bluuebunny/crossref_metadata_2025 huggingface dataset:
An Examination of the Effects of Organizational Norms, Organizational Structure, and Environmental Uncertainty on Entrepreneurial Strategy
Authors: Russell Robert D. , Russell Craig J.
Published: March 2006

Investigators have examined the impact of organizations' structural and environmental characteristics on innovation. We developed a measure of the innovation management process, specifically organizational norms toward innovation, and examined its relationship to innovation (as measured by effective entrepreneurial strategy) in combination with measures of organizational structure and environment. Survey responses from respondents within 77 strategic business units were analyzed. Innovation norms, degree of decentralization in organizational structure, and environmental uncertainty explained significant and meaningful variance in entrepreneurial strategy. Interestingly, correlations between success of entrepreneurial strategy and (a) organizational structure and (b) environmental uncertainty approach zero when innovation-related norms are partialled out. Implications are discussed for the integration of this previously unexamined process variable innovation norms-to extend theories of innovation and corporate entrepreneurship.
Interorganizational and Collective Strategies in Small Firms: Environmental Effects and Performance
Authors: Dollinger Marc J. , Golden Peggy A.
Published: March 2006

This study provides evidence that collective strategy is prevalent in small firms in fragmented industries. COMPUSTAT data were combined with afield survey of small manufacturingfirms to test hypotheses concerning the relative frequencies of various collective strategies, the effects of environmental variables on collective activity, and the contribution of collective behavior to firm performance. Results indicate that agglomerate and organic collective strategies are the most frequently employed, and that munificent environments were positively associated with collective behavior and performance. Complex environments were negatively associated with collective strategy and no effect was found for volatile environments. The study also discusses methodological issues concerning the use of the COMPUSTAT database, and the usual practice of omitting cases with missing financial information.
Shareholder Value and Investment Strategy Using the General Portfolio Model
Authors: Slater Stanley F. , Zwirlein Thomas J.
Published: March 2006

Portfolio planning has been the subject of much debate, but little testing in strategic management. Building on the assumptions that relative ROA and sales growth are valid indicators of competitive position and industry attractiveness, this study examines whether an investment strategy that is consistent with prescriptions from the general portfolio model is associated with excess returns to shareholders. Evidence reported in this study indicates that this strategy is actually associated with subpar returns to shareholders. The implications of this finding for scholars and managers are discussed.
The Social Implications of Punishing Unethical Behavior: Observers' Cognitive and Affective Reactions
Authors: Trevino Linda Klebe , Ball Gail A.
Published: March 2006

This experiment investigated how punishment of varying severity (no punishment, appropriate punishment, and harsh punishment) in response to unethical organizational behavior influenced observers' outcome expectancies, justice evaluations, and emotional responses. Results suggested that only the harshest disciplinary response influenced outcome expectancies. In addition, observers' justice evaluations and emotional responses were generally most positive in the harshest vicarious punishment condition. Implications for future research and management practice are discussed.
Pulp and Paper Fiction: On the Discursive Legitimation of Global Industrial Restructuring
Authors: Vaara Eero , Tienari Janne , Laurila Juha
Published: March 2006

Despite the central role of legitimacy in social and organizational life, we know little of the subtle meaning-making processes through which organizational phenomena, such as industrial restructuring, are legitimated in contemporary society. Therefore, this paper examines the discursive legitimation strategies used when making sense of global industrial restructuring in the media. Based on a critical discourse analysis of extensive media coverage of a revolutionary pulp and paper sector merger, we distinguish and analyze five legitimation strategies: (1) normalization, (2) authorization, (3) rationalization, (4) moralization, and (5) narrativization. We argue that while these specific legitimation strategies appear in individual texts, their recurring use in the intertextual totality of the public discussion establishes the core elements of the emerging legitimating discourse.
Effects of Changing Environment and Loading Speed on Mechanical Behavior of FRP Composites
Authors: Ray B. C.
Published: March 2006

Durability of fiber reinforced polymer composites (FRP) are controlled by the durability of their constituents: reinforcement fibers, resin matrices, and the status of interfaces. A great deal of research has been focused on attempting to assess the relationship between interfacial structure and properties of fiber-matrix composites. It is at the interfacial area where stress concentration develops because of differences in the thermal expansion coefficients between the reinforcement and the matrix phase. A significant mismatch in the environmentally induced degradation of matrix and fiber leads to the evolution of localized stress and strain fields in the FRP composite. The present investigation aims to study the effects of changing hygrothermal conditioning cycles (either by changing relative humidity (RH) and keeping the temperature constant, or by changing the temperature while RH the same is maintained) on moisture gain/loss kinetics and on interlaminar shear strength (ILSS) of varied weight fraction glass fiber reinforced epoxy and polyester matrices composites. The mechanical assessment is extended to evaluate the loading rate sensitivity of hygrothermally shocked glass/epoxy and glass/polyester laminates at 2 and 50 mm/min crosshead speeds, respectively. Observations on absorption/desorption kinetics are noticed to be dependent on the nature of hygrothermal shock cycle and on the weight fraction of fiber reinforcement. The results of mechanical performance are statistically significant at different stages of conditioning. Shear values are found to be greater at higher crosshead speed for all undertaken situations. Mechanical responses are observed to be dependent on the matrix resin and the type of hygrothermal shock cycle. Very little and limited literature is open to address the important interactions of polymer composites with this kind of realistic environmental situation.
Simulation of Mold Filling in Simultaneous Resin Injection/Compression Molding
Authors: Chang Chih-Yuan
Published: March 2006

