bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenine-N3 in the DNA Minor Groove - An Emerging Target for Platinum Containing Anticancer Pharmacophores
Authors: Guddneppanavar Rajsekhar , Bierbach Ulrich
Published: April 2008

The minor-groove is an important receptor for enzymes and proteins involved in the processing and expression of genomic DNA. Small molecules capable of interfering with these processes by virtue of their ability to form adducts within the recognition sequences targeted by these enzymes/proteins have potential applications as cytotoxic and generegulating agents. Until recently, the targeting of the minor groove by platinum-based agents has been a widely unexplored opportunity. As part of this focused review on irreversible minor-groove modifying agents acting on adenine-N3, we summarize work performed in our laboratory and by our collaborators on a novel platinum-acridine conjugate, PTACRAMTU ([PtCl(en)(ACRAMTU)](NO3)2, en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3- dimethylthiourea, acridinium cation). The design of this agent as a non-cisplatin type pharmacophore has led to a groundbreaking discovery, the unprecedented intercalator-driven formation of platinum-adenine-N3 adducts in the minor groove of DNA. The minor-groove reactivity of PT-ACRAMTU represents a new paradigm in platinum-DNA interactions, which opens new avenues in the design of platinum-based therapeutics acting by a mechanism different from that of agents currently in clinical use.
Editorial [Hot Topic: Anticancer Platinum Complexes - State of the Art and Future Prospects (Guest Editor: Markus Galanski)]
Authors: Galanski Mathea Sophia
Published: April 2008

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Biochemical Mechanisms of Cisplatin Cytotoxicity
Authors: Cepeda Victoria , Fuertes Miguel A. , Castilla Josefina , Alonso Carlos , Quevedo Celia , Perez Jose M.
Published: April 2008

Since the discovery by Rosenberg and collaborators of the antitumor activity of cisplatin 35 years ago, three platinum antitumor drugs (cisplatin, carboplatin and oxaliplatin) have enjoyed a huge clinical and commercial hit. Ever since the initial discovery of the anticancer activity of cisplatin, major efforts have been devoted to elucidate the biochemical mechanisms of antitumor activity of cisplatin in order to be able to rationally design novel platinum based drugs with superior pharmacological profiles. In this report we attempt to provide a current picture of the known facts pertaining to the mechanism of action of the drug, including those involved in drug uptake, DNA damage signals transduction, and cell death through apoptosis or necrosis. A deep knowledge of the biochemical mechanisms, which are triggered in the tumor cell in response to cisplatin injury not only may lead to the design of more efficient platinum antitumor drugs but also may provide new therapeutic strategies based on the biochemical modulation of cisplatin activity.
The Role of Sulfur in Platinum Anticancer Chemotherapy
Authors: Wang Xiaoyong , Guo Zijian
Published: April 2008

Sulfur manifests its influence on platinum anticancer chemotherapy in two aspects: endogenous sulfurcontaining molecules such as cysteine, methionine, glutathione, metallothionein and albumin affect the metabolism of platinum drugs and exert adverse effects on the therapeutic efficacy; exogenous congeners such as amifostine (WR-2721) and dimesna (BNP7787) mitigate the toxic side effects of platinum drugs and serve as chemoprotectants. The platinumsulfur interactions are ubiquitous in the human body and many occurrences encountered during platinum chemotherapy such as uptake, excretion, resistance, and toxicity are related to them. Thus, sulfur-containing molecules play significant roles in the anticancer mechanism of platinum drugs. In this review, the platinum-sulfur interactions are summarized in detail, which may be important for efficient clinical use of the existing platinum agents and beneficial to the rational design of new generation of platinum-based anticancer drugs.
Trans-Platinum Complexes in Cancer Therapy
Authors: Coluccia Mauro , Natile Giovanni
Published: April 2008

The research of new platinum drugs active towards cisplatin refractory/resistant tumors has been mostly focussed on compounds with cis geometry because transplatin, the trans-isomer of cisplatin, is inactive. It is widely accepted that transplatin inactivity stems from two major factors: i) the kinetic instability promoting its deactivation and ii) the formation of DNA adducts characterized by a regioselectivity and a stereochemistry different from those of cisplatin. However, several exceptions to the general rule that the presence of two leaving groups in cis positions is necessary for antitumor activity of platinum complexes, have been reported. Substitution of transplatin ammine ligands by aromatic Ndonor heterocycles, branched aliphatic amines, or imino ligands has lead to compounds with relevant in vitro tumor cell growth inhibitory potency, often active towards cisplatin refractory/resistant tumor cells, and in some cases endowed with significant activity also in vivo. From a mechanistic point of view, substitution of bulky ligands for ammines can retard substitution of the two chloride ligands, thus reducing the kinetic instability of the trans-platinum compounds. On the other hand, the formation of DNA adducts qualitatively and quantitatively different from those of cisplatin strongly supports the hypothesis that antitumor-active trans-platinum complexes can have a different spectrum of activity. It is hoped that the increasing knowledge of the biochemical and cellular processes underlying the antitumor-activity of transplatinum complexes will foster their clinical development.
Recent Progress in Discovery and Development of Antimitotic Agents
Authors: Kiselyov Alex , Balakin Konstantin V. , Tkachenko Sergey E. , Savchuk Nikolay , Ivachtchenko Alexandre V.
Published: April 2008

This review highlights structural diversity of antimitotic agents. In particular, we emphasized current antimitotic therapies based on modulation of microtubule dynamics. With several successful anticancer drugs on the market and numerous compounds in clinical developments, tubulin-binding agents remain among the most important categories of anticancer agents. Compounds targeting mitotic kinases and kinesins are also discussed.
Antitumor Carbazoles
Authors: Asche Christian , Demeunynck Martine
Published: April 2008

