bluuebunny/crossref_metadata_2025 huggingface dataset:
Die Sulzbachbrücke bei Dürnkrut
Authors: Flicker Erich , Kothmayer Herbert , Naderer Otto
Published: February 2009

Brücken dienen der Überführung von Verkehrswegen über natürliche oder künstlich geschaffene lokale topologische Tieflagen, wobei im Regelfall Konstruktionsart und Baustoff hauptsächlich von geometrischen, betrieblichen und herstellungsspezifischen Randbedingungen bestimmt werden. Im vorliegenden Beitrag wird eine hinsichtlich der Funktion und Formgebung wohl ungewöhnliche Stahlbeton‐Eisenbahnbrücke vorgestellt, deren extrem schlanke Bauweise und faltwerksartige Gestalt sich aus der Forderung ergab, neben ihrer ursächlichen Tragfunktion gleichzeitig auch zwei Hochwasserschutzdämme im Kreuzungsbereich mit einer Eisenbahnstrecke wasserdicht miteinander zu verbinden und dabei vor allem auch die damit verbundene Anhebung der Strecke zu minimieren. Die konstruktiven und streckenbezogenen Randbedingungen für die Systemfindung werden in diesem Aufsatz nachvollzogen sowie die grundsätzlichen Überlegungen erläutert, die zur ungewöhnlichen Formgebung dieses Brückenobjekts führten. Die Ergebnisse der im Vorfeld durchgeführten dynamischen Simulationsrechnungen werden vorgestellt und spezifische Konstruktionsdetails näher betrachtet. Schließlich erfolgt ein kurzer Abriss über die wesentlichen Etappen der baulichen Umsetzung.
“…︁ die richtige Art wissenschaftlicher Objekte…︁”: Ein Epilog mit Warren McCullochs Embodiments of Mind
Authors: Dotzler Bernhard J.
Published: February 2009

“…︁the right kind of scientific objects…︁”: An Epilogue with Warren McCulloch's Embodiments of Mind. Warren McCulloch marks the brain explicitly as an epistemic object. Since then, to see ’in statu nascendi' what brain research means implies the irrefutability of the truth that the mind is in the head. And it implies to see the contingency of this knowledge. This again allows to ask for more details about the object and its destiny – beginning with the riddle, why McCulloch is not forgotten until today, but his clear designation is forgotten. A comparison between McCulloch's Embodiments of Mind and John von Neumann's The Computer and the Brain should help to follow the traces of this riddle.
Das reine Sein des Schreibens. Écriture automatique in der Psychiatrie des späten 19. Jahrhunderts und im frühen Surrealismus (Breton/Soupault: Les champs magnétiques)
Authors: Bergengruen Maximilian
Published: February 2009

The Pure Being of Writing. Écriture automatique in 19th Century Psychiatry and Early Surrealism (Breton/Soupault: Les champs magnétiques). ‘Écriture automatique’ and psychoanalysis are often lumped together in literary studies, almost as a knee‐jerk reaction. However, on closer inspection it can be seen that the discoverers of automatic writing – the surrealists – were more interested in the hysteria research that prevailed around the year 1900 (Pierre Janet, Alfred Binet) and in parapsychology (Frederic Myers). In these two branches of medicine, the theory and practice of automatic writing are based on an experimental constellation in which the relationship between the psychiatrist/experiment organiser and the patient/participant takes centre stage. Here, the latter writes in response to an order or question from the former, mostly while overcoming a physical or memory block. André Breton and Philippe Soupault set up a very similar constellation in the Champs magnétiques, though with some key alterations. Indeed, surrealism liberates the patient engaging in automatic writing from the dictates of the psychiatrist – but only to submit him to a yet more overwhelming force, a pure violence of writing, so to speak: the automatism of a ‘higher reality’.
“Streng genommen reflexartig”. Ivan Michajlovič Sečenov und die Gründungsmythen des ‘russischen Reflex‐Imperiums’
Authors: Wurm Barbara
Published: February 2009

“Reflex – in a Strict Sense”. Ivan Michajlovič Sečenov and the Founding Myths of the ‘Russian reflex empire’. This paper aims to reconstruct Ivan Michajlovič Sečenov's impact on reflex theory by looking at the different narratives which constitute his specific position in the history of science, where he is considered the Russian founder of a purely materialist framing of consciousness and behaviour, the father figure of objective psychology, and the predecessor of the ‘great’ Ivan Pavlov. I argue that Sečenov himself was very much aware of the symbolic significance of the term “reflex” and that the rhetorical strategies in his opus magnum, The Reflexes of the Brain (1863), deliberately enforce the precarious twofold potential of reflexological conceptions as psycho‐physiological structures as well as social programs. Also within the cultural and political settings of the 19th and 20th century, Sečenov's comprehensive and multifaceted research work in the field of nerve physiology was gradually reduced to a strong, ideologically interpretable message: “All movements bearing the name of voluntary in physiology are reflex in a strict sense”.
Reflexe in Hirnforschung, Kunst und Technik. Einleitende Bemerkungen
Authors: Wübben Yvonne , Vöhringer Margarete
Published: February 2009

