Clones: what is that smell?

Clones are generally considered bad programming practice in software engineering folklore. They are identified as a bad smell?(Fowler et?al. 1999) and a major contributor to project maintenance difficulties. Clones inherently cause code bloat, thus increasing project size and maintenance costs. In this work, we try to validate the conventional wisdom empirically to see whether cloning makes code more defect prone. This paper analyses the relationship between cloning and defect proneness. For the four medium to large open source projects that we studied, we find that, first, the great majority of bugs are not significantly associated with clones. Second, we find that clones may be less defect prone than non-cloned code. Third, we find little evidence that clones with more copies are actually more error prone. Fourth, we find little evidence to support the claim that clone groups that span more than one file or directory are more defect prone than collocated clones. Finally, we find that developers do not need to put a disproportionately higher effort to fix clone dense bugs. Our findings do not support the claim that clones are really a “bad smell”?(Fowler et?al. 1999). Perhaps we can clone, and breathe easily, at the same?time.     

A digital library framework for heterogeneous music collections: from document acquisition to cross-modal interaction

In this paper, we present a digital library system for managing heterogeneous music collections. The heterogeneity refers to various document types and formats as well as to different modalities, e. g., CD-audio recordings, scanned sheet music, and lyrics. The system offers a full-fledged, widely automated document processing chain: digitization, indexing, annotation, access, and presentation. Our system is implemented as a generic and modular music repository based on a service-oriented software architecture. As a particular strength of our approach, the various documents representing aspects of a piece of music are jointly considered in all stages of the document processing chain. Our user interfaces allow for a multimodal and synchronized presentation of documents (WYSIWYH: what you see is what you hear), a score- or lyrics-based navigation in audio, as well as a cross- and multimodal retrieval. Hence, our music repository may be called a truly cross-modal library system. In our paper, we describe the system components, outline the techniques of the document processing chain, and illustrate the implemented functionalities for user interaction. We describe how the system is put into practice at the Bavarian State Library (BSB) Munich as a part of the German PROBADO Digital Library Initiative (PDLI).     

A population-based iterated greedy algorithm for the minimum weight vertex cover problem

Given an undirected, vertex-weighted graph, the goal of the minimum weight vertex cover problem is to find a subset of the vertices of the graph such that the subset is a vertex cover and the sum of the weights of its vertices is minimal. This problem is known to be NP-hard and no efficient algorithm is known to solve it to optimality. Therefore, most existing techniques are based on heuristics for providing approximate solutions in a reasonable computation time.Population-based search approaches have shown to be effective for solving a multitude of combinatorial optimization problems. Their advantage can be identified as their ability to find areas of the space containing high quality solutions. This paper proposes a simple and efficient population-based iterated greedy algorithm for tackling the minimum weight vertex cover problem. At each iteration, a population of solutions is established and refined using a fast randomized iterated greedy heuristic based on successive phases of destruction and reconstruction. An extensive experimental evaluation on a commonly used set of benchmark instances shows that our algorithm outperforms current state-of-the-art approaches.     

Conception assistée par ordinateur des circuits intégrés monolithiques hyperfréquences

Computer aided design of microwave monolithic integrated circuits must combine two different fields. The first domain is the simulation of microwave circuits taking into account non linear aspects development of time domain and harmonic balance simulation algorithms specialized for microwave circuits. In the second place are found, the layout algorithms which were developed for logic circuits (on Si or GaAs). The association of these two types of algorithms leads to the constitution of aCad workstation for microwave monolithic integrated circuits. Two examples of design and realization of integrated circuits with these tools are presented.     

Isolation and enzymatic fragmentation of the coeliac-active gliadin peptide CT-1

Summary Investigations on the structure/toxicity relationships of gliadin peptides were continued with the coeliac-active gliadin peptide CT-1, which is derived from the N-terminal portion (residues 3–24 of the amino acid sequence) of-gliadins [this journal (1986) 182:115–117]. CT-1 was produced by chymotryptic digestion and reversed-phase (RP) HPLC from the peptide fraction G3 [this journal (1992) 194:1–6] and digested with the proteases endoproteinase Glu-C, pancreatin, papain and thermolysin. The fragment peptids were separated by preparative RP-HPLC and characterized by amino acid analysis. On the basis of the specifity of the enzymes for CT-1 and the toxic effect of enzymatic hydrolysates of gliadin described in the literature, the significance of partial sequences, in particular of the sequence -Pro-Ser-Gln-Gln-Gln-Pro- for the coeliac-toxicity effect, is discussed.

