bluuebunny/crossref_metadata_2025 huggingface dataset:
Flow cytometry as a tool to study phytotoxic modes of action
Authors: Adler Nicole E. , Schmitt-Jansen Mechthild , Altenburger Rolf
Published: January 2007

—The objective of the present investigation was to provide a diagnostic tool for the analysis of phytotoxic interactions between environmental contaminants and algae by application of flow cytometry. Therefore, an experimental design was developed consisting of synchronized Scenedesmus vacuolatus cell populations at defined cell-cycle stages, short-term exposure against different inhibitors with known molecular targets, and fluorochrome labeling of different metabolic processes. To discriminate cells with compromised metabolic processes from intact and metabolically inactive cells, references for every fluorochrome were defined using control and heat-treated populations. The experimental results showed that fluorescence markers are able to detect disturbance of specific cellular characteristics, such as membrane integrity, chlorophyll synthesis, and degradation. A differentiation of impacts on specific metabolic process caused by the reference inhibitors in concentration-dependent patterns could be seen using flowcytometric fluorochrome analysis. These findings were compared with effects observed for N-phenyl-2-naphthylamine (PNA), a sediment contaminant of high phytotoxicity but unclear mode of action. Rhodamine 123 and cyano-ditolyl tetrazolium chloride detected significant metabolic changes for relevant exposures against PNA, thus pointing to compromised mitochondrial activity and changes in membrane potential as causes of phytotoxicity.
Identification of potentially toxic compounds in complex extracts of environmental samples using gas chromatography-mass spectrometry and multivariate data analysis
Authors: Bergknut Magnus , Kucera Adam , Frech Kristina , Andersson Erika , Engwall Magnus , Rannug Ulf , Koci Vladimir , Andersson Patrik L. , Haglund Peter , Tysklind Mats
Published: January 2007

—In this study, we examined 31 samples of varying chemical composition, including samples of soils from gasworks, coke production sites, and sites where wood preservatives were heavily used; ash and soot from municipal solid waste incinerators; antiskid sand; and dust from areas with heavy road traffic. The samples were comprehensively chemically characterized, especially their polycyclic aromatic compound contents, using gas chromatography-time-of-flight mass spectrometry, whereas their biological effects were assessed using dehydrogenase activity, root growth (Hordeum vulgare), reproduction of springtails (Folsomia candida), algal growth (Desmodesmus subspicatus), germinability (Sinapis alba), Vibrio fischeri, DR-CALUX, and Ames Salmonella assays. The number of compounds detected in the samples ranged from 123 to 527. Using the multivariate regression technique of partial-least-squares projections to latent structures, it was possible to find individual compounds that exhibited strong correlations with the different biological responses. Some of the results, however, indicate that a broader chemical characterization may be needed to identify all the compounds that may cause the measured biological responses.
Bioremediation of benzene, ethylbenzene, and xylenes in groundwater under iron-amended, sulfate-reducing conditions
Authors: Jin Song , Fallgren Paul H. , Bilgin A. Azra , Morris Jeffrey M. , Barnes Paul W.
Published: January 2007

—Elevated concentrations of sulfide in groundwater (∼63 mg S2−/L in water and 500 mg dissolved H2S/L dissipating from the wellhead) at a field site near South Lovedale (OK, USA) were inhibiting the activity of sulfate-reducing bacteria (SRB) that are known to degrade contaminants, including benzene, toluene, ethylbenzene, and xylenes. Elevated concentrations of these contaminants, except for toluene, also were present in this groundwater. Microcosms were established in the laboratory using groundwater and sediment collected from the field site and amended with various nutrient, substrate, and inhibitor treatments. All microcosms initially were amended with FeCl2 to induce FeS precipitation and, thereby, to reduce aqueous sulfide concentrations. Complete removal of benzene, ethylbenzene, and m+p-xylenes (BEX; o-xylene not detected) was observed within 39 d in treatments with various combinations of nutrient and substrate amendments, including treatments with no amendments (other than FeCl2). This indicates that the elevated concentration of sulfide is the only limiting factor to BEX biodegradation at this site under anaerobic conditions and that treating the groundwater with FeCl2 may be a simple remedy to both facilitate and enhance BEX degradation by the indigenous SRB population.
Sorption of male hormones by soils and sediments
Authors: Kim Il , Yu Zhiqiang , Xiao Baohua , Huang Weilin
Published: January 2007

—This paper reports the sorption of two male hormones, testosterone and androstenedione, by four soil and sediment samples at both equilibrium and rate-limiting conditions. Unlike prior studies, androstenedione was studied independently of testosterone. Apparent sorption equilibrium is achieved in one to two weeks when the initial aqueous hormone concentrations (C0) at 10,000 μg/L (∼30% of their solubility limits [Sw]) and two to three weeks when the C0 is 300 μg/L (less than 1% of Sw). The Freundlich model parameter n ranged from 0.698 to 0.899 for all soil—solute systems indicating nonlinear sorption isotherms. Isotherm nonlinearity leads to an inverse correlation between single-point organic carbon—normalized sorption distribution coefficients (KOC) and equilibrium androgen concentration (Ce). When Ce/Sw = 0.012, the log KOC values for testosterone and androstenedione on the various sorbents ranged from 6.18 to 6.75 and 6.83 to 6.04, respectively, compared to 6.30 to 6.80 and 6.16 to 6.92 when Ce/Sw = 0.004. This study suggests that male hormones may exhibit slow rates of sorption over 14 d or longer and that soils and sediments may have greater sorption distribution coefficients when concentrations fall into the ng/L range.
Search and identification methods that owners use to find a lost dog
Authors: Lord Linda K. , Wittum Thomas E. , Ferketich Amy K. , Funk Julie A. , Rajala-Schultz Päivi J.
Published: January 2007

Objective—To characterize the process by which owners search for lost dogs and identify factors associated with time to recovery.

Design—Cross-sectional study.

Sample Population—Owners of 187 dogs lost in Montgomery County, Ohio, between June 1 and September 30, 2005.

Procedures—A telephone survey was conducted.

Results—132 of the 187 (71%) dogs were recovered; median time to recovery was 2 days (range, 0.5 to 21 days). Dogs were recovered primarily through a call or visit to an animal agency (46 [34.8%]), a dog license tag (24 [18.2%]), and posting of neighborhood signs (20 [15.2%]). Eighty-nine (48%) dogs had some type of identification at the time they were lost (ie, identification tag, dog license tag, rabies tag, or microchip). Owners had a higher likelihood of recovery when they called an animal agency (hazard ratio, 2.1), visited an animal agency (1.8), and posted neighborhood signs. Dogs that were wearing a dog license tag also had a higher likelihood of recovery (hazard ratio, 1.6). Owners were less likely to recover their dogs if they believed their dogs were stolen (hazard ratio, 0.3).

Conclusions and Clinical Relevance—Results suggest that various factors are associated with the likelihood that owners will recover a lost dog. Both animal agencies and veterinarians can play a role in educating dog owners on the importance of identification tags, licensing, and microchips and can help to emphasize the importance of having a search plan in case a dog is lost.
Search and identification methods that owners use to find a lost cat
Authors: Lord Linda K. , Wittum Thomas E. , Ferketich Amy K. , Funk Julie A. , Rajala-Schultz Päivi J.
Published: January 2007

Objective—To characterize the process by which owners search for lost cats and identify factors associated with time to recovery.

Design—Cross-sectional study.

Sample Population—Owners of 138 cats lost in Montgomery County, Ohio, between June 1 and September 30, 2005.

Procedures—A telephone survey was conducted.

Results—73 of the 138 (53%) cats were recovered; median time to recovery was 5 days (range, 0.5 to 81 days). Most cats (48 [66%]) that were recovered returned home on their own or were found in the neighborhood (5 [7%]); most other cats were recovered through posting of neighborhood signs (8 [11%]) or calling or visiting an animal agency (5 [7%]). The highest success rate for any of the search methods that were used was only 12% (posting neighborhood signs). Only 26 of the 138 (19%) cats had some type of identification at the time they were lost (ie, identification tag, rabies tag, or microchip). Owners allowed 82 (59%) cats to spend at least some time outdoors. The percentage of sexually intact cats recovered by their owners (4/16 [25%]) was significantly lower than the percentage of neutered cats recovered (69/122 [57%]).

Conclusions and Clinical Relevance—Results suggest that the percentage of lost cats recovered by their owners is low, possibly in part because of the lack of use of traditional identification methods and the general acceptance that cats may roam. Veterinarians can help educate owners about the importance of identification and the need to keep cats indoors.
Prevalence of oxacillin- and multidrug-resistant staphylococci in clinical samples from dogs: 1,772 samples (2001–2005)
Authors: Jones Rebekah D. , Kania Stephen A. , Rohrbach Barton W. , Frank Linda A. , Bemis David A.
Published: January 2007

Objective—To determine whether resistance to oxacillin and other antimicrobials in 3 Staphylococcus spp commonly isolated from dogs increased from 2001 to 2005.

Design—Retrospective case series.

Sample Population—1,772 clinical samples of various types obtained from dogs examined at the University of Tennessee Veterinary Teaching Hospital or at regional veterinary hospitals and submitted to the bacteriology and mycology laboratories associated with the teaching hospital.

Procedures—Samples were submitted by attending veterinarians to the bacteriology and mycology laboratories for routine aerobic microbial culture. Identification and antimicrobial susceptibility procedures were performed on all isolates. Susceptibility reports for each antimicrobial and Staphylococcus spp were determined from aggregate electronically archived test results. Oxacillin and multidrug resistance for Staphylococcus intermedius was analyzed by reviewing disk diffusion zone measurements.

Results—Oxacillin resistance increased among S intermedius isolates during the past 5 years, and the increase was associated with multidrug resistance. In 2005, 1 in 5 Staphylococcus spp isolates from canine clinical samples was resistant to oxacillin. The most common staphylococcal species isolated were S intermedius (n = 37), Staphylococcus schleiferi (21), and Staphylococcus aureus (4), and frequencies of oxacillin resistance in isolates of these species were 15.6%, 46.6%, and 23.5%, respectively.

Conclusions and Clinical Relevance—Veterinarians should be aware of the potential for empiric drug treatment failures in instances where Staphylococcus spp infections are common (eg, pyoderma). Judicious use of bacterial culture and susceptibility testing is recommended.
Gold‐Nanoparticle‐Doped TiO2 Semiconductor Thin Films: Optical Characterization
Authors: Buso D. , Pacifico J. , Martucci A. , Mulvaney P.
Published: January 2007

A simple procedure for creating titania sol–gel‐based semiconductor thin films is described. Gold nanoparticles are doped homogeneously into the precursor mixture and the particles are homogeneously distributed in the resultant films when prepared using spin‐coating. The effects of particle loading and annealing temperature on the optical properties of the resultant films are characterized. Ellipsometry, X‐ray diffraction, atomic force microscopy, and surface plasmon spectroscopy are used to monitor the crystallization and porosity changes during film synthesis.
Magnetic Anisotropies and (Ga,Mn)As‐based Spintronic Devices
Authors: Gould C. , Pappert K. , Schmidt G. , Molenkamp L. W.
Published: January 2007

In this Review, we discuss the rich anisotropic properties of the ferromagnetic semiconductor (Ga,Mn)As, and their implications in transport studies. We review the various sources and types of anisotropy seen in the material, discuss its magnetization reversal process, and demonstrate how basic transport properties, such as resistivity and Hall measurements, can be used as very sensitive tools to investigate the magnetization properties of the material. We also discuss how the magnetic anisotropy, coupled with large spin–orbit coupling, leads to an anisotropy in the transport density of states, which in turn leads to fundamentally novel behavior such as tunneling anisotropic magnetoresistance (TAMR).
Isolierte molekulare Drähte
Authors: Frampton Michael J. , Anderson Harry L.
Published: January 2007

In den erstaunlich unterschiedlichen Strukturen, die bisher als “isolierte molekulare Drähte” (insulated molecular wires, IMWs) beschrieben wurden, zeigt sich, wie vielfältig die Ansätze zur elektrisch‐chemischen Isolierung auf molekularer Ebene sind. Gemeinsam verdeutlichen diese Systeme die Bedeutung von Einkapselungsstrategien bei der Entwicklung optoelektronischer Materialien und organischer Halbleiter. Dieser Aufsatz beleuchtet die Synthese und die strukturelle Charakterisierung von IMWs. Struktur‐Eigenschafts‐Beziehungen sollen zudem erklären, wie eine Isolierung die Leistungsmerkmale eines molekularen Drahtes verbessern kann. Wir konzentrieren uns auf drei IMW‐Arten: Polyrotaxane, polymerumhüllte π‐Systeme und dendronisierte Polymere. Die Eigenschaften dieser Systeme werden mit denjenigen von konjugierten Polymeren verglichen, die in mesoporöse Netzwerke und Zeolithe eingefädelt sind. Der Einschluss molekularer Drähte verstärkt so unterschiedliche Eigenschaften wie Lumineszenz, elektrische Transportgrößen und die chemische Beständigkeit, sodass Anwendungen in Elektrolumineszenzdisplays, Sensoren und der photochemischen Wasserstofferzeugung denkbar werden.
Asymmetrische organokatalytische Dominoreaktionen
Authors: Enders Dieter , Grondal Christoph , Hüttl Matthias R. M.
Published: January 2007

Der derzeitige Stand der organischen Synthese macht oft kostspielige Schutzgruppenstrategien und aufwändige Reinigungsschritte nach jeder Synthesestufe erforderlich. Um diese Probleme zu umgehen, werden zunehmend Mehrkomponentendominoreaktionen zum effizienten und stereoselektiven Aufbau von komplexen Molekülen aus einfachen Vorstufen in einem einzigen Prozess genutzt. Organokatalytische Dominoreaktionen sind in gewisser Weise biomimetisch, da dieses Prinzip bei der Biosynthese von komplexen Naturstoffen aus einfachen Bausteinen sehr effizient verwirklicht ist. In diesem Kurzaufsatz werden die aktuellen Entwicklungen des sich rasch entwickelnden Gebiets diskutiert.
Insulated Molecular Wires
Authors: Frampton Michael J. , Anderson Harry L.
Published: January 2007

An astonishing assortment of structures have been described as “insulated molecular wires” (IMWs), thus illustrating the diversity of approaches to molecular‐scale insulation. These systems demonstrate the scope of encapsulation in the molecular engineering of optoelectronic materials and organic semiconductors. This Review surveys the synthesis and structural characterization of IMWs, and highlights emerging structure–property relationships to determine how insulation can enhance the behavior of a molecular wire. We focus mainly on three IMW architectures: polyrotaxanes, polymer‐wrapped π systems, and dendronized polymers, and compare the properties of these systems with those of conjugated polymers threaded through mesoporous frameworks and zeolites. Encapsulation of molecular wires can enhance properties as diverse as luminescence, electrical transport, and chemical stability, which points to applications in electroluminescent displays, sensors, and the photochemical generation of hydrogen.
Asymmetric Organocatalytic Domino Reactions
Authors: Enders Dieter , Grondal Christoph , Hüttl Matthias R. M.
Published: January 2007

The current status of organic synthesis is hampered by costly protecting‐group strategies and lengthy purification procedures after each synthetic step. To circumvent these problems, the synthetic potential of multicomponent domino reactions has been utilized for the efficient and stereoselective construction of complex molecules from simple precursors in a single process. In particular, domino reactions mediated by organocatalysts are in a way biomimetic, as this principle is used very efficiently in the biosynthesis of complex natural products starting from simple precursors. In this Minireview, we discuss the current development of this fast‐growing field.
Die Kämpf‐Stegträger der Eissporthalle Bad Reichenhall – Eine typische Holzkonstruktion der 1950er und 1960er Jahre?
Authors: Voormann Friedmar , Pfeifer Matthias
Published: January 2007

Kämpf‐Stegträger wie die der Eissporthalle in Bad Reichenhall wurden, wenn auch meist in geringeren Dimensionen, in den 1950er und 1960er Jahren vielfach eingesetzt. Sie sind ein Beispiel für die großen Anstrengungen, die man in Forschung und Praxis in diesen Jahren unternahm, um die Leimbauweise im Ingenieurholzbau endgültig zu etablieren. Spätestens Ende der 1960er Jahre war dieses Ziel erreicht. Gleichwohl wurden die Ursprünge des Leimbaus bereits ein halbes Jahrhundert früher durch Otto Hetzer und andere gelegt. Und so ist die Entwicklungsgeschichte des Brettschichtholzträgers einmal mehr ein Beispiel dafür, daß der als Diffusion bezeichnete Prozeß – von der Innovation bis zur allgemeinen Verbreitung und Anwendung einer Neuerung – sich gerade im Bauwesen oftmals über ein bis zwei Generationen erstreckt.
Herstellung von Verpreßpfählen zur Auftriebssicherung unter dem Einfluß kalklösender Kohlensäure
Authors: Schäfer René , Höfer Ulrich , Triantafyllidis Theodor
Published: January 2007

Im Zuge der Gründungsarbeiten eines Regenüberlaufbeckens in Kierspe wurden Verpreßpfähle als Auftriebssicherung eingebaut. Auf Grund des CO2‐Gehalts des Grundwassers war es erforderlich, vor der Pfahlherstellung Bohrlochvergütungen durchzuführen, um einen möglichen Tragkraftverlust der Pfähle infolge Betonkorrosion zu minimieren. Im Vorfeld wurde dazu eine Arbeitsanweisung erstellt, welche die technische Vorgehensweise und die erforderlichen Qualitätssicherungsmaßnahmen der Vergütungsarbeiten regelt. Die Bohrlochvergütung erfolgte über großkalibrige Pilotbohrungen, über die Zementmörtel in den anstehenden Fels eingepreßt wurde. Als Vergütungskriterium wurde eine äquivalente Wasserdurchlässigkeit des Bodens vorgegeben, welche je Bohrung über einen W/D‐Test nachzuweisen war. Im Zuge der Ausführungsarbeiten zeigte sich jedoch, daß aufgrund der geologischen Randbedingungen die Arbeitsanweisung mehrfach zu modifizieren und eine spezielle Betonrezeptur zu verwenden war, um eine erfolgreiche Bohrlochvergütung durchführen zu können.
PPP‐Projekte: Strukturelle Kostenvergleichsuntersuchungen zwischen Eigenrealisierung der öffentlichen Auftraggeber und PPP‐Anbietern
Authors: Blecken Udo , Gralla Mike , Holthaus Ursula
Published: January 2007

Im Rahmen struktureller Vergleichsuntersuchungen werden Herstellkosten, Nutzungskosten und weitere Einflüsse zwischen Eigenrealisierung und Betrieb der öffentlichen Hand mit den Kosten der PPP‐Anbieter im Rahmen einer umfangreichen Literaturuntersuchung verglichen und darüber hinaus durch eigene Daten ergänzt. Die Kosten werden nach dem in PPP‐Projekten üblichen Kostenvergleichsverfahren der Discounted Cash Flow‐Methode berechnet und verglichen. Für die privaten PPP‐Anbieter werden bei den üblichen Zinssätzen Kostenvorteile von mehr als 30% festgestellt, ohne daß alle Kostennachteile (Bauzeit, Nachträge) der öffentlichen Bauverwaltung berücksichtigt sind.

Eine Ausweitung des PPP‐Marktes über die z.Z. 5% des öffentlichen Bauvolumens hinaus ist nicht nur aus ökonomischen Motiven, sondern auch aufgrund der desolaten Haushaltslage der Kommunen, Länder und des Bundes dringend geboten. Es könnte mit den gleichen Finanzmitteln ca. 30% mehr Bauvolumen umgesetzt werden.
Zur Bemessung von Betonbauteilen auf Basis der Coulombschen Hypothese – Interpretation und Verifizierung experimenteller Daten
Authors: Bussler Leonid
Published: January 2007

Im Beitrag wird gezeigt, wie man die Coulombsche mehrachsige Betonfestigkeit im Zusammenhang mit der Spannungs‐Dehnungs‐Linie benutzt. Eine Durchführung der Differenzspannungsanalyse bei ein‐ und dreiachsigem symmetrischen Druck erlaubt, nicht ausreichende experimentelle Daten bei unsymmetrischem zwei‐ und dreiachsigen Druck richtig zu interpretieren. Dabei läßt sich eine reale und nichtproportionale Belastung in Konstruktionen besonders bei positivem mehrachsigen Druck auf die einfache proportionale Belastung ohne jegliche negative Folgen zurückführen.
Die große Kuppel von Florenz – Statik und Intuition im 15. Jahrhundert
Authors: Peil Udo
Published: January 2007

Die große Kuppel des Doms von St. Maria del Fiore zu Florenz gehört zu den bedeutenden kulturellen Denkmälern der Welt. Die fast 100 m hohe Kuppelschale mit einem Durchmesser von ca. 42 m wurde völlig ohne unterstützende Lehrgerüste nach den Ideen und unter der Leitung von Fillipo Brunelleschi zu Beginn des 15. Jahrhunderts erbaut. Es wird der geschichtliche Hintergrund dargestellt, vor dem der Bau erfolgte. Die statischen und konstruktiven Probleme, die von Brunelleschi intuitiv richtig gelöst wurden, werden beschrieben und erläutert.

Der Bericht schließt mit einer Darstellung der heutigen Probleme, die sich durch die seit Jahrhunderten vorhandenen Risse ergeben und schildert kurz die Überlegungen zur möglichen Sanierung.
An Exact Test for Detecting Inconsistency in Readers Interpretation Over Time in Screening Mammograms
Authors: Lee Ji‐Hyun , Eschrich Steven , Beam Craig
Published: January 2007

Radiologists' interpretation on screening mammograms is measured by accuracy indices such as sensitivity and specificity. The hypothesis that radiologists' interpretation on screening mammograms is constant across time can be tested by measuring overdispersion. However, small sample sizes are problematic for the accuracy of asymptotic approaches. In this article, we propose an exact conditional distribution for testing overdispersion of the binomial assumption that is assumed for the accuracy indices. An exact p ‐value can be defined from the developed distribution. We also describe an algorithm for computing this exact test. This proposed method is applied to data from a study in reading screening mammograms in a population of US radiologists (Beam et al., 2003). The exact method is compared analytically with a currently available method based on large sample approximations. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Rabies virus glycoprotein expression in Drosophila S2 cells. I. Functional recombinant protein in stable co‐transfected cell line
Authors: Yokomizo Adriana Y. , Jorge Soraia A. C. , Astray Renato M. , Fernandes Irene , Ribeiro Orlando G. , Horton Denise S. P. Q. , Tonso Aldo , Tordo Noel , Pereira Carlos Augusto
Published: January 2007

Recombinant rabies virus glycoprotein (rRVGP) was expressed in Drosophila melanogaster Schneider 2 (S2) cells. The cDNA encoding the entire RVGP gene was cloned in an expression plasmid under the control of the constitutive actin promoter (Ac), which was co‐transfected into S2 cells together with a hygromycin selection plasmid. Selected S2 cell populations (S2AcRVGP) had a decreased ability to grow and consume substrates, when compared to the non‐transfected cells (S2). They were shown, by PCR, to express the RVGP gene and mRNA and, by immunoblotting, to synthesize the rRVGP in its expected molecular mass of 65 kDa. ELISA kinetic studies showed the rRVGP expression in cell lysates and supernatants attaining concentrations of 300 μg/L. By flow cytometry analysis, about 30% of the cells in the co‐transfected populations were shown to express the rRVGP. Cell populations selected by limiting dilution expressed higher rRVGP yields. Mice immunized with rRVGP were shown to synthesize antibodies against rabies virus and be protected against experimental infection with rabies virus. The data presented here show that S2 cells can be suitable hosts for the rRVGP expression, allowing its synthesis in a high degree of physical and biological integrity.
Whole genome genotyping technologies on the BeadArray™ platform
Authors: Steemers Frank J. , Gunderson Kevin L.
Published: January 2007

The ability to simultaneously genotype hundreds of thousands of single‐nucleotide polymorphisms (SNPs) in a single assay has recently become feasible due to innovative combinations of assay and array platform multiplexing. In this review, we describe the development of the Infinium® whole genome genotyping technology and the BeadArray™ platform. We discuss the automated use and performance of a series of genotyping BeadChips, including data quality, technology scalability, and flexibility in designing array content. We describe high‐density tag SNP‐based Bead‐Chips and various multi‐sample BeadChip configurations with their respective applications. These technologies are enabling large‐scale whole genome association studies that have the potential to revolutionize our ability to detect common genetic variants with a significant role in identifying disease‐associated loci, proteins, biomarkers, and pharmacogenomic responses.
Identification of intracellular targets of small molecular weight chemical compounds using affinity chromatography
Authors: Guiffant Damien , Tribouillard Déborah , Gug Fabienne , Galons Hervé , Meijer Laurent , Blondel Marc , Bach Stéphane
Published: January 2007

Efforts to characterize small molecular weight chemical inhibitors of pharmacological interest tend to identify molecules with high efficiency and selectivity, to meet the two criteria required for the clinical development of a drug: efficacy and harmlessness. Drug candidates are expected to inhibit efficiently the target they have been optimized against (for example, a particular type of protein kinase). These hits are also designed to not interfere (or as little as possible) with the activity of other cellular enzymes/proteins to reduce undesired side effects. Here we discuss the use of immobilized drugs as affinity chromatography matrices to purify and identify their bona fide intracellular targets. This method not only allows the systematic investigation of the selectivity of pharmacological compounds but also the anticipation of their putative adverse effects.
Results at up to 20 years after ileal pouch–anal anastomosis for chronic ulcerative colitis
Authors: Hahnloser D , Pemberton J H , Wolff B G , Larson D R , Crownhart B S , Dozois R R
Published: January 2007

Background

Ileal pouch–anal anastomosis (IPAA) is performed routinely for chronic ulcerative colitis.

Methods

Using data from a prospective database and annual standardized questionnaires, functional outcome, complications and quality of life (QoL) after IPAA were assessed.

Results

Some 1885 IPAA operations were performed for chronic ulcerative colitis over a 20-year period (mean follow-up 11 years). The mean age at the time of IPAA was 34·1 years, increasing from 31·2 years (1981–1985) to 36·3 years (1996–2000). The overall rate of pouch success at 5, 10, 15 and 20 years was 96·3, 93·3, 92·4 and 92·1 per cent respectively. Mean daytime stool frequency increased from 5·7 at 1 year to 6·4 at 20 years (P < 0·001), and also increased at night (from 1·5 to 2·0; P < 0·001). The incidence of frequent daytime faecal incontinence increased from 5 to 11 per cent during the day (P < 0·001) and from 12 to 21 per cent at night (P < 0·001). QoL remained unchanged and 92 per cent remained in the same employment. Seventy-six patients were eventually diagnosed with indeterminate colitis and 47 with Crohn's disease.

Conclusion

IPAA is a reliable surgical procedure for patients requiring proctocolectomy for chronic ulcerative colitis and indeterminate colitis. The clinical and functional outcomes are excellent and stable for 20 years after operation.
Long-term function and manovolumetric characteristics after ileal pouch–anal anastomosis for ulcerative colitis
Authors: Bengtsson J , Börjesson L , Lundstam U , Öresland T
Published: January 2007

Background

Long-term pouch function and physiological characteristics after ileal pouch–anal anastomosis (IPAA) are poorly described. The aim of this study was to undertake a prospective investigation of long-term pouch function and manovolumetric characteristics.

Methods

Forty-two patients with a median follow-up of 16 years after IPAA were included. Function was assessed using a questionnaire and a score was calculated ranging from 0 to 15 (15 being the worst). Manovolumetry was performed and pouchitis recorded. A paired analysis was conducted, as the results were compared with previous data for each patient.

Results

The median functional score was 3·5 (range 0–10) at 2 years and 5 (range 1–11) at 16 years (P = 0·013). Resting anal canal pressures were higher (P < 0·001) and squeeze pressures lower (P = 0·008) at long-term follow-up. Ileal pouch volumes at distension pressures of 10, 20 and 40 cmH2O were diminished at 16 years (P < 0·001, P = 0·005 and P = 0·058 respectively). The volume and pressure for first sensation and urge to defaecate were reduced. Increased age correlated positively with a poor functional score. A history of pouchitis did not affect functional or physiological characteristics.

Conclusion

Ileal pouch function declines in the long term. The reasons are unclear, but the ageing process may have an impact.
The Use of Quantum Molecular Calculations to Guide a Genetic Algorithm: A Way to Search for New Chemistry
Authors: Durrant Marcus C.
Published: January 2007

The process of gene‐based molecular evolution has been simulated in silico by using massively parallel density functional theory quantum calculations, coupled with a genetic algorithm, to test for fitness with respect to a target chemical reaction in populations of genetically encoded molecules. The goal of this study was the identification of transition‐metal complexes capable of mediating a known reaction, namely the cleavage of N2to give the metal nitride. Each complex within the search space was uniquely specified by a nanogene consisting of an eight‐digit number. Propagation of an individual nanogene into successive generations was determined by the fitness of its phenotypic molecule to perform the target reaction and new generations were created by recombination and mutation of surviving nanogenes. In its simplest implementation, the quantum‐directed genetic algorithm (QDGA) quickly located a local minimum on the evolutionary fitness hypersurface, but proved incapable of progressing towards the global minimum. A strategy for progressing beyond local minima consistent with the Darwinian paradigm by the use of environmental variations coupled with mass extinctions was therefore developed. This allowed for the identification of nitriding complexes that are very closely related to known examples from the chemical literature. Examples of mutations that appear to be beneficial at the genetic level but prove to be harmful at the phenotypic level are described. As well as revealing fundamental aspects of molecular evolution, QDGA appears to be a powerful tool for the identification of lead compounds capable of carrying out a target chemical reaction.
Tuning the Polarization Along Linear Polyaromatic Strands for Rationally Inducing Mesomorphism in Lanthanide Nitrate Complexes
Authors: Terazzi Emmanuel , Guénée Laure , Morgantini Pierre‐Yves , Bernardinelli Gérald , Donnio Bertrand , Guillon Daniel , Piguet Claude
Published: January 2007

The opposite orientation of the ester spacers in the rodlike ligands L 4C12 (benzimidazole‐OOC‐phenyl) and L 5C12 (benzimidazole‐COO‐phenyl) drastically changes the electronic structure of the aromatic systems, without affecting their meridional tricoordination to trivalent lanthanides, LnIII, and their thermotropic liquid crystalline (i.e., mesomorphic) behaviors. However, the rich mesomorphism exhibited by the complexes [Ln(L 4C12)(NO3)3] (Ln=La–Lu) vanishes in [Ln(L 5C12)(NO3)3], despite superimposable molecular structures and comparable photophysical properties. Density functional theory (DFT) and time‐dependant DFT calculations performed in the gas phase show that the inversion of the ester spacers has considerable effects on the electronic structure and polarization of the aromatic groups along the strands, which control residual intermolecular interactions responsible for the formation of thermotropic liquid‐crystalline phases. As a rule of thumb, an alternation of electron‐poor and electron‐rich aromatic rings favors intermolecular interactions between the rigid cores and consequently mesomorphism, a situation encountered for L 4C12, L 5C12, [Ln(L 4C12)(NO3)3], but not for [Ln(L 5C12)(NO3)3]. The intercalation of an additional electron‐rich diphenol ring on going from [Ln(L 5C12)(NO3)3] to [Ln(L 6C12)(NO3)3] restores mesomorphism despite an unfavorable orientation of the ester spacers, in agreement with our simple predictive model.
Bond Orders and Atomic Properties of the Highly Deformed Halogenated Fullerenes C60F18 and C60Cl30 Derived from their Charge Densities
Authors: Hübschle Christian B. , Scheins Stephan , Weber Manuela , Luger Peter , Wagner Armin , Koritsánszky Tibor , Troyanov Sergey I. , Boltalina Olga V. , Goldt Il'ya V.
Published: January 2007

The experimental charge densities of the halogenated C60 fullerenes C60F18 and C60Cl30 were determined from high‐resolution X‐ray data sets measured with conventional MoKα radiation at 20 K for C60Cl30 and with synchrotron radiation at 92 K for the fluorine compound. Bond topological and atomic properties were analyzed by using Bader's AIM theory. For the different CC bonds, which vary in lengths between 1.35 and 1.70 Å bond orders n between n=2 and significantly below n=1 were calculated from the bond topological properties at the bond critical points (BCP's). The low bond orders are seen for 5/6 bonds with each contributing carbon carrying a halogen atom. By integration over Bader's zero flux basins in the electron density gradient vector field atomic properties were also obtained. In contrast to free C60, in which all carbon atoms have a uniform volume of 11 Å3 and zero charge, atomic volumes vary roughly between 5 and 10 Å3 in the halogenated compounds. Almost zero atomic charges are also found in the Cl derivative but a charge separation up to ±0.8 e exists between C and F in C60F18 due to the higher fluorine electronegativity, which is also seen in the electrostatic potential for which the electronegativity difference between carbon and fluorine, and the addition to one hemisphere of the fullerene cage leads to a strong potential gradient along the C60F18 molecule. From the summation over all atomic volumes it follows that the halogen addition does not only lead to a dramatic distortion of the C60 cage but also to a significant shrinkage of its volume.
Enantioselective preparative HPLC separation of the HBCD—Stereoisomers from the technical product and their absolute structure elucidation using X‐ray crystallography
Authors: Koeppen Robert , Becker Roland , Emmerling Franziska , Jung Christian , Nehls Irene
Published: January 2007

1,2,5,6,9,10‐Hexabromocyclododecane (HBCD) is a widely used flame retardant, which tends to persist in the environment and accumulates in biota. The six stereoisomers (three racemates named α‐, β‐, and γ‐HBCD) of the technical mixture were isolated with high‐performance liquid chromatography (HPLC). Direct separations were performed on a chiral stationary phase containing permethylated β‐cyclodextrin (NUCLEODEX β‐PM column) and the pure enantiomers of α‐, β‐, and γ‐HBCD were physically characterized for the first time. The absolute configurations of all six isomers were determined by anomalous dispersion using single crystal X‐ray crystallography. Optical rotations αD in tetrahydrofuran were +4.2/−4.0 (α‐HBCD), +26.1/−27.5 (β‐HBCD), and +68.0/−66.3 (γ‐HBCD). The sense of rotation could be correlated with the absolute configurations of α‐, β‐, and γ‐HBCD enantiomers and their order of elution on a chiral permethylated β‐cyclodextrin‐bonded stationary phase. The diastereomersα‐, β‐, and γ‐HBCD displayed distinctly different melting points as well as 1H‐, 13C NMR, and IR spectra. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
Neuronal morphology and neuropil structure in the stomatogastric ganglion of the lobster, Homarus americanus
Authors: Bucher Dirk , Johnson Christian D. , Marder Eve
Published: January 2007

The stomatogastric nervous system (STNS) has long been used as a model system for the study of central pattern generation, neuromodulation, and network dynamics. Anatomical studies of the crustacean stomatogastric ganglion (STG) in different species have mostly been restricted to subsets of neurons and/or general structural features. For the first time, we describe the morphology of all STG neurons belonging to the two circuits that produce the well‐described pyloric and gastric rhythms in the lobster, Homarus americanus. Somata sit on the dorsal and lateral surface of the STG and send a single primary neurite into the core of the neuropil, which is mostly made up of larger lower order branches. The perimeter of the neuropil consists mostly of finer higher order branches. Immunohistochemical labeling for synaptic proteins is associated with the small diameter branches. Somata positions are not constant but show preferred locations across individuals. The number of copies is constant for all neuron types except the PY and GM neurons (PY neuron number ranges from 3 to 7, and GM neuron number ranges from 6 to 9). Branch structure is largely nondichotomous, and branches can deviate substantially from cylindrical shape. Diameter changes at branch points can be as large as 20‐fold. Clearly, the morphology of a specific neuron type can be quite variable from animal to animal. J. Comp. Neurol. 501:185–205, 2007. © 2007 Wiley‐Liss, Inc.
Primary visual cortex volume and total neuron number are reduced in schizophrenia
Authors: Dorph‐Petersen Karl‐Anton , Pierri Joseph N. , Wu Qiang , Sampson Allan R. , Lewis David A.
Published: January 2007

A number of studies that assessed the visual system in subjects with schizophrenia found impairments in early visual processing. Furthermore, functional imaging studies suggested changes in primary visual cortex activity in subjects with schizophrenia. Interestingly, postmortem studies of subjects with schizophrenia reported an increased density of neurons in the primary visual cortex (Brodmann's area 17, BA17). The observed changes in visual processing may thus be reflected in structural changes in the circuitry of BA17. To characterize the structural changes further we used stereological methods based on unbiased principles of sampling (Cavalieri's principle and the optical fractionator) to estimate the total volume and neuron number of BA17 in postmortem brains from 10 subjects with schizophrenia and 10 matched normal comparison subjects. In addition, we assessed cortical thickness. We found a marked and significant reduction in total neuron number (25%) and volume (22%) of BA17 in the schizophrenia group relative to the normal comparison subjects. In contrast, we found no changes in neuronal density or cortical thickness between the two groups. Subjects with schizophrenia therefore have a smaller cortical area allocated to primary visual perception. This finding suggests the existence of a schizophrenia‐related change in cortical parcellation. J. Comp. Neurol. 501:290–301, 2007. © 2007 Wiley‐Liss, Inc.
Macrophage depletion in the murine olfactory epithelium leads to increased neuronal death and decreased neurogenesis
Authors: Borders Aaron S. , Getchell Marilyn L. , Etscheidt Jordan T. , van Rooijen Nico , Cohen Donald A. , Getchell Thomas V.
Published: January 2007

Apoptosis of olfactory sensory neurons (OSNs) induced by olfactory bulbectomy (OBX) leads to the activation of resident macrophages within the olfactory epithelium (OE). These macrophages phagocytose degenerating OSNs and secrete chemokines, which recruit additional macrophages into the OE, and cytokines/growth factors, which regulate basal cell proliferation and differentiation and maturation of OSNs. In this study we apply for the first time the use of liposome‐encapsulated clodronate to selectively deplete macrophages during the OSN degeneration/regeneration cycle in order to elucidate the role(s) of macrophages in regulating cellular mechanisms that lead to apoptosis and neurogenesis. Mice were injected intranasally and intravenously with either liposome‐encapsulated clodronate or empty liposomes prior to and after OBX or sham OBX. At 48 hours after surgery the numbers of macrophages in the OE of both sham and OBX clodronate‐treated mice were significantly reduced compared to liposome‐treated controls (38% and 35%, respectively, P < 0.05). The reduction in macrophage numbers was accompanied by significant decreases in OE thickness (22% and 21%, P < 0.05), the number of mOSNs (1.2‐ and 1.9‐fold, P < 0.05), and basal cell proliferation (7.6‐ and 3.8‐fold, P < 0.005) in sham and OBX mice, respectively, compared to liposome‐treated controls. In OBX mice there was also increased immunoreactivity for active caspase‐3 in the OE and olfactory nerves of clodronate‐treated OBX mice compared to liposome‐treated controls. These results indicate that macrophages modulate the OSN population in the normal and target‐ablated murine OE by influencing neuronal survival and basal cell proliferation, resulting in neurogenesis and replacement of mature OSNs. J. Comp. Neurol. 501:206–218, 2007. © 2007 Wiley‐Liss, Inc.
Occipital sulci of the human brain: Variability and probability maps
Authors: Iaria Giuseppe , Petrides Michael
Published: January 2007

The morphological variation of the sulci of the occipital region of the human brain was examined in both the left and the right hemispheres in 40 normal adult human brains on magnetic resonance images. We identified the occipital sulci and marked their corresponding gray matter voxels on the magnetic resonance images, which had been transformed into the Montreal Neurological Institute standard proportional stereotaxic space in order to construct probability maps. In the medial occipital region, the calcarine sulcus was the longest and most constant sulcus. We identified, in the inferior part of the medial occipital lobe, the lingual sulcus and the posterior collateral sulcus, and, in the superior part, the inferior and superior sagittal sulci of the cuneus. On the lateral surface of the occipital lobe, the lateral occipital, the lunate, and the transverse and inferior occipital sulci were identified. The parieto‐occipital fissure and the temporo‐occipital incisure were also identified on the lateral and medial surfaces. Finally, the patterns of the occipital sulci and gyri were examined in 20 post‐mortem human hemispheres fixed in formalin. Probability maps of the occipital sulci were constructed, which provide a quantitative description of the variability of the sulci in standard stereotaxic space and may be used to identify the location of voxels in other magnetic resonance images transformed into the same streotaxic space. These maps are a useful tool in the study of functional activations related to visual processing. J. Comp. Neurol. 501:243–259, 2007. © 2007 Wiley‐Liss, Inc.
The Preparation of Diamond/Tungsten‐ Carbide Composite Films by Microwave Plasma‐Assisted CVD
Authors: Samra H. A. , Hong R. , Jiang X.
Published: January 2007

Diamond/tungsten carbide composite films are deposited on Si and W by microwave plasma‐assisted CVD using a CH4/H2/WCl6 gas mixture. The composite films are studied by SEM, laser Raman scattering and X‐ray diffraction. The film composition and morphology can be adjusted by controlling the concentration of WCl6 in the gas mixture. Such a diamond‐based composite film can serve as an interlayer to improve the adhesion of diamond films.
Phase‐Selective CVD of Vanadium Oxide Nanostructures
Authors: Mathur S. , Ruegamer T. , Grobelsek I.
Published: January 2007

Phase‐selective synthesis of crystalline vanadium oxides is achieved by the CVD of vanadium oxo‐tri‐isopropoxide [VO(OiPr)3]. Preformed V–O and V=O units and their differential thermal stability present in the precursor enabled precise modulation of the vanadium/oxygen stoichiometry in the products of the CVD. No additional oxygen carrier is employed during the deposition processes. Subject to deposition temperature (400–700 °C), different phase compositions (V2O5, V7O13, and VO2) are directly obtained and are investigated regarding structural and electrical properties. Hall measurements on VO2 films show a sharp metal‐to‐semiconductor transition at 78 °C (single crystal, 68 °C) depending on their microstructure formed by an oriented aggregation of individual crystallites.
Flow cytometric immunphenotyping of epithelial cancer cells in effusions—Technical considerations and pitfalls
Authors: Dong Hiep P. , Holth Arild , Berner Aasmund , Davidson Ben , Risberg Björn
Published: January 2007

Background:

Data regarding the role of flow cytometry (FCM) in the characterization of malignant effusions are limited to date. In the present study, we optimized the conditions for FCM immunphenotyping of effusions using a four‐color analysis and investigated aspects related to the advantages and limitations of this method in this setting.

Methods:

FCM analysis optimization for the study of epithelial cells was undertaken using five carcinoma cell lines, and subsequently applied to malignant pleural and peritoneal effusions using antibodies against epithelial and mesothelial markers (Ber‐EP4 and EMA), CD138, and integrin subunits. FCM of frozen versus fresh specimens and the performance of FCM compared to immunhistochemistry were evaluated.

Results:

FCM optimization was achieved and applied to clinical specimens, with resulting detection of epithelial markers and adhesion molecules on cancer cells. Frozen clinical specimens and cell lines showed reduced CD138 expression compared to fresh specimens, with conservation of the remaining epitopes. FCM generally showed comparable performance to immunhistochemistry.

Conclusions:

FCM is an effective method for characterization of cancer cells in clinical effusion specimens in both the diagnostic and research setting, and is comparable to immunhistochemistry in terms of sensitivity and specificity, with the additional advantage of providing quantitative data. The majority of epitopes are conserved in frozen cells, but a minority may be lost, suggesting that the thorough testing of each antibody in both conditions is mandatory. © 2007 Clinical Cytometry Society