The Circulation of Reflexes in Brain Research, Art and Technology. Introductory Remarks. The introduction deals with two main issues: First, it focuses on the question why a history of scientific concepts should not be limited to the analysis of scientific texts alone. Secondly, it shows how the history of the reflex concept gains from looking at various fields such as art, literature and brain research. The crucial role the reflex played in 19th and 20th century and the different meanings it adopted allowed us to conclude with Bruno Latour that the distinction between art and science is in itself historical. Thus, the distinction proves to be of little use for the historiography of complex concepts such as the reflex which rarely appear to be purely scientific.
New insights into structure‐function relationships between archeal ATP synthase (A1A0) and vacuolar type ATPase (V1V0)
Authors: Grüber Gerhard , Marshansky Vladimir
Published: February 2009

Adenosine triphosphate, ATP, is the energy currency of living cells. While ATP synthases of archae and ATP synthases of pro‐ and eukaryotic organisms operate as energy producers by synthesizing ATP, the eukaryotic V‐ATPase hydrolyzes ATP and thus functions as energy transducer. These enzymes share features like the hydrophilic catalytic‐ and the membrane‐embedded ion‐translocating sector, allowing them to operate as nano‐motors and to transform the transmembrane electrochemical ion gradient into ATP or vice versa. Since archaea are rooted close to the origin of life, the A‐ATP synthase is probably more similar in its composition and function to the “original” enzyme, invented by Nature billion years ago. On the contrary, the V‐ATPases have acquired specific structural, functional and regulatory features during evolution. This review will summarize the current knowledge on the structure, mechanism and regulation of A‐ATP synthases and V‐ATPases. The importance of V‐ATPase in pathophysiology of diseases will be discussed. BioEssays 30:1096–1109, 2008. © 2008 Wiley Periodicals, Inc.
Bacterial microcompartments: their properties and paradoxes
Authors: Cheng Shouqiang , Liu Yu , Crowley Christopher S. , Yeates Todd O. , Bobik Thomas A.
Published: February 2009

Many bacteria conditionally express proteinaceous organelles referred to here as microcompartments (Fig. 1). These microcompartments are thought to be involved in a least seven different metabolic processes and the number is growing. Microcompartments are very large and structurally sophisticated. They are usually about 100–150 nm in cross section and consist of 10,000–20,000 polypeptides of 10–20 types. Their unifying feature is a solid shell constructed from proteins having bacterial microcompartment (BMC) domains. In the examples that have been studied, the microcompartment shell encases sequentially acting metabolic enzymes that catalyze a reaction sequence having a toxic or volatile intermediate product. It is thought that the shell of the microcompartment confines such intermediates, thereby enhancing metabolic efficiency and/or protecting cytoplasmic components. Mechanistically, however, this creates a paradox. How do microcompartments allow enzyme substrates, products and cofactors to pass while confining metabolic intermediates in the absence of a selectively permeable membrane? We suggest that the answer to this paradox may have broad implications with respect to our understanding of the fundamental properties of biological protein sheets including microcompartment shells, S‐layers and viral capsids. BioEssays 30:1084–1095, 2008. © 2008 Wiley Periodicals, Inc.
The role of the ubiquitin proteasome system in synapse remodeling and neurodegenerative diseases
Authors: Ding Mei , Shen Kang
Published: February 2009

The ubiquitin proteasome system is a potent regulatory mechanism used to control protein stability in numerous cellular processes, including neural development. Many neurodegenerative diseases are featured by the accumulation of UPS‐associated proteins, suggesting the UPS dysfunction may be crucial for pathogenesis. Recent experiments have highlighted the UPS as a key player during synaptic development. Here we summarize recent discoveries centered on the role of the UPS in synapse remodeling and draw attention to the potential link between the synaptic UPS dysfunction and the pathology of neurodegenerative diseases. BioEssays 30:1075–1083, 2008. © 2008 Wiley Periodicals, Inc.
Proposed three‐letter abbreviations for homologues of the coded amino acids
Authors: Burton James A.
Published: February 2009

DEAR EDITOR:

A three‐letter code to identify homologues of the coded amino acids is proposed. The first letter is taken from the one‐letter code used for amino acids and identifies the side chain functional group that distinguishes the coded amino acid. To this is added two lower case letters identifying the number of carbon atoms in the homologue. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 132–136, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
T7 phage display as a method of peptide ligand discovery for PDZ domain proteins
Authors: Sharma Sudhir C. , Memic Adnan , Rupasinghe Chamila N. , Duc Anne‐Cécile E. , Spaller Mark R.
Published: February 2009

