bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimuli-Sensitive Polymeric Micelles as Anticancer Drug Carriers
Authors: Na Kun , Sethuraman Vijay T. , Han Bae You , Sethuraman Vijay A.
Published: April 2008

Amphiphilic block copolymers often form core-shell type micelles by self-organization of the blocks in an aqueous medium or under specific experimental conditions. Polymeric micelles constructed from these polymers that contain a segment whose physical or chemical properties respond to small changes in environmental conditions are collectively called ‘stimuli-sensitive ’ micelles. This class of nano-scaled constructs has been investigated as a promising anticancer drug carrier because the micelles are able to utilize small environmental changes and modify drug release kinetics, biodistribution and the interactions with tissues and cells. This review summarizes the recent progress in stimuli-sensitive micelles for tumor chemotherapy, particularly for those responding to hyperthermic conditions, tumor pH and endosomal/ lysosomal pH.
3-(4-Geranyloxy-3-Methoxyphenyl)-2-trans Propenoic Acid: A Novel Promising Cancer Chemopreventive Agent
Authors: Curini Massimo , Epifano Francesco , Genovese Salvatore , Carla Marcotullio Maria , Menghini Luigi
Published: April 2008

3-(4-Geranyloxy-3-methoxyphenyl)-2-trans propenoic acid is a secondary metabolite biosynthetically related to ferulic acid in which a geranyl chain is attached to the phenolic group, extracted from Acronychia baueri Schott (Fam. Rutaceae). In the last five years some of the pharmacological properties of 3-(4-geranyloxy-3-methoxyphenyl)-2-trans propenoic acid and its semisynthetic derivatives began to be characterized. In particular the ethyl ester showed a series of interesting biological effects such colon and tongue cancers chemoprevention by dietary feeding in rats and other effects closely related to cancer growth and development. Then 3-(4-geranyloxy-3-methoxyphenyl)-2-trans propenoic acid becomes a novel candidate as chemopreventive drug for the cure of various types of cancer and synthesis of some novel derivatives of 3-(4-geranyloxy-3-methoxyphenyl)-2-trans propenoic acid, other than esters, has been recently reported. The aim of this review is to examine in detail the properties of the title compound so far reported in the literature from a chemical and pharmacological point of view.
Searching for the Magic Bullet: Anticancer Platinum Drugs Which Can Be Accumulated or Activated in the Tumor Tissue
Authors: Galanski Mathea Sophia , Keppler Bernhard K.
Published: April 2008

Cisplatin, carboplatin and oxaliplatin are anticancer drugs, which are efficiently used in the clinics all over the world. Besides a remarkable therapeutic efficacy in a series of solid tumors and outstanding activity of cisplatin against testicular germ-cell cancer, the platinum-based therapy is in part accompanied by a set of severe toxic side-effects. The design of platinum complexes being equipped with an exclusive selectivity for the tumoral tissue and exhibiting a lack of systemic toxicity (‘magic bullets’) is the great hope in the fight against cancer and also a motor within the expanding field of bioinorganic chemistry. In this review article, two promising strategies, namely accumulation and activation of tumor inhibiting platinum complexes specifically at the tumor site is presented, demonstrating a stepwise approach towards the ‘magic bullet’ concept propagated by Paul Ehrlich.
Preclinical and Clinical Studies on the Use of Platinum Complexes for Breast Cancer Treatment
Authors: Ott Ingo , Gust Ronald
Published: April 2008

Platinum complexes such as cisplatin and carboplatin are widely used in todays cancer chemotherapy but not in the present therapy of breast cancer, the most frequent epithelial malignancy among women. As platinum compounds display high antitumoral efficacy against several breast cancer cell lines in-vitro they may be an interesting option for future clinical therapy of this disease. On the preclinical stage hormonally active and tissue selective platinum anticancer drugs have been investigated. Clinical trials on established platinum drugs (mainly cisplatin and carboplatin) showed that they can be efficient cytostatics for breast cancer therapy, if patients are carefully selected and suitable combination regimens (e.g. including taxanes) are administered. This review covers the latest findings about new platinum complexes in preclinical studies on the use against breast cancer as well as the outcome of the most relevant clinical trials.
Meta-Analysis of Anticancer Drug Structures - Significance of Their Polar Allylic Moieties
Authors: Radin Norman S.
Published: April 2008

This meta-analysis examines a wide range of small molecule anticancer drugs to search for a structure common to all. Although they encompass a very wide range of structures, nearly all reveal the presence of an allylic O, N, or S atom. In some, the allylic oxygen is a carbonyl group, or an alcohol group, which can be substituted (ester, lactone, glycoside, ether) or replaced by an amino or imino nitrogen Some antineoplastic drugs do not exhibit this moiety but are converted in vivo to allylic derivatives. An allylic hydroxyl is also present in most sphingolipids, ubiquitous body components that control proliferative and anti-proliferative cell functions. Ceramide, the precursor of all the allylic sphingolipids, seems to be a general inducer of apoptosis in cancer cells. Further examination of sphingolipids and anticancer drugs shows the frequent occurrence of [i] double bonds conjugated to the allylic bond, (ii) two or more allylic moieties in each molecule, (iii) lipophilic features, especially linear chains, and (iv) attachment of an O, N, or S atom to a carbon atom of the allylic double bond, e.g., -CH2-C(OMe)=CH-CH(OH)-CH2-. Suggested mechanisms of action: (a) allylic ketone drugs undergo a Michael condensation with tumor thiols or other reactive groups; (b) allylic OH drugs undergo oxidation to an allylic ketone, generating reactive oxygen; (c) some interfere with mitochondrial ubiquinone, blocking ATP production; (d) some act as a ceramide mimic (inhibitor or agonist) in ceramide-controlled kinases, phosphatases, and proteases; (e) many antineoplastic drugs stimulate ceramide-forming processes.
Labeling Biomolecules with Radiorhenium - A Review of the Bifunctional Chelators
Authors: Liu Guozheng , Hnatowich Donald J.
Published: April 2008

