werden. Sowohl in Prasentationen, als auch bei der Erstellung und Rezeption von solchen Diagrammen uberfordert die Menge an dargestellten Informationen schnell die individuelle Fahigkeit zur Wahrnehmung. Dass maximale Explizitheit zu minimaler Verstandlichkeit fuhrt, ist ein in der Kommunikationstheorie bekanntes Problem (Ungeheuer 1987). Dies wirkt sich in vielen Situationen von Projekten aus: Muhsam entwickelte Diagramme konnen beispielsweise nicht direkt in Prasentationen und Diskussionen eingesetzt werden. Statt dessen werden zusatzlich vereinfachte Diagramme erstellt, um sie breiterem Publikum zu prasentieren. Ein moglicher Weg, derartige Probleme anzugehen, besteht darin, in einem Werkzeug Diagramme interaktiv individuell und situationsbezogen anpassbar und prasentierbar zu machen. Betrachter sollen einerseits innerhalb der existierenden semantischen Beziehungen, die relevanten und interessanten Inhalte ansteuern konnen (Exploration). Andererseits sollen solche Navigationswege wiederholbar werden, um sich einem Erzahlfluss anzupassen und diese in Prasentationen wieder abrufen zu konnen. Dabei ist es auch wichtig angemessene variierende Abstraktionsniveaus wahlen zu konnen. Der in Java 2 entwickelte Prototyp EasySeeMe setzt dazu eine Reihe von Konzepten zur flexiblen Prasentation von Prozessmodellen um, wie sie in Herrmann 1999 beschrieben wurden.

To determine concentrations of environmental estrogens, antiandrogens, and organochlorine compounds in human endometrium and body fat.Cross-sectional, population-based study.Patient recruitment was done at a university hospital; chemical analysis was performed in a specialized private laboratory.Premenopausal, unexposed women undergoing hysterectomy for uterine myoma.None.Concentrations of environmental modulators in human endometrium and body fat were quantified by high-resolution gas chromatography/high-resolution mass spectrometry.Among known endocrine modulators, the antiandrogenic p, p'-dichlorodiphenyl-dichloroethylene was found in the highest concentrations in endometrium (median 4.7 microg/kg wet weight) and body fat (median 446 microg/kg wet weight). Only trace amounts of the identified environmental estrogens beta-hexachlorocyclohexane, o, p'-dichlorodiphenyl-trichloroethane, bisphenol A, hydroxylated polychlorinated biphenyls, and genistein were found in the endometrium (median1 microg/kg wet weight). As major organochlorine contaminants without endocrine activities, polychlorinated biphenyls and hexachlorobenzene were found.Our data demonstrate that nonchlorinated environmental estrogens do not build up cumulative tissue concentrations in the endometrium. The risk of reduced fertility because of ambient levels of environmental estrogens in the endometrium is negligible.

RNA bulges constitute versatile structural motifs in the assembly of RNA architectures. Three-dimensional structures of RNA molecules and their complexes reveal the role of bulges in RNA architectures and illustrate the molecular mechanisms by which they confer intramolecular interactions and intermolecular recognition.

In [5] Lim and Lee present an algorithm for fast exponentiation in a given group which is optimized for a limited amount of storage. The algorithm uses one precomputation for several computations in order to minimize the average time needed for one exponentiation. This paper generalizes the previous work proposing several improvements and a method for fast precomputation. The basic Lim/Lee algorithm is improved by determining the optimal segmentation of the exponent. Finally, it is shown that the improved Lim/Lee algorithm is faster than the previous one in average case.

Essen, Univ., Diss., 2000