The use of bacteriophage T7 is presented as a peptide display platform to identify short binding sequences for PDZ domain proteins. Two different domains are examined, the 10th PDZ domain (PDZ10) of the multi‐PDZ domain protein 1 (MUPP1) and the third PDZ domain (PDZ3) of postsynaptic density‐95 (PSD‐95) protein. Using the T7Select 415‐1b construct, which displays 415 peptides per phage particle, a random heptapeptide and focused octapeptide libraries were constructed and subjected to iterative selection‐enrichment cycles against surface‐immobilized PDZ3 and PDZ10 proteins. The derived consensus sequences, together with those of high‐frequency clones, were used as the basis for individual chemically synthesized peptides. Each peptide was subjected to isothermal titration calorimetry binding determinations against the corresponding PDZ domain under standard solution conditions. For MUPP1 PDZ10, binding analysis demonstrated that one of the heptapeptides, Ac‐IGRISRV, displayed a two‐fold improved affinity over the octapeptide derived from the carboxy terminus of the hc‐Kit protein, which we had recently demonstrated as among the highest affinity ligands reported to date for that domain. In the case of PSD‐95 PDZ3, peptides were found that possessed low‐micromolar dissociation constants, as well as those that rediscovered the C‐terminal sequence (KQTSV) of the protein CRIPT, a known natural binding protein of PDZ3. These successful examples of ligand discovery against two distinctly different PDZ domains demonstrate that the T7 phage platform could prove broadly applicable to the numerous other PDZ domains for which binding peptides are absent or of insufficient affinity. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 183–193, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Multivalent interactions with gp120 are required for the anti‐HIV activity of Cyanovirin
Authors: Liu Yinan , Carroll Jacob R. , Holt Lindsey A. , McMahon James , Giomarelli Barbara , Ghirlanda Giovanna
Published: February 2009

Cyanovirin‐N (CV‐N) is a cyanobacterial lectin that binds to specific oligomannoses on the surface of gp120, resulting in nanomolar antiviral activity against HIV. In its monomeric form, CV‐N contains two functional carbohydrate‐binding domains, A and B. When refolded at high concentration, the protein can form a domain‐swapped dimer. To clarify the role of multiple‐binding sites in CV‐N, we previously designed a monomeric mutant, P51G‐m4‐CVN, in which the binding site on domain A was rendered ineffective by four mutations (m4); in addition, a hinge region mutation (P51G) hinders the formation of a domain swapped dimer. The protein bound gp120 with diminished affinity and was completely inactive against HIV. Here, we present two mutants, ΔQ50‐m4‐CVN and S52P‐m4‐CVN, which fold exclusively as domain‐swapped dimers while containing the four mutations that abolish domain A. The dimers contain two intact B domains, thus restoring multivalency. ΔQ50‐m4‐CVN and S52P‐m4‐CVN bind gp120 at low‐nanomolar concentrations and recover in part the antiviral activity of wt CV‐N. These results indicate that the number of carbohydrate binding domains, rather than their identity, is crucial to CV‐N functionality. © 2009 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 92: 194–200, 2009.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Local‐loop based robot action control module using independent microprocessors
Authors: Chen Chao Hung , Lin Hsiung Cheng , Liu Ying Chu , Hsu Wei Chung
Published: February 2009

With increasing demand of robot applications in industry or other areas, the development of both reliable and low‐cost robot action control system is getting much attention in recent years. This paper has proposed a local‐loop based robot action control module using independent microprocessors. The robot action commands transmitted from PC via RS232 can be received by the individual authorized microprocessor. There are up to tens of modules to be operated for a variety of robot actions simultaneously and independently. Real world performance results are presented to demonstrate the effectiveness of the proposed approach in term of simple, flexible and efficient performance. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 593–606, 2010; View this article online atwileyonlinelibrary.com; DOI 10.1002/cae.20250
Real‐time motor current signature analysis tool for undergraduate laboratory
Authors: Idowu Peter , Root Christopher
Published: February 2009

The typical electrical engineering (EE) undergraduate curriculum is packed with foundational materials and offers limited room for other desirable materials that could be readily applied in the power industry. A Motor Current Signature Analysis (MCSA) tool is developed for effectively teaching the concepts of induction motor fault detection within one lecture or laboratory period. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 634–639, 2010; View this article online at wileyonlinelibrary.com; DOI 10.1002/cae.20263
Simulations as a new physics teaching tool
Authors: Martinez Elvira , Carbonell Victoria , Florez Mercedes , Amaya Jose
Published: February 2009

In the past 15 years, physics education research has shed light on the difficulties students encounter in learning physics. In response, a wide variety of new models of physics instruction have become available. In the last 4 years, we developed a physics remedial course to decrease the dropout rate of university students while promoting more efficient learning of the principles and laws of physics. To motivate students to do research on physical phenomena we focused our attention on simulations to help students learn different subjects concerning physics word. This article presents examples of simulations generated by the authors using Modellus software for interactive learning of simple harmonic motion. In addition, videotapes, tests and other didactic material are available for students in a virtual environment. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 757–761, 2010; View this article online at wileyonlinelibrary.com; DOI 10.1002/cae.20266
A remotely accessible and configurable electronics laboratory implementation by using LabVIEW
Authors: Azaklar Sezen , Korkmaz Hayriye
Published: February 2009

In this article, selected applications from the experiments included in undergraduate Electronics and Computer Education curriculum are transformed into remotely accessible and configurable manner. The experiment user interfaces and publishing over the internet is developed in LabVIEW. These experiments are suitable for online conduction where students are either in‐class or laboratory on‐campus and/or at home. In this work, four different remotely configurable experiment modules are designed and implemented. Remotely configurable facility in a predefined range is performed by using switches activated by DO terminals of a data acquisition card through a web‐based application. In this way, students can select the desired experiment from the ones stored on the PCB, adjust the voltage applied to the input terminal of the circuit and change the circuit elements values by using telepresence methodology. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 709–720, 2010; View this article online atwileyonlinelibrary.com; DOI 10.1002/cae.20276
Scaffolding for automotive air conditioning learning environment
Authors: Liang Janus S.
Published: February 2009