For radiotherapy, biomolecules such as intact antibodies, antibody fragments, peptides, DNAs and other oligomers have all been labeled with radiorhenium (186Re and 188Re). Three different approaches have been employed that may be referred to as direct, indirect and integral labeling. Direct labeling applies to proteins and involves the initial reduction of endogenous disulfide bridges to provide chelation sites. Indirect labeling can apply to most biomolecules and involves the initial attachment of an exogenous chelator. Finally, integral labeling is a special case applying only to small molecules in which the metallic radionuclide serves to link two parts of a biomolecule together in forming the labeled complex. While the number of varieties for the direct and integral radiolabeling approaches is rather limited, a fairly large and diverse number of chelators have been reported in the case of indirect labeling. Our objective herein is to provide an overview of the various chelators that have been used in the indirect labeling of biomolecules with radiorhenium, including details on the labeling procedures, the stability of the radiolabel and, where possible, the influence of the label on biological properties.
Bone Seeking Radiopharmaceuticals for Palliation of Pain in Cancer Patients with Osseous Metastases
Authors: M.G.E.H. Lam  , J.M.H. de Klerk  , P.P. van Rijk  , B.A. Zonnenberg
Published: April 2008

Many patients with cancer develop symptomatic skeletal metastases at an advanced stage of their disease. Skeletal metastases are often complicated by pain. They cause considerable morbidity and mortality. Besides analgesics, treatment options include external beam radiotherapy, bisphosphonates, chemotherapy, surgery and bone seeking radiopharmaceuticals. Pain palliation with bone seeking radiopharmaceuticals has proved to be an effective treatment modality in patients with metastatic bone pain. Radiopharmaceuticals bind to the bone matrix in areas of increased bone turnover, due to a metastatic response. Beta rays from the specific radionuclide, bound to its carrier ligand, result in the therapeutic effect. Various radiopharmaceuticals have been developed for this purpose. All have their own characteristics. The radiopharmaceuticals Samarium-153-ethylenediaminetetramethylenephosphonic acid (153Sm-EDTMP) and Strontium- 89-Chloride, which are approved in the USA and Europe, as well as the not universally approved Rhenium-186-hydroxyethylidenediphosphonic acid (186Re-HEDP), will be discussed in greater detail. Depending on the half-life and radiation energy of the specific radionuclide, they exert a different effect and toxicity profile. In most cases, bone marrow toxicity is limited and reversible, which makes repetitive treatment relatively safe. Several studies have shown encouraging clinical results of palliative therapy using bone seeking radiopharmaceuticals, with an overall reported pain response rate in the order of ± 70-80% of patients. This systemic form of radionuclide therapy is simple to administer and complements other treatment options. It has been associated with marked pain reduction, improved mobility in many patients, reduced dependence on analgesics, and improved performance status and quality of life. Additionally, new therapeutic strategies hold the promise of enhancement of the palliative and anticancer effects of this form of therapy.
Targeted Multifunctional Lipid-Based Nanocarriers for Image-Guided Drug Delivery
Authors: Gerben A. Koning  , Gerard C. Krijger
Published: April 2008

Lipid-based nanocarriers have proven successful in the delivery of mainly chemotherapeutic agents, and currently they are being applied clinically in the treatment of various types of cancer. These drug delivery systems achieve increased therapeutic efficacy by altering the pharmacokinetics and biodistribution of encapsulated drugs, resulting in decreased drug toxicity and enhanced accumulation in tumor tissue. This increased accumulation is due to the relatively leaky immature vasculature of a tumor. After the clinical relevance of such drug delivery systems was demonstrated, research in this area focused on optimization, both by cell specific targeting and including controlled and triggered release concepts within the carrier. These more advanced targeted nanocarriers in general have clearly shown their potential in various animal tumor models and await clinical application. The development of targeted nanocarriers in which therapeutic and imaging agents are merged into a single carrier will certainly be of importance in the near future. Indeed, scientists active in the field of imaging (e.g. nuclear and magnetic resonance imaging) have already started to exploit nanocarriers for molecular imaging. Image-guided drug delivery using these multifunctional nanocarriers, containing therapeutic and imaging agents, will ultimately allow for online monitoring of tumor location, tumor targeting levels, intratumoral localization and drug release kinetics prior and during radio- and/or chemotherapeutic treatment. This review describes the current status and challenges in the field of nanocarrier-aided drug delivery and drug targeting and discusses the opportunities of combining imaging probes with these drug carriers and the potential of these multifunctional lipid-based nanocarriers within image-guided drug delivery.
Smac/DIABLO and Colon Cancer
Authors: Y.M. Anguiano-Hernandez  , A. Chartier  , S. Huerta
Published: April 2008

