bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular cytogenetic characterization of a 4p15.1‐pter duplication and a 4q35.1‐qter deletion in a recombinant of chromosome 4 pericentric inversion
Authors: Maurin M‐L. , Labrune P. , Brisset S. , Le Lorc'h M. , Pineau D. , Castel C. , Romana S. , Tachdjian G.
Published: January 2009

To date, 10 cases of recombinant of chromosome 4 pericentric inversion involving sub‐bands p14p15 and q35 have been described. We report on the first case analyzed using array‐CGH in a female infant presenting psychomotor and growth retardation, facial anomalies, axial hypotonia, short neck, wide spaced nipples and cardiac defects. Conventional karyotype associated to FISH revealed a recombinant chromosome 4 with partial 4p duplication and 4q deletion derived from a paternal pericentric inversion. Array‐CGH allowed us to precise rec4 breakpoints: the proposita carried a small 4.82–4.97 Mb 4q35.1 terminal deletion and a large 35.3–36.7 Mb 4p15.1 terminal duplication. Duplications of the distal 2/3 of short arm of chromosome 4 give rise to recognizable craniofacial features but no specific visceral malformation. A contrario small terminal 4q deletions are associated with cardiac defects. This case and review of literature suggest that two genes ArgBP2 and PDLIM3, located at 4q35.1 and both involved in cardiac and muscle development, could be responsible for cardiac defects observed in terminal 4q35.1 deletions. © 2009 Wiley‐Liss, Inc.
Familial 14.5 Mb interstitial deletion 13q21.1–13q21.33: Clinical and array‐CGH study of a benign phenotype in a three‐generation family
Authors: Filges Isabel , Röthlisberger Benno , Noppen Christoph , Boesch Nemya , Wenzel Friedel , Necker Judith , Binkert Franz , Huber Andreas R. , Heinimann Karl , Miny Peter
Published: January 2009

We report on the clinical and cytogenetic findings as well as the array‐based characterization of an interstitial familial 13q21 deletion initially recognized by standard karyotyping. Although 13q deletions are known to imply a wide variability of clinical consequences, the deletion carriers of the familial deletion in three generations did not reveal a relevant phenotype. The breakpoints and the deletion size in all three carrier individuals were determined by molecular karyotyping confirming a large 14.5 Mb deletion encompassing the 13q21.1–13q21.33 region identical in all three carriers. Gene paucity and the lack of dosage‐sensitive genes in the delineated region might explain the apparently innocuous nature of this chromosomal anomaly. The example of this family presents evidence for describing the chromosomal region 13q21.1–13q21.33 as a large euchromatic variant or benign copy number variation without phenotypic consequences. Our data underline the importance of a phenogenetic approach combining clinical and laboratory evidence in the interpretation of segmental chromosomal anomalies especially in genetic counseling related to prenatal diagnosis. © 2009 Wiley‐Liss, Inc.
Lokale, spitzeninduzierte Oxidation von selbstorganisierten Monoschichten: Schablonen für die Herstellung funktionaler Nanostrukturen
Authors: Wouters Daan , Hoeppener Stephanie , Schubert Ulrich S.
Published: January 2009

Oberflächen mit Funktion: Die elektroinduzierte Strukturierung selbstorganisierter Monoschichten ermöglicht die Herstellung vielfältiger komplexer Nanostrukturen. Der Aufsatz beleuchtet die Möglichkeiten, die sich durch die Einführung chemischer Selektivität auf Oberflächen durch die lokale Generierung chemisch aktiver Gruppen und deren Weiterverarbeitung bieten, mit dem Schwerpunkt auf der Entwicklung dieses Forschungsgebietes in den letzten vier Jahren.

magnified image

Die lokale Oxidation von selbstorganisierten Monoschichten mithilfe von Rastersonden ist eine neue, vielversprechende Methode, um Strukturen mit einer Präzision im Nanometermaßstab zu generieren. Damit wird eine schrittweise, gesteuerte Herstellung von komplexen Strukturen möglich, wobei die hohe chemische Stabilität von selbstorganisierten Monoschichten genutzt wird. Die so hergestellten Oberflächenstrukturen können (z. B. durch den nachfolgenden Aufbau weiterer Schichten und/oder durch Anwendung weiterer Oberflächenreaktionen) zur gezielten Herstellung funktionaler Bauelemente verwendet werden.
Molekulare Katalysatoren für die Oxidation von Wasser zu Disauerstoff
Authors: Sala Xavier , Romero Isabel , Rodríguez Montserrat , Escriche Lluís , Llobet Antoni
Published: January 2009

Wasseroxidation: Ein guter Katalysator für die Umsetzung von Wasser zu Sauerstoff ist für die nachhaltige Umwandlung von Sonnenenergie essenziell. Die Schlüsselfaktoren für die Leistungsfähigkeit erfolgreicher molekularer Katalysatoren und die Notwendigkeit für ein katalytisches System auf Festkörperbasis werden erläutert, und die ersten Versuche, molekulare Katalysatoren für die Wasseroxidation auf Trägermaterial herzustellen, werden analysiert.