Natural and synthetic carbazoles, either in a pure substituted or in an annellated substituted form, represent an important and heterogeneous class of anticancer agents, which has grown considerably over the last two decades. Many carbazole derivatives have been tested for cyctotoxic activity, some of them have entered clinical trials, but only very few have been approved for the treatment of cancer so far, since the clinical application of many carbazoles has encountered problems like severe side effects or multidrug resistance. Due to their polycyclic, planar and aromatic structure carbazoles are predestined for intercalation into DNA and therefore DNA remains one of the main targets for cytotoxic carbazoles. For many carbazoles cytotoxicity can be related to DNA-dependent enzyme inhibition such as topoisomerase I/II and telomerase. But also other targets such as cyclin-dependent kinases and estrogen receptors have emerged.
Vascular Endothelial Growth Factor (VEGF) Inhibition - A Critical Review
Authors: Sousa Moreira Irina , Alexandrino Fernandes Pedro , Joao Ramos Maria
Published: April 2008

Angiogenesis, or formation of new blood capillaries from preexisting vessels, plays both beneficial and damaging roles in the organism. It is a result of a complex balance of positive and negative regulators, and vascular endothelial growth factor (VEGF) is one of the most important pro-angiogenic factors involved in tumor angiogenesis. VEGF increases vascular permeability, which might facilitate tumor dissemination via the circulation causing a greater delivery of oxygen and nutrients; it recruits circulating endothelial precursor cells, and acts as a survival factor for immature tumor blood vessels. The endotheliotropic activities of VEGF are mediated through the VEGF-specific tyrosine-kinase receptors: VEGFR-1, VEGFR-2 and VEGFR-3. VEGF and its receptors play a central role in tumor angiogenesis, and therefore the blockade of this pathway is a promising therapeutic strategy for inhibiting angiogenesis and tumor growth. A number of different strategies to inhibit VEGF signal transduction are in development and they include the development of humanized neutralizing anti-VEGF monoclonal antibodies, receptor antagonists, soluble receptors, antagonistic VEGF mutants, and inhibitors of VEGF receptor function. These agents can be divided in two broad classes, namely agents designed to target the VEGF activity and agents designed to target the surface receptor function. The main purpose of this review is to summarize all the available information regarding the importance of the proangiogenic factor VEGF in cancer therapy. After an overview of the VEGF family and their respective receptors, we shall focus our attention on the different VEGF-inhibitors existent nowadays. Agents based upon anti-VEGF therapy have provided solid proofs about their success, and therefore we believe that a critical review is of the utmost importance to help researchers in their future work.
Radiolabelled Regulatory Peptides for Imaging and Therapy
Authors: de Jong M. , Visser T. J. , de Blois E. , P. Breeman W. A. , Kwekkeboom D. J. , Krenning E. P.
Published: April 2008

Radiolabelled peptides have shown to be an important class of radiopharmaceuticals for imaging and therapy of malignancies expressing receptors of regulatory peptides. These peptides have high affinity and specificity for their receptors. The majority of these receptors are present at different levels in different tissues and tumours. This review focuses on the application of regulatory peptides radiolabelled with 67/68Ga , 90Y, 111In or 177Lu. Due attention is given to the current status of research, limitations and future perspectives of the application of these radiolabelled peptides for imaging and radiotherapy. It also covers elements of the basic science and preclinical and clinical aspects in general, however, mostly based on somatostatin receptor-mediated imaging and therapy. New analogues, chelators, radionuclides and combinations thereof are discussed.
Radionuclide Liver Cancer Therapies: From Concept to Current Clinical Status
Authors: Maarten A.D. Vente  , Monique G.G. Hobbelink  , Alfred D. van het Schip  , Bernard A. Zonnenberg  , Johannes F.W. Nijsen
Published: April 2008

Primary and secondary liver cancer have longtime been characterized by an overall poor prognosis since the majority of patients are not candidates for surgical resection with curative intent, systemic chemotherapy alone has rarely resulted in long-term survival, and the role of conventional external beam radiation therapy has traditionally been limited due to the relative sensitivity of the liver parenchyma to radiation. Therefore, a host of new treatment options have been developed and clinically introduced, including radioembolization techniques, which are the main topic of this paper. In these locoregional treatments liver malignancies are passively targeted because, unlike the normal liver, the blood supply of intrahepatic tumors is almost uniquely derived from the hepatic artery. These internal radiation techniques consist of injecting either yttrium-90 (90Y) microspheres, or iodine-131 (131I) or rhenium-188 (188Re) labeled lipiodol into the hepatic artery. Radioactive lipiodol is used exclusively for treatment of primary liver cancer, whereas 90Y microsphere therapy is applied for treatment of both primary and metastatic liver cancers. Favorable clinical results have been achieved, particularly when 90Y microspheres were used in conjunction with systemic chemotherapy. The main advantages of radiolabeled lipiodol treatment are that it is relatively inexpensive (especially 188Re-HDD-lipiodol) and that the administration procedure is somewhat less complex than that of the microspheres. Holmium-166 (166Ho) loaded poly(L-lactic acid) microspheres have also been developed and are about to be clinically introduced. Since 166Ho is a combined beta-gamma emitter and highly paramagnetic as well, it allows for both (quantitative) scintigraphic and magnetic resonance imaging.
Use of Radiopharmaceuticals for Diagnosis, Treatment, and Follow-Up of Differentiated Thyroid Carcinoma
Authors: Frederik A. Verburg  , Bart de Keizer  , Johannes W. van Isselt
Published: April 2008