In the present article, an open gap is present between the fibrous reinforcements and the upper mold during the filling stage of resin injection/compression molding (I/CM). Thus resin can quickly fill up the gap. After that, the mold platens are brought together and drive the resin through the preform. The resin motion in the gap is simplified using the Hele-Shaw flow model, while Darcy’s law is used to calculate the flow fields in the fiber mats. The numerical simulation is based on the body-fitted finite element method (FEM). Results show that the resin injection time is short and most filling time is elevated to the closing of the cavity in the simultaneous I/CM filling process. Small gap size and high compression speed can be used to achieve the minimum mold filling time. However, the improper process parameters can cause the incomplete filling or reversed flow at the gate. In order to avoid the above conditions, the restrictive conditions of simultaneous I/CM are also discussed. The simultaneous I/CM can reduce either the mold filling time or injection pressure significantly compared to resin transfer molding (RTM).
Recycle Polypropylene (RPP) - Wood Saw Dust (WSD) Composites - Part 1: The Effect of Different Filler Size and Filler Loading on Mechanical and Water Absorption Properties
Authors: Khalil H. P. S. A. , Shahnaz S. B. Sharifah , Ratnam M. M. , Ahmad Faiz , Fuaad N. A. Nik
Published: March 2006

The compounding of recycled polypropylene (RPP) and wood saw dust (WSD) are carried out using five different filler loadings (0, 10, 20, 30, 40, and 50%) with three WSD filler sizes (100, 212, and 300 mm). The composites are mixed and extruded using Haake Rheodrive 500 twin screw extruder. The mechanical and water absorption properties of composites are characterized accordingly. The results show that composites with a smaller particle size (100 mm) have remarkably higher properties compared to others (212 and 300 mm). Composites filled up to 30% WSD exhibits improved mechanical properties but the value dramatically decreased above 30% filler loading. The evidence of fiber-matrix interphase is analyzed using scanning electron microscope (SEM).
Influence of Modified Phenolic Resins on the Fade and Recovery Properties of the Friction Materials: Supportive Evidence Multiple Criteria Decision-making Method (MCDM)
Authors: Nidhi  , Satapathy B. K. , Bijwe J. , Majumdar N.
Published: March 2006

Multiple criteria decision-making method (MCDM), called balancing and ranking method, is employed for the ranking of five non asbestos fiber reinforced organic friction materials (FMs). This variant of MCDM uses three steps to derive a transitive overall final order of a finite set of options. First, an outranking matrix is derived in which pairwise comparison indicates the frequency with which one option is superior to all other options based on each criterion. Second, the outranking matrix is triangularized to obtain an implicit pre ordering or provisional order of options. Third, the provisional order of options is subjected to various screening and balancing operations that require sequential application of a balancing principle to the advantage and disadvantage table.

Five FMs based on five different phenolic resins are evaluated on Krauss friction tester according to ECE R-90 regulation (Economic Commission for European regulation). Resins used for friction composites are; (i) straight phenolic resin, (ii) alkyl benzene modified resin, (iii) cashew nut shell liquid modified resin, (iv) NBR modified resin, and (v) linseed oil modified resin. The various performance criteria selected for the analysis are: performance-μ,% recovery in μ,% Fade in μ, wear, and temperature rise in the rotor disc. After optimization of various performance parameters of five FMs it was observed that the alkyl benzene modified phenolic resin composite performed well and linseed oil modified phenolic resin based composite was poor. The order obtained after evaluating this method complies with the results presented theoretically.
Safety and pharmacokinetics of recombinant factor XIII-A2 administration in patients with congenital factor XIII deficiency
Authors: Lovejoy Amy E. , Reynolds Tom C. , Visich Jennifer E. , Butine Michael D. , Young Guy , Belvedere Melissa A. , Blain Rachelle C. , Pederson Susan M. , Ishak Laura M. , Nugent Diane J.
Published: March 2006

Congenital factor XIII (FXIII) deficiency is associated with a tendency for severe bleeding, a risk for spontaneous abortion, and a high rate of spontaneous intracranial hemorrhage. This phase 1 escalating-dose study was developed to evaluate the safety and pharmacokinetics of a single administration of human recombinant FXIII-A2 (rFXIII-A2) homodimer in adults with congenital FXIII deficiency. Pharmacokinetics and activity of rXIII and changes in endogenous B subunit levels were assessed. Recombinant FXIII-A2 homodimer were complexed with endogenous FXIII-B subunits to form an FXIII-A2B2 heterotetramer with a half-life of 8.5 days, similar to that of endogenous FXIII. The median dose response was a 2.4% increase in FXIII activity based on unit per kilogram rFXIII administered. After the administration of rFXIII-A2, clot solubility normalized as measured by clot lysis in urea. Clot strength and resistance to fibrinolysis, as assessed by thromboelastography, also improved. Safety reviews were conducted before each dose escalation; no serious adverse events, including bleeding or thrombosis, were noted during the study. In addition, there was no evidence of the generation of specific antibodies to rFXIII or yeast proteins. Recombinant FXIII appears to be a safe and potentially effective alternative for FXIII replacement in patients with FXIII deficiency. (Blood. 2006;108:57-62)
Caspase-2 is activated at the CD95 death-inducing signaling complex in the course of CD95-induced apoptosis
Authors: Lavrik Inna N. , Golks Alexander , Baumann Simone , Krammer Peter H.
Published: March 2006