magnified image

In den letzten vier Jahren wurden wir Zeugen einer Revolution auf dem Gebiet der katalytischen Wasseroxidation: Definierte Moleküle eröffnen neue Möglichkeiten, robustere und effizientere Katalysatoren maßzuschneidern. Angestoßen wurde diese Revolution durch zwei Faktoren: den dringenden Bedarf an sauberen und erneuerbaren Kraftstoffen und das dem Menschen innewohnende Verlangen, die Reaktionen der Natur nachzuahmen – in diesem Fall die des sauerstofferzeugenden Komplexes (OEC) des Photosystems II (PSII). Im Folgenden geben wir einen kurzen Überblick über die wohlbekannten Grundlagen der Oxidation von Wasser zu Disauerstoff und präsentieren anschließend die neuen Entwicklungen auf diesem Forschungsfeld, die neuen Ansätze, Katalysatordesign und ‐leistung zu verbessern, und die Fragen, die diese Entwicklungen insbesondere aus mechanistischer Sicht aufwerfen. Schließlich werden wir noch die Herausforderungen diskutieren, denen sich das Forschungsfeld gegenübersieht.
Catalytic Asymmetric Synthesis of 2,2‐Disubstituted Oxetanes from Ketones by Using a One‐Pot Sequential Addition of Sulfur Ylide
Authors: Sone Toshihiko , Lu Gang , Matsunaga Shigeki , Shibasaki Masakatsu
Published: January 2009

Ring frei zur zweiten Runde: Die Titelverbindungen wurden durch einen doppelten Methylentransfer in einem Eintopfverfahren synthetisiert, wobei ein La‐Li‐Heterodimetallkomplex als Katalysator wirkte. Eine Chiralitätsverstärkung im zweiten Schritt stellte sicher, dass die Oxetanprodukte mit hohen Enantiomerenüberschüssen erhalten wurden (siehe Schema).

magnified image
Flow cytometric cell cycle analysis of muscle precursor cells cultured within 3D scaffolds in a perfusion bioreactor
Authors: Flaibani Marina , Luni Camilla , Sbalchiero Elisa , Elvassore Nicola
Published: January 2009

It has been widely demonstrated that perfusion bioreactors improve in vitro three‐dimensional (3D) cultures in terms of high cell density and uniformity of cell distribution; however, the studies reported in literature were primarily based on qualitative analysis (histology, immunofluorescent staining) or on quantitative data averaged on the whole population (DNA assay, PCR). Studies on the behavior, in terms of cell cycle, of a cell population growing in 3D scaffolds in static or dynamic conditions are still absent. In this work, a perfusion bioreactor suitable to culture C2C12muscle precursor cells within 3D porous collagen scaffolds was designed and developed and a method based on flowcytometric analyses for analyzing the cell cycle in the cell population was established. Cells were extracted by enzymatic digestion of the collagen scaffolds after 4, 7, and 10 days of culture, and flow cytometric live/dead and cell cycle analyses were performed with Propidium Iodide. A live/dead assay was used for validating the method for cell extraction and staining. Moreover, to investigate spatial heterogeneity of the cell population under perfusion conditions, two stacked scaffolds in the 3D domain, of which only the upstream layer was seeded, were analyzed separately. All results were compared with those obtained from static 3D cultures. The live/dead assay revealed the presence of less than 20% of dead cells, which did not affect the cell cycle analysis. Cell cycle analyses highlighted the increment of cell fractions in proliferating phases (S/G2/M) owing to medium perfusion in long‐term cultures. After 7–10 days, the percentage of proliferating cells was 8–12% for dynamic cultures and 3–5% for the static controls. A higher fraction of proliferating cells was detected in the downstream scaffold. From a general perspective, this method provided data with a small standard deviation and detected the differences between static and dynamic cultures and between upper and lower scaffolds. Our methodology can be extended to other cell types to investigate the influence of 3D culture conditions on the expression of other relevant cell markers. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Building complex remote learning laboratories
Authors: Calvo I. , Marcos M. , Orive D. , Sarachaga I.
Published: January 2009

The interaction with real plants is a key issue in control engineering education in order to consolidate the concepts learned in the classroom. Unfortunately, for several reasons, real laboratories are not always available. On the other hand, Internet technologies have proved to be mature and reliable, becoming a common alternative in the creation of remote laboratories. However, the use of these technologies in complex remote laboratories is not a trivial task as several requisites must be satisfied simultaneously. This article proposes a methodology that eases the creation of remote laboratories establishing the steps to build up a remote access system. This methodology proposes a set of key components that can be used to define the access to a remote plant from a functional point of view. Some of these components are generic being reusable in most applications whereas others are application specific. In summary, the methodology allows designers to concentrate more on the functionality of the applications than on the technical aspects of the underlying technology. The use of this methodology is illustrated with a relatively complex example: A laboratory manufacturing cell. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 53–66, 2010; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.20239
BONDSYM: SIMULINK‐based educational software for analysis of dynamic system
Authors: Calvo J.A. , Boada M.J. , Román J.L. San , Olmeda E.
Published: January 2009

This article presents an educational software called BONDSYM developed to allow engineering students to learn easily and quickly about the analysis of dynamic systems through the Bond Graph method. This software uses the SIMULINK library of MATLAB, which has proven to be an excellent choice in order to implement and solve the dynamic equations involved. The application allows for the representation of the behavior of a dynamic system analyzed through the Bond Graph theory in order to understand the dynamic equations and the physical phenomena involved. Based on block diagram of SIMULINK, the different “bonds” of Bond Graph can be integrated as SIMULINK blocks in order to generate the dynamic model. A few simple models are analyzed through this application. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 238–251, 2010; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.20246
Melt fraction estimation using solid modeling for melting inside a sphere
Authors: Tan F. L. , Fok S. C.
Published: January 2009

