bluuebunny/crossref_metadata_2025 huggingface dataset:
Managerial Styles and Institutional Control
Authors: Bartollas Clemens , Miller Stuart J. , Dinitz Simon
Published: December 2006

Based on a 30-year examination of managerial styles at a maximum-security training school in Ohio, this study examines three managerial styles that emerged: charismatic, bureaucratic, and technocratic. Extensive interviewing with staff members, some of whom had been present during the 30-year period, identified that the three basic managerial styles could be further divided into five categories: (a) charismatic control, (b) charismatic reform, (c) bureaucratic control, (d) bureaucratic reform, and (e) technocratic control. The thesis proposed in this article is that the management styles will, to a large degree, effect the quality of life that takes place within juvenile correctional institutions, especially training schools. The various management styles are evaluated concerning what they contributed to the quality of institutional care, and a number of general managerial recommendations based on the findings of this study are offered to guide the improvement of juvenile care in long-term training schools.
Nucleic Acid Therapeutics for Hematologic Malignancies—Theoretical Considerations
Authors: OPALINSKA JOANNA B. , KALOTA ANNA , CHATTOPADHYAYA JYOTI , DAMHA MASAD , GEWIRTZ ALAN M.
Published: December 2006

Abstract:  Our work is motivated by the belief that RNA targeted gene silencing agents can be developed into effective drugs for treating hematologic malignancies. In many experimental systems, antisense nucleic acids of various composition, including antisense oligodeoxynucleotides (AS ODNs) and short interfering RNA (siRNA), have been shown to perturb gene expression in a sequence specific manner. Nevertheless, our clinical experience, and those of others, have led us to conclude that the antisense nucleic acids (ASNAs) we, and others, employ need to be optimized with regard to intracellular delivery, targeting, chemical composition, and efficiency of mRNA destruction. We have hypothesized that addressing these critical issues will lead to the development of practical and effective nucleic acid drugs. An overview of our recent work which seeks to addresses these core issues is contained within this review.
Neuromuscular Therapeutics by RNA‐Targeted Suppression of ACHE Gene Expression
Authors: DORI AMIR , SOREQ HERMONA
Published: December 2006

Abstract: RNA‐targeted therapeutics offers inherent advantages over small molecule drugs wherever one out of several splice variant enzymes should be inhibited. Here, we report the use of Monarsen, a 20‐mer acetylcholinesterase‐targeted antisense agent with three 3′‐2′o‐methyl‐protected nucleotides, for selectively attenuating the stress‐induced accumulation of the normally rare, soluble “readthrough” acetylcholinesterase variant AChE‐R. Acetylcholine hydrolysis by AChE‐R may cause muscle fatigue and moreover, limit the cholinergic anti‐inflammatory blockade, yielding inflammation‐associated pathology. Specific AChE‐R targeting by Monarsen was achieved in cultured cells, experimental animals, and patient volunteers. In rats with experimental autoimmune myasthenia gravis, oral delivery of Monarsen improved muscle action potential in a lower dose regimen (nanomolar versus micromolar), rapid and prolonged manner (up to 72 h versus 2–4 h) as compared with the currently used small molecule anticholinesterases. In central nervous system neurons of both rats and cynomolgus monkeys, systematic Monarsen treatment further suppressed the levels of the proinflammatory cytokines interleukin‐1 (IL‐1) and IL‐6. Toxicology testing and ongoing clinical trials support the notion that Monarsen treatment would offer considerable advantages over conventional cholinesterase inhibitors with respect to dosing, specificity, side effects profile, and duration of efficacy, while raising some open questions regarding its detailed mechanism of action.
TLR9 and the Recognition of Self and Non‐Self Nucleic Acids
Authors: LAMPHIER MARC S. , SIROIS CHERILYN M. , VERMA ANJALI , GOLENBOCK DOUGLAS T. , LATZ EICKE
Published: December 2006

Abstract:  Toll‐like receptors (TLRs) are involved in the innate recognition of foreign material and their activation leads to both innate and adaptive immune responses directed against invading pathogens. TLR9 is intracellularly expressed in the endo‐lysosomal compartments of specialized immune cells. TLR9 is activated in response to DNA, in particular DNA containing unmethylated CpG motifs that are more prevalent in microbial than mammalian DNA. By detecting foreign DNA signatures TLR9 can sense the presence of certain viruses or bacteria inside the cell and mount an immune response. However, under certain conditions, TLR9 can also recognize self‐DNA and this may promote immune pathologies with uncontrolled chronic inflammation. The autoimmune disease systemic lupus erythematosis (SLE) is characterized by the presence of immune stimulatory complexes containing autoantibodies against endogenous DNA and DNA‐ and RNA‐associated proteins. Recent evidence indicates that the autoimmune response to these complexes involves TLR9 and the related single‐stranded RNA‐responsive TLRs 7 and 8, and therefore some breakdown in the normal ability of these TLRs to distinguish self and foreign DNA. Evidence suggests that immune cells use several mechanisms to discriminate between stimulatory and nonstimulatory DNA; however, it appears that TLR9 itself binds rather indiscriminately to a broad range of DNAs. We therefore propose that there is an additional recognition step by which TLR9 senses differences in the structures of bound DNA.
RNAi in Combination with a Ribozyme and TAR Decoy for Treatment of HIV Infection in Hematopoietic Cell Gene Therapy
Authors: LI MINGJIE , LI HAITANG , ROSSI JOHN J.
Published: December 2006