Apoptosis is a genetically programmed process of controlled and orderly cell suicide, which is critical for multicellular organisms during development and tissue homeostasis. In cancer, the ratio of apoptosis to cell division is altered, resulting in a net gain of malignant tissue. Tumor cells may acquire resistance to apoptosis by the expression of anti-apoptotic proteins, or by the down-regulation or mutation of pro-apoptotic mediators. In the classic pathway of apoptosis, this process is primarily coordinated by activation of caspases. Decreased expression of caspases inversely correlates with the aggressiveness of cancer. Increased activity of caspases renders cancer cells susceptible to chemoradiotherapeutic modalities. Thus, caspase activity is pivotal in carcinogenesis. The functions of activated caspases are inhibited by the binding of inhibitors of apoptosis (IAPs). The function of IAPs is regulated by pro-apoptotic protein Second Mitochondria-Derived Activator of Caspases (Smac) or Direct IAP Binding Protein with low isoelectric point, pI (DIABLO). Induction of apoptosis leads to increased mitochondrial permeability to Smac/DIABLO, which adheres to IAPs inhibiting their caspase-binding activity. The role of Smac/DIABLO, therefore, may have significant diagnostic and therapeutic features in carcinogenesis. The role of Smac/DIABLO in colorectal carcinogenesis is ill defined. Data continues to accumulate to suggest that decreased levels of Smac/DIABLO may be important in chemoradiation-resistance to apoptosis in advanced colon cancer. The aim of this review is to provide the available evidence of the role of Smac/DIABLO in colon carcinogenesis.
Brachytherapy: State of the Art and Possible Improvements
Authors: S. Buono  , N. Burgio  , M. Hamoudeh  , H. Fessi  , E. Hiltbrand  , L. Maciocco  , S. Mehier-Humbert
Published: April 2008

Cancer often remains an incurable disease, despite significant progresses in diagnosis and treatment that have been made. Specifically, the use of nuclear medicine in oncology is greatly contributing to both imaging and therapy aspects. Targeted therapies are a major field of interest since it increases efficiency and reduces side effects. Brachytherapy is among the most valuable of recent developments for treating localized tumours resulting in improvements in improved quality of life. This is primarily because it irradiates cancerous cells most exclusively while barely effecting healthy tissue. The use of radiochemicals implies specific management for production, transport and handling that have limited the development of this technique. This review article describes brachytherapy and their latest developments. Furthermore, alternative activation methods for the production of radioisotopes and a novel delivery system for targeted multi-therapy by using PLA-ferrite nanospheres are described.
The IFN-λ Family (IL-28/29)
Authors: Kotenko Sergei V. , Donnelly Raymond P.
Published: April 2008

IFN-λs or type III IFNs are also known as IL-28/29. This group of cytokines is the latest addition to the family of cytokines that signal through receptors of the class II cytokine receptor family (CRF2). Although IFN-λs and IFN-α/β (type I IFNs) utilize distinct receptor complexes for signaling, type I and type III IFNs activate the same intracellular signaling pathway and many similar biological activities, including the ability to induce antiviral state in cells. Consistent with their antiviral activity, the expression of IFN-λ mRNAs is inducible by viral an infections. Therefore, IFN-λs functionally resemble type I IFNs, supporting their designation as IFNs. However, IFN- λs also share several common features with cytokines of the IL-10 family that includes IL-19, IL-20, IL-22, IL-24 and IL-26. Their genes have a similar intron-exon structure, they share some sequence homology, and most likely they share a similar structural organization. IFN-λs also share a common receptor subunit, IL-10R2, with IL-10, IL- 22 and IL-26. However, the ligand-binding chain, IFN-λR1, is a unique component of the IFN-λ receptor complex. Although the relative importance of the IFN-λs remains to be fully determined, recent experiments demonstrate their strong potential as antiviral and antitumor therapeutics.
Interleukin 20
Authors: Rich B. E. , Kupper T. S.
Published: April 2008

IL-20 is a member of the IL-10 family of cytokines that also includes IL-10, IL-19, IL-22, IL-24, and IL-26 as well as a number of viral homologs. Keratinocytes and monocytes in states of activation can produce IL-20. It transmits signals via two different cell-surface receptor complexes resulting in the activation of STAT3 in keratinocytes and other epithelial cells. Thus it appears to be primarily an inducible autocrine and paracrine factor that regulates proliferation and differentiation of keratinocytes in the context of inflammation. Several findings indicate that IL-20 mediates the hyperproliferation of keratinocytes associated with cutaneous inflammation. As such it is likely to have a central role in inflammatory skin diseases such as psoriasis and eczema. IL-20 also promotes the expansion of multipotential hematopoietic progenitor cells indicating a role beyond the response of epithelial cells to inflammation. Increased understanding of the biology of IL-20 may provide novel opportunities for diagnostic methods and therapeutic intervention.
Interleukin-10
Authors: Asadullah K. , Sabat R. , Friedrich M. , Docke W. D. , Volk H. D. , Sterry W.
Published: April 2008