Caspase-2 was reported to be involved in a number of apoptotic pathways triggered by various stimuli. However, the molecular mechanism of procaspase-2 activation in the course of apoptosis remains poorly defined. In this report, we demonstrate that procaspase-2 is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex (DISC) in human T- and B-cell lines. We show that procaspase-2 is activated at the DISC on CD95 stimulation. Despite its presence at the DISC, caspase-2 does not initiate apoptosis on CD95 stimulation in caspase-8–deficient cell lines. Taken together, our data reveal that caspase-2 is activated at the DISC but does not play an initiating role in the CD95-induced apoptosis.
Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells
Authors: Carter Bing Z. , Mak Duncan H. , Schober Wendy D. , McQueen Teresa , Harris David , Estrov Zeev , Evans Randall L. , Andreeff Michael
Published: March 2006

Triptolide, a diterpenoid isolated from the Chinese herb Tripterygium wilfordii Hook.f, has shown antitumor activities in a broad range of solid tumors. Here, we examined its effects on leukemic cells and found that, at 100 nM or less, it potently induced apoptosis in various leukemic cell lines and primary acute myeloid leukemia (AML) blasts. We then attempted to identify its mechanisms of action. Triptolide induced caspase-dependent cell death accompanied by a significant decrease in XIAP levels. Forced XIAP overexpression attenuated triptolide-induced cell death. Triptolide also decreased Mcl-1 but not Bcl-2 and Bcl-XL levels. Bcl-2 overexpression suppressed triptolide-induced apoptosis. Further, triptolide induced loss of the mitochondrial membrane potential and cytochrome C release. Caspase-9 knock-out cells were resistant, while caspase-8–deficient cells were sensitive to triptolide, suggesting criticality of the mitochondrial but not the death receptor pathway for triptolide-induced apoptosis. Triptolide also enhanced cell death induced by other anticancer agents. Collectively, our results demonstrate that triptolide decreases XIAP and potently induces caspase-dependent apoptosis in leukemic cells mediated through the mitochondrial pathway at low nanomolar concentrations. The potent antileukemic activity of triptolide in vitro warrants further investigation of this compound for the treatment of leukemias and other malignancies.
Comparison of a tetravalent single-chain antibody-streptavidin fusion protein and an antibody-streptavidin chemical conjugate for pretargeted anti-CD20 radioimmunotherapy of B-cell lymphomas
Authors: Pagel John M. , Lin Yukang , Hedin Nathan , Pantelias Anastasia , Axworthy Donald , Stone Diane , Hamlin Don K. , Wilbur D. Scott , Press Oliver W.
Published: March 2006

The efficacy of radioimmunotherapy (RIT) for patients with relapsed non-Hodgkin lymphoma (NHL) is limited by nonspecific delivery of radiation to normal tissues due to the long circulating half-life of radiolabeled anti-CD20 antibodies (Abs). Pretargeted RIT using a covalent conjugate of the 1F5 anti-CD20 Ab with streptavidin (SA) has been shown to augment the efficacy of RIT and decrease toxicity compared with a directly labeled 1F5 Ab. We have engineered a tetravalent singlechain 1F5 (scFv)4SA fusion protein and compared it to the 1F5-SA conjugate. Athymic mice bearing Ramos lymphoma xenografts received either the conjugate or fusion protein, followed 20 hours later by a biotin-N-acetyl-galactosamine clearing agent, followed 4 hours later by 111In-DOTA-biotin. After 24 hours, 11.4% ± 2.1% of the injected dose of radionuclide was present per gram of tumor (% ID/g) using 1F5 (scFv)4SA compared with 10.8% ± 2.5% ID/g with 1F5 Ab-SA. Superior tumor-to-normal organ ratios of radioactivity were consistently seen using the fusion protein compared with the chemical conjugate (eg, tumor-to-blood ratio > 65:1 after 48 hours with the fusion protein, but < 7:1 with the conjugate). More than 90% of lymphomabearing mice could be cured with minimal toxicity using either reagent followed by 1200 μCi (44.4 MBq) 90Y-DOTA-biotin. (Blood. 2006;108:328-336)
The Influence of Ease of Retrieval on Judgment as a Function of Attention to Subjective Experience
Authors: Danziger Shai , Moran Simone , Rafaely Vered
Published: March 2006

The ease with which information comes to mind can impact judgment. We examine whether the influence of ease of retrieval is moderated by situational factors that call it to attention before judgment and by individual differences in experiential processing style, as measured by the rational experiential inventory scale (Pacini & Epstein, 1999). An ease of retrieval effect, indicated by less favorable evaluations of a proposal following the retrieval of many reasons advocating the proposal than following the retrieval of only a few, was found for high‐experiential style processors regardless of situational factors that made ease of retrieval salient. However, the effect was found among low‐experiential style processors only when ease of retrieval was explicitly called to their attention prior to judgment.
Avian MyoD and c-Jun Coordinately Induce Transcriptional Activity of the 3,5,3′-Triiodothyronine Nuclear Receptor c-ErbAα1 in Proliferating Myoblasts
Authors: Busson Muriel , Daury Laetitia , Seyer Pascal , Grandemange Stéphanie , Pessemesse Laurence , Casas François , Wrutniak-Cabello Chantal , Cabello Gérard
Published: March 2006