Abstract:  Combinatorial therapies for the treatment of HIV infection have changed the course of the AIDS epidemic in developed nations where the antiviral drug combinations are readily available. Despite this progress, there are many problems associated with chemotherapy for AIDS including toxicities and emergence of viral mutants resistant to the drugs. Our goal has been the development of a hematopoietic gene therapy treatment for HIV infection. Like chemotherapy, gene therapy for treatment of HIV infection should be used combinatorially. We have thus combined three different inhibitory genes for treatment of HIV infection into a single lentiviral vector backbone. The inhibitory agents engage RNAi via a short hairpin RNA targeting HIV tat/rev mRNAs, a nucleolar localizing decoy that binds and sequesters the HIV Tat protein, and a ribozyme that cleaves and downregulates the CCR5 chemokine receptor used by HIV for cellular entry. This triple combination has proven to be highly effective for inhibiting HIV replication in primary hematopoietic cells, and is currently on track for human clinical application.
CpG Oligonucleotides Improve the Protective Immune Response Induced by the Licensed Anthrax Vaccine
Authors: KLINMAN DENNIS M. , XIE HANG , IVINS BRUCE E.
Published: December 2006

Abstract:  Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs act as immune adjuvants, improving the response elicited by a coadministered vaccine. Combining CpG ODN with anthrax vaccine adsorbed (AVA, the licensed human vaccine) increases the speed, magnitude, and avidity of the resultant antibody response. IgG Abs against anthrax protective antigen (PA) protect mice, guinuea pigs, and rhesus macaques from infection.
Anti‐HIV Activity of Steric Block Oligonucleotides
Authors: IVANOVA GABRIELA , ARZUMANOV ANDREY A. , TURNER JOHN J. , REIGADAS SANDRINE , TOULMÉ JEAN‐JACQUES , BROWN DOUGLAS E. , LEVER ANDREW M.L. , GAIT MICHAEL J.
Published: December 2006

Abstract:  The unabated increase in spread of HIV infection worldwide has redoubled efforts to discover novel antiviral and virucidal agents that might be starting points for clinical development. Oligonucleotides and their analogs targeted to form complementary duplexes with highly conserved regions of the HIV RNA have shown significant antiviral activity, but to date clinical studies have been dominated by RNase H‐inducing oligonucleotide analog phosphorothioates (GEM 91 and 92) that have specificity and efficacy limitations. However, they have proven the principle that oligonucleotides can be safe anti‐HIV drugs. Newer oligonucleotide analogs are now available, which act as strong steric block agents of HIV RNA function. We describe our ongoing studies targeting the HIV‐1 trans‐activation responsive region (TAR) and the viral packaging signal (psi) with steric block oligonucleotides of varying chemistry and demonstrate their great potential for steric blocking of viral protein interactions in vitro and in cells and describe the first antiviral studies. Peptide nucleic acids (PNA) disulfide linked to cell‐penetrating peptides (CPP) have been found to have particular promise for the lipid‐free direct delivery into cultured cells and are excellent candidates for their development as antiviral and virucidal agents.
Multitargeted Approach Using Antisense Oligonucleotides for the Treatment of Asthma
Authors: ALLAKHVERDI Z. , ALLAM M. , GUIMOND A. , FERRARI N. , ZEMZOUMI K. , SÉGUIN R. , PAQUET L. , RENZI P. M.
Published: December 2006

Abstract:  Asthma is characterized by inflammation and hyperresponsiveness related to the accumulation of inflammatory cells, particularly eosinophils, within the airways. We tested the hypothesis that a multitargeted approach is better than a single‐targeted approach in a rat model of asthma. We simultaneously delivered oligonucleotides (ODNs) targeting the chemokine receptor CCR3 and the common beta chain subunit of the receptors for IL‐3, IL‐5, and GM‐CSF at the time of ovalbumin challenge in sensitized Brown Norway rats. Fewer eosinophils were detected in bronchoalveolar lavage (BAL) of rats treated with both ODNs as compared to each ODN alone. Moreover, airway responsiveness to LTD4 was significantly decreased at lower doses in the 2 ODN‐treated groups compared to a single ODN. As ODN therapy has raised concerns of toxicity we therefore examined ODNs prepared with modified DNA bases, specifically 2′amino, 2′deoxyadenosine (DAP) in place of adenosine. In vivo, administration of individual DAP‐ODN was efficacious in inhibiting airway hyperresponsiveness, whereas delivery of 2 DAP‐ODNs (targeting CCR3 and common beta chain) reduced the influx not only of eosinophils but also lymphocytes and macrophages in the lungs of rats as compared to the unmodified ODNs. Blocking multiple inflammatory pathways simultaneously is more effective in preventing eosinophilia and airway hyperresponsiveness than inhibiting either pathway alone. The challenges associated with the development of a product containing two oligonucleotides in humans are discussed.
RNA Silencing in the Struggle against Disease
Authors: PATZEL VOLKER , DIETRICH ISABELL , KAUFMANN STEFAN H.E.
Published: December 2006

Abstract:  Numerous acquired and hereditary diseases are caused by aberrant cellular or microbial gene expression. As a result of sequencing of the human genome and the genomes of various human pathogens, researchers have gained access to a large number of genes with residual functions. For functional validation of unknown genes, their functions can be specifically inhibited by antisense nucleic acids or small interfering RNAs (siRNAs) and the consequences of the functional loss, that is, the resulting phenotypes, can be analyzed. While antisense nucleic acids block the translation stoichiometrically by docking on the mRNA, siRNAs induce a highly effective cellular mechanism that causes catalytic destruction of several mRNA molecules by a single siRNA molecule. This mechanism, called RNA interference (RNAi), is only intrinsic to eukaryotic cells. Consequently, only eukaryotic target validation is pushed by RNAi whereas time‐consuming conventional knockout techniques or the less efficient antisense strategies have to be applied for prokaryotic target validation. We succeeded in triggering gene silencing by siRNA in prokaryotic cells. This opens promising perspectives regarding validation of prokaryotic gene functions.
SiRNA‐Mediated Selective Inhibition of Mutant Keratin mRNAs Responsible for the Skin Disorder Pachyonychia Congenita
Authors: HICKERSON ROBYN P. , SMITH FRANCES J. D. , IRWIN McLEAN W. H. , LANDTHALER MARKUS , LEUBE RUDOLF E. , KASPAR ROGER L.
Published: December 2006