Interleukin (IL)-10, initially described as cytokine synthesis inhibitory factor, is a pleotropic cytokine produced by many cell populations. Its main biological functions appear to be quite diverse: on the one hand it is involved in the limitation and termination of inflammatory responses and the regulation of differentiation and proliferation of several immune cells, and on the other hand it mediates immunostimulatory properties that support the elimination of infectious and non-infectious particles with limited inflammation. Numerous investigations, including expression analyses in patients, and both in vitro and in vivo studies suggest a major physiological and pathophysiological impact of IL-10. Activation of the neuro-endocrine axis following acute stress reactions leads to systemic IL-10 release, preventing hyperinflammatory reactions. IL-10 is overexpressed in many solid tumors and lymphomas and considered to promote further tumor development. In contrast, a relative IL-10 deficiency has been observed and is regarded to be of pathophysiological relevance in certain inflammatory disorders characterized by a type 1 cytokine pattern such as psoriasis. Recombinant human IL-10 has been tested in several clinical trials including rheumatoid arthritis, inflammatory bowel disease, psoriasis, organ transplantation, and hepatitis C. The results are heterogeneous and give new insight into the immunobiology of IL-10. However, further investigations would be desirable to better determine the effect/side effect profile as well as the best first line target indication and optimal therapeutic regimen.
Membrane-Bound Receptors of the Interleukin-10 Family of Cytokines
Authors: Zdanov Alexander
Published: April 2008

The interleukin-10 (IL-10) family of cytokines includes IL-10, its viral homologs, and eight cellular cytokines: IL-19, IL-20, IL-22, IL-24, IL-26, IFN-λ1, IFN-λ2, and IFN-λ3. Cellular homologs use for signaling five recently discovered membrane-bound receptors: three long receptor chains (IL-20R1, IL-22R1, and IFN-λR) and two short receptor chains (IL-20R2 and IL-10R2). Signal transduction is initiated when cytokine binds two receptor chains, one long and one short, forming a ternary complex. Based on the analysis of known structures of ternary and binary complexes, a homology model of the structure of the ternary complex of IL-10/sIL-10R1/sIL-10R2 has been generated. The structure agrees well with all published experimental data, including the crystal structure of the binary IL-10/sIL-10R1 complex and data of peptide scans, mapping the sIL-10R2 binding site. sIL-10R1, sIL-10R2, and inter-receptor interface sites show that most of the intermolecular interactions have a polar nature, although hydrophobic interactions constituting between 20% and 35% from the total number of interactions are also important. Putative complexes of other cytokines of the IL-10 family and the role of glycosylation in ligand/receptor interactions and how it affects biological activity are also discussed.
No association between vulvovaginitis-bacterial vaginosis, related drug treatments of pregnant women, and congenital abnormalities in their offspring — A population-based case-control study
Authors: Ács Nándor , Bánhidy Ferenc , Puhó Erzsébet , Czeizel Andrew
Published: April 2008

The possible association between prospectively and medically recorded vulvovaginitis-bacterial vaginosis (VV-BV) and different congenital abnormalities (CA) has not been studied. The data set of the population-based Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996 were evaluated, i.e. 22,843 pregnant women who had newborns or fetuses with congenital abnormality (cases) and 38,151 pregnant women who delivered newborn babies without any congenital abnormality (controls). The main outcome measures were different congenital abnormalities. Of 22,843 cases with CA, 1,536 (6.7%) had mothers with VV-BV, while of 38,151 matched controls without CA, 2,698 (7.1%) had mothers with VV-BV in the second and/or third gestational month of pregnancy. Nearly all pregnant women with VV-BV were treated during pregnancy, but a higher risk for the total group of CAs (adjusted POR with 95% CI: 0.95, 0.89–1.02) or any CA group was not found. In addition, the risk for total CAs was significantly lower in cases born to mothers with VV-BV and appropriate treatment than born to mothers with VV-BV but without treatment. Thus maternal VV-BV needs treatment during pregnancy as well, because it helps reduce the rate of preterm birth without a risk for CAs.
siRNA-mediated silencing of the 37/67-kDa high affinity laminin receptor in Hep3B cells induces apoptosis
Authors: Susantad Tharinee , Smith Duncan
Published: April 2008

The laminin-binding protein, variously called the 37/67-kDa high affinity laminin receptor or p40, mediates the attachment of normal cells to the laminin network, and also has a role as a ribosomal protein. Over-expression of this protein has been strongly correlated with the metastatic phenotype. However, few studies have investigated the cellular consequence of the ablation of this gene’s expression. To address this issue, the expression of the 37/67-kDa high affinity laminin receptor was knocked out with several siRNA constructs via RNA interference in transformed liver (Hep3B) cells. In each case where the message was specifically ablated, apoptosis was induced, as determined by annexin V/propidium iodide staining, and by double staining with annexin V and an antibody directed against the 37/67-kDa high affinity laminin receptor. These results suggest that this protein plays a critical role in maintaining cell viability.
EDITORIAL: THE FIFTH DECADE
Authors: Zavadskas Edmundas Kazimieras
Published: April 2008

„Editorial: The fifth decade" Journal of Civil Engineering and Management, 14(1), p. 5-10
Schedule‐Induced Polydipsia: A Rat Model of Obsessive‐Compulsive Disorder
Authors: Platt Brian , Beyer Chad E. , Schechter Lee E. , Rosenzweig‐Lipson Sharon
Published: April 2008