In 1942, Dr. Seidlin of the Memorial Hospital in New York was faced with a 51-year- old patient who had undergone a thyroidectomy in 1923 [1]. At the time, the histologic diagnosis was a ‘malignant adenoma’ of the thyroid. In 1938 the patient returned with overt signs of thyroid hyperfunction (hyperthyroidism) and lower back pain. A metastasis was found in the lower spine, and surgically removed. Over the next years the patient remained hyperthyroid and developed more bone metastases. At the time of presentation to Dr. Seidlin, the patient was in an extremely poor condition: he was in severe pain, severely hyperthyroid, and severely underweight. At this time radioiodine therapy had just reached the clinical arena. In 1937 Hertz, Roberts and Evans investigated the rabbits thyroid function using I-128 [2]. Later they pursued therapeutic goals for e.g. Graves disease using I-130. They used dosages that we now know would have been merely diagnostic if it were not for a probable 10% I-131 contaminant [3]. Livingood and Seaborg identified I-131 as a separate isotope. In 1942 two groups independently reported on the successful treatment of hyperthyroidism with I-131 sodium iodide [4,5]. Radioiodine was so rare that it was recovered from the urine, purified and re-administered to the patient. The patient responded favourably to the radioiodine treatment, and he received several more courses of I-131. Geiger-counter examination of the patient revealed two previously unknown metastases, thereby indicating the diagnostic capabilities of radioiodine. The patient did very well on these courses: the hyperthyroidism subsided, the body-weight kg increased from 38 to 53 kilograms, and the pains diminished. This report of a potential cure for terminally ill patients fuelled the public imagination to a degree that it hit the political agenda. Effective on August 1, 1946, the Atomic Energy Act (AEA) made radioisotopes available for medical use in the USA. This date marks the beginning of ‘atomic medicine’, later named nuclear medicine.
Nicotine, Lung and Cancer
Authors: Alessia Grozio  , Alessia Catassi  , Zita Cavalieri  , Laura Paleari  , Alfredo Cesario  , Patrizia Russo
Published: April 2008

The respiratory epithelium expresses the cholinergic system including nicotinic receptors (nAChRs). It was reported that normal human bronchial epithelial cells (BEC), which are the precursor for squamous cell carcinomas, and small airway epithelial cells (SAEC), which are the precursor for adenocarcinomas, have slightly different repertoires of nAChRs. Studies shown that nAChRs expressed on lung carcinoma or mesothelioma form a part of an autocrine-proliferative network facilitating the growth of neoplastic cells; others demonstrated that nicotine can promote the growth of colon, gastric, and lung cancers. Nicotine and structurally related carcinogens like NNK [4-(methylnitrosoamino)- 1-(3-pyridyl)-1-butanone] and NNN (N-nitrosonornicotine) could induce the proliferation of a variety of small cell lung carcinoma cell lines and endothelial cells and nicotine in non-neuronal tissues -including lung- induces the secretion of growth factors (bFGF, TGF-α, VEGF and PDGF), up regulation of the calpain family proteins, COX-2 and VEGFR-2, causing the eventual activation of Raf/MAPK kinase/ERK (Raf/MEK/ERK) pathway contributing to the growth and progression of tumors exposed to nicotine through tobacco smoke or cigarette substitutes. It has been demonstrated that nicotine promotes the growth of solid tumors in vivo, suggesting that might induce the progression of tumors already initiated. While tobacco carcinogens can initiate and promote tumorigenesis, the exposure to nicotine could confer a proliferative advantage to early tumors but there is no evidence that nicotine itself provokes cancer. This is supported by the findings that nicotine can prevent apoptosis induced by various agents - such as chemotherapeutic in NSCLC, conferring a survival advantage as well.
Human Interleukin-19: Structure, Function and Disease Associations
Authors: Gallagher Grant , Eskdale Joyce , Jordan William , Boniotto Michele , Rodia Michelle , Kellner Danielle , Witte Ellen , Sabat Robert , Wolk Kerstin
Published: April 2008

Interleukin(IL) -19 is a member of the recently described IL-10 family of cytokines. Based on the genomic localization of its gene, its structure, conserved amino acids, cellular sources and receptor, IL-19 forms a subfamily with IL- 20 and IL-24. The IL-19-encoding gene comprises seven exons and is located on chromosome 1. Secreted IL-19 is composed of 159 amino acids that form an α-helical structure. IL-19 is produced by activated monocytes, and to a lesser extent, by B cells. As known so far, IL-19 functions through a receptor complex composed of IL-20R1 and IL-20R2, which is also utilized by IL-20 and IL-24. High levels of both receptor chains are present in several stromal tissues including the skin, lungs, and tissues from the reproductive organs. However, no expression is found in any immune cell population. Nonetheless, all effects of IL-19 described so far concern immune cells. Such conflicting data may be due to the existence of an additional (so far undiscovered) receptor complex for IL-19, or to the ability of the known IL-19 receptor to mediate its effects when present on the cell surface at a very low density. IL-19 has been shown to enhance the production of Th2 cytokines in T cells. Furthermore, it induced IL-10 expression in monocytes. Apart from the implied role for IL-19 in atopic and allergic responses and disorders, it also seems to be involved in the pathogenesis of the Th1-type skin disease psoriasis. IL-19 therefore represents an exciting new cytokine with immunoregulatory functions.
IL-22 and Its Receptors, New Players in the Inflammatory Network
Authors: Dumoutier Laure , Renauld Jean-Christophe
Published: April 2008