Abstract:  RNA interference offers a novel approach for treating genetic disorders including the rare monogenic skin disorder pachyonychia congenita (PC). PC is caused by mutations in keratin 6a (K6a), K6b, K16, and K17 genes, including small deletions and single nucleotide changes. Transfection experiments of a fusion gene consisting of K6a and a yellow fluorescent reporter (YFP) resulted in normal keratin filament formation in transfected cells as assayed by fluorescence microscopy. Similar constructs containing a single nucleotide change (N171K) or a three‐nucleotide deletion (N171del) showed keratin aggregate formation. Mutant‐specific small inhibitory RNAs (siRNAs) effectively targeted these sites. These studies suggest that siRNAs can discriminate single nucleotide mutations and further suggest that “designer siRNAs” may allow effective treatment of a host of genetic disorders including PC.
Inhibition of Hepatitis C IRES‐Mediated Gene Expression by Small Hairpin RNAs in Human Hepatocytes and Mice
Authors: ILVES HEINI , KASPAR ROGER L. , WANG QIAN , SEYHAN ATTILA A. , VLASSOV ALEXANDER V. , CONTAG CHRISTOPHER H. , LEAKE DEVIN , JOHNSTON BRIAN H.
Published: December 2006

Abstract:  The ability of small hairpin RNAs (shRNAs) to inhibit hepatitis C virus internal ribosome entry site (HCV IRES)‐dependent gene expression was investigated in cultured cells and a mouse model. The results indicate that shRNAs, delivered as naked RNA or expressed from vectors, may be effective agents for the control of HCV and related viruses.
Cellular Dynamics of Antisense Oligonucleotides and Short Interfering RNAs
Authors: LEE LI KIM , DUNHAM BRANDEE M. , LI ZHUTING , ROTH CHARLES M.
Published: December 2006

Abstract:  We aim to compare quantitatively the dynamics of the effectiveness of antisense oligonucleotides (AS ODNs) versus short interfering RNAs (siRNAs) and relate their effectiveness to sequence metrics (e.g., predicted free energy of binding). AS ODNs against a quantitative model target, pd1EGFP (destabilized enhanced GFP [green fluorescent protein]), were selected using our thermodynamic model, and siRNA sequences were designed to be identical to the AS ODN sequences in the antisense strand. We evaluated d1EGFP inhibition in transiently and stably transfected Chinese hamster ovary (CHO) cells over time using flow cytometry. Overall, our results show that the rationally designed AS ODN and siRNA sequences proved effective inhibitors of GFP expression and suggest that certain regions of mRNA may be susceptible to both AS ODNs and siRNAs.
Anti‐VEGF Aptamer (Pegaptanib) Therapy for Ocular Vascular Diseases
Authors: NG EUGENE W.M. , ADAMIS ANTHONY P.
Published: December 2006

Abstract:  Vascular endothelial growth factor (VEGF) is a central regulator of both physiological and pathological angiogenesis. Pegaptanib, a 28‐nucleotide RNA aptamer specific for the VEGF165 isoform, binds to it in the extracellular space, leaving other isoforms unaffected, and inhibits such key VEGF actions as promotion of endothelial cell proliferation and survival, and vascular permeability. Pegaptanib already has been examined as a treatment for two diseases associated with ocular neovascularization, age‐related macular degeneration (AMD) and diabetic macular edema (DME). Preclinical studies have shown that VEGF165 alone mediates pathological ocular neovascularization and that its inactivation by pegaptanib inhibits the choroidal neovascularization observed in patients with neovascular AMD. In contrast, physiological vascularization, which is supported by the VEGF121 isoform, is unaffected by this inactivation of VEGF165. In addition, animal model studies have shown that intravitreous injection of pegaptanib can inhibit the breakdown of the blood–retinal barrier characteristic of diabetes and even can reverse this damage to some degree. These preclinical findings formed the basis for randomized controlled trials examining the efficacy of pegaptanib as a therapy for AMD and DME. The VEGF Inhibition Study in Ocular Neovascularization (VISION) trial comprising two replicate, pivotal phase 3 studies, demonstrated that intravitreous injection of pegaptanib resulted in significant clinical benefit, compared with sham injection, for all prespecified clinical end points, irrespective of patient demographics or angiographic subtype, and led to pegaptanib's approval as a treatment for AMD. A phase 2 trial has provided support for the efficacy of intravitreous pegaptanib in the treatment of DME.
Mechanism of PNA Transport to the Nuclear Compartment
Authors: STANKOVA LENKA , ZIEMBA AMY J. , ZHILINA ZHANNA V. , EBBINGHAUS SCOT W.
Published: December 2006

Abstract:  We evaluated the nuclear uptake of fluorescently labeled peptide nucleic acids and measured the binding of unlabeled peptide nucleic acids (PNAs) to the endogenous HER‐2/neu promotor in digitonin‐permeabilized SK‐BR‐3 cells. Fluorescently labeled PNAs readily enter the nucleus of digitonin‐permeabilized cells, and binding to the chromosomal target sequence was detected with a bis‐PNA. Nuclear uptake and target sequence binding were inhibited by N‐ethylmaleimide (NEM) and GTPγS. We conclude that PNAs are transported into the nucleus through an energy‐dependent process involving the nuclear pore complex.
Selection of Thioaptamers for Diagnostics and Therapeutics
Authors: YANG XIANBIN , WANG HE , BEASLEY DAVID W. C. , VOLK DAVID E. , ZHAO XU , LUXON BRUCE A. , LOMAS LEE O. , HERZOG NORBERT K. , ARONSON JUDITH F. , BARRETT ALAN D. T. , LEARY JAMES F. , GORENSTEIN DAVID G.
Published: December 2006