Obsessive‐compulsive disorder (OCD) is difficult to model in animals due to the involvement of both mental (obsessions) and physical (compulsions) symptoms. Due to limitations of using animals to evaluate obsessions, OCD models are limited to evaluation of the compulsive and repetitive behaviors of animals. Of these, models of adjunctive behaviors offer the most value in regard to predicting efficacy of anti‐OCD drugs in the clinic. Adjunctive behaviors are those that are maintained indirectly by the variables that control another behavior, rather than directly by their own typical controlling variables. Schedule‐induced polydipsia (SIP) is an adjunctive model in which rats exhibit exaggerated drinking behavior (polydipsia) when presented with food pellets under a fixed‐time schedule. The polydipsic response is an excessive manifestation of a normal behavior (drinking), providing face validity to the model. Furthermore, clinically effective drugs for the treatment of OCD decrease SIP. This protocol describes a rat SIP model of OCD and provides preclinical data for drugs that decrease polydipsia and are clinically effective in the treatment of OCD. Curr. Protoc. Neurosci. 43:9.27.1‐9.27.8. © 2008 by John Wiley & Sons, Inc.
Interaction Trap/Two‐Hybrid System to Identify Interacting Proteins
Authors: Golemis Erica A. , Serebriiskii Ilya , Finley Russell L. , Kolonin (hunt by interaction mating) Mikhail G. , Gyuris Jeno , Brent Roger
Published: April 2008

The yeast two‐hybrid method (or interaction trap) is a powerful technique for detecting protein interactions. The procedure is performed using transcriptional activation of a dual reporter system in yeast to identify interactions between a protein of interest (the bait protein) and the candidate proteins for interaction. The method can be used to screen a protein library for interactions with a bait protein or to test for association between proteins that are expected to interact based on prior evidence. Interaction mating facilitates the screening of a library with multiple bait proteins.Curr. Protoc. Mol. Biol. 82:20.1.1‐20.1.35. © 2008 by John Wiley & Sons, Inc.
Mutation Detection Using Automated Fluorescence‐Based Sequencing
Authors: Montgomery Kate T. , Iartchouck Oleg , Li Li , Perera Anoja , Yassin Yosuf , Tamburino Alex , Loomis Stephanie , Kucherlapati Raju
Published: April 2008

The development of high‐throughput DNA sequencing techniques has made direct DNA sequencing of PCR‐amplified genomic DNA a rapid and economical approach to the identification of polymorphisms that may play a role in disease. Point mutations as well as small insertions or deletions are readily identified by DNA sequencing. The mutations may be heterozygous (occurring in one allele while the other allele retains the normal sequence) or homozygous (occurring in both alleles). Sequencing alone cannot discriminate between true homozygosity and apparent homozygosity due to the loss of one allele due to a large deletion. In this unit, strategies are presented for using PCR amplification and automated fluorescence‐based sequencing to identify sequence variation. The size of the project and laboratory preference and experience will dictate how the data is managed and which software tools are used for analysis. A high‐throughput protocol is given that has been used to search for mutations in over 200 different genes at the Harvard Medical School – Partners Center for Genetics and Genomics (HPCGG, http://www.hpcgg.org/). Curr. Protoc. Hum. Genet. 57:7.9.1‐7.9.31. © 2008 by John Wiley & Sons, Inc.
Multiplexed Detection of Fungal Nucleic Acid Signatures
Authors: Diaz Mara R. , Dunbar Sherry A. , Jacobson James W.
Published: April 2008

Diagnoses of opportunistic mycotic infections constitute an increasing clinical problem. Conventional diagnostic tests are time consuming and lack specificity and sensitivity for accurate and timely prognoses. This unit provides a comprehensive description of a fungal detection method that combines nucleic acid signatures with flow cytometry. The multiplexed assay, which uses xMAP technology, consists of unique fluorescent microspheres covalently bound to species‐specific fungal oligonucleotide probes. In the presence of the complementary target sequence, the probe hybridizes to its biotinylated target. Quantification of the reaction is based on the fluorescence signal of the reporter molecule that binds to the biotin moieties of the target. The assay can be expanded to include other microorganisms and has the capability to simultaneously test 100 different fungal probes per tube/well. The speed, flexibility in design, and high‐throughput capability makes this assay an attractive diagnostic tool for fungal infections and other related maladies. Curr. Protocol. Cytom. 44:13.9.1‐13.9.21. © 2008 by John Wiley & Sons, Inc.
Culture of Mouse Embryonic Stem Cells
Authors: Tremml Gabi , Singer Matthew , Malavarca Richard
Published: April 2008

In this unit standard culture conditions for mouse embryonic stem cells (mESCs) on primary murine embryonic fibroblast (PMEF or MEF) monolayers, culture conditions without MEF for feeder‐independent mESCs, and culture conditions in chemically defined media for both feeder‐independent mESCs and feeder‐dependent mESCs are described. For expansion of an mESC line, it is crucial that cells maintain their undifferentiated state and their self‐renewal capacity, and that they remain karyotypically normal, all of which are necessary for successful chimerization of the germ line upon blastocyst injection. Derivation and culture conditions for the original mESCs have been described (notably Robertson, 1987; Smith, 1991; Nagy et al., 2003), however, as there are more and more mESC lines available, it becomes evident that culture conditions are cell‐line specific to some extent, and there is a constant demand for culturing details for mESC lines derived from different mouse strains. Curr. Protoc. Stem Cell Biol. 5:1C.4.1‐1C.4.19. © 2008 by John Wiley & Sons, Inc.
Studies on the Bisoxazoline‐ and (−)‐Sparteine‐Mediated Enantioselective Addition of Organolithium Reagents to Imines
Authors: Denmark Scott E. , Nakajima Noriyuki , Stiff Cory M. , Nicaise Olivier J.‐C. , Kranz Michael
Published: April 2008