Originally identified as a gene specifically induced by IL-9 in a mouse T cell lymphoma, IL-22 is mainly produced by TH1 cells or by activated T cells. Human IL-22, which shares 79% amino acid identity with its mouse orthologue and 25% with IL-10 is encoded by a single copy gene and located on chromosome 12, close to the IFNγ gene, whereas the murine IL-22 gene is located on chromosome 10 and is duplicated in some mouse strains. Structurally, IL-22 appears to be a monomer composed of six alpha helices, whose organization is reminiscent of the helices of the IL-10 dimer. Despite its structural relationship with IL-10, IL-22 exerts completely different activities, acting mainly on non hematopoietic cells, such as epithelial cells from lung and colon, hepatocytes and keratinocytes. IL-22 might therefore be involved in inflammatory processes, at least in liver and skin. IL-22 exerts its activity via a complex formed by IL-10Rβ and IL-22R, associated with Tyk2 and Jak1, respectively. The main signaling pathways triggered by IL-22 involve STAT-1, - 3, -5 and the ERK, JNK and p38 MAPKinases. Beside its transmembrane receptor, IL-22 also binds to a soluble receptor, called IL-22BP. This soluble receptor turns out to be a natural antagonist of IL-22 biological activities at least in vitro.
Soluble Receptors of the Interleukin-10 Family of Cytokines: Interleukin-22 Receptor Alpha 2
Authors: Sabat R. , Wallace E. , Asadullah K. , Sterry W. , Volk H.-D. , Wolk K.
Published: April 2008

The interleukin (IL)-10 family of cytokines comprising IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28α, IL- 28β, and IL-29 uses receptors of the cytokine receptor family class 2. Here we review the current knowledge about IL-22 receptor-α2 (IL-22Rα2) which is the first known soluble receptor of that cytokine family. The human IL-22Rα2-encoding gene includes seven exons and is located on chromosome 6 between the genes for interferon-γ receptor-1 and IL-20 receptor- 1. The products of this gene are three different mRNA splice variants. The genes for the mouse and rat IL-22Rα2 have a very similar genomic location and structure to those in humans, although they lack the human exon 4 counterpart and produce only one variant which corresponds to the human variant 2. Irrespective of the species and splice variant, IL- 22Rα2 lacks any sequence for a transmembrane or an intracellular part, and is a secreted protein. It is particularly expressed in the placenta, the mammary glands, and the lymph nodes but also in the gastrointestinal system, the lungs, the skin, and other lymphatic organs. It seems, however, that the variants 3 and 1 are more restricted in their expression. Variant 2 binds to and inhibits the activity of IL-22 in vitro, whereas the specificity of variants 3 and 1 has not been identified. The discovery of IL-22Rα2 represents a first step towards understanding the regulatory network regarding the action of IL-22 and perhaps of other members of the IL-10 family. It also may open up new ways for targeting the action of these cytokines for therapeutic interests.
The Potential of Group Visits in Diabetes Care
Authors: Davis Andrew M. , Sawyer Devin R. , Vinci Lisa M.
Published: April 2008

IN BRIEF

Compared to more ambitious practice redesign, group visits are a relatively straightforward innovation that offer promise in improving efficiency and encouraging patient self-management. This article reviews recent literature and explores practical issues from the authors' experience in a Midwest academic medical center and a West Coast family medicine residency.
USEFULNESS AND CREDIBILITY OF SCORING METHODS IN CONSTRUCTION INDUSTRY/TAŠKŲ SKAIČIAVIMO METODŲ NAUDINGUMAS IR PATIKIMUMAS STATYBOS PRAMONĖJE
Authors: Kapliński Oleg
Published: April 2008

The methods presented in the paper clarify the route of a company towards bankruptcy. The information comes from the so called early warning systems, among which a special attention has been paid to statistical scoring methods. A review of scoring methods informing about the financial standing of a company has been made. Examples have been selected among construction companies listed on Warsaw Stock Exchange. Credibility of models and results has been highlighted. Results point at the fact that the synthetic Z‐score index should be adjusted to economic conditions of a given country, or even to an industry. Santrauka Metodai, pateikiami straispnyje, atskleidžia kompanijos kelią į bankrotą. Informacija gaunama iš vadinamųjų išankstinio perspėjimo sistemų, kuriose daugiausia dėmesio skiriama statistinio taskų (balų) skaičiavimo metodams. Pateikiama taškų skaičiavimo metodų, atskleidžiančių finansinę įmonės padėtį, apžvalga. Pavyzdžiai paimti iš Varšuvos biržos statybos kompanijų sąrašo. Nustatytas modelių ir rezultatų patikimumas. Rezultatai rodo, kad sintetinė Z reikšmė turi būti koreguojama pagal ekonomines konkrečios šalies arba pramonės sąlygas.
THE INFLUENCE OF FLAME RETARDANT ADDITIVES ON FIRE PROPERTIES OF EPOXY MATERIALS/DEGUMO GRUPĘ AUKŠTINANČIŲ PRIEDŲ ĮTAKA EPOKSIDINIŲ MEDŽIAGŲ GAISRINIAM PAVOJINGUMUI
Authors: Półka Marzena
Published: April 2008