Abstract:  Thioaptamers offer advantages over normal phosphate ester backbone aptamers due to their enhanced affinity, specificity, and higher stability, largely due to the properties of the sulfur backbone modifications. Over the past several years, in vitro thioaptamer selection and bead‐based thioaptamer selection techniques have been developed in our laboratory. Furthermore, several thioaptamers targeting specific proteins such as transcription factor NF‐κB and AP‐1 proteins have been identified. Selected thioaptamers have been shown diagnostic promise in proteome screens. Moreover, some promising thioaptamers have been shown in preliminary animal therapeutic dosing to increase survival in animal models of infection with West Nile virus.
Negative Magneto-resistance Observed on an Ion-radical Salt of a TTF-based Spin-polarized Donor
Authors: Matsushita Michio M , Kawakami Hironori , Kawada Yuzo , Sugawara Tadashi
Published: December 2006

A novel diselena analogue of TTF-based spin-polarized donor was synthesized. An ion-radical salt of the donor electro-crystallized on an interdigitated electrode with 2 μm gap showed negative magneto-resistance below 15 K. This is the first example detecting the interaction between localized spin and conducting electron in a genuine organic system.
Fabrication and Magnetic Properties of Multiferroic BiFeO3 Nanotube Arrays
Authors: Xu Xueqin , Qian Tian , Zhang Genqiang , Zhang Tao , Li Guang , Wang Wei , Li Xiaoguang
Published: December 2006

Multiferroic BiFeO3 nanotube arrays have been successfully prepared by means of a sol–gel method utilizing porous anodic alumina templates. The magnetic field and temperature dependencies of magnetizations demonstrate the superparamagnetism behavior with the most sound evidence, which can be attributed to the uncompensated surface spins induced by the size effect.
Simple Vanadium(V) Catalyst for Oxidation of Alkane with O2 under Mild Conditions
Authors: Kobayashi Hirokazu , Yamanaka Ichiro
Published: December 2006

Selective oxidation of cyclohexane and adamantane was performed by simple V(5+) catalyst with 1 atm O2 in acetic acid at 338–393 K. UV–vis and electron spin resonance studies suggested that peroxide species on V(5+) functioned during the oxidation. The oxidation activity was enhanced three times for cyclohexane and 6.5 times for adamantane by addition of a small amount of CF3SO3H.
Direct Visible Spectral Analysis of Solid Samples by Optical Waveguide Spectroscopy due to Adsorbed Sample Molecules after Sublimation
Authors: Takahashi Hiromi , Fujita Kyoko , Ohno Hiroyuki
Published: December 2006

Visible spectra of solid samples were obtained by optical waveguide (OWG) spectroscopy. The spectra were confirmed to be due not to the powder samples themselves but to molecules sublimed from the solid samples and adsorbed on the waveguide. This result is supported by the observation that no spectrum was obtained from nonsublimed samples.
Preparation of Polymeric Nanocapsules by Gamma-ray-initiated Miniemulsion Polymerization
Authors: Wang Shijie , Yunchen  , Zhang Zhicheng
Published: December 2006

Hollow polystyrene (PS) nanocapsules were synthesized through gamma-ray-initiated miniemulsion polymerization by using an alkali-soluble polymeric surfactant (ASPS) as surfactant in the presence of hexadecane (HD). The results indicated that nanocapsules with different particle size and shell thickness could easily prepared by this method, and ASPS can promote the formation of completely hollow structures.
Low-valent Niobium-mediated Synthesis of Indenes: Intramolecular Coupling Reaction of CF3 Group with Alkene C–H Bond
Authors: Fuchibe Kohei , Mitomi Ken , Akiyama Takahiko
Published: December 2006

CF3 group of o-alkenyl-α,α,α-trifluorotoluenes underwent intramolecular coupling reaction with the alkene C–H bond under NbCl5/LiAlH4 system. Substituted indenes were obtained in good yields.
Chloroform Is Not Solvent but Activator for Cobalt Complex Catalyst of Enantioselective Borohydride Reduction
Authors: Kokura Ai , Tanaka Saiko , Teraoka Haruna , Shibahara Atsushi , Ikeno Taketo , Nagata Takushi , Yamada Tohru
Published: December 2006

For the enantioselective borohydride reduction of carbonyl compounds catalyzed by the optically active ketoiminatocobalt complexes, chloroform has been employed as a unique solvent for achieving a high enantioselectivity, whereas it was found that a catalytic amount of chloroform effectively activated the present catalytic system to convert various ketones into the corresponding reduced product with a high ee in the THF solvent.
A New Synthetic Method for Methyl Ketones from Carboxylic Acids Using Metallic Strontium and Methyl Iodide
Authors: Miyoshi Norikazu , Matsuo Tsuyoshi , Asaoka Masashi , Matsui Aki , Wada Makoto
Published: December 2006

Carboxylic acids reacted with metallic strontium and methyl iodide to give methyl ketones preferentially in moderate to good yields.
Asymmetric Autocatalysis Induced by Octahedral Tris(acetylacetonato)chromium(III) Complex as a Homogeneous Chiral Initiator
Authors: Kawasaki Tsuneomi , Omine Toshiki , Sato Mirai , Morishita Yosuke , Soai Kenso
Published: December 2006