This paper describes a method using CAD software (SolidWorks) and digitizing software (WinDIG) to estimate the melt fraction of the phase change material (PCM) during melting inside a sphere. The solid–liquid interface of the PCM inside the sphere is captured using a digital camera at a particular instant of time. Using the digitizing software, the coordinates of the solid–liquid interface are captured. The coordinates are imported into the CAD software to create the solid model of the melted solid PCM. The amount of solid melted inside the sphere can then be estimated and thus the melt fraction at that particular instant can be determined. The method described could be useful in the analysis of experimental data during materials processing. © 2009 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 290–297, 2010; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.20258
Manipulating Cell Migration and Proliferation with a Light‐Activated Polypeptide
Authors: Miller Danielle S. , Chirayil Sara , Ball Haydn L. , Luebke Kevin J.
Published: January 2009

Remote control of cells: A polypeptide has been made that stimulates proliferation and migration of cells upon photochemical activation. This light‐activated polypeptide enables spatially defined control of cell populations at the scale of tissue organization; this is accomplished without physically contacting the cells or modifying their substrate.

magnified image

Polypeptide growth and differentiation factors modulate a wide variety of cell behaviors and can be used to manipulate cells in vitro for tissue engineering and basic studies of cell biology. To emulate in vitro the spatial aspect of growth factor function, new methods are needed to generate defined spatial gradients of activity. Polypeptide factors that are engineered to be activated with light provide a method for creating concentration gradients with the fine precision in space and time with which light can be directed. As a first test of this approach, we have chemically synthesized a polypeptide with the sequence of epidermal growth factor in which a critical glutamate is “caged” with a photoremovable group. Photolysis of this polypeptide afforded maximal mitogenic and chemokinetic activity at concentrations at which the caged factor was inactive. Spatially resolved photolysis of the factor resulted in spatial patterning of fibroblasts. This system will be useful for ex vivo tissue engineering and for investigating the interactions of cells with their matrix and the role of chemical gradients in biological pattern formation.
Inhibiting Islet Amyloid Polypeptide Fibril Formation by the Red Wine Compound Resveratrol
Authors: Mishra Rajesh , Sellin Daniel , Radovan Diana , Gohlke Andrea , Winter Roland
Published: January 2009

Grapes for amyloids: The red wine compound resveratrol can effectively inhibit the formation of IAPP amyloid that is found in type II diabetes. Our in vitro inhibition results do not depend on the antioxidant activity of resveratrol. Further, the markedly enhanced cell survival in the presence of resveratrol also indicates that the small oligomeric structures that are observed during β‐sheet formation are not toxic and could be off‐pathway assembly products.

magnified image
Ferrocenyl‐Ended Thieno–Vinylene Oligomers: Donor–Acceptor Polarization and Mixed‐Valence Properties with Emphasis on the Raman Mapping of Localized‐to‐Delocalized Transitions
Authors: Casado Juan , Rodríguez González Sandra , Ruiz Delgado M. Carmen , Moreno Oliva María , López Navarrete Juan T. , Caballero Ruben , de la Cruz Pilar , Langa Fernando
Published: January 2009

What's your role? New oligothiophene–vinylene compounds have been synthesized to study the role of the conjugated chain in two different cases (see scheme; MV=mixed valence). The electronic and molecular structures were analyzed by means of electronic, X‐ray photoelectron, and Raman spectroscopy, together with thermo spectroscopy, electrochemistry, and DFT calculations.

magnified image

New oligothiophene–vinylene compounds have been synthesized in order to study the role of the conjugated chain in two different cases: 1) when push–pull action operates between an electron‐donor and an electron‐acceptor group at the ends of the thiophene–vinylene conjugated chain, and 2) when mixed‐valence action is induced by single oxidation of the same chain functionalized at both terminal positions with ferrocene groups leading to competition between the donor groups. The electronic and molecular structures are analyzed by means of electronic, X‐ray photoelectron and Raman spectroscopies, together with thermospectroscopy, electrochemistry and density functional theory calculations. The cyclic voltammetry processes have been followed by spectrochemistry. It is shown that the radical cation of the diferrocenyl derivative is a class III mixed‐valence system (i.e., fully delocalized) according to its Raman spectrum. Moreover, by Raman thermo‐spectroscopy the thermal transition of this radical cation from a delocalized (class III, room temperature) to a localized (class II, −160 °C) state is scanned. In all cases the Raman study is paralleled by an electronic absorption spectroscopic analysis. Structure–property relationships are proposed for molecules of two important fields of very active research as that of the non‐linear optics (i.e., organic optoelectronic) and that of the mixed‐valence systems (i.e., charge‐transfer processes).
The changing face of Phase 1 cancer clinical trials
Authors: Craft Barbara S. , Kurzrock Razelle , Lei Xiudong , Herbst Roy , Lippman Scott , Fu Siqing , Karp Daniel D.
Published: January 2009