Fire properties of modified and unmodified epoxy materials have been studied. The following types of additives were used: MoO3, Sb2O3, melamine. Heat and smoke release rates in different external fluxes (30, 50 kW/m) were studied by the Cone calorimeter. The results of investigation have shown that molibdenum oxide (VI) is more smoke supres‐sant than antimony oxide (III) and melamine in the range of heat exposure under consideration. Santrauka Atlikta modifikuotų ir nemodifikuotų epoksidinių medžiagų gaisrinio pavojingumo analizė. Panaudotos šios degumo grupę aukštinančios medžiagos: MoO3, Sb2O3, melaminas. Kūginiu kalorimetru nustatytas šilumos ir dūmų išsiskyrimo intensyvumas, esant skirtingam išoriniam šilumos srautui (30, 50 kW/m2 ). Remiantis tyrimo rezultatais nustatyta, kad molibdeno oksidas (VI) efektyviau mažina dūmų išsiskyrimą nei stibio oksidas (III) ir apsvarstyta melamino poveikis šilumai išsiskirti.
FUZZY PROBABILITY ANALYSIS OF THE FATIGUE RESISTANCE OF STEEL STRUCTURAL MEMBERS UNDER BENDING/FUZI TIKIMYBINĖ ANALIZĖ VERTINANT LENKIAMŲ PLIENINIŲ ELEMENTŲ ATSPARĮ NUOVARGIUI
Authors: Kala Zdeněk
Published: April 2008

The paper is aimed at the fuzzy probabilistic analysis of fatigue resistance due to uncertainty of input parameters. The fatigue resistance of the steel member is evaluated by linear fracture mechanics as the number of cycles leading to the propagation of initial cracks into a critical crack resulting in brittle fracture. When the histogram of stress range is known, the fatigue resistance is a random variable. In the event that the histogram is unknown or was acquired from a small number of experiments, another source of uncertainty is of an epistemic origin. Two basic approaches, which make provision for uncertainty of input histograms of stress range, are illustrated in the paper. Uncertainty of histograms of stress range is taken into account by the variability of equivalent stress range in the first stochastic approach. Input histograms as considered as members of a fuzzy set in the second approach. Santrauka Straipsnyje nagrinėjamas atspario nuovargio esant neapibrėžtiems pradiniams duomenims vertinimas naudojant fuzi tikimybinę analizę. Plieninių elementų atsparis nuovargiui pagal tiesinę irimo mechaniką apibūdinamas ciklų skaičiumi, kai pradiniai plyšiai perauga į kritinį plyšį, sukeliantį trapų suirimą. Kai įtempimų kitimo histograma yra žinoma, atsparis nuovargiui yra atsitiktinis dydis. Kai histograma yra nežinoma arba ji atitinka mažą eksperimentų skaičių, atsiranda kitas episteminės kilmės neapibrėžtumas. Pateikiami du pagrindiniai būdai, rodantys histogramos neapibrėžtumą. Pirmuoju, stochastiniu būdu, įtempių kitimo diapazono histograma yra modeliuojama ekvivalentinio įtempio kitimu. Antruoju būdu pradinės histogramos nagrinėjamos kaip fuzi aibės elementai.
Dissection and Culture of Embryonic Spinal Commissural Neurons
Authors: Moore Simon W. , Kennedy Timothy E.
Published: April 2008

Studies of spinal commissural neurons have provided substantial insight into the mechanisms that regulate axon guidance. Explants of embryonic spinal cords and isolated spinal commissural neurons have been important experimental tools for the identification and characterization of several guidance cues, including netrins, semaphorins, slits, sonic hedgehog, BMPs, and wnts. In this unit, protocols are provided for establishing these explant assays to assess the outgrowth and turning capacity of commissural axons. In addition, methods are included for preparing cultures highly enriched with embryonic commissural neurons, which have been used to probe the biochemical signaling mechanisms regulating axon guidance. Curr. Protoc. Neurosci. 43:3.20.1‐3.20.17. © 2008 by John Wiley & Sons, Inc.
EMS and UV Mutagenesis in Yeast
Authors: Winston Fred
Published: April 2008

Many fundamental biological processes have been elucidated by the isolation and analysis of mutants that are defective in such processes. Therefore, the methods to generate mutants are of great importance in model organisms. This unit describes two protocols for mutagenesis of yeast—using ethyl methanesulfate (EMS) and ultraviolet (UV) light. Each of these methods has been used successfully for many years. Curr. Protoc. Mol. Biol. 82:13.3B.1‐13.3B.5. © 2008 by John Wiley & Sons, Inc.
Using CellProfiler for Automatic Identification and Measurement of Biological Objects in Images
Authors: Vokes Martha S. , Carpenter Anne E.
Published: April 2008

Visual analysis is required to perform many biological experiments, from counting yeast colonies to measuring the size and shape of individual cells or the intensity of fluorescently labeled proteins within them. This unit outlines the use of CellProfiler, a free, open‐source image analysis tool that extracts quantitative information from biological images. It includes a step‐by‐step protocol for automated analysis of the number, color, and size of yeast colonies growing on agar plates, but the methods can be adapted to identify and measure any objects in images. The flexibility of the software allows users to tailor pipelines of adjustable modules to fit different biological experiments, to generate accurate measurements from dozens or even hundreds of thousands of images. Curr. Protoc. Mol. Biol. 82:14.17.1‐14.17.12. © 2008 by John Wiley & Sons, Inc.
Production of a Heterozygous Mutant Cell Line by Homologous Recombination (Single Knockout)
Authors: Mortensen Richard
Published: April 2008

Gene targeting by homologous recombination is a powerful and widely used technique for introduction of specific gene mutations (frequently a gene inactivation) in transgenic animals. The basic method detailed in this unit uses sequences homologous to the endogenous gene flanking the mutation. While methods using bacterial artificial chromosomes (BACs) and recombineering may be used, in most cases simpler bacterial plasmid clones with several kb of homology are sufficient. This protocol details the strategic factors in designing the constructs for selection and screening for homologous recombination. Curr. Protoc. Mol. Biol. 82:23.5.1‐23.5.11. © 2008 by John Wiley & Sons, Inc.
Production of a Homozygous Mutant Embryonic Stem Cell Line (Double Knockout)
Authors: Mortensen Richard
Published: April 2008