Enantioselective addition of diisopropylzinc to 2-t-butylethynylpyrimidine-5-carbaldehyde in the presence of chiral Δ- and Λ-tris(acetylacetonato)chromium(III) complex [Cr(acac)3] affords highly enantiomerically enriched (S)- and (R)-5-pyrimidyl alkanols, respectively, in conjunction with asymmetric autocatalysis. The absolute configuration of the corresponding 2-t-butylethynyl-5-pyrimidyl alkanol is dependent upon the chirality of the octahedral chromium(III) complex.
Studies toward Stable Analogues of Guanofosfocins. Synthesis of the Protected Derivative of 8-(5a-Carba-α-d-mannopyranosyloxy)purine Nucleoside
Authors: Sugimura Hideyuki , Hosogai Naoya
Published: December 2006

As a preliminary study directed towards the synthesis of a stable analogue of the guanofosfocins, a methylene analogue of the endocyclic oxygen atom in the mannose moiety, was designed. The construction of the pseudo-α-mannosyl linkage at the 8-position of the purine nucleoside was accomplished by the regioselective ring-opening substitution of the 1,2-O-cyclic sulfate derivative of 5a-carba-mannopyranose.
An Expeditious Synthesis of Lasofoxifene and Nafoxidine via the Novel Three-component Coupling Reaction
Authors: Sano Yoshiyuki , Nakata Kenya , Otoyama Takafumi , Umeda Sei , Shiina Isamu
Published: December 2006

The simple and efficient synthesis of lasofoxifene (4), a possible candidate for alleviating osteoporosis, via the novel three-component coupling reaction among 4-pivaloyloxybenzaldehyde (5), cinnamyltrimethylsilane (6), and anisole in the presence of HfCl4 is illustrated. The successive cationic cyclization of the coupling product, olefin formation, and migration of the double-bond are performed to afford the common synthetic intermediate of lasofoxifene (4) and nafoxidine (3) via a very concise procedure.
Effective Synthesis of 5-Substituted Butenolide Derivatives by Using Cinchonidine-derived Quaternary Ammonium Phenoxide Catalyst
Authors: Nagao Hitoshi , Yamane Yoshinobu , Mukaiyama Teruaki
Published: December 2006

A vinylogous aldol-type reaction between 4-methyl-2-(trimethylsiloxy)furan and aldehydes catalyzed by cinchonidine-derived quaternary ammonium phenoxide proceeded smoothly to afford the corresponding 5-substituted butenolide derivatives in high yields with good to excellent diastereo- and enantio-selectivities.
Number of Osteoporotic Sites and Fracture Risk Assessment: A Cohort Study From the Manitoba Bone Density Program
Authors: Leslie William D , Tsang James F , Caetano Patricia A , Lix Lisa M ,   for the Manitoba Bone Density Program
Published: December 2006

Site-discordance in BMD assessment is common and significantly affects patient categorization. Greater number of osteoporotic sites correlates with lower T scores at each index site. This largely explains the positive association between number of osteoporotic sites and fracture risk.

Introduction: Site-discordance in BMD is common when used to classify patients based on a cut-off T score of −2.5. It is unclear whether fracture risk assessment is improved by considering BMD information from multiple sites. Our objective was to assess the contribution of number of osteoporotic sites to overall fracture risk.

Materials and Methods: The study population was drawn from the regionally based clinical database of the Manitoba Bone Density Program that includes all clinical DXA test results for the Province of Manitoba, Canada. Analyses were limited to 16,505 women ≥50 years of age at the time of baseline DXA of the spine (L1–L4) and hip (three sites). During follow-up (3.2 ± 1.5 years), longitudinal health service records showed 765 women with at least one osteoporotic fracture code (hip, forearm, spine, or humerus).

Results: Of 5012 women classified as osteoporotic by at least one site (T score −2.5 or lower), almost one half (2370; 47%) were abnormal at only a single site. Among the 1856 women with an osteoporotic total hip measurement, mean total hip T scores decreased as the number of additional osteoporotic sites increased (−2.58, no other osteoporotic sites; −2.69, one other site; −2.87, two other sites; −3.17, three other sites; Spearman r = −0.44, p < 0.0001). Age-adjusted fracture risk from a Cox proportional hazards model increased as the number of osteoporotic sites increased (p < 0.0001), but number of osteoporotic sites was no longer an independent predictor after total hip BMD was included as a covariate (p = 0.19). Covariate adjustment for other sites of BMD measurement attenuated, but did not eliminate, the effect of number of osteoporotic sites.

Conclusions: Site-discordance is common and significantly affects patient categorization when different skeletal sites are used for diagnosis. Greater number of osteoporotic sites correlates with lower T scores at each index site. This largely explains the positive association between number of osteoporotic sites and fracture risk.
Circadian Oscillation of Gene Expression in Murine Calvarial Bone
Authors: Zvonic Sanjin , Ptitsyn Andrey A , Kilroy Gail , Wu Xiying , Conrad Steven A , Scott L Keith , Guilak Farshid , Pelled Gadi , Gazit Dan , Gimble Jeffrey M
Published: December 2006

The genes encoding the core circadian transcription factors display an oscillating expression profile in murine calvarial bone. More than 26% of the calvarial bone transcriptome exhibits a circadian rhythm, comparable with that observed in brown and white adipose tissues and liver. Thus, circadian mechanisms may directly modulate oxidative phosphorylation and multiple metabolic pathways in bone homeostasis.

Introduction: Although circadian rhythms have been associated historically with central regulatory mechanisms, there is emerging evidence that the circadian transcriptional apparatus exists in peripheral tissues. The aim of this study was to determine the presence and extent of circadian oscillation in the transcriptome of murine calvarial bone.