Phase 1 studies in cancer have changed in recent years. Now, with the advent of new, less toxic, targeted agents, more patients may be candidates for new drug studies earlier in the course of their disease. It is to the advantage of the members of the oncology community to know more regarding the details and requirements for participation in early‐phase clinical trials so they can advocate for their patients and help them decide when such trials may be an appropriate choice. To examine the work intensity of early phase cancer clinical trials, the authors of this report compared the study requirements of phase 1 and 2 protocols. Five parameters were studied as a surrogate of study complexity—the number of physical examinations, vital sign determinations, electrocardiograms (ECGs), nonpharmacokinetic laboratory tests, and pharmacokinetic (PK) sampling—in the first 4 weeks of protocol in 90 studies (49 phase 1 studies and 41 phase 2 studies). From July 2004 through March 2007, there were 49 phase 1 trials in the phase 1 Program, 9 phase 2 studies that were conducted by physicians appointed in that program, and 32 phase 2 trials with accessible data in the Department of Thoracic/Head & Neck Medical Oncology. In the phase 1 trials versus the phase 2 trials, there were significantly more (P < .05) physical examinations (mean ± standard error, 3.16 ± 0.24 vs 2.22 ± 0.13), vital sign determinations (5.63 ± 0.61 vs 2.80 ± 0.26), ECGs (4.36 ± 1.16 vs 0.80 ± 0.17), nonpharmacokinetic laboratory tests (18.08 ± 1.31 vs 10.12 ± 0.65), and PK sampling (15.14 ± 1.79 vs 1.02 ± 0.53). These values also differed significantly (P < .005 for each) when the median values were compared in nonparametric tests. Although both phase 1 and phase 2 trials had substantial study requirements, those for the phase 1 studies were significantly higher. The successful conduct of early‐phase clinical trials requires significant research infrastructure. Cancer 2009. © 2009 American Cancer Society.
How an Inert‐Gas Matrix Can Modify the Molecular Properties of Lanthanide Trifluoride
Authors: Lanza Giuseppe , Minichino Camilla
Published: January 2009

Ab initio computations performed on LaF3⋅Arn (n=1–21) complexes allow a quantification of the short‐range many‐body interactions arising in the argon matrix. It is shown that the molecular properties of LaF3 are strongly influenced by the embedding medium. The largest investigated cluster, LaF3⋅Ar21, resembles an hcp structure with the LaF3 molecule occupying the central substitutional site (see figure).

magnified image
Absence of TGFβ signaling in embryonic vascular smooth muscle leads to reduced lysyl oxidase expression, impaired elastogenesis, and aneurysm
Authors: Choudhary Bibha , Zhou Jingjing , Li Peng , Thomas Simmy , Kaartinen Vesa , Sucov Henry M.
Published: January 2009

To address the requirement for TGFβ signaling in the formation and maintenance of the vascular matrix, we employed lineage‐specific mutation of the type II TGFβ receptor gene (Tgfbr2) in vascular smooth muscle precursors in mice. In both neural crest‐ and mesoderm‐derived smooth muscle, absence of TGFβ receptor function resulted in a poorly organized vascular elastic matrix in late‐stage embryos which was prone to dilation and aneurysm. This defect represents a failure to initiate formation of the elastic matrix, rather than a failure to maintain a preexisting matrix. In mutant tissue, lysyl oxidase expression was substantially reduced, which may contribute to the observed pathology. genesis 47:115–121, 2009. © 2009 Wiley‐Liss, Inc.
The Use of Silver Solid Amalgam Working Electrode for Determination of Nitrophenols by HPLC with Electrochemical Detection
Authors: Danhel Ales , Shiu Kwok Keung , Yosypchuk Bogdan , Barek Jiri , Peckova Karolina , Vyskocil Vlastimil
Published: January 2009

The use of a silver solid amalgam working electrode for HPLC with electrochemical detection has been investigated. The thin‐layer and wall‐jet detectors based on this electrode were constructed and applied for the determination of a mixture of nitrophenols. The optimal separation and detection conditions for the determination of 2‐nitrophenol, 4‐nitrophenol, 2,4‐dinitrophenol and 2‐methoxy‐5‐nitrophenol in mixture were found using RP‐HPLC at Nova‐Pack C18 column and amperometric detection with the above mentioned detectors. It has been proved that the silver solid amalgam electrode is a suitable working electrode for HPLC‐ED and provides sufficient sensitivity for determination of tested nitrophenols.
Differential Pulse Voltammetric Determination of Selected Nitro‐Compounds on Silver, Solid Silver Composite, and Solid Graphite Composite Electrodes
Authors: Navrátil Tomáš , Barek Jiří , Fašinová‐Šebková Světlana
Published: January 2009

Three different types of solid electrodes, namely silver electrode, silver composite electrode containing 20% (m/m) of silver powder, 20% (m/m) of graphite powder and 60% (m/m) of methacrylate resin and graphite composite electrode containing 30% (m/m) of graphite powder and 70% (m/m) of epoxy resin were tested for differential pulse voltammetric determination of selected genotoxic nitro‐compounds using 2‐nitronaphthalene, 6‐nitroquinoline, and 5‐nitrobenzimidazole as model compounds. It was found that all three electrodes can be used for the determination of micromolar concentrations of tested model substances, the limit of detection and other figures of merits being dependent both on the electrode used and the substance to be determined.
Analysis of PTH‐Cysteine by Adsorptive Stripping Square‐Wave Voltammetry
Authors: Vilaseca C. , Quintana M. C. , Hernández P. , Vicente J. , Hernández L.
Published: January 2009