The enantioselective addition of organolithium reagents to N‐anisylaldimines promoted by chiral bisoxazolines and (−)‐sparteine as external ligands is described. This reaction proceeds readily with a wide range of aldimine substrates (aliphatic, aromatic, olefinic) and organolithium nucleophiles (Me, n‐Bu, Ph, vinyl) in excellent yields (81–99%) and with high enantioselectivities (up to 97:3.0 er). The external ligands can be used in substoichiometric amounts albeit with slightly attenuated enantioselectivities. A systematic evaluation of the structural features of the bisoxazolines revealed a primary contribution from the substituent at C(4) and a secondary influence from the bridging substituents. A computational analysis (PM3) provided a clear rationalization for the origin of enantioselectivity.
High‐pressure viscosity and density of carbon dioxide + pentaerythritol ester mixtures: Measurements and modeling
Authors: Pensado A. S. , Pádua A. A. H. , Comuñas M. J. P. , Fernández J.
Published: April 2008

This article reports densities and viscosities up to 60 MPa and from 303.15 to 353.15 K on two binary mixtures of CO2 and lubricant pentaerythritol tetra‐2‐ethylhexanoate with 7.8% and 14.4% mass fraction of lubricant. Because CO2 and the lubricant are not in the same phase at atmospheric pressure and room temperature, a specially‐designed vibrating‐wire apparatus has been used. The experimental data, together with our previous data for six mixtures of CO2 and three polyolesters, have been used to test the predictive and correlation ability of several models: simple mixing laws, the self‐referencing method, and the hard‐sphere and free volume models. In general, it is not possible to predict the viscosity with deviations smaller than 10%. The hard‐sphere model and the self‐referencing model are the more adequate to represent the viscosity of these mixtures. Most of the models studied underestimate the viscosities over the investigated (T,p) range. © 2008 American Institute of Chemical Engineers AIChE J, 2008
Optimal purchasing of raw materials: A data‐driven approach
Authors: Muteki Koji , MacGregor John F.
Published: April 2008

An approach to the optimal purchasing of raw materials that will achieve a desired product quality at a minimum cost is presented. A PLS (Partial Least Squares) approach to formulation modeling is used to combine databases on raw material properties and on past process operations and to relate these to final product quality. These PLS latent variable models are then used in a sequential quadratic programming (SQP) or mixed integer nonlinear programming (MINLP) optimization to select those raw materials, among all those available on the market, the ratios in which to combine them and the process conditions under which they should be processed. The approach is illustrated for the optimal purchasing of metallurgical coals for coke making in the steel industry. However, it is well suited to many similar problems such as the purchasing of crude oils for refining, of ingredients for processed foods and of polymeric materials to blend into functional polymers. © 2008 American Institute of Chemical Engineers AIChE J, 2008
A collision efficiency model for flow‐induced coagulation of fractal aggregates
Authors: Bäbler Matthäus U.
Published: April 2008

A model for flow‐induced collisions of fractal aggregates is developed. The model is based on the analysis of the relative trajectories between a pair of aggregates that takes into account their hydrodynamic and their colloidal interactions. Regarding the former, the aggregates are modeled as permeable spheres where the Brinkman equation is used to describe the flow inside the aggregates. Interparticle forces are incorporated by considering the forces between the primary particles in the two aggregates that are the nearest. The model results in a collision efficiency that depends on the masses of the colliding aggregates, the fractal dimension, and a nondimensional Hamaker constant characterizing the interparticle forces. The collision efficiency model is used to investigate the dynamics of a suspension undergoing coagulation. Significant deviations with respect to existing collision efficiency models are evidenced. © 2008 American Institute of Chemical Engineers AIChE J, 2008
Olivine as a tar removal catalyst during fluidized bed gasification of plastic waste
Authors: Mastellone Maria Laura , Arena Umberto
Published: April 2008

Natural olivine was used as bed material during the gasification of plastic waste in a pilot‐scale bubbling fluidized bed reactor. The results indicate that it works as an excellent in‐situ tar reduction agent, considerably improving the quality of the gas produced, in terms of low tar content, high hydrogen volume fraction and large syngas yield. The phenomena concurring to the activation of the catalyst are described together with those that can contribute to deactivate it. A phenomenological description of the different stages occurring during gasification of plastic waste in a fluidized bed of olivine particles is also reported. © 2008 American Institute of Chemical Engineers AIChE J, 2008
Gender differences in genetic linkage and association on 11p15 in obsessive–compulsive disorder families
Authors: Wang Y. , Samuels J.F. , Chang Y.C. , Grados M.A. , Greenberg B.D. , Knowles J.A. , McCracken J.T. , Rauch S.L. , Murphy D.L. , Rasmussen S.A. , Cullen B. , Hoehn‐Saric R. , Pinto A. , Fyer A.J. , Piacentini J. , Pauls D.L. , Bienvenu O.J. , Riddle M. , Shugart Y.Y. , Liang K.Y. , Nestadt G.
Published: April 2008