Materials and Methods: Cohorts of 8-week-old male AKR/J mice were maintained in a controlled 12-h light:12-h dark cycle on an ad libitum diet for 2 weeks. Groups of three mice were killed every 4 h over a 48-h period. The level of gene expression at successive times-points was determined by quantitative RT-PCR and Affymetrix microarray. Data were analyzed using multiple statistical time series algorithms, including Cosinor, Fisher g-test, and the permutation time test.

Results: Both the positive (Bmal1, Npas2) and negative (Cry1, Cry2, Per1, Per2, Per3) elements of the circadian transcriptional apparatus and their immediate downstream targets and mediators (Dbp, Rev-erbα, Rev-erbβ) exhibited oscillatory expression profiles. Consistent with findings in other tissues, the positive and negative elements were in antiphase relative to each other. More than 26% of the genes present on the microarray displayed an oscillatory profile in calvarial bone, comparable with the levels observed in brown and white adipose tissues and liver; however, only a subset of 174 oscillating genes were shared among all four tissues.

Conclusions: Our findings show that the components of the circadian transcriptional apparatus are represented in calvarial bone and display coordinated oscillatory behavior. However, these are not the only genes to display an oscillatory expression profile, which is seen in multiple pathways involving oxidative phosphorylation and lipid, protein, and carbohydrate metabolism.
Topochemical investigations of wood extractives and their influence on colour changes in American black cherry (Prunus serotina Borkh.)
Authors: Mayer Ingo , Koch Gerald , Puls Jürgen
Published: December 2006

The topochemical distribution of accessory compounds responsible for wood colouration during heartwood formation and processing of black cherry (Prunus serotina) is restricted to the axial and ray parenchyma cells. (+)-Catechin, taxifolin, aromadendrin, eriodictyol, naringenin, 4′-methoxynaringenin and prunin were identified in acetone/water extracts. However, the colour of wood after extraction is still reddish-brown, indicating that the coloured material is polymeric (cross-linked, condensed). It was demonstrated that (+)-catechin plays a pivotal role in the development of heartwood colour. Its concentration at the sapwood/heartwood boundary decreases, presumably due to the formation of non-soluble polymeric proanthocyanidins. Heat treatment of heartwood during veneer production intensifies the reddish-brown heartwood colour, probably by promoting the polymerisation of (+)-catechin and other flavonoid monomers.
Wound effects in the xylem of poplar: A UV microspectrophotometric study
Authors: Frankenstein Claus , Schmitt Uwe
Published: December 2006

Cell wall modifications in vessels and fibres of wound wood ofPopulus tremulaL.×P. tremuloidesMichx. formed after mechanical wounding have been examined by light microscopy, transmission electron microscopy, and UV microspectrophotometry (in scanning and point measurement mode), mainly focusing on the lignin distribution. With this goal, wound xylem within lateral wound callusis was collected after response periods of up to 23 months. Vessels and fibres in wound xylem deviated from their usual axial orientation. Vessels within the wound xylem were smaller in diameter and shorter in length. Xylem fibres were also shorter and developed thicker walls, especially in tissue adjacent to the wound. Cell walls and cell corners of these fibres showed on average a higher lignin content and a modified lignin composition. These wall changes probably enhance disease resistance of the wound tissue. With increasing distance from the wound edge, the modifications diminished and finally disappeared.
Morphological and chemical characterisation of the G-layer in tension wood fibres of Populus tremula and Betula verrucosa: Labelling with cellulose-binding module CBM1 Hj Cel7A and fluorescence and FE-SEM microscopy
Authors: Daniel Geoffrey , Filonova Lada , Kallas Åsa M. , Teeri Tuula T.
Published: December 2006

The gelatinous layer (G-layer) formed on the lumen wall in early- and latewood fibres of poplar and birch tension wood was characterised using a novel molecular marker specific for crystalline cellulose in conjunction with fluorescence and FE-SEM microscopy. Crystalline cellulose was localised using a cloned Cel7A cellulose-binding module (CBM1
Hj

Cel7A) from the fungus Hypocrea jecorina conjugated directly to FITC/TRITC or indirectly via a secondary antibody conjugated to FITC for fluorescence microscopy or to gold/silver for FE-SEM. With the CBM1
Hj

Cel7A conjugate, the G-layer was clearly distinguished from other secondary cell-wall layers as a bright green layer visible in fibres of tension wood in fluorescence microscopy. FEM-SEM images revealed the supramolecular architecture of the G-layer of poplar wood, which consists of well-defined, often concentrically orientated, cellulose aggregates of the order of 30–40 nm. The cellulose aggregates typically have a microfibril angle of almost 0°. Studies on cellulose marked with CBM1
Hj

Cel7A followed by Au labelling and Ag enhancement complemented the fluorescence observations. The studies demonstrate the usefulness of this novel molecular marker for crystalline cellulose in situ, which was previously difficult to localise. Further proof of distinct cellulose aggregates was observed.
Iron-reducing capacity of low-molecular-weight compounds produced in wood by fungi
Authors: Goodell Barry , Daniel Geoffrey , Jellison Jody , Qian Yuhui
Published: December 2006

Birch and pine wood specimens were colonized by individual isolates of 12 brown-rot, 26 white-rot, six soft-rot and four blue (sap)-stain fungi. Homogenized wood was subsequently extracted in 75% ethyl acetate and centrifuged. The filtered extracts were analyzed for their iron-reducing capabilities using a ferrozine-based assay. Agar fungal cultures were also examined directly using a spot test for iron reduction. Extracts from wood colonized by brown-rot fungi showed significantly greater iron-reducing capability than extracts from wood colonized by white-rot or non-decay fungi. Results of the spot test ratings were highly variable, but in general the greatest color responses were associated with the brown-rot cultures. The ability of brown-rot fungi to produce compounds and/or modify the wood components that reduce iron is of relevance to the “chelator-mediated Fenton mechanism” that has been advanced as a theory for the non-enzymatic degradation of wood by brown-rot fungi.
Analysis of the hyphal load during early stages of wood decay by basidiomycetes in the presence of the wood preservative fungicides CuSO4 and cyproconazole
Authors: Vesentini Damiano , Dickinson David J. , Murphy Richard J.
Published: December 2006