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Isolierung und enzymatische Fragmentierung des coeliakieaktiven Gliadinpeptids CT-1

Zusammenfassung Die Untersuchungen über die Zusammenhänge zwischen der Struktur von Gliadinpeptiden und ihrer Toxizität wurden mit dem coeliakieaktiven Gliadinpeptid CT-1 fortgesetzt, das aus dem N-terminalen Bereich (Positionen 3–24 der Aminosäuresequenz) von-Gliadinen stammt [diese Zeitschrift (1986) 182:115–117]. CT-1 wurde aus der Peptidfraktion G3 [diese Zeitschrift (1992) 194:1–6] durch chymotryptische Partialhydrolyse und Umkehrphasen-HPLC gewonnen und mit den Proteasen Endoproteinase Glu-C, Pankreatin, Papain und Thermolysin umgesetzt. Die entstandenen Fragmentpeptide wurden durch präparative Umkehrphasen-HPLC getrennt und durch Aminosäurenanalyse charakterisiert. Anhand der Spezifität der Enzyme gegenüber CT-1 und der aus der Literatur bekannten toxischen Wirkung von enzymatischen Gliadinhydrolysaten wird die Bedeutung einzelner Sequenzabschnitte, insbesondere der Sequenz-Pro-Ser-Gln-Gln-Gln-Pro-, für die coeliakiespezifische Wirkung diskutiert.

     

Coeliac activity of the gliadin peptides CT-1 and CT-2

Summary The coeliac active peptide B 3142, which has been isolated from a peptic-tryptic digest of gliadin [1] and which consists of 53 amino-acid sequences [2], was partially hydrolyzed with -chymotrypsin. The two fragment peptides CT-1 (positions 1–22 of B 3142) and CT-2 (positions 23–53) were separated by high-performance liquid chromatography on octadecyl silica gel and purified by gel filtration on Biogel P2. The examination in the organ-culture test including 18 coeliac patients on normal diet and 7 control persons have shown that the toxicity is preserved after the chymotryptic treatment and that the peptides B 3142, CT-1 and CT-2 do not significantly differ from one another according to their coeliac-specific effect.

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Coeliakieaktivitat der Gliadinpeptide CT-1 und CT-2

Zusammenfassung Das coeliakieaktive Peptid B 3142, das aus einem peptisch-tryptischen Partialhydrolysat von Gliadin gewonnen wurde [1] und aus einer Sequenz von 53 Aminosäureresten besteht [2], wurde mit -Chymotrypsin partiell hydrolysiert. Die beiden Fragment-peptide CT-1 (Positionen 1–22 von B 3142) und CT-2 (Positionen 23–53) wurden durch Hochdruckflüssig-keitschromatographie an Octadecyl-Kieselgel aufgetrennt und an Biogel P2 gereinigt. Die Prüfung im Organkultur-Test unter Einbeziehung von 18 Coeliakie-patienten unter Normalkost und von 7 Kontrollpersonen zeigte, daß die Toxizität nach chymotryptischer Spaltung erhalten bleibt, und daß sich die Peptide B 3142, CT-1 und CT-2 in ihrer coeliakiespezifischen Wirkung nicht wesentlich unterscheiden.

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Supported by a grant from Deutsche Forschungsgemeinschaft. We gratefully acknowledge the excellent assistance given by Mrs. U. Schützler and Ms. B. Mosler     

Complement-Opsonized Nano-Carriers Are Bound by Dendritic Cells (DC) via Complement Receptor (CR)3, and by B Cell Subpopulations via CR-1/2, and Affect the Activation of DC and B-1 Cells

The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses.     

Prediction of Functional Consequences of Missense Mutations in ANO4 Gene

The anoctamin (TMEM16) family of transmembrane protein consists of ten members in vertebrates, which act as Ca²⁺-dependent ion channels and/or Ca²⁺-dependent scramblases. ANO4 which is primarily expressed in the CNS and certain endocrine glands, has been associated with various neuronal disorders. Therefore, we focused our study on prioritizing missense mutations that are assumed to alter the structure and stability of ANO4 protein. We employed a wide array of evolution and structure based in silico prediction methods to identify potentially deleterious missense mutations in the ANO4 gene. Identified pathogenic mutations were then mapped to the modeled human ANO4 structure and the effects of missense mutations were studied on the atomic level using molecular dynamics simulations. Our data show that the G80A and A500T mutations significantly alter the stability of the mutant proteins, thus providing new perspective on the role of missense mutations in ANO4 gene. Results obtained in this study may help to identify disease associated mutations which affect ANO4 protein structure and function and might facilitate future functional characterization of ANO4.     

Auxin and Root Gravitropism: Addressing Basic Cellular Processes by Exploiting a Defined Growth Response

Root architecture and growth are decisive for crop performance and yield, and thus a highly topical research field in plant sciences. The root system of the model plant Arabidopsis thaliana is the ideal system to obtain insights into fundamental key parameters and molecular players involved in underlying regulatory circuits of root growth, particularly in responses to environmental stimuli. Root gravitropism, directional growth along the gravity, in particular represents a highly sensitive readout, suitable to study adjustments in polar auxin transport and to identify molecular determinants involved. This review strives to summarize and give an overview into the function of PIN-FORMED auxin transport proteins, emphasizing on their sorting and polarity control. As there already is an abundance of information, the focus lies in integrating this wealth of information on mechanisms and pathways. This overview of a highly dynamic and complex field highlights recent developments in understanding the role of auxin in higher plants. Specifically, it exemplifies, how analysis of a single, defined growth response contributes to our understanding of basic cellular processes in general.