This research is to construct a scaffold‐based learning environment of automotive air conditioning system repair and maintenance by using technologies of Internet, virtual reality, CAD graphic processing and 2D animation. It is a useful system of air conditioning system troubleshooting training for such learners as colleague or vocational school students or novices in automotive repair industry, etc. This environment is composed of different units, helping learns to understand different types of automotive air conditioning system troubles, their causes and corresponding troubleshooting steps. In this research, an experiment composed of a pre‐test and a post‐test on the sampled learners was conducted to measure if the learning environment was helpful for them in improving their automotive air conditioning system troubleshooting knowledge and skills. In addition, a user satisfaction questionnaire survey was also conducted and the user satisfaction rate reached as high as nearly 0.98, indicating the learners did find the learning system satisfactory and helpful. In conclusion, the learning system developed in this research can help promote the training of automotive air conditioning system maintenance and repair. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 736–749, 2010; View this article online atwileyonlinelibrary.com; DOI 10.1002/cae.20280
Description and evaluation of an introductory course to Matlab for a heterogeneous group of university students
Authors: Soria‐Olivas Emilio , Martín‐Guerrero José David , Martínez‐Sober Marcelino , Ayuso‐Moya Amparo
Published: February 2009

This paper presents the experience of the authors in teaching the Matlab™ software to students with different levels of academic training, even though all of them belong to the field of Science. Matlab™ is a worldwide standard in technical programming and computing, and its use is still growing; therefore, it is taught in many different university degree programs (Physics, Mathematics, Engineering, etc.). The course analyzed in this paper contains examples of different fields of knowledge to show the students the versatility and power of this tool. At the end of each course, which consists of 30 h, the students expressed their opinions about the content in a private opinion poll (questionnaire). The results of these opinion polls show that the methodology followed is considered appropriate and useful by the students who attended the course. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 750–756, 2010; View this article online at wileyonlinelibrary.com; DOI 10.1002/cae.20282
A computer application for teaching and learning approximation and interpolation algorithms of curves
Authors: Gutiérrez de Ravé E. , Jiménez‐Hornero F. J. , Giráldez J. V.
Published: February 2009

A computer teaching and learning application to help to understand the approximation and interpolation algorithms most used in engineering design has been developed. It is aimed at providing students with a visual, practical and easy‐to‐manage tool for learning and applying the principles of modelling and depicting the results of different curve generation algorithms. This application permits the user to carry out any operation related to the handling of curves depending on the characteristics and parameters of each of the algorithms included within an interactive interface. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 19: 40–47, 2011
Computer‐aided power system fault analysis
Authors: Ekici Sami
Published: February 2009

Most of power systems courses contain mathematical analysis, animations, simulations, and technical tours to power stations. However, experimental studies particularly in fault analysis are very difficult due to high voltages and currents passed through short circuits. Although there are experimental equipments and prototype systems for the students, they are very expensive. This paper presents a new computer‐aided approach for power system analysis course at The University of Firat. The new course covers the previous course which contains only a short experiment by using a prototype power system. The sequence of new updated course for high‐voltage fault analysis is following: experimental implementations, simulation, signal processing and fault classification. A questionnaire containing 11 questions has been applied to students to determine the effectiveness of the new course. According to questionnaire; the updated course has been found more useful to analyze and understand the transmission line faults than the previous course. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 19: 66–70, 2011
Comparison of the most popular object‐oriented software languages and criterions for introductory programming courses with analytic network process: A pilot study
Authors: Anik Zelal , Baykoç Ömer Faruk
Published: February 2009

This study has primarily aimed at finding a tool which will facilitate the choice of programming language and making this program well‐arranged. But, choosing the proper programming language is a kind of decision making problem with multiple criterions which require the consideration of many factors which are closely interrelated. The Analytic Network Process (ANP) methodology is particularly useful for decision making in a multi‐criteria context where interaction exists between the criterions. A set of criteria for the selection of a programming language for introductory courses proposed in Parker et al. [J Inform Technol Edu USA 5: 135–142, 2006] is used in this study. These selection criterions and the criterion groups were analyzed by using the ANP, and the obtained ranking for software languages and criteria were given. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 19: 89–96, 2011
Remote monitoring and control of horticultural cool storage over the Internet
Authors: Omid M. , Sajjadiye S. M. , Alimardani R.
Published: February 2009

In this article, a distributed architecture that allows remote control and monitoring of horticultural cool storage (HCS) is presented. The various stages in the design and implementation of system for monitoring temperature and relative humidity and controlling HCS environment conditions are presented and discussed. The required hardware include a microcontroller and accompanying electronic circuitry, a server computer, serial port, temperature and relative humidity sensors and two actuators. Microcontroller transfers the sensors data to the server via serial port. Both the client and the server side programs are coded in VB programming language. They use VB MSComm control in order to communicate with the microcontroller. Internet communications is relied on socket programming. Winsock is used for network communications via the TCP/IP protocol. Sockets are configured to listen to a data port or to connect and then transmit to a remote one. Consequently information can be easily and reliably transmitted, monitored and/or controlled by the two machines. The performance of system was evaluated for 2 weeks and the results were quite satisfactory. This system can be easily adapted in other agricultural facilities such as greenhouses and silos. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 19: 136–145, 2011
Learning by developing a satellite navigation simulator
Authors: Aydin Serkan , Kaptan Hakan
Published: February 2009