Although physical interactions with other receptors have been reported, heterodimeric complexes of T3 nuclear receptors (TR) with retinoid X receptors (RXRs) are considered as major regulators of T3 target gene expression. However, despite the potent T3 influence in proliferating myoblasts, RXR isoforms are not expressed during proliferation, raising the question of the nature of the complex involved in TRα transcriptional activity. We have previously established that c-Jun induces TRα1 transcriptional activity in proliferating myoblasts not expressing RXR. This regulation is specific to the muscle lineage, suggesting the involvement of a muscle-specific factor. In this study, we found that MyoD expression in HeLa cells stimulates TRα1 activity, an influence potentiated by c-Jun coexpression. Similarly, in the absence of RXR, MyoD or c-Jun overexpression in myoblasts induces TRα1 transcriptional activity through a direct repeat 4 or an inverted palindrome 6 thyroid hormone response element. The highest rate of activity was recorded when c-Jun and MyoD were coexpressed. Using c-Jun-negative dominants, we established that MyoD influence on TRα1 activity needs c-Jun functionality. Furthermore, we demonstrated that TRα1 and MyoD physically interact in the hinge region of the receptor and the transactivation and basic helix loop helix domains of MyoD. RXR expression (spontaneously occurring at the onset of myoblast differentiation) in proliferating myoblasts abrogates these interactions. These data suggest that in the absence of RXR, TRα1 transcriptional activity in myoblasts is mediated through a complex including MyoD and c-Jun.
Progesterone and Interferon-τ Regulate Cystatin C in the Endometrium
Authors: Song Gwonhwa , Spencer Thomas E. , Bazer Fuller W.
Published: March 2006

Cystatin C (CST3) is a secreted inhibitor of lysosomal cysteine proteases cathepsins B (CTSB) and CTSL, which are abundant in the ovine endometrium and conceptus. In mice, cathepsins and cystatins play important roles in implantation and placentation. This study determined effects of the estrous cycle, pregnancy, progesterone (P4), and interferon-τ (IFNT) on CST3 in the ovine uterus. In cyclic ewes, CST3 mRNA was low on d 10, increased about 12-fold by d 12, and declined thereafter. In early pregnant ewes, CST3 mRNA was low on d 10 and increased about 130-fold from d 10 to d 20. CST3 mRNA and protein were abundant in the endometrial luminal epithelium (LE) and glandular epithelium and also in conceptus trophectoderm. In uterine flushes from pregnant ewes, CST3 protein was not detected on d 10 but was abundant on d 12, 14, and 16. In another study, treatment of ovariectomized, cyclic ewes with P4 induced a 14-fold increase in endometrial CST3 mRNA, and IFNT stimulated an additional 2-fold increase in CST3 mRNA in P4-treated ewes but not in ewes treated with P4 and the antiprogestin ZK 136,317. CST3 mRNA and protein were abundant in the endometrial luminal epithelium and superficial glandular epithelium of P4-treated ewes but were very low or not detectable in endometria of P4- and ZK-treated ewes. These results indicate that CST3 is a novel P4-induced and IFNT-stimulated gene expressed only in the epithelial cells of the ovine endometrium and implicate CST3 in regulation of uterine cathepsin activity during conceptus implantation.
Targeted Ablation of the Chromogranin A (Chga) Gene: Normal Neuroendocrine Dense-Core Secretory Granules and Increased Expression of Other Granins
Authors: Hendy Geoffrey N. , Li Tong , Girard Martine , Feldstein Richard C. , Mulay Shree , Desjardins Roxane , Day Robert , Karaplis Andrew C. , Tremblay Michel L. , Canaff Lucie
Published: March 2006

Chromogranin A (CgA), originally identified in adrenal chromaffin cells, is a member of the granin family of acidic secretory glycoproteins that are expressed in endocrine cells and neurons. CgA has been proposed to play multiple roles in the secretory process. Intracellularly, CgA may control secretory granule biogenesis and target neurotransmitters and peptide hormones to granules of the regulated pathway. Extracellularly, peptides formed as a result of proteolytic processing of CgA may regulate hormone secretion. To investigate the role of CgA in the whole animal, we created a mouse mutant null for the Chga gene. These mice are viable and fertile and have no obvious developmental abnormalities, and their neural and endocrine functions are not grossly impaired. Their adrenal glands were structurally unremarkable, and morphometric analyses of chromaffin cells showed vesicle size and number to be normal. However, the excretion of epinephrine, norepinephrine, and dopamine was significantly elevated in the Chga null mutants. Adrenal medullary mRNA and protein levels of other dense-core secretory granule proteins including chromogranin B, and secretogranins II to VI were up-regulated 2- to 3-fold in the Chga null mutant mice. Hence, the increased expression of the other granin family members is likely to compensate for the Chga deficiency.
Cell Proliferation and Vascularization in Mouse Models of Pituitary Hormone Deficiency
Authors: Ward Robert D. , Stone Brandon M. , Raetzman Lori T. , Camper Sally A.
Published: March 2006

Mutations in the transcription factors PIT1 (pituitary transcription factor 1) and PROP1 (prophet of Pit1) lead to pituitary hormone deficiency and hypopituitarism in mice and humans. To determine the basis for this, we performed histological analysis of Pit1- and Prop1-deficient dwarf mouse pituitaries throughout fetal and postnatal development. Pit1-deficient mice first exhibit pituitary hypoplasia after birth, primarily caused by reduced cell proliferation, although there is some apoptosis. To determine whether altered development of the vascular system contributes to hypopituitarism, we examined vascularization from embryonic d 14.5 and throughout development. No obvious differences in vascularization are evident in developing Pit1-deficient pituitaries. In contrast, the Prop1-deficient mouse pituitaries are poorly vascularized and dysmorphic, with a striking elevation in apoptosis. At postnatal d 11, apoptosis-independent caspase-3 activation occurs in thyrotropes and somatotropes of normal but not mutant pituitaries. This suggests that Prop1 and/or Pit1 may be necessary for caspase-3 expression. These studies provide further insight as to the mechanisms of Prop1 and Pit1 action in mice.
The Peroxisome Proliferator-Activated Receptor N-Terminal Domain Controls Isotype-Selective Gene Expression and Adipogenesis
Authors: Hummasti Sarah , Tontonoz Peter
Published: March 2006