Under some circumstances, it may be desirable to produce a mouse cell clone in which both alleles of a desired gene are mutated. This may be because the mutation causes embryonic lethality in homozygous animals, or to test cultured cells before an animal is produced. This protocol details an easy method for obtaining homozygous cells by homologous recombination without the need for two targeting events. Curr. Protoc. Mol. Biol. 82:23.6.1‐23.6.4. © 2008 by John Wiley & Sons, Inc.
Calculation and Use of the Hardy‐Weinberg Model in Association Studies
Authors: Ryckman Kelli , Williams Scott M.
Published: April 2008

Hardy‐Weinberg equilibrium (HWE) is an important tool for understanding population structure. If certain assumptions are met, genotype and allele frequencies can be estimated from one generation to the next. In genetic association studies, HWE principles have been applied to detect genotyping error and disease susceptibility loci. The focus of this unit is to review the key principles and assumptions of HWE. There is a brief discussion on how the significance of HWE is tested, and a review of current applications of HWE in association studies. The applications discussed include estimating penetrance, evaluating genotyping errors, testing for population stratification, and testing for association. Curr. Protoc. Hum. Genet. 57:1.18.1‐1.18.11. © 2008 by John Wiley & Sons, Inc.
p53 Testing for Li‐Fraumeni and Li‐Fraumeni‐Like Syndromes
Authors: Gonzalez Kelly , Fong Cindy , Buzin Carolyn , Sommer Steve S. , Saldivar Juan‐Sebastian
Published: April 2008

Li‐Fraumeni Syndrome (LFS; OMIM #151623) is an autosomal dominant cancer predisposition syndrome characterized by early onset tumors including sarcomas, breast cancer, leukemia, brain tumors, and adrenocortical carcinoma. Li‐Fraumeni syndrome is primarily attributed to germline mutations in the p53 tumor suppressor gene, which encodes tumor protein 53. In addition to germline p53 mutations, the p53 gene is the most commonly mutated gene in human cancers, with as much as 50% of tumors containing somatic p53 mutations. This unit provides a protocol to perform germline mutation analysis of the p53 gene. The protocol includes steps for amplification and sequencing of the entire coding region of the p53 gene (exons 2 to 11). The protocol was designed for detecting germline alterations from DNA extracted from blood; however, with some additional optimization, it could also be used to detect somatic mutations in DNA extracted from tumors. Curr. Protoc. Hum. Genet. 57:10.10.1‐10.10.11. © 2008 by John Wiley & Sons, Inc.
Parallel high‐resolution finite volume simulation of particulate processes
Authors: Gunawan Rudiyanto , Fusman Irene , Braatz Richard D.
Published: April 2008

Population balance models (PBMs) are widely used to describe the dynamics of particulate systems. The simulation of PBMs becomes challenging with increasing numbers of dimensions and integral terms associated with phenomena, such as coalescence and breakage, which has motivated efforts to develop more computationally efficient numerical algorithms. This article presents high‐resolution finite‐volume methods for the parallel simulation of PBMs that scale well to ∼100 processors on a linux cluster. The high‐resolution methods provide second‐order accuracy with an accurate tracking of sharp fronts. The ParticleSolver software implementing these methods is verified by application to PBMs for (1) aerosol coagulation and condensation, (2) the formation of gold nanoparticles by nucleation, disproportionation, and coagulation, and (3) the nucleation and growth of inorganic crystals with a time‐varying shape distribution. © 2008 American Institute of Chemical Engineers AIChE J, 2008
Mechanical properties and water sorption behavior of phenol–formaldehyde hybrid composites reinforced with banana fiber and glass fiber
Authors: Joseph Seena , Sreekala M. S. , Koshy Peter , Thomas Sabu
Published: April 2008

Banana fiber, which is rich in cellulose, relatively inexpensive, and abundantly available, has potential for polymer reinforcement. This study explores the merits of combining high‐modulus glass fibers with banana fiber in phenolic resoles to develop high‐performance, cost‐effective, lightweight hybrid composites. Of particular interest is the effect of varying layering patterns of banana fiber and glass fiber on the tensile, flexural, and impact properties of hybrid composites. The highest tensile strength value has been obtained for an intimate mixture of both fibers, and the maximum flexural and impact strength has been obtained for composite samples prepared from interleaving layers of banana fiber and glass fiber. Tensile, flexural, and impact properties of the composites increase with an increasing volume fraction of glass fiber. The water uptake of these composites decreases with the incorporation of glass fiber into banana fiber, and the composites with glass fiber at the periphery and banana fiber at the core have the maximum resistance to water absorption. Scanning electron micrographs show the fracture mechanism and fiber/matrix adhesion in these composites © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
An improvement on water absorbing and permeating properties: Heparin immobilizing on acrylic acid‐grafted and collagen/chitosan‐immobilized wound dressing
Authors: Wang Chyung‐Chyung , Chen Cheng‐Chi , Chen Frank‐Len , Lin Nien‐Shih
Published: April 2008

Various concentrations of heparin were employed in this study to immobilize on the acrylic acid‐grafted and collagen/chitosan‐immobilized polypropylene (PP‐AAg‐CCi) nonwoven fabric to improve the water absorbing and permeating properties. The immobilized heparin was verified by analyzing of the spectra of surface reflection infrared spectroscopy. It was found that the values of water absorbing and water diffusion coefficient for the PP‐AAg‐CCi sample immobilized with heparin (PP‐AAg‐CCHi) were significantly higher than those for the PP‐AAg‐CCi. The bacteria inhibition percentage and bacteria inhibition zone for the PP‐AAg‐CCHi were excellently. The pore and agent distribution for PP‐AAg‐CCi were examined with scanning electron microscope photographs. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Effect of solvent composition on transparency and surface hardness of poly(methyl methacrylate)‐silica nanocomposites provided on polycarbonate
Authors: Saito Reiko , Kobayashi Shin‐Ichiro , Hayashi Hidetaka , Shimo Toshihisa
Published: April 2008