This article describes a methodology to explain and understand Satellite Navigation concepts by developing simulators in the Marmara University, Technical Education Faculty, Electronics and Computer Education Department (MUTEFEC) Istanbul. At present, senior students of MUTEFEC take graduation projects interested in their professional skills. In addition some students have got developing projects related with Global Positioning System (GPS)/Galileo (EU Satellite Navigation System). In this study; to help students and accelerate their perceptions while building their project, a teaching concept for simulator‐based project developing issues in computerized environment supports the possibility of distance learning as well as a computer‐aided teaching is presented. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 19: 501–507, 2011
Rapid Matrix‐Assisted Refolding of Histidine‐Tagged Proteins
Authors: Dashivets Tetyana , Wood Nichole , Hergersberg Christoph , Buchner Johannes , Haslbeck Martin
Published: February 2009

Matrix refolded: The formation of inclusion bodies, which are amorphous aggregates of misfolded insoluble protein, during recombinant protein expression, is one of the biggest bottlenecks in protein science. We report a stepwise, rational optimization procedure for refolding of insoluble proteins (see scheme). In comparison to refolding in‐solution, this parallelized, matrix‐assisted approach allows the refolding of various proteins in a fast and efficient manner.

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The formation of inclusion bodies (IBs)—amorphous aggregates of misfolded insoluble protein—during recombinant protein expression, is still one of the biggest bottlenecks in protein science. We have developed and analyzed a rapid parallel approach for matrix‐assisted refolding of recombinant His6‐tagged proteins. Efficiencies of matrix‐assisted refolding were screened in a 96‐well format. The developed methodology allowed the efficient refolding of five different test proteins, including monomeric and oligomeric proteins. Compared to refolding in‐solution, the matrix‐assisted refolding strategy proved equal or better for all five proteins tested. Interestingly, specifically oligomeric proteins displayed significantly higher levels of refolding compared to refolding in‐solution. Mechanistically, matrix‐assisted folding seems to differ from folding in‐solution, as the reaction proceeds more rapidly and shows a remarkably different concentration dependence—it allows refolding at up to 1000‐fold higher protein concentration than folding in‐solution.
Cover Picture: Two‐Dimensional Oligo(phenylene‐ethynylene‐butadiynylene)s: All‐Covalent Nanoscale Spoked Wheels (Chem. Eur. J. 11/2009)
Authors: Lei Shengbin , Ver Heyen An , De Feyter Steven , Surin Mathieu , Lazzaroni Roberto , Rosenfeldt Sabine , Ballauff Matthias , Lindner Peter , Mössinger Dennis , Höger Sigurd
Published: February 2009

Defined two‐dimensional…︁organic structures in the 5 nm regime have been rarely produced without meeting the limits of solubility, synthetic feasibility, or uniformity. In their full paper on page 2518 ff., S. Höger, S. De Feyter, R. Lazzaroni, S. Rosenfeldt et al. present a spoked wheel that is molecularly defined, shape‐persistent, and yet fully characterizable. The 2D oligomer is formed by sixfold coupling of rim modules to a central hub and subsequent template‐directed cyclization. The structure and rigidity are confirmed by detailed STM/AFM and SANS experiments.

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A Click Approach to Structurally Diverse Conjugates Containing a Central Di‐1,2,3‐triazole Metal Chelate
Authors: Mindt Thomas L. , Schweinsberg Christian , Brans Luc , Hagenbach Adelheid , Abram Ulrich , Tourwé Dirk , Garcia‐Garayoa Elisa , Schibli Roger
Published: February 2009

Assemble & chelate: Click chemistry enables the efficient and selective synthesis of structurally diverse conjugates containing a central di‐1,2,3‐triazole chelator for complexation with [99mTc(CO)3]+. Use of appropriate building blocks allows the modulation of pharmacological relevant characteristics of the conjugate, or the introduction of secondary probes suitable for imaging modalities other than single photon emission computed tomography (SPECT).

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The selective and efficient synthesis of novel tridentate metal chelating systems containing two 1,4‐disubstituted 1,2,3‐triazole heterocycles obtained via the copper(I)‐catalyzed cycloaddition of alkynes and azides (click reaction) is described. The constructs are shown to be efficient ligand systems for the chelation of fac‐[M(CO)3(H2O)3]+ (M=99mTc, Re) yielding well‐ defined and stable complexes. The organometallic 99mTc conjugates are suitable for application as diagnostic radiotracers for single photon emission computed tomography (SPECT) as demonstrated in vivo with a fragment of the tumor‐targeting bombesin peptide functionalized with a di‐1,2,3‐triazole chelator and radiolabeled with [99mTc(CO)3]+. Starting from readily available dialkyne precursors, the central chelating systems are formed as the conjugates are assembled by click reaction with azide‐functionalized entities. Depending on the nature of the azide substrates employed (e.g. lipophilic or hydrophilic residues) pharmacologically relevant characteristics of the final metal conjugate such as hydrophilicity or overall charge can be readily modulated. The procedures described also enable the facile introduction of other probes into the metal conjugate, providing access to potential multimodal imaging agents.
Adjuvant chemotherapy for the “oldest old” ovarian cancer patients
Authors: Moore Kathleen N. , Frank Summer G. , Alward Erin K. , Landrum Lisa M. , Myers Tashanna K. , Walker Joan L. , Gold Michael A. , McMeekin D. Scott , Vesely Sara K. , Mannel Robert S.
Published: February 2009