Peroxisome proliferator-activated receptors (PPARγ, PPARα, and PPARδ) are important regulators of lipid metabolism. Although they share significant structural similarity, the biological effects associated with each PPAR isotype are distinct. For example, PPARα and PPARδ regulate fatty acid catabolism, whereas PPARγ controls lipid storage and adipogenesis. The different functions of PPARs in vivo can be explained at least in part by the different tissue distributions of the three receptors. The question of whether the receptors have different intrinsic activities and regulate distinct target genes, however, has not been adequately explored. We have engineered cell lines that express comparable amounts of each receptor. Transcriptional profiling of these cells in the presence of selective agonists reveals partially overlapping but distinct patterns of gene regulation by the three PPARs. Moreover, analysis of chimeric receptors points to the N terminus of each receptor as the key determinant of isotype-selective gene expression. For example, the N terminus of PPARγ confers the ability to promote adipocyte differentiation when fused to the PPARδ DNA binding domain and ligand binding domain, whereas the N terminus of PPARδ leads to the inappropriate expression of fatty acid oxidation genes in differentiated adipocytes when fused to PPARγ. Finally, we demonstrate that the N terminus of each receptor functions in part to limit receptor activity because deletion of the N terminus leads to nonselective activation of target genes. A more detailed understanding of the mechanisms by which the individual PPARs differentially regulate gene expression should aid in the design of more effective drugs, including tissue- and target gene-selective PPAR modulators.
The LEAFY target LMI1 is a meristem identity regulator and acts together with LEAFY to regulate expression ofCAULIFLOWER
Authors: Saddic Louis A. , Huvermann Bärbel , Bezhani Staver , Su Yanhui , Winter Cara M. , Kwon Chang Seob , Collum Richard P. , Wagner Doris
Published: March 2006

The timing of the switch from vegetative to reproductive development is crucial for species survival. The plant-specific transcription factor and meristem identity regulator LEAFY (LFY) controls this switch in Arabidopsis, in part via the direct activation of two other meristem identity genes, APETALA1 (AP1) and CAULIFLOWER(CAL). We recently identified five new direct LFY targets as candidates for the missing meristem identity regulators that act downstream of LFY. Here, we demonstrate that one of these, the class I homeodomain leucine-zipper transcription factor LMI1, is a meristem identity regulator. LMI1 acts together with LFY to activate CAL expression. The interaction between LFY, LMI1 and CAL resembles a feed-forward loop transcriptional network motif. LMI1 has additional LFY-independent roles in the formation of simple serrated leaves and in the suppression of bract formation. The temporal and spatial expression of LMI1 supports a role in meristem identity and leaf/bract morphogenesis.
Dibenzo[c,h]-1,6-diisopropyl-1,6-disilabicyclo[4.4.0]deca-3,8-dienes
Authors: Kyushin Soichiro , Izumi Yukiko , Tsunakawa Satoshi , Matsumoto Hideyuki
Published: March 2006

cis- and trans-Dibenzo[c,h]-1,6-diisopropyl-1,6-disilabicyclo[4.4.0]deca-3,8-dienes were prepared. Strong σ-π conjugation was found to operate in both isomers, which was shown in UV spectra, cyclic voltammetry, and charge-transfer spectra with TCNE.
A Convenient Synthesis of Platelet-Activating Factors and Their Analogues from Chiral Epichlorohydrin
Authors: Tsuboi Sadao , Takeda Shinji , Yamasaki Yasuhisa , Sakai Takashi , Utaka Masanori , Ishida Shiro , Yamada Eiichi , Hirano Jiro
Published: March 2006

Two platelet activating factors (PAF) were conveniently prepared from optically active epichlorohydrin via 5 steps in 15–16% total yield. Four analogues containing oleoyl, propyl, p-trifluoromethylphenoxy, and N,N-dimethyldithiocarbamoyl groups were also prepared.
Regio- and Stereo-defined Synthesis of Organosilicon Compounds via Rearrangement of Silyl Group
Authors: Marumoto Shinji , Kuwajima Isao
Published: March 2006

On treating with LDBB, 2-substituted 3-phenylthioalkyl silyl ethers were converted to the corresponding 3-silylated alkanols with high anti selectivity. Application to silyl ethers containing allylic sulfide moieties provided a useful methodology for the regio- and stereo-defined synthesis of allylsilanes.
Syntheses of l-Fucopyranose and Its Homologs with Ring Heteroatoms Other than Oxygen. Stereocontrolled Conversion of a Common d-Arabinofuranoside Intermediate
Authors: Takahashi Shunya , Kuzuhara Hiroyoshi
Published: March 2006

l-Fucopyranose and a couple of l-fucosidase inhibitors, 5-deoxy-5-thio-l-fucopyranose and 1,5-dideoxy-1,5-imino-l-fucitol, were prepared from a common pentose intermediate with α-d-arabino configuration. Stereoselectivities on carbon chain elongation of the key intermediate were successfully controlled by choosing the appropriate organometallic reagents.
Stereo-Modulating Catalysis by Europium(III) Complexes in Aldol Reactions of Chiral α-Alkoxy Aldehydes with Ketene Silyl Acetals
Authors: Terada Masahiro , Gu Jin-Hua , Deka Dibakar C , Mikami Koichi , Nakai Takeshi
Published: March 2006