Poly(methyl methacrylate)‐silica nanocomposites with 49 vol % of silica were prepared by blending poly(methyl methacrylate‐co‐2‐hydroxyethyl methacrylate) [content of 2‐hydroxyethyl methacrylate: 15.1 mol %] with perhydropolysilazane in a ethylacetate/cyclohexane/xylene mixture, casting on polycarbonate (PC) substrates and drying for 24 h at room temperature. When the cyclohexane content in the solution was in a range from 21.7 to 32.3 vol %, composites were transparent in a wide range from 400 to 1000 nm of wavelength, the maximum surface hardness of composites on the substrate measured by nanoindentation was 1.07 GPa. Dynamic light scattering and viscometric analysis indicated that aggregates of poly(methyl methacrylate‐co‐2‐hydroxyethyl methacrylate) was formed in the mixture when the transparent composites were obtained on the PC substrates. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Melting behavior, isothermal and nonisothermal crystallization kinetics of PP/mLLDPE blends
Authors: Qin Jianglei , Guo Shaoqiang , Li Zhiting
Published: April 2008

Melting behavior, nonisothermal crystallization and isothermal crystallization kinetics of polypropylene (PP) with metallocene‐catalyzed linear low density polyethylene (mLLDPE) were studied by differential scanning calorimetry (DSC). The results show that PP and mLLDPE were partially miscible. The Avrami analysis was applied to analyze the nonisothermal and isothermal crystallization kinetics of the blends, the Mo Z.S. method was used to take a comparison in nonisothermal kinetics. Values of Avrami exponent indicate the crystallization nucleations of both pure PP and PP in the blends were heterogeneous, the growth of spherulites is tridimensional and the spherulites in the blends were more perfect than that in pure PP. The crystallization activation energy was estimated by Kissinger method and Arrhenius equation and the two methods draw similar results. The mLLDPE increased the crystallization rate of PP in nonisothermal crystallization process and decreased it in isothermal process. The results from nonisothermal crystallization and isothermal crystallization kinetics were not consistent because the two processes were completely different. Addition of minor mLLDPE phase favors to increase the overall crystallinity of PP, showing the mLLDPE entered the PP crystals. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Mechanical and thermal properties of polycarbonate, part 1: Influence of free quenching
Authors: Rouabah F. , Fois M. , Ibos L. , Boudenne A. , Picard C. , Dadache D. , Haddaoui N.
Published: April 2008

The effect of different thermal treatments on the mechanical and thermal properties of polycarbonate was investigated. The first quenching procedure which involves the quench of the samples from the melt state to different temperatures allowed improving impact strength and elongation at break for a quenching temperature of 0°C. A second quenching procedure, corresponding to specimens heated again at 160°C (Tg + 15°C) and quenched a second time, showed a better enhancement of the impact strength and elongation at break to the detriment of other properties such as elastic modulus, density, yield stress, and heat distortion temperature, for a quenching temperature of 40°C. This effect was associated to the existence of a relaxation mode around 35°C. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Phosphorescent Iridium(III) Complexes with Nonconjugated Cyclometalated Ligands
Authors: Song Yi‐Hwa , Chiu Yuan‐Chieh , Chi Yun , Cheng Yi‐Ming , Lai Cheng‐Hsuan , Chou Pi‐Tai , Wong Ken‐Tsung , Tsai Ming‐Han , Wu Chung‐Chih
Published: April 2008

A series of blue phosphorescent iridium(III) complexes 1–4 with nonconjugated N‐benzylpyrazole ligands were synthesized and their structural, electrochemical, and photophysical properties were investigated. Complexes 1–4 exhibit phosphorescence with yields of 5–45 % in degassed CH2Cl2. Of the compounds, 1 showed emission that was nearly true blue at 460 nm with a lack of vibronic progression. These photophysical data clearly demonstrate that the methylene spacer of the cyclometalated N‐benzylpyrazole chelate effectively interrupts the π conjugation upon reacting with a third L^X chelating chromophore. This gives a feasible synthesis for the blue phosphorescent complexes with a sufficiently large energy gap. In another approach, these complexes were investigated for their suitability for the host material in phosphorescent OLEDs. The device was synthesized by using 1 as the host for the green‐emitting [Ir(ppy)3] dopant, which exhibits an external quantum conversion efficiency (EQE) of up to 11.4 % photons per electron (and 36.6 cdA−1), with 1931 Commission Internationale de L'Eclairage (CIE) coordinates of (0.30, 0.59), a peak power efficiency of 21.7 lmW−1, and a maximum brightness of 32000 cdm−2 at 14.5 V. At the practical brightness of 100 cdm−2, the efficiency remains above 11 % and 18 lmW−1, demonstrating its great potential as the host material for phosphorescent organic light‐emitting diodes.
The effect of material, thermal and laser conditioning on the damage threshold of type II tripler‐cut DKDP crystals
Authors: Sun Shao‐Tao , Ji Lai‐Lin , Wang Zheng‐Ping , Xu Ming‐Xia , Liang Xiao‐Liang , Liu Bing , Mu Xiao‐Ming , Sun Xun , Xu Xin‐Guang
Published: April 2008