BACKGROUND:

Patients aged ≥80 years who are diagnosed with advanced ovarian cancer (OC) have been reported to have a poor prognosis. In the current study, chemotherapy‒related toxicity data were evaluated between patients aged ≥80 years and those aged <80 years.

METHODS:

Patients with OC who underwent cytoreductive surgery with chemotherapy were included. Self‐reported toxicity data were obtained from National Cancer Institute Common Toxicity Criteria (CTC) forms. Objective indicators of status including albumin level, weight, and creatinine clearance were abstracted both before and after therapy. Data were compared between patients by decade of age.

RESULTS:

A total of 246 patients were included. A presenting Karnofsky performance status >2 was recorded in 17% of patients aged ≥80 years versus 0% to 4% of patients aged <80 years (P = .002). Platinum‐based chemotherapy was used in all patients. For patients aged <80 years, combination chemotherapy was used in >90% versus 69% in those aged ≥80 years (P < .0001). Standard‒dose combination therapy was used in 72% to 86% of patients aged <80 years versus 28% of patients aged ≥80 years (P < .0001). Patients aged ≥80 years completed ≥6 cycles of therapy approximately 57% of the time versus 84% to 97% of the time for those aged <80 years (P = .0001). CTC forms identified no self‐reported toxicities to be more common among patients aged ≥80 years. Multivariate logistic regression identified creatinine clearance <65 mL/minute (odds ratio [OR] of 4.6), 5% weight loss (OR of 2.5), prechemotherapy albumin level of <2 g/dL (OR of 3.65), and initiation of therapy with a single agent (OR of 3.9) as independent predictors of failure to complete chemotherapy.

CONCLUSIONS:

Despite initial treatment modifications as well as toxicity assessment, only 57% of patients aged ≥80 years completed planned chemotherapy. It was confirmed that further studies into the pharmacokinetics of chemotherapy in the elderly and more sensitive assessment of therapy‒related toxicity are required. Cancer 2009. © 2009 American Cancer Society.
Mandatory second opinion in cytopathology
Authors: Lueck Nathan , Jensen Chris , Cohen Michael B. , Weydert Jamie A.
Published: February 2009

BACKGROUND:

Mandatory review of outside pathologic material is intended to detect interpretive errors that may have a clinically significant impact on patient care. Prior to definitive treatment of referred patients, the University of Iowa Carver College of Medicine requires a review of pertinent pathologic material previously obtained at outside institutions. The aims of this study were to determine if this local standard of practice has a measurable impact on patient care.

METHODS:

The pathologic diagnoses of 499 second opinion cytology cases seen at the University of Iowa Carver College of Medicine were studied. Each second opinion was classified as “no diagnostic disagreement”, “minor disagreement”, or “major disagreement” with respect to the originating institution's interpretation. The clinical impact of major disagreement cases was determined by pathologic and clinical follow‐up via chart review.

RESULTS:

Second opinion cytology resulted in 37 cases (7.4% of total cases) with major diagnostic disagreements. Clinical and pathologic follow‐up was available in 30 of the major disagreement cases; second opinion diagnosis was better supported in 22 of these cases compared to the outside diagnosis. The second opinion in 6 major disagreement cases prompted changes in clinical management.

CONCLUSIONS:

Major disagreements in second opinion cytology are common, likely reflective of the challenges inherent in the interpretation of cytologic specimens. Although mandatory second opinion of outside cytologic material prompted changes in clinical management in only a small fraction of cases (1.2%), this rate was similar to those previously published for surgical pathology second opinion. These findings support the notion that mandatory second opinion policy as an important part of patient care. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.
Distribution of growth hormone‐releasing hormone‐like peptide: Immunoreactivity in the central nervous system of the adult zebrafish (Danio rerio)
Authors: Castro Antonio , Becerra Manuela , Manso María Jesús , Tello Javier , Sherwood Nancy M. , Anadón Ramón
Published: February 2009