The Eu(fod)3- or Eu(dppm)3-catalyzed aldol reactions of the four chiral α-alkoxy aldehydes having different protecting groups with (E)- or (Z)-ketene silyl acetals are shown to provide the high levels of diastereocontrol, the sense depending on the nature of the protecting group. The catalytic stereo-modulation is explained in terms of the mode of aldehyde/catalyst complexation (chelation vs. nonchelation).
Selective Solid-State Intercalation of cis-trans Isomers into Montmorillonite
Authors: Ogawa Makoto , Hirata Masahiro , Kuroda Kazuyuki , Kato Chuzo
Published: March 2006

Maleic and methylmaleic acids were intercalated into montmorillonite by solid-solid reactions, whereas their geometrical isomers (trans-forms), fumaric and methylfumaric acids, were not intercalated. Both maleic and fumaric acids were intercalated into Na-montmorillonite, when the ethanolic solutions were used. Both the difference in the crystal structures of the guest species and the ability of cis-isomer to form a chelate like structure with the interlayer cations are thought to be concerned for the novel selectivity in the solid-state.
“Highly Destabilized Carbocations,” Generation and Rearrangements in the Reaction of 8,9,10,11-Tetrahydrocyclohepta[a]phenalen-6(12H)-one-12-ol and -7(12H)-one-12-ol with Sulfuric Acid
Authors: Kuroda Shigeyasu , Guan Guan-Jin , Ozaki Toshiaki , Saka Masayuki , Murotani Masahiro , Takahashi Yoshiyuki , Hidenaga Tomoaki , Hirooka Syuzi , Yamada Masaki , Shimao Ichiro
Published: March 2006

The reaction of 8,9,10,11-Tetrahydrocyclohepta[a]phenalen-6(12H)-one-12-ol and -7(12H)-one-12-ol with H2SO4 gave skeletally rearranged 9- and 10-methylbenz[de]anthracen-6-one and -7-one via destabilized vicinal dications.
Determination of Catalyst Surface Acidity in Liquids by a Pulse Liquid Chromatographic Technique
Authors: Carniti Paolo , Gervasini Antonella , Biella Serena
Published: March 2006

A pulse liquid chromatographic technique, set up by using an HPLC apparatus, is proposed for the characterization of the surface acidity of solid acids in liquids in view of their use as catalysts in liquid–solid reactions. Dosed amounts of solutions of two different basic probe molecules (2-phenylethylamine, pKa = 9.84 and aniline, pKa = 4.63) in solvents of different polarity were injected onto solid samples (acidic resins, Amberlites and a mixed silica–zirconia oxide) at a constant solvent flow rate. Titration with the weakest basic probe (aniline) rather than 2-phenylethylamine generally led to a lower amount of acidic sites. The amount of acidic sites determined at the surface was greatly affected by the solvent. With silica–zirconia, a higher amount of acidic sites was established by titration in apolar rather than polar solvents. The results have been compared with those obtained by conventional methods, i.e. ion exchange employing salts and, for silica–zirconia, Hammett titrations. The quite satisfactory results obtained are of some importance in establishing valuable relationships between catalyst acidity and catalytic activity in various solvents.
Identification of nucleotides inE. coli16S rRNA essential for ribosome subunit association
Authors: Pulk Arto , Maiväli Ülo , Remme Jaanus
Published: March 2006

The ribosome consists of two unequal subunits, which associate via numerous intersubunit contacts. Medium-resolution structural studies have led to grouping of the intersubunit contacts into 12 directly visualizable intersubunit bridges. Most of the intersubunit interactions involve RNA. We have used an RNA modification interference approach to determineEscherichia coli16S rRNA positions that are essential for the association of functionally active 70S ribosomes. Modification of the N1 position of A702, A1418, and A1483 with DMS, and of the N3 position of U793, U1414, and U1495 with CMCT in 30S subunits strongly interferes with 70S ribosome formation. Five of these positions localize into previously recognized intersubunit bridges, namely, B2a (U1495), B2b (U793), B3 (A1483), B5 (A1418), and B7a (A702). The remaining position displaying interference, U1414, forms a base pair with G1486, which is a part of bridge B3. We contend that these five intersubunit bridges are essential for reassociation of the 70S ribosome, thus forming the functional core of the intersubunit contacts.
Mechanism of ribosome shunting in Rice tungro bacilliform pararetrovirus
Authors: Pooggin Mikhail M. , Ryabova Lyubov A. , He Xiaoyuan , Fütterer Johannes , Hohn Thomas
Published: March 2006

In plant pararetroviruses, pregenomic RNA serves both as a template for replication through reverse transcription and a polysictronic mRNA. This RNA has a complex leader sequence preceding the first large ORF. The leader contains multiple short ORFs and strong secondary structure, both inhibiting ribosome scanning. Translation on this RNA is initiated by shunting, in which scanning ribosomes bypass a large portion of the leader with the inhibitory secondary structure and short ORFs. In Cauliflower mosaic virus (CaMV), the ribosome shunting mechanism involves translation of the 5′-proximal short ORF terminating in front of the secondary structure that appears to force ribosomes to take off and resume scanning at a landing site downstream of the structure. Using two plant protoplast systems and shunt-competent wheat-germ extracts, we demonstrate that in Rice tungro bacilliform virus (RTBV) shunting also depends on the first short ORF followed by strong secondary structure. Swapping of the conserved shunt elements between CaMV and RTBV revealed the importance of nucleotide composition of the landing sequence for efficient shunting. The results suggest that the mechanism of ribosome shunting is evolutionary conserved in plant pararetroviruses.
Identification of inhibitors of ribozyme self-cleavage in mammalian cells via high-throughput screening of chemical libraries
Authors: Yen Laising , Magnier Maxime , Weissleder Ralph , Stockwell Brent R. , Mulligan Richard C.
Published: March 2006