The aim of this work is the study of cysteine by its derivative form. Cysteine derivation is done by Edman degradation and we obtain the phenylthiohydantoin of cysteine. Edman degradation is one of the most usual procedures for sequentate proteins. From this reaction, the phenylthiohydantoin amino acid derivative (PTH‐amino acid) from the N‐terminal one is obtained, leaving the new amino terminus for the next degradation cycle. To identify the produced PTH‐derivative, a square‐wave cathodic stripping voltammetry method is developed. In this work we show the results obtained for the optimization the instrumental and chemical conditions, and we can conclude that it is an electrochemically irreversible system with adsorptive reduction phemomenon. Under the best conditions we found a new method to analyze proteins with LOD of 2 μg L−1 and LOQ of 5 μg L−1, a RSD less than 10% and a Er minor than 9%. Results of the application of this methodology to a real protein are included.
Single‐Walled Carbon Nanotubes Modified Graphite Electrodes for Electrochemical Monitoring of Nucleic Acids and Biomolecular Interactions
Authors: Erdem Arzum , Karadeniz Hakan , Caliskan Ayfer
Published: January 2009

Single‐walled carbon nanotubes (SWCNT) modified disposable graphite electrodes (SWCNT‐PGEs) were investigated in our study for the improved electrochemical monitoring of nucleic acids and biomolecular interactions based on the higher signal enhancement comparison to bare PGEs. The surface morphologies of bare PGE and SWCNT‐PGE were firstly explored using scanning electron microscopy (SEM) analysis. The easy surface modification of disposable graphite electrodes with carbon nanotubes was performed by passive adsorption, and DNA was then immobilized onto the SWCNT‐PGEs by the formation of covalent coupling between the carboxylated ends of nanotubes and the amine group in the guanine bases of DNA. The overall performance of SWCNT‐PGEs has also been studied, and discussed in terms of optimum analytical conditions; such as, the effect of pretreatment step, CNT concentration, DNA concentration, etc. The reproducible detection of DNA represent a very attractive approach for the further detection of interaction between the anticancer drug, daunorubicin (DNR) and double stranded DNA (dsDNA). Voltammetric results were complemented with electrochemical impedance spectroscopy (EIS), that was used to characterize the successful construction of carbon nanotubes modification onto the surface of PGEs.
Global health partnerships in practice: taking stock of the GAVI Alliance's new investment in health systems strengthening
Authors: Naimoli Joseph F.
Published: January 2009

Despite a burgeoning literature on global health partnerships (GHPs), there have been few studies of how GHPs, particularly those trying to build a bridge between horizontal and vertical modes of delivering essential health services, operate at global and country levels. This paper will help address this knowledge gap by describing and analyzing the GAVI Alliance's early experience with health systems strengthening (HSS) to improve immunization coverage and other maternal‐child health outcomes. To date, the strengths of HSS reside in its potential to optimize GAVI's overall investment in immunization, efforts to harmonize with other initiatives, willingness to acknowledge risk and identify mitigation strategies, engagement of diverse stakeholders, responsiveness to country needs, and effective management of an ambitious grant‐making enterprise. The challenges have been forging a common vision and approach, governance, balancing pressure to move money with incremental learning, managing partner roles and relationships, managing the “value for money” risk, and capacity building. This mid‐point stock‐taking makes recommendations for moving GAVI forward in a thoughtful manner. The findings should be of interest to other GHPs because of their larger significance. This is a story about how a successful alliance that decided to broaden its mandate has responded to the technical, organizational, and political complexities that challenge its traditional business model. Copyright © 2009 John Wiley & Sons, Ltd.
Understanding hydrological processes in a highly stressed granitic aquifer in southern India
Authors: Reddy D. V. , Nagabhushanam P. , Sukhija B. S. , Reddy A. G. S.
Published: January 2009

The results of a study evaluating the recharge/discharge conditions of an unconfined stressed granitic aquifer situated in a semi‐arid region of Andhra Pradesh, Southern India are presented. Over the last three decades, excessive withdrawal of groundwater has drastically lowered the water table to the bedrock. The watershed studied was divided into four zones based on geomorphology and hydrogeological conditions. Using environmental chloride data pertaining to groundwater, soil depth profiles, and some hydrogeologic and hydrochemical observations, a recharge model for the watershed was developed. The model revealed that the bulk of the vertical recharge in the western elevated land occurs through preferred pathways and that a small fraction occurs through the soil matrix. In addition, the watershed has a poor hydrogeologic fabric, as indicated by the small range of matrix flow recharge (1 to 1·5% of rainfall) among the four zones. The dominating preferential flow was high (∼16% of the annual average rainfall) in the valley fills, but decreased to 5–5·5% in the plains. Furthermore, although the bulk of the recharge occurs vertically, considerable lateral movement of groundwater down the slope indicates that sequential hydrochemical changes occur. Distinct geomorphological features that exist in the watershed support the proposed model. Situations similar to those described above may exist in numerous watersheds in the granitic hard rock region; therefore, information obtained from investigations conducted in this watershed can aid in the development of plans enabling the sustainable exploitation of watersheds that have not yet been developed, as well as implementation of appropriate rainwater conservation measures in over‐exploited watersheds. Copyright © 2009 John Wiley & Sons, Ltd.
Serum lipids and endometrial cancer risk: Results from the HUNT‐II study
Authors: Lindemann Kristina , Vatten Lars J. , Ellstrøm‐Engh Marie , Eskild Anne
Published: January 2009