The distribution of growth hormone‐releasing hormone‐like peptides (GHRH‐LP) in the central nervous system of the zebrafish was investigated by using immunohistochemical techniques with polyclonal antibodies. ELISAs showed that the antiserum raised against salmon (s)GHRH‐LP recognized both zebrafish GHRH‐LP1 and ‐2, whereas the antiserum raised against carp (c)GHRH‐LP was more sensitive but detected only zebrafish GHRH‐LP1. Neither antiserum detected the true GHRH. Large cells in the nucleus lateralis tuberis were immunoreactive with both antisera, which suggests that they contained zebrafish GHRH‐LP1, but not excluding GHRH‐LP2. Also, immunoreactive fibers, which putatively originated from these hypothalamic neurons, were present in the hypophysis; both antisera detected fibers, although only sGHRH‐LP antiserum stained fibers in the neurointermediate lobe. These fibers may have a neuroendocrine role. Candidates for a role in feeding include several areas in which both antisera labeled cells and fibers, implying a strong reaction for GHRH‐LP1 and possibly GHRH‐LP2. These areas include the isthmus with cells in the secondary gustatory/visceral nucleus, which were also calretinin immunoreactive. Numerous GHRH‐LP‐immunoreactive fibers (also labeled by both antisera) probably originate from the gustatory/visceral nucleus to innervate the ventral area of the telencephalon, preglomerular nuclei, torus lateralis and hypothalamic diffuse nucleus, habenula, torus semicircularis, and dorsolateral funiculus of the spinal cord. Present results in the zebrafish brain suggest involvement of GHRH‐LP in both neuroendocrine and feeding‐associated nervous circuits. The present data on the location of the two GHRH‐LPs are the first clue to the possible functions of these two hormones. J. Comp. Neurol. 513:685–701, 2009. © 2009 Wiley‐Liss, Inc.
Widespread changes in dendritic and axonal morphology in Mecp2‐mutant mouse models of rett syndrome: Evidence for disruption of neuronal networks
Authors: Belichenko Pavel V. , Wright Elena E. , Belichenko Nadia P. , Masliah Eliezer , Li Hong Hua , Mobley William C. , Francke Uta
Published: February 2009

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X‐linked gene MECP2. Girls with RTT show dramatic changes in brain function, but relatively few studies have explored the structure of neural circuits. Examining two mouse models of RTT (Mecp2B and Mecp2J), we previously documented changes in brain anatomy. Herein, we use confocal microscopy to study the effects of MeCP2 deficiency on the morphology of dendrites and axons in the fascia dentata (FD), CA1 area of hippocampus, and motor cortex following Lucifer yellow microinjection or carbocyanine dye tracing. At 3 weeks of age, most (33 of 41) morphological parameters were significantly altered in Mecp2B mice; fewer (23 of 39) were abnormal in Mecp2J mice. There were striking changes in the density and size of the dendritic spines and density and orientation of axons. In Mecp2B mice, dendritic spine density was decreased in the FD (∼11%), CA1 (14–22%), and motor cortex (∼16%). A decreased spine head size (∼9%) and an increased spine neck length (∼12%) were found in Mecp2B FD. In addition, axons in the motor cortex were disorganized. In Mecp2J mice, spine density was significantly decreased in CA1 (14–26%). In both models, dendritic swelling and elongated spine necks were seen in all areas studied. Marked variation in the type and extent of changes was noted in dendrites of adjacent neurons. Electron microscopy confirmed abnormalities in dendrites and axons and showed abnormal mitochondria. Our findings document widespread abnormalities of dendrites and axons that recapitulate those seen in RTT. J. Comp. Neurol. 514:240–258, 2009. © 2009 Wiley‐Liss, Inc.
Collateral projection from the locus coeruleus to whisker‐related sensory and motor brain regions of the rat
Authors: Lee Sat‐Byol , Beak Suk K. , Park Seung H. , Waterhouse Barry D. , Lee Hyun S.
Published: February 2009

The primary goal of this study was to examine whether the locus coeruleus (LC) provides collateral projections to whisker‐related, sensorimotor brain regions. After injections of retrograde tracers into the primary sensory (S1) barrel field/primary whisker motor (M1) cortices, ventroposteromedial (VPM)/ventrolateral (VL) thalamic nuclei, or principal sensory trigeminal (Pr5)/facial motor (Mo7) nuclei, the distribution of double‐labeled neurons within the LC was examined. Our observations indicated that a large number of individual LC cells provided axon collaterals to S1‐M1 or VPM‐VL regions, whereas only a few projected to Pr5‐Mo7 nuclei. The laterality and the distribution of dual‐projecting LC neurons were as follows. 1) The neurons projecting to the S1‐M1 cortices were predominantly ipsilateral (96% ± 0.7%). Labeled neurons were located ventrally at the rostral pole but were evenly distributed along the dorsoventral aspect of the principal LC. 2) The cells projecting to the VPM‐VL nuclei were bilateral, with ipsilateral (68% ± 2.3%) dominance. Neurons were observed at the rostrocaudal extent of the LC, where the labeling was most pronounced at the ventral, principal LC. 3) The neurons projecting to the Pr5‐Mo7 regions exhibited slightly contralateral (56% ± 2.9%) dominance, where labeled cells were confined within the ventral margin of the principal subdivision. Taken together, the present observations demonstrate that each subdivision of the LC possesses a differential functional organization with respect to its collateral projection to whisker‐related sensorimotor targets, suggesting that the nucleus might play a modulatory role in vibrissal sensorimotor integration that allows the guidance of behavioral action essential for the survival of the animal. J. Comp. Neurol. 514:387–402, 2009. © 2009 Wiley‐Liss, Inc.
Corticofugal projections to trigeminal motoneurons innervating antagonistic jaw muscles in rats as demonstrated by anterograde and retrograde tract tracing
Authors: Yoshida Atsushi , Taki Ikuro , Chang Zheng , Iida Chie , Haque Tahsinul , Tomita Akiko , Seki Shinichiro , Yamamoto Shinya , Masuda Yuji , Moritani Masayuki , Shigenaga Yoshio
Published: February 2009