We have recently described an RNA-only gene regulation system for mammalian cells in which inhibition of self-cleavage of an mRNA carrying ribozyme sequences provides the basis for control of gene expression. An important proof of principle for that system was provided by demonstrating the ability of one specific small molecule inhibitor of RNA self-cleavage, toyocamycin, to control gene expression in vitro and vivo. Here, we describe the development of the high-throughput screening (HTS) assay that led to the identification of toyocamycin and other molecules capable of inhibiting RNA self-cleavage in mammalian cells. To identify small molecules that can serve as inhibitors of ribozyme self-cleavage, we established a cell-based assay in which expression of a luciferase (luc) reporter is controlled by ribozyme sequences, and screened 58,076 compounds for their ability to induce luciferase expression. Fifteen compounds able to inhibit ribozyme self-cleavage in cells were identified through this screen. The most potent of the inhibitors identified were toyocamycin and 5-fluorouridine (FUR), nucleoside analogs carrying modifications of the 7-position and 5-position of the purine or pyrimidine bases. Individually, these two compounds were able to induce gene expression of the ribozyme-controlled reporter ∼365-fold and 110-fold, respectively. Studies of the mechanism of action of the ribozyme inhibitors indicate that the compounds must be incorporated into RNA in order to inhibit RNA self-cleavage.
Assembly of AUF1 with eIF4G–poly(A) binding protein complex suggests a translation function in AU-rich mRNA decay
Authors: Lu Jin-Yu , Bergman Naomi , Sadri Navid , Schneider Robert J.
Published: March 2006

An AU-rich element (ARE) located in the 3′-untranslated region of many short-lived mRNAs functions as an instability determinant for these transcripts. AUF1/hnRNP D, an ARE-binding protein family consisting of four isoforms, promotes rapid decay of ARE-mRNAs. The mechanism by which AUF1 promotes rapid decay of ARE-mRNA is unclear. AUF1 has been shown to form an RNase-resistant complex in cells with the cap-initiation complex and heat shock proteins Hsp70 and Hsc70, as well as other unidentified factors. To understand the function of the AUF1 complex, we have biochemically investigated the association of AUF1 with the components of the translation initiation complex. We used purified recombinant proteins and a synthetic ARE RNA oligonucleotide to determine the hierarchy of protein interactions in vitro and the effect of AUF1 binding to the ARE on the formation of protein complexes. We demonstrate that all four AUF1 protein isoforms bind directly and strongly to initiation factor eIF4G at a C-terminal site regardless of AUF1 interaction with the ARE. AUF1 is shown to directly interact with poly(A) binding protein (PABP), both independently of eIF4G and in a complex with eIF4G. AUF1–PABP interaction is opposed by AUF1 binding to the ARE or Hsp70 heat shock protein. In vivo, AUF1 interaction with PABP does not alter PABP stability. Based on these and other data, we propose a model for the molecular interactions of AUF1 that involves translation-dependent displacement of AUF1–PABP complexes from ARE-mRNAs with possible unmasking of the poly(A) tail.
Discriminatory RNP remodeling by the DEAD-box protein DED1
Authors: Bowers Heath A. , Maroney Patricia A. , Fairman Margaret E. , Kastner Berthold , Lührmann Reinhard , Nilsen Timothy W. , Jankowsky Eckhard
Published: March 2006

DExH/D proteins catalyze NTP-driven rearrangements of RNA and RNA-protein complexes during most aspects of RNA metabolism. Although the vast majority of DExH/D proteins displays virtually no sequence-specificity when remodeling RNA complexes in vitro, the enzymes clearly distinguish between a large number of RNA and RNP complexes in a physiological context. It is unknown how this discrimination between potential substrates is achieved. Here we show one possible way by which a non-sequence specific DExH/D protein can discriminately remodel similar RNA complexes. We have measured in vitro the disassembly of model RNPs by two distinct DExH/D proteins, DED1 and NPH-II. Both enzymes displace the U1 snRNP from a tightly bound RNA in an active, ATP-dependent fashion. However, DED1 cannot actively displace the protein U1A from its binding site, whereas NPH-II can. The dissociation rate of U1A dictates the rate by which DED1 remodels RNA complexes with U1A bound. We further show that DED1 disassembles RNA complexes with slightly altered U1A binding sites at different rates, but only when U1A is bound to the RNA. These findings suggest that the “inability” to actively displace other proteins from RNA can provide non-sequence specific DExH/D proteins with the capacity to disassemble similar RNA complexes in a discriminatory fashion. In addition, our study illuminates possible mechanisms for protein displacement by DExH/D proteins.
Initiation factor-independent translation mediated by the hepatitis C virus internal ribosome entry site
Authors: Lancaster Alissa M. , Jan Eric , Sarnow Peter
Published: March 2006