Several clinical and genetic studies have reported gender differences in obsessive–compulsive disorder (OCD). Previously, we conducted a linkage genome scan using multipoint allele‐sharing methods to test for linkage in 219 families participating in the OCD Collaborative Genetics Study. When these families were stratified by proband's gender, suggestive linkage to chromosome 11p15 at marker D11S2362 (KACall = 2.92,P = 0.00012) was detected in families with male probands, but not in the ones with female probands. We have since conducted fine mapping with a denser microsatellite marker panel in the region of 11p15, and detected a significant linkage signal at D11S4146 (KACall = 5.08,P < 0.00001) in the families of male probands. Subsequently, 632 SNPs were genotyped spanning a 4.0 Mb region of the 1 LOD unit interval surrounding the linkage peak in the original families and an additional 165 families. Six SNPs were associated with OCD (P < 0.001): two SNPs were identified when all the families were included, and four SNPs only in male proband families. No SNP showed significant association with the OCD phenotype only in the families with a female proband. The results suggest a possible gender effect in the etiology of OCD. © 2008 Wiley‐Liss, Inc.
Air‐hole properties of calcite‐filled polypropylene copolymer films
Authors: Biswas Jagannath , Kim Hyun , Lee Byung Hyung , Choe Soonja
Published: April 2008

This work was designed to study the effects of inorganic calcite powder on structurally different copolymer [poly(propylene‐co‐ethylene)] and terpolymer [poly (propylene‐co‐ethylene‐co‐1‐butene)] matrices and the possibility of making a suitable porous composite film. The yield stress of the composites did not improve, but the modulus increased gradually with the filler loading. The theoretical and experimental modulus and yield stress of the composites provided evidence of filler and polymer adhesion behavior. The impact strength showed little enhancement up to a 20 wt % loading for the poly(propylene‐co‐ethylene‐co‐1‐butene) system. The number‐average, weight‐average, and z‐average air‐hole diameters were compared with respect to the draw ratio as well as the calcite loading. The morphology of a micromechanically deformed composite, studied with an image analyzer, revealed that the aspect ratio and area of the air holes increased linearly as a function of the draw ratio, but the change in the aspect ratio upon filler loading was not remarkable. A suitable loading of a filler up to 30 wt % was good for controlling the porosity in the composite films. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Augmenting the performance of acrylonitrile–butadiene–styrene plastics for low‐noise dynamic applications
Authors: Ganguly Anirban , Saha Swatilekha , Bhowmick Anil K. , Chattopadhyay Santanu
Published: April 2008

The main objective of this study was to enhance the performance of acrylonitrile–butadiene–styrene (ABS) plastics for dynamic structural applications, including those of automobile relevance. First, ABS was modified by blending with maleic anhydride grafted styrene–ethylene–butadiene–styrene block copolymer (MA‐g‐SEBS) in various proportions. Squeaking noise characteristics were evaluated by measurement of the frictional behavior in an in‐house fabricated friction testing apparatus, and the results are explained on the basis of the change in surface energy upon modification. Detailed dynamic mechanical analyses (strain, frequency, and temperature sweep) revealed significant improvements in the damping characteristics of the modified ABS, especially that modified with 10 wt % MA‐g‐SEBS, without much sacrifice in its mechanical strength. The modulus values predicted with Kerner's model of the blends were well correlated with the morphological changes upon modification. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
A comparative study of short nylon fiber—Natural rubber composites prepared from dry rubber and latex masterbatch
Authors: P. K. Bipinbal , Kutty Sunil K. N.
Published: April 2008

A novel method for the preparation of short nylon fiber–natural rubber composites was developed in which short fibers chopped to approximately 6 mm were incorporated in the latex stage and processed into sheet form. By this method, mixing cycle time was reduced without compromising the fiber dispersion. Fiber breakage during mixing was reduced. The new composites when compounded with a dry bonding system based on hexamethylenetetramine, resorcinol and hydrated silica (HRH) showed improved modulus, tensile strength and abrasion resistance compared to conventional composites. Tear strength, resilience, and compression set were similar to the conventional composites. SEM analysis indicated better interaction between matrix and fibers in the case of latex master batch. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Hydrogel characteristics of a novel temperature‐sensitive polymer, poly(N‐2‐methoxyisopropylacrylamide)
Authors: Şölener Musa
Published: April 2008

In this study, a novel temperature‐sensitive polymer, poly(N‐2‐methoxyisopropylacrylamide), PNMIPA, in the crosslinked hydrogel form was obtained. The monomer, N‐2‐methoxyisopropylacrylamide (NMIPA) was synthesized by the nucleophilic substitution reactions of acryloyl chloride with 2‐methoxyisopropylamine. Hydrogel matrix of PNMIPA was obtained by the bulk polymerization method. The bulk polymerization experiments were performed at +4°C, by using N,N‐methylenebisacrylamide (MBA) as crosslinker, polyethyleneglycol (PEG) 4000 as diluent, and potassium persulfate (KPS) and tetramethylethylenediamine (TEMED) as the initiator and accelerator, respectively. The same polymerization procedures were applied by changing monomer, initiator, crosslinker and diluent concentrations in order to obtain crosslinked gel structures having different temperature–sensitivity properties. The equilibrium swelling ratio of PNIMPA gel matrices at constant temperature increased with increasing initiator concentration and decreasing monomer concentration. The use of PEG 4000 as diluent in the gel synthesis resulted in about two times increase in equilibrium swelling ratios in the low temperature region. A decrease in the equilibrium swelling ratios of gel matrices started at 30°C and the decrease became insignificant at 55°C. Temperature‐sensitivities were determined in two different media. Distilled water medium was used in order to observe the temperature‐sensitivity of the gel clearly and the phosphate buffer medium was used in order to represent the temperature‐sensitive swelling behavior of the gel when it is used in biological media. Step effect was applied on ambient temperature in two opposite directions in order to examine the dynamic swelling and shrinking behaviors of the gels. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Polymeric thermal actuation using laminates based on polymer–clay nanocomposites
Authors: Chen Biqiong , Liu Shuo , Evans Julian R. G.
Published: April 2008