Obesity is a major risk factor for endometrial cancer. Still, the association of obesity‐related metabolic factors, such as serum lipids and lipoprotein levels, is unclear. We prospectively examined the association of serum levels of triglycerides, total cholesterol, low‐density lipoprotein cholesterol, non–high‐density lipoprotein (non‐HDL), and HDL cholesterol with endometrial cancer risk among 31,473 women. During 9 years of follow‐up, 100 cases of endometrial cancer were identified by linkage to the Cancer Registry of Norway. There was a positive association of serum triglyceride levels with endometrial cancer risk. Comparing the highest to the lowest quartile of triglycerides, the age‐adjusted hazard ratio was 2.34 (95% CI: 1.04–5.28), and further adjustment for body mass index attenuated the association (hazard ratio 1.79, 95% CI: 0.79–4.05). For total serum cholesterol, low‐density lipoprotein cholesterol and HDL cholesterol there were no associations with endometrial cancer risk, either without or after adjustment for body mass index. Serum triglyceride levels were positively associated with the risk of endometrial cancer, and some of the association seems to be attributable to obesity. Apart from higher estrogen levels produced in adipose tissue, mechanisms more specifically related to triglycerides may also be involved in endometrial cancer. Further prospective studies on this subject are needed to better understand the association of blood lipids with endometrial cancer risk. © 2009 UICC
Common variants in the UBC9 gene encoding the SUMO‐conjugating enzyme are associated with breast tumor grade
Authors: Dünnebier Thomas , Bermejo Justo Lorenzo , Haas Susanne , Fischer Hans‐Peter , Pierl Christiane B. , Justenhoven Christina , Brauch Hiltrud , Baisch Christian , Gilbert Michael , Harth Volker , Spickenheuer Anne , Rabstein Sylvia , Pesch Beate , Brüning Thomas , Ko Yon‐Dschun , Hamann Ute
Published: January 2009

UBC9 encodes a protein that conjugates small ubiquitin‐related modifier (SUMO) to target proteins resulting in a change of their localization, activity or stability. Genetic variability may affect expression and activity of UBC9 and may have an impact on breast tumor progression. We investigated associations between UBC9 genotypes and histopathological parameters in 1,021 breast cancer cases of the GENICA collection using a single nucleotide polymorphism (SNP) tagging approach. Genotyping analyses were performed by TaqMan® allelic discrimination. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by ordinal logistic regression. Multiple imputation based on HapMap data was applied to boost the power of the study. The study revealed significant associations of three UBC9 SNPs with histological grade (rs7187167, ptrend = 0.001; rs11248866, ptrend = 0.009; rs8052688, ptrend = 0.008). Model selection identified a recessive penetrance model for rs7187167 as the best representation of tumor grade (global p = 0.001). This model did not improve by inclusion of additional SNPs in linkage disequilibrium. Imputation of SNPs in a 300 kb region around the genotyped SNPs supported rs7187167 as a major contributor to tumor grade. Compared with common allele carriers, rare homozygotes presented less frequently with high grade tumors (G3 vs. G1: OR 0.26, 95% CI 0.11–0.62; G3 vs. G2: OR 0.45, 95% CI 0.23–0.86). In addition to tumor size, nodal status and estrogen receptor status, multivariate analyses confirmed an independent role of rs7187167 as predictor of tumor grade (p = 0.0003). The present results underline the value of genetic variation in UBC9 for breast cancer prognosis. © 2009 UICC
Hyperforin and aristoforin inhibit lymphatic endothelial cell proliferation in vitro and suppress tumor‐induced lymphangiogenesis in vivo
Authors: Rothley Melanie , Schmid Anja , Thiele Wilko , Schacht Vivien , Plaumann Diana , Gartner Michael , Yektaoglu Aybike , Bruyère Françoise , Noël Agnès , Giannis Athanassios , Sleeman Jonathan P.
Published: January 2009

The phloroglucinol derivative hyperforin, a major bioactive constituent of St. John's wort, is increasingly recognized as being able to regulate a variety of pathobiological processes and, thus, to possess potential therapeutic properties. In the context of cancer, hyperforin induces the apoptosis of cancer cells, inhibits angiogenesis and suppresses metastasis formation. Here, we report a new pharmacological function of hyperforin and its stabilized derivative aristoforin, namely the suppression of lymphatic endothelial cell (LEC) growth and lymphangiogenesis. At concentrations less than 10 μM, we found that these compounds induce cell cycle arrest of LECs, and at higher concentrations induce apoptosis. The loss of mitochondrial membrane potential and the activation of caspase‐9 during the induction of apoptosis indicate that the intrinsic pathway of apoptosis is stimulated by these compounds, similar to the situation in tumor cells. In thoracic duct ring outgrowth assays, hyperforin and aristoforin both inhibited lymphangiogenesis, as evidenced by the suppression of lymphatic capillary outgrowth. In an in vivo animal model, both compounds were able to inhibit tumor‐induced lymphangiogenesis. Together these data substantiate a new role for hyperforin and its derivatives as suppressors of lymphangiogenesis, and support their further investigation as potential anticancer drugs that target tumor growth and metastasis at multiple levels. © 2009 UICC
Optimal design of water‐conveying canal considering seismic stability of side slopes
Authors: Bhattacharjya Rajib Kumar , Satish Mysore G.
Published: January 2009