By using the traditional temperature‐reduction method, KD2PO4 (DKDP) crystals were grown from 85%‐deuterated aqueous solution synthesized by different kind of KH2PO4 (KDP) raw materials. An experimental technique was employed to measure the variation of bulk damage threshold in plates of DKDP crystals. Bulk laser damage in unconditioned, thermal‐conditioned and laser‐conditioned type II tripler‐cut DKDP crystals has been studied using 1064 nm (ω) and 355 nm (3ω) laser at pulse lengths of 5ns, 5ns respectively. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electrochemical Processing of Carbon Dioxide
Authors: Oloman Colin , Li Hui
Published: April 2008

With respect to the negative role of carbon dioxide on our climate, it is clear that the time is ripe for the development of processes that convert CO2 into useful products. The electroreduction of CO2 is a prime candidate here, as the reaction at near‐ambient conditions can yield organics such as formic acid, methanol, and methane. Recent laboratory work on the 100 A scale has shown that reduction of CO2 to formate (HCO2−) may be carried out in a trickle‐bed continuous electrochemical reactor under industrially viable conditions. Presuming the problems of cathode stability and formate crossover can be overcome, this type of reactor is proposed as the basis for a commercial operation. The viability of corresponding processes for electrosynthesis of formate salts and/or formic acid from CO2 is examined here through conceptual flowsheets for two process options, each converting CO2 at the rate of 100 tonnes per day.
Einschalige Kalksandstein‐Außenwände mit Wärmedämm‐Verbundsystem (WDVS)
Authors: Prepens Manfred
Published: April 2008

Einschalige Außenwände mit Wärmedämm‐Verbundsystem (WDVS) – auch Thermohaut genannt – haben sich seit über 40 Jahren in der Praxis sowohl bei Neubauten als auch bei der Sanierung älterer Gebäude sehr gut bewährt. Zuerst kamen Systeme mit expandierten Polystyrol‐Hartschaumplatten EPS und seit etwa Mitte der 70er Jahre auch Systeme mit Mineralfaserdämmplatten zu Anwendung.
Neubau einer Seniorenwohnanlage in Göttingen – Verbesserter Schallschutz mit Ziegel‐Innenwand‐System
Authors: Bischof Ramona
Published: April 2008

Der Wunsch nach Ruhe in den eigenen vier Wänden hat einen hohen Stellenwert. Durch die neuen europäischen Normen des baulichen Schallschutzes wird diesem Bedürfnis stärker als bisher Rechnung getragen. hnlich wie bei der EnEV steht auch bei der neuen DIN EN 12354 nicht mehr das einzelne Bauteil im Vordergrund, sondern eine ganzheitliche akustische Betrachtung aller Übertragungswege. Insbesondere die flankierende Schallübertragung erhält deutlich mehr Beachtung. Das heißt, künftig müssen – schon bei der Planung – nicht nur die Eigenschaften des einzelnen Bauteils, sondern auch die akustischen Eigenschaften von Bauteilverbindungen (Stoßstellen, Knotenpunkte) einbezogen werden.
Infrared Spectra of Insertion, Methylidene, and Methylidyne Complexes in Reactions of Laser‐Ablated Ruthenium Atoms with Halomethanes and Methane
Authors: Cho Han‐Gook , Andrews Lester
Published: April 2008

Reactions of laser‐ablated Ru atoms with halomethanes and methane have been investigated. Small carbyne and carbene complexes or insertion products are produced in the reactions of halomethanes via C–X insertion and halogen migration, whereas only the insertion complex is formed in the reactions of methane. The results are consistent with computed product stabilities. The diagnostic C–H and C–X stretching absorptions of the carbyne complexes are observed on the blue side of the corresponding precursor bands. The high C–H and C–X stretching frequencies are explained with the higher s character in hybridization and combination with the C≡Ru stretching motion, respectively. The structures of the carbyne complexes are highly distorted and show a large variation with the ligands, and the extra electron pair on the Ru atom evidently plays an important role in the carbyne. In contrast to early transition‐metal analogs, the Ru carbene complexes show no agostic distortion.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Packed‐column capillary electrochromatography and capillary electrochromatography‐mass spectrometry using a lithocholic acid stationary phase
Authors: Norton Dean , Shamsi Shahab A.
Published: April 2008

The preparation and characterization of a novel lithocholic acid (LCA)‐based liquid crystalline (LC) stationary phase (SP) suitable for application in packed‐column CEC and CEC coupled to MS is described. The extent of bonding reactions of LCA‐SP was assessed using 1H‐NMR, 13C‐NMR and elemental analysis. This characterization is followed by application of the LCA‐SP for separation of β‐blockers, phenylethylamines (PEAs), polyaromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Using the optimum mobile phase operating conditions (pH 3.0–4.5, 10 mM ammonium acetate, 85% v/v ACN), a comparison of the chromatographic ability of the aminopropyl silica phase vs. the LCA‐bonded phase was conducted. The results showed improved selectivity for all test analytes using the latter phase. For example, the CEC‐MS of β‐blockers demonstrated that the LCA‐bonded phase provides separation of six out of seven β‐blockers, whereas the amino silica phase provides four peaks of several co‐eluting β‐blockers. For the CEC‐MS analysis of PEAs, the LCA‐bonded phase showed improved resolution and different selectivity as compared to the aminopropyl phase. An evaluation of the retention trends for PEAs on both phases suggested that the PEAs were retained based on varying degree of hydroxyl substitution on the aromatic ring. In addition, the MS characterization shows several PEAs fragment in the electrospray either by loss of an alkyl group and/or by loss of H2O. Finally, the LCA‐bonded phase displayed significantly higher separation selectivity for PAHs and PCBs as compared to the amino silica phase.