Polymer and polymer–clay nanocomposite laminates were prepared as transparent thermal actuators with possible uses in automatic aeration and ventilation or as thermal switches. Low levels of smectite clay addition reduced the thermal expansion coefficient of poly(methyl methacrylate) (PMMA) but retained optical clarity and reduced water absorption. X‐ray diffraction and transmission electron microscopy were used to confirm the formation of PMMA–clay nanocomposites, and dynamic mechanical analysis was used to measure the coefficients of thermal expansion. The experimental values of the radius of curvature of the laminates from cantilever bending tests were in good agreement with the theoretical predictions for composite bars with only 4 wt % (nominally 1.3 vol %) mineral reinforcement. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Synthesis and Structure of Monomeric, Trimeric, and Mixed Phenylcyanamides
Authors: Brand Harald , Mayer Peter , Schulz Axel , Soller Thomas , Villinger Alexander
Published: April 2008

In a new synthetic approach phenylcyanamide (Hpca) was synthesized by methylation of phenylthiourea followed by a basic work‐up. All products along the synthetic route have been fully characterized by means of NMR, IR, and X‐ray studies. The first structural report of neutral mixed crystals of phenylcyanamide containing monomeric and trimeric Hpca is presented. Examination of these intriguing mixed crystals revealed the formation of distinct layers of monomeric and trimeric Hpca. These layers are interconnected by weak hydrogen bonds. The trimer represents triphenylisomelamine, which readily isomerizes to the triphenylmelamine in the melt, in accord with computations at the B3LYP level, indicating an exothermic process (ΔH=−49.4 kcal mol−1). Pure trimeric Hpca (triphenylisomelamine) was obtained either by recrystallization of the mixed crystals from boiling water or by trimerization of monomeric Hpca in isopropanol for 12 h under reflux conditions. For comparison tritylcyanamide (Htca) and potassium phenylcyanamide as an [18]crown‐6 complex [K([18]crown‐6)pca] have been synthesized, and the solid‐state structures were determined using X‐ray diffraction techniques. The thermal behavior was studied by thermo‐analytical experiments. In agreement with the experimental results, computations predict an exothermic cyclotrimerization process for Hpca (ΔH=−41.3 kcal mol−1).
Botulinum toxin for recurrent anal fissure following lateral internal sphincterotomy
Authors: Brisinda G , Cadeddu F , Brandara F , Marniga G , Vanella S , Nigro C , Maria G
Published: April 2008

Background

The aim of the study was to evaluate the efficacy of botulinum toxin injection in the treatment of recurrent anal fissure following lateral internal sphincterotomy.

Methods

Eighty patients were treated with botulinum toxin (30 units Botox® or 90 units Dysport®), injected into two sites of the internal sphincter. Clinical and manometric results were recorded before and after treatment. If symptoms persisted at 2 months, the examiners could decide to re-treat the patient. The same preparation of serotype A of botulinum neurotoxin was used for reinjection.

Results

One month after injection there was complete healing in 54 patients (68 per cent). Eight patients (10 per cent) reported mild incontinence of flatus that had disappeared spontaneously within 2 months. At 2 months, 59 patients (74 per cent) had a healing scar. After reinjection, 11 of 21 re-treated patients reported mild incontinence to flatus that lasted for a few weeks and resolved spontaneously. Anorectal manometry at 1 month demonstrated a significant reduction in both resting anal pressure and maximum voluntary squeeze pressure (P < 0·001). There were no relapses during a mean value of 57·9 months of follow-up.

Conclusion

Botulinum toxin is efficacious in patients with recurrent anal fissure following lateral internal sphincterotomy.
Use of enoxaparin results in more haemorrhagic complications after breast surgery than unfractionated heparin
Authors: Hardy R G , Williams L , Dixon J M
Published: April 2008

Background

Low molecular weight heparin (LMWH) is used in preference to unfractionated heparin (UFH) for the prevention of postoperative thromboembolism in many UK surgical units. There are, however, conflicting reports on the relative risk of significant bleeding in surgical patients, and no data exist in the literature for patients undergoing breast surgery.

Methods

Data for patients in the Edinburgh Breast Unit with postoperative breast haematoma that needed surgical intervention were analysed for two 12-month intervals in which either UFH (2001) or LMWH (2005–2006) was used for thromboprophylaxis. Haematoma rates in the 6 months after UFH was reintroduced in 2006–2007 were also determined.

Results

The rate of haematoma requiring surgical intervention was 0·4 per cent (six of 1452 wounds) in patients who had UFH, compared with 1·8 per cent (32 of 1780 wounds) for LMWH. The rate fell to 0·5 per cent (four of 773 wounds) on reinstituting UFH. The relative risk of haematoma was significantly higher with LMWH than with UFH (4·00 (95 per cent confidence interval 1·97 to 8·11); P < 0·001). No significant postoperative thromboembolic complications were recorded.

Conclusion

LMWH thromboprophylaxis was associated with a significant increase in haemorrhagic complications after breast surgery compared with UFH.