A new methodology is proposed in this study for determination of a cost‐effective canal section considering the seismic stability of homogeneous canal side slopes. In order to consider the seismic stability of canal side slopes, an external seismic slope stability model is required to incorporate with the canal optimization model. During the iterations for optimal solution, the canal optimization model uses the seismic stability model at every iteration. As a result, the efficiency of the combined model is mostly dependent on the efficiency of the seismic slope stability model. The computational efficiency of the combined model can be enhanced using an approximate model to check the stability of the side slope of the canal. Therefore, an artificial neural network (ANN) model is used in this study to approximate the seismic slope stability model. The developed ANN model is linked externally with the canal optimization model to obtain the dimensions of the cost‐effective canal section with seismic‐resistant side slopes. Pseudo‐static analysis is carried out for evaluation of the seismic stability of the slope. An example problem is solved to demonstrate the field applicability of the developed model. Copyright © 2009 John Wiley & Sons, Ltd.
Phosphatidylserine decarboxylases, key enzymes of lipid metabolism
Authors: Schuiki Irmgard , Daum Günther
Published: January 2009

Phosphatidylserine decarboxylases (PSDs) (E.C. 4.1.1.65) are enzymes which catalyze the formation of phosphatidylethanolamine (PtdEtn) by decarboxylation of phosphatidylserine (PtdSer). This enzymatic activity has been identified in both prokaryotic and eukaryotic organisms. PSDs occur as two types of proteins depending on their localization and the sequence of a conserved motif. Type I PSDs include enzymes of eukaryotic mitochondria and bacterial origin which contain the amino acid sequence LGST as a characteristic motif. Type II PSDs are found in the endomembrane system of eukaryotes and contain a typical GGST motif. These characteristic motifs are considered as autocatalytic cleavage sites where proenzymes are split into α‐ and β‐subunits. The S‐residue set free by this cleavage serves as an attachment site of a pyruvoyl group which is required for the activity of the enzymes. Moreover, PSDs harbor characteristic binding sites for the substrate PtdSer. Substrate supply to eukaryotic PSDs requires lipid transport because PtdSer synthesis and decarboxylation are spatially separated. Targeting of PSDs to their proper locations requires additional intramolecular domains. Mitochondrially localized type I PSDs are directed to the inner mitochondrial membrane by N‐terminal targeting sequences. Type II PSDs also contain sequences in their N‐terminal extensions which might be required for subcellular targeting. Lack of PSDs causes various defects in different cell types. The physiological relevance of these findings and the central role of PSDs in lipid metabolism will be discussed in this review. © 2009 IUBMB IUBMB Life, 61(2): 151–162, 2009
Towards oncological application of Raman spectroscopy
Authors: Nijssen Annieke , Koljenović Senada , Schut Tom C. Bakker , Caspers Peter J. , Puppels Gerwin J.
Published: January 2009

As the possibilities in the treatment of cancer continue to evolve, its early detection and correct diagnosis are becoming increasingly important. From the early detection of cancer to the guidance of oncosurgical procedures new sensitive in vivo diagnostic tools are much needed. Many studies report the Raman spectroscopic detection of malignant and premalignant tissues in different sites of the body with high sensitivities. The great appeal of this technique lies in its potential for in vivo clinical implementation. We present an overview of the in vitro and in vivo work on the oncological application of Raman spectroscopy and discuss its potential as a new tool in the clinico‐oncological practice. Opportunities for integration of Raman spectroscopy in oncological cure and care as a real‐time guidance tool during diagnostic (i.e. biopsy) and therapeutic (surgical resection) modalities as well as technical shortcomings are discussed from a clinician's point of view. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Mechanical properties of small‐diameter polyurethane vascular grafts reinforced by weft‐knitted tubular fabric
Authors: Xu Weilin , Zhou Fei , Ouyang Chenxi , Ye Wenxiang , Yao Mu , Xu Bugao
Published: January 2009

Polyester filament yarns of different Deniers were knitted into tubular fabrics with different densities and thicknesses on a specially designed weft‐knitting machine. The developed tubular fabric was used to reinforce polyurethane vascular graft and thus a kind of composite vascular graft was fabricated with a small inner diameter of 4 mm. Tensile properties of the reinforced composite vascular grafts were compared with the control tubular fabric and the pure PU vascular grafts. Elasticity and strength of the reinforced vascular grafts were improved compared with the weft‐knitted tubular fabrics. Strength of the reinforced composite vascular grafts was almost 5–10 times of the strength of the pure PU vascular grafts. As the PU content increased in the reinforced composite vascular grafts, the wall thickness of the vascular graft and its strength increased, but the initial modulus of the reinforced composite vascular grafts remained similar to that of the weft‐knitted tubular fabric, and the PU content showed little influence on the initial modulus of the reinforced composite vascular grafts. Microporous structure can also be fabricated in the wall of the reinforced composite vascular grafts. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Response of UMR 106 cells exposed to titanium oxide and aluminum oxide nanoparticles
Authors: Di Virgilio Ana L. , Reigosa Miguel , de Mele Monica Fernández Lorenzo
Published: January 2009