Little is known about the organization of corticofugal projections controlling antagonistic jaw muscles. To address this issue, we employed retrograde (Fluorogold; FG) and anterograde (biotinylated dextran amine; BDA) tracing techniques in rats. Three groups of premotoneurons were identified by injecting FG into the jaw‐closing (JC) and ‐opening (JO) subdivisions of the trigeminal motor nucleus (Vmo). These were 1) the intertrigeminal region (Vint) and principal trigeminal sensory nucleus for JC nucleus; 2) the reticular region medial to JO nucleus (RmJO) for JO nucleus; and 3) the parabrachial (Pb) and supratrigeminal (Vsup) nuclei, reticular regions medial and ventral to JC nucleus, rostrodorsomedial oralis (Vor), and juxtatrigeminal region (Vjuxt) containing a mixture of premotoneurons to both the nuclei. Subsequently, FG was injected into the representative premotoneuron structures. The JC and JO premotoneurons received main afferents from the lateral and medial agranular fields of motor cortex (Agl and Agm), respectively, whereas afferents to the nuclei with both JC and JO premotoneurons arose from Agl also and from primary somatosensory cortex (S1). Finally, BDA was injected into each of the three cortical areas representing the premotoneuron structures to complement the FG data. The Agl and Agm projected to reticular regions around the Vmo, whereas the Pb, Vsup, Vor, and Vjuxt received input from Agl. The S1 projected to the trigeminal sensory nuclei as well as to the Pb, Vsup, and Vjuxt. These results suggest that corticofugal projections to Vmo via premotoneuron structures consist of multiple pathways, which influence distinct patterns of jaw movements. J. Comp. Neurol. 514:368–386, 2009. © 2009 Wiley‐Liss, Inc.
Binge‐like postnatal alcohol exposure triggers cortical gliogenesis in adolescent rats
Authors: Helfer Jennifer L. , Calizo Lyngine H. , Dong Willie K. , Goodlett Charles R. , Greenough William T. , Klintsova Anna Y.
Published: February 2009

The long‐term effects of binge‐like postnatal alcohol exposure on cell proliferation and differentiation in the adolescent rat neocortex were examined. Unlike the hippocampal dentate gyrus, where proliferation of progenitors results primarily in addition of granule cells in adulthood, the vast majority of newly generated cells in the intact mature rodent neocortex appear to be glial cells. The current study examined cytogenesis in the motor cortex of adolescent and adult rats that were exposed to 5.25 g/kg/day of alcohol on postnatal days (PD) 4–9 in a binge manner. Cytogenesis was examined at PD50 (through bromodeoxyuridine [BrdU] labeling) and survival of these newly generated cells was evaluated at PD80. At PD50, significantly more BrdU‐positive cells were present in the motor cortex of alcohol‐exposed rats than controls. Confocal analysis revealed that the majority (>60%) of these labeled cells also expressed NG2 chondroitin sulfate proteoglycan (NG2 glia). Additionally, survival of these newly generated cortical cells was affected by neonatal alcohol exposure, based on the greater reduction in the number of BrdU‐labeled cells from PD50 to PD80 in the alcohol‐exposed animals compared to controls. These findings demonstrate that neonatal alcohol exposure triggers an increase in gliogenesis in the adult motor cortex. J. Comp. Neurol. 514:259–271, 2009. © 2009 Wiley‐Liss, Inc.
Distinct roles of neuropilin 1 signaling for radial and tangential extension of callosal axons
Authors: Hatanaka Yumiko , Matsumoto Tomoko , Yanagawa Yuchio , Fujisawa Hajime , Murakami Fujio , Masu Masayuki
Published: February 2009

Cortical excitatory neurons migrate from their origin in the ventricular zone (VZ) toward the pial surface. During migration, these neurons exhibit a stellate shape in the intermediate zone (IZ), transform into bipolar cells, and then initiate radial migration, extending a trailing process, which may lead to an axon. Here we examined the role of neuropilin 1 (NRP1) in these developmental events. Both NRP1 mRNA and protein were highly expressed in the IZ, where stellate‐shaped cells were located. DiI labeling experiments showed that neuronal migration occurred normally in Nrp1 mutant mice up to embryonic day (E) 14.5, the latest day to which the mutant survives, with only subtle axonal defasciculation. However, interference with Nrp1 signaling at a later stage caused pathfinding errors: when a dominant negative form of Nrp1 was electroporated into the cortical VZ cells at E12.5 or E15.5 and examined perinatally, guidance errors were found in tangential axonal extension toward the midline. In contrast, no significant effect was noted on the migration of cortical excitatory neurons. These findings indicate that NRP1 plays an important role in the guidance of callosal axons originating from cortical excitatory neurons but does not support a role in their migration. Moreover, insofar as radial axonal extension within the cortical plate was unaffected, the present findings imply that molecular mechanisms for the axonal extension of excitatory neurons within the cortical plate are distinct from those in the white matter. J. Comp. Neurol. 514:215–225, 2009. © 2009 Wiley‐Liss, Inc.