The hepatitis C viral mRNA initiates translation using an internal ribosome entry site (IRES) located in the 5′ noncoding region of the viral genome. At physiological magnesium ion concentrations, the HCV IRES forms a binary complex with the 40S ribosomal subunit, recruits initiation factor eIF3 and the ternary eIF2/GTP/Met-tRNAiMet complex, and joins 60S subunits to assemble translation-competent 80S ribosomes. Here we show that in the presence of 5 mM MgCl2, the HCV IRES can initiate translation by an alternative mechanism that does not require known initiation factors. Specifically, the HCV IRES was shown to initiate translation in a reconstituted system consisting only of purified 40S and 60S subunits, elongation factors, and aminoacylated tRNAs at high magnesium concentration. Analyses of assembled complexes supported a mechanism by which preformed 80S ribosomes can assemble directly on the HCV IRES at high cation concentrations. This mechanism is reminiscent of that employed by the divergent IRES elements in the Dicistroviridae, exemplified by the cricket paralysis virus, which mediates initiation of protein synthesis without initiator tRNA.
Use of transcriptional synergy to augment sensitivity of a splicing reporter assay
Authors: Levinson Noah , Hinman Rochelle , Patil Ashwini , Stephenson Corey R.J. , Werner Stefan , Woo Grace H.C. , Xiao Jingbo , Wipf Peter , Lynch Kristen W.
Published: March 2006

A primary limitation in the development and use of screens to identify factors that regulate mammalian pre-mRNA splicing has been the development of sensitive reporter assays. Alternative splicing typically involves relatively small (< 10-fold) changes in isoform ratios. Therefore, reporter constructs designed to allow direct analysis of isoform expression historically have at most a 10-fold window of discrimination between a positive signal and background. Here we describe the design and application of a reporter cell line that makes use of the phenomenon of transcriptional synergy to amplify the detection of changes in splicing, such that a three- to five-fold change in splicing pattern is observed as a 30- to 50-fold change in GFP expression. Using this cell line we have identified two small molecules, from a library of approximately 300 synthetic compounds, that can induce partial repression of a variable exon from theCD45gene. We propose that the concept of transcription-based amplification of signal will allow the development of true high-throughput screening approaches to identify effectors of mammalian alternative splicing.
Designing a New Organization at NASA: An Organization Design Process Using Simulation
Authors: Carroll Timothy N. , Gormley Thomas J. , Bilardo Vincent J. , Burton Richard M. , Woodman Keith L.
Published: March 2006

The challenge for NASA’s Systems Analysis Integrated Discipline Team (SAIDT) is to develop a new organization design capable of performing complex modeling and analysis tasks, using team members at various NASA centers. The focus is on: (1) design as a process, (2) the effect of design tools on the process as well as alternative designs, (3) the fit between the tools and their fit with the organization, (4) the effect of an ongoing agencywide transformation, and (5) implications for organizational contingency theory.
Designing the Boundaries of the Firm: From “Make, Buy, or Ally” to the Dynamic Benefits of Vertical Architecture
Authors: Jacobides Michael G. , Billinger Stephan
Published: March 2006

The concept of “vertical architecture” defines the scope of a firm and the extent to which it is open to final and intermediate markets; it describes the configurations of transactional choices along a firm’s value chain. A firm can make or buy inputs, and transfer outputs downstream or sell them. Permeable vertical architectures are partly integrated and partly open to the markets along a firm’s value chain. Increased permeability enables more effective use of resources and capacities, better matching of capabilities with market needs, and benchmarking to improve efficiency. Partial integration promotes a more dynamic, open innovation platform and enhances strategic capabilities by linking key parts of the value chain. This permeable vertical architecture, accompanied by appropriate transfer prices and incentive design, facilitates resource allocation and guides a firm’s growth process. Our longitudinal study of a major European manufacturer suggests that to understand how firm boundaries are set and what their impacts are, we need to complement the microanalytic focus on transactions with a systemic analysis at the level of the firm. It also shows how, over and above transactional alignment, decisions about boundaries and vertical architectures can transform a firm’s strategic and productive capabilities and prospects.
From Organization Design to Organization Designing
Authors: Yoo Youngjin , Boland Richard J. , Lyytinen Kalle
Published: March 2006

Organization design in its verb form is explored through a study of the design practices of a major contemporary architect, Frank O. Gehry, and his firm, Gehry Partners, LLP. Through four case studies, we explore how the organization design of his architectural projects is an outcome of Gehry Partner’s design gestalt. We argue that this design gestalt is a primary source of their organization designing and is composed of an architectural vision, the tight coupling of multiple representation technologies, and a commitment to a collaborative process of design and construction. These elements of design together form a holistic, organizing pattern—their design gestalt—that is evident in all of Gehry Partners projects, both their buildings and their organizational forms. We offer three characteristics of organization designing—focus on form giving, relation to environment, and temporality. We argue that developing a design gestalt and strengthening the capacity for organization designing is crucial for firms in our increasingly knowledge- and experience-based economy.
Power to the Principals: Decentralization in Three Large School Districts
Authors: Ouchi William G.
Published: March 2006

School districts have made several attempts at decentralizing. However, decentralization in school districts can mean so many different things that the term has nearly lost its meaning.

This paper reports a study of three large urban school districts that, over almost 30 years, adopted nearly identical approaches to decentralizing, granting control to principals and expanding freedom of choice for families. In all three cases, the goal of improving student achievement was achieved, although with a very small sample.

These three districts are compared to the three largest public districts in North America. The comparisons reveal that the three decentralized districts attained a high level of principal control over school budgets, staffing, schedule, and teaching methods.