bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal regulation of cdc2 mitotic kinase activity and cyclin degradation in cell-free extracts of Xenopus eggs
Authors: Felix Marie-Anne , Pines Jonathan , Hunt Tim , Karsenti Eric
Published: May 2013

In cleaving Xenopus eggs, the cell division cycle is abbreviated to a rapid succession of S and M phases. During mitosis a number of proteins show increased phosphorylation due to the activation of a histone Hl kinase, the homologue of the cdc2+ gene product of the yeast Schizosaccharomyces pombe. We have studied the regulation of the activity of this enzyme in cell-free extracts of Xenopus eggs. In extracts of activated eggs incubated at 22°C, histone Hl kinase activity shows two peaks of activation and disappearance. Activation occurs in two stages. The first stage requires protein synthesis, whereas the second does not. The second stage of activation involves post-translational activation of the kinase. Kinase activity rises to a peak and then abruptly disappears. Added sea urchin cyclin is degraded at the time of disappearance of kinase activity. The oscillation in kinase activity is then repeated, usually with lower amplitude.

Post-translational activation of the kinase requires a membrane-containing particulate cellular component, whose role has yet to be defined. The kinase can still be activated in the presence of EDTA or in the presence of the ATP analogue, 6-dimethylaminopurine, which implies that phosphorylation of the kinase complex is not required for activation. Under these conditions, however, the kinase activity does not show its normal sudden disappearance, and added cyclin is perfectly stable. These observations are consistent with the idea that post-translational activation of the kinase involves protein phosphatase activity, whereas switching off the kinase requires an ATP-Mg2+-dependent reaction, perhaps due to protein phosphorylation.
Transforming growth factor-β receptors and binding proteoglycans
Authors: Boyd Frederick T. , Cheifetz Sela , Andres Janet , Laiho Marikki , Massagué Joan
Published: May 2013

Transforming growth factors-beta (TGFs-β) are representative of a superfamily whose members were first identified as regulators of morphogenesis and differentiation, and subsequently found to be structurally related. Other members of the family include the activins and inhibins, BMPs, MIS, the DPP-C gene product and Vg-1. When assayed by affinity-labelling techniques, TGFs-β bind to three distinct cell surface proteins which are present on most cells. These proteins are all of relatively low abundance but bind TGFs-β with affinities consistent with the biological potency of the factors. The Type I and Type II binding proteins are glycoproteins with estimated molecular weights of 53 and 73×103Mr, respectively. They both bind TGFS-β significantly better than TGFS-β. The Type I receptor has been identified as the receptor which mediates many of the responses of TGFs-β, based on somatic cell genetic studies of epithelial cell mutants unresponsive to TGFs-β. Betaglycan is the third binding protein present on many, but not all, cell types and is a large proteoglycan (∼280×103Mr) with 100–120 ×103Mr core proteins. A soluble form of this molecule is present in conditioned media of many cell lines and may be derived from the cell surface-associated molecule by cleavage of a small membrane anchor. Betaglycan binds TGFS-β and TGFS-β with similar affinity and this binding is to the core proteins, not the glycosaminoglycan side chains. This molecule may have a function in the localization and delivery or the clearance of activated TGFs-β. The molecular basis of TGFS-β signalling is still largely unknown, but it is possible that one or more of these cell surface molecules signals via a novel mechanism, as the TGFs-β are biologically quite distinct from other factors that act via well-characterized signalling systems.
Growth factors influencing bone development
Authors: Wozney J. M. , Rosen V. , Byrne M. , Celeste A. J. , Moutsatsos I. , Wang E. A.
Published: May 2013

We have approached the study of growth factors affecting cartilage and bone development by investigating those factors present in bone which are able to initiate new cartilage and bone formation in vivo. This has led to the identification and molecular cloning of seven novel human factors which we have named BMP-1 through BMP-7. Six of these molecules are related to each other, and are also distantly related to TGF-β. The presence of one of these molecules, recombinant human BMP-2 (rhBMP-2) is sufficient to produce the complex developmental system of cartilage and bone formation when implanted subcutaneously in a rat assay system. In this model, administration of rhBMP-2 ultimately results in the formation of a piece of trabecular bone, which is filled with mature bone marrow. While our studies demonstrate that rhBMP-2 by itself has the ability to induce cartilage and bone formation in vivo, we find other BMP molecules present along with BMP-2 in our highly purified nonrecombinant bone-inductive material. These results suggest that the bone inductive capacity of bone-derived proteins may reside in the combinatorial or synergistic activities of this set of BMP-2 related molecules.
Structure function relationships in EGF, TGF-α and IGFI
Authors: CAMPBELL IAIN D. , Cooke Robert M.
Published: May 2013

The solution structures of the homologous growth factors hEGF and hTGF-α-, have been determined independently from high resolution nuclear magnetic resonance (NMR) data. A model of the insulin-like growth factor structure based on insulin coordinates (Blundell et al. (1978)Proc natn. Acad. Sci. U.S.A. 75, 180-184), has also been refined using molecular dynamics simulations with NMR-determined restraints. Knowledge of these structures, together with known sequences of other homologous proteins and experiments with site-specific residue changes, allows predictions to be made about growth factor residues which might be involved in the receptor-ligand interfaces.
Regulation of the interaction between smooth muscle myosin and actin
Authors: Trybus Kathleen M. , Warshaw David M.
Published: May 2013

Phosphorylation of the regulatory light chain of smooth muscle myosin efficiently regulates the actin- activated ATPase activity of myosin filaments in solution and actin movement in an in vitro motility assay, independently of thin-filament regulatory proteins. Filaments containing both phosphorylated and dephosphorylated heads move actin at intermediate rates, depending on the relative proportions of the two myosin species. The decrease in velocity can be accounted for by mechanical interactions between phosphorylated heads and ‘weak-binding’ dephosphorylated crossbridges. These results imply that shortening velocity could be modulated in any muscle by varying the relative proportions of two populations of crossbridges with different cycling rates.
MAPs and motors in insect ovaries
Authors: Stebbings Howard , Hunt Cherryl , Anastasi Angela
Published: May 2013

MAPs and microtubule motor proteins from the massive microtubule translocation complexes within the ovaries of hemipteran insects have been identified and characterized. Both classes of proteins have been compared with those of other systems, and the function of both in the insect ovaries is speculated upon.
Self-assembly pathway of nonsarcomeric myosin II
Authors: Cross R. A. , Hodge T. P. , Kendrick-Jones J.
Published: May 2013

Cells need to control the location and timing of actomyosin-dependent force generation, and appear to do so in the first instance by regulating myosin filament self-assembly (Yumura and Fukui, 1985). The mechanism of the self-assembly is little understood. In vitro it is a true self-assembly, which requires a short domain at the C terminus of the myosin molecule. The availability of this domain appears suppressed by the folding of the molecule into a compact, looped state. In vitro, the rate at which these