This study considers variations in hyphal load in decaying wood in the presence of the fungicides CuSO4and cyproconazole. Variations in the chitin content of hyphae following exposure to both fungicides have been detected. Increasing concentrations of CuSO4and cyproconazole in wood caused an increase in the amount ofN-acetyl glucosamine in the mycelia ofCoriolus versicolorandGloeophyllum trabeum, which may be associated with increased deposition of chitin. This may in turn be an expression of the formation of a thicker cell wall at increased fungicide concentrations. Low concentrations of both fungicides also caused an increase in the amount of mycelium produced byG. trabeum. However, the same concentrations were effective at preventing mass loss, indicating that the fungal mycelium was less effective at decaying wood, despite being present in relatively large amounts. In the case ofC. versicolor, this effect was not observed, as increasing concentrations of both fungicides caused an initial decrease in the amount of mycelium, followed by a recovery phase at intermediate chemical concentrations. Again, mass loss was greatly inhibited by the presence of low concentrations of both fungicides.
Prediction of natural durability of commercial available European and Siberian larch by near-infrared spectroscopy
Authors: Sykacek Eva , Gierlinger Notburga , Wimmer Rupert , Schwanninger Manfred
Published: December 2006

The natural durability of larch wood is described as being highly variable, ranging from non-durable to durable. In this study, FT-NIR spectroscopy was investigated for its ability to predict the natural durability of commercially available larch wood. Samples originated from approximately 60 European and 25 Siberian larch trees, provided by three Austrian-based wood industries. Natural durability tests were performed using the test fungi Gloeophyllum trabeum and Coniophora puteana. FT-NIR spectra were recorded and average spectra were calculated for calibration modelling. The models were strong [R2 (CV)=70.7–95.19, RMSEP=0.063–0.026] and showed better suitability with spectra acquired from radial surfaces compared to those from axial surfaces. The prediction model was valid across larch species (European and Siberian), so that exact knowledge of the growth and site conditions was not required.
Retention of Bacillus cereus and its toxin, cereulide, in cellulosic fibres
Authors: Hoornstra Douwe , Dahlman Olof , Jääskeläinen Elina , Andersson Maria A. , Weber Assi , Aurela Birgit , Lindell Henry , Salkinoja-Salonen Mirja S.
Published: December 2006

Bacillus cereusis the only pathogen that is occasionally found in paper and paper products, but there is no information on its prevalence. The aim of this work was to obtain data for a risk assessment ofB. cereusin cellulosic fibre-based products. Handsheets were formed using laboratory papermaking equipment from stocks admixed withB. cereus.Then the distribution ofB. cereusand its heat-stable toxin, cereulide, between the fibre web and the wire filtrate was measured. The handsheets retained 5% of the vegetative cells and spores ofB. cereusand 10–15% of the cereulide. Transfer of cereulide into food or drink through contact with paper was investigated using ethanol and hot and cold water as food and drink simulants. Less than 0.2% of the cereulide from handsheets was recovered from hot and cold water, as measured by LC/MS and the boar sperm bioassay. Total immersion in 95% v/v ethanol leached nearly all cereulide present in the paper. The results obtained with the bioassay were equivalent to those obtained by LC/MS for the leachates, indicating that cereulide retained its toxicity through the handsheet-making process. The results indicate that cereulide in pulps is probably also present in paper products made from them, but the concentration appears to be too low to be relevant in terms of toxicity.
Chemical structure elucidation of total lignins in woods. Part II: Analysis of a fraction of residual wood left after MWL isolation and solubilized in lithium chloride/N,N-dimethylacetamide
Authors: Furuno Hiroyuki , Takano Toshiyuki , Hirosawa Shuichi , Kamitakahara Hiroshi , Nakatsubo Fumiaki
Published: December 2006

The residual wood meal left after extraction of milled wood lignin (MWL) was extracted with lithium chloride/N,N-dimethylacetamide, which is a well-known cellulose solvent, to afford a soluble fraction (cellulose-lignin fraction; CL) in 36.7% yield. The UV elution curve of CL acetate has the same profile as its refractive index (RI) elution curve. After partial degradation of CL by cellulase, the UV elution curve of CL acetate shifted to the low-molecular-mass region in a similar fashion as its RI elution curve. These results indicate that the lignin in CL (CL lignin) is chemically bonded to cellulose. On the other hand, half of the CL lignin was removed by xylanase treatment. It was concluded that approximately half of the CL lignin existed as a lignin-cellulose-xylan complex.
Amphiphilicity of a lignin-carbohydrate complex
Authors: Uraki Yasumitsu , Usukura Yuriko , Kishimoto Takao , Ubukata Makoto
Published: December 2006

A lignin-carbohydrate complex (LCC) fraction isolated from the residue of milled wood lignin extraction of birch was found to form self-aggregates in water. The aggregates had relatively strong hydrophobic domains, comparable to the hydrophobicity of 80% ethanol. Dynamic light scattering analysis showed that the aggregates were transformed into small particles by sonication with a number-average diameter of 43.7±9.6 nm, and were stable in water. The surface pressure (π)-surface area (A) profile showed that the LCC also formed a monolayer on the water surface. Based on these results, we suggest that the LCC is amphiphilic in nature, despite its insolubility in low-polarity organic solvents.
Spatial relationships between polymers in Sitka spruce: Proton spin-diffusion studies
Authors: Altaner Clemens , Apperley David C. , Jarvis Michael C.
Published: December 2006

The spatial arrangement of polymers in Sitka spruce (Picea sitchensis) was investigated by NMR proton spin-diffusion studies, supplemented by deuterium-exchange experiments monitored by FTIR spectroscopy. The FTIR spectra of earlywood sections after vapour-phase exchange with deuterium oxide showed that 43% of the hydroxyl groups were accessible to deuteration. This value is lower than predicted in the absence of aggregation of cellulose microfibrils into larger units, but greater than the predicted level of deuteration if 3.5-nm microfibrils surrounded by hemicellulose sheaths were aggregated into 4×4 arrays without space for deuterium oxide to penetrate between the microfibrils. The rate of proton spin diffusion between lignin and cellulose was consistent with the presence of microfibril arrays with approximately these dimensions and with lignin located outside them, in both earlywood and latewood. Proton spin-diffusion data for hemicelluloses were complicated by difficulties in assigning signals to glucomannans and xylans, but there was evidence for the spatial association of one group of hemicelluloses, including acetylated glucomannans, with cellulose surfaces, while another group of hemicelluloses was in spatial proximity to lignin. These data are consistent with a number of nanoscale models for the Sitka spruce cell wall, including a model in which glucomannans are associated with microfibril surfaces within the aggregate and water can penetrate partially between these surfaces, and one in which all non-cellulosic polymers and water are excluded from the interior of each microfibril aggregate.
Pilot investigation of the mechanical properties of wood flooring paint films by in situ imaging nanoindentation
Authors: Jiang Zehui , Yu Yan , Qin Daochun , Wang Ge , Zhang Bo , Fu Yuejin
Published: December 2006

In situ imaging nanoindentation was used to characterize the mechanical properties of pure paint films on eight types of plywood-based flooring with different wear resistance. Correlation between the mechanical properties of paint films and the wear resistance of wood-based floorings was investigated. The average modulus of elasticity (MOE) and hardness of the paint film tested were 3.33–5.77 and 0.19–0.34 GPa, respectively. A strong linear relationship (r2=0.87) between the MOE and hardness of the paint film was found. Neither of these properties was directly correlated to the macro wear resistance of the floorings. Moreover, the composite index H1.5E-1– frequently used as an indicator of wear resistance in materials science – was not useful either in evaluating the wear resistance of wood floorings. However, in situ imaging nanoindentation was suitable for characterization of the mechanical properties of paint films, although this technique was not suited for direct evaluation of the wear resistance of wood floorings.
Legal aspects of “black biotechnology” – Counter-terrorism between prevention and use of biotechnological products
Authors: Lachmayer Konrad
Published: December 2006

This article describes the legal framework as well as legal limits within biotechnological counter-terrorism with a special focus on these points:
Petrography: Distinguishing Natural Cement from Other Binders in Historical Masonry Construction Using Forensic Microscopy Techniques
Authors: Walsh JJ
Published: December 2006

Petrography is a microscopy method providing a revealing view of inorganic materials. Hydraulic cements rarely react completely and telltale residuals are detected by the petrographer. Combined with accurate chemical analysis, the petrographic examination not only identifies the original components but often allows for a quantitative assessment of material proportions. Such data are crucial for the proper conservation and rehabilitation of historic masonry structures. Portland cement, lime, and natural cement in any combination may be present in historic American masonry construction. A comprehensive petrographic examination serves as the basis for the successful creation and implementation of an historically accurate project specification. This paper provides insight into how various binders are properly distinguished. While technical data will be offered, the goal is to provide the architect or conservator with a general understanding of the methods employed by the petrographer and to demystify the often complicated mortar analysis report.
FOTOSSÍNTESE DE LARANJEIRA 'VALÊNCIA' ENXERTADA SOBRE QUATRO PORTA-ENXERTOS E SUBMETIDA À DEFICIÊNCIA HÍDRICA
Authors: MEDINA CAMILO LÁZARO , MACHADO EDUARDO CARUSO , PINTO JOSÉ MARIA
Published: December 2006

Avaliou-se a taxa de assimilação de CO2 e o potencial da água nas folhas, em laranjeiras `Valência' com 18 meses de idade, em vasos, enxertadas em quatro tipos de porta-enxertos: limoeiro `Cravo', Trifoliata, citrange `Troyer' e tangerina `Cleópatra'. A deficiência hídrica foi obtida pela suspensão da irrigação até que a taxa de assimilação de CO2 atingisse valores aproximadamente nulos, quando, então, foram reirrigadas. Avaliou-se, também, a condutividade hidráulica dos porta-enxertos utilizados. Sem deficiência hídrica, a taxa de assimilação de CO2 foi menor nas plantas sobre os porta-enxertos `Troyer' e `Cleópatra', quando comparadas àquelas plantas sobre limoeiro `Cravo', que não se diferenciaram do Trifoliata. As maiores taxas de assimilação de CO2 foram observadas por volta das 11h, com 8 mmol/m2.s, seguidas por uma diminuição, provavelmente, em vista do aumento do déficit de pressão de vapor e da temperatura ambiente entre as 11 e as 14h. Após a suspensão da irrigação, a queda do potencial da água na folha foi semelhante em todas as plantas, independentemente dos porta-enxertos usados, porém, sobre `Cravo', a taxa de assimilação de CO2 decaiu mais rapidamente e recuperou-se mais vagarosamente. As plantas sobre esse porta-enxerto apresentaram, durante todo o período de deficiência hídrica, menor taxa de assimilação de CO2 que aquelas sobre Trifoliata e `Cleópatra', e semelhante ao `Troyer'. As plantas sobre Trifoliata recuperaram-se em três dias, enquanto as outras não se recuperaram totalmente. A condutividade hidráulica foi superior para o limoeiro `Cravo' e semelhante entre os demais porta-enxertos.