The cytotoxicity potential of TiO2 and Al2O3 nanoparticles (NP) in UMR 106 cells was studied by evaluating the lysosomal activity with neutral red uptake assay (NR), and the mitochondrial activity with tetrazolium MTT test. Different NP concentrations (10–300 μg/mL range) were used. A significant (p < 0.001) increase in the absorbance (stronger for TiO2 NP) was detected in both NR and MTT assays after 24‐h exposure to the NP. However, the total cell proteins and the cell proliferation rate demonstrated (p < 0.05) that the cell viability decreased after 96 h exposure to NP. The formation of NP‐containing vesicles within the cells was observed by transmission electronic microscopy. Such event could explain the high cellular activity detected during the early stages of exposure not related to the increase in cell viability. Results showed that the effects of NP on cell lines are dependent on the chemical composition of the particles, their concentration, exposure time, and the type of treated cell. It can be concluded that the presence of TiO2 and Al2O3 NP in the cell surroundings can lead to cytotoxic effects. In the case of osteoblast cells, such events may induce osseointegration failures in orthopedic and dental implants that release NP. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Expression of Concern: Different apoptosis modalities in periprosthetic membranes
Authors: Sabbatini Maurizio , Piffanelli Valentina , Boccafoschi Francesca , Gatti Silvia , Renò Filippo , Bosetti Michela , Leigheb Massimiliano , Massè Alessandro , Mario Cannas
Published: January 2009

This study reports on an investigation into apoptotic and proliferation signals in leukocyte and membrane fibroblasts in periprosthetic membranes collected during revision surgery for loosened total hip joint arthroplasty. Cementless and cemented prosthesis were studied under both aseptic and septic conditions. Fluorescence colocalization immunohistochemistry and colorimetric immunohistochemistry were used to investigate cell death signals. In aseptic cementless prosthesis macrophages and membrane fibroblasts show high bax signal, implying the occurrence of toxic/oxidative cell death caused by the debris of titanium alloy metal implant. Instead in aseptic cemented prosthesis only a moderate number of apoptotic leukocytes were observed, whilst the fibroblasts were affected by a diffuse apoptotic‐like cell death, the Co‐Cr ions debris released from cemented stem, may be at basis of apoptotic cell death induction. Furthermore cement debris is recognized to induce macrophages to produce cytokine, that may be responsible for the cell death observed and implant failure. The septic environment seems to protect leukocytes cell death. Septic cementless prosthesis showed only a few apoptotic leukocytes, instead fibroblasts remain affected by cell death signals. Similarly in septic cemented prosthesis, scanty apoptotic leukocytes were detected, whereas membrane fibroblasts showed an increase in proliferation index (Ki‐67) along with caspase‐3 activation. These findings indicate some kind of caspase‐3 involvement in tissue proliferation, rather than in cell death pathway. Apoptotic periprosthetic sites have been interpreted as signs of inflammation resolution and normal tissue turnover. Nevertheless apoptosis may also be a sign of cell renewal associated to tissue proliferation. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Sensitivity of insulin production from encapsulated islets to endotoxin‐stimulated macrophage inflammatory mediators
Authors: Lyle Daniel B. , Shallcross Jonathan C. , Langone John J.
Published: January 2009

Chronic inflammation may compromise function of implanted encapsulated islets. Increased purity of alginate used for encapsulation prolongs encapsulated graft function, correlating with decreased presence of impurities like bacterial endotoxin. Limits for endotoxin contamination in biomaterials based on indirect inhibition of function of embedded cells have yet to be established. In a coculture system with RAW 264.7 monocyte/macrophage cells in the presence of 50 ng/mL murine recombinant gamma‐interferon (mrIFN‐γ), the insulin response to glucose challenge of both rat and pig unencapsulated islets was prevented by endotoxin (LPS) in the medium down to 0.3 EU/mL (LOEL), but not 0.06 EU/mL (NOEL). Evaluation of nitrite concentrations in supernatants revealed that pig islets were more resistant to LPS‐stimulated macrophage mediators than rat islets. Encapsulation in highly purified alginate produced little change in observed inhibitory effects of macrophage‐generated nitric oxide (NO) toward islet function. Chemically released NO was much less effective in inhibiting insulin responsiveness to glucose challenge than was coculture of islets with LPS and mrIFN‐γ‐stimulated RAW 264.7. These results taken together with other data suggest that an upper limit of 0.3 EU/mL LPS within the encapsulating alginate will not impair the function of implanted encapsulated islets by toxic concentrations of macrophage‐mediated inflammatory agents. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Properties of experimental titanium‐silver‐copper alloys for dental applications
Authors: Kang Dong‐Kuk , Moon Seoung‐Kyun , Oh Keun‐Taek , Choi Good‐Sun , Kim Kyoung‐Nam
Published: January 2009

The aim of this study was to develop Ti‐Ag‐Cu alloys with a higher corrosion resistance, better biocompatibility, and better mechanical properties than commercially pure titanium and its alloys. The microstructure, corrosion resistance, mechanical property and cytotoxicity of the Ti‐Ag‐Cu alloys were investigated. The corrosion resistance was evaluated by open circuit potential measurements and potentiodynamic polarization tests in artificial saliva at 37°C. The mechanical properties were evaluated using tensile and microhardness tests. The biocompatibility was tested by evaluating the cytotoxicity of the alloys using an agar‐overlay test and MTT assay. It was found that the open circuit potentials of the Ti‐Ag‐Cu alloys were higher than that of pure Ti. However, the passive current densities of the Ti‐Ag‐Cu alloys were similar to that of pure titanium. The mechanical properties improved with increasing Ag and Cu content. All the Ti‐Ag‐Cu alloys examined were found to be noncytotoxic similar to pure Ti. Therefore, Ti‐Ag‐Cu alloys can be used as biomaterials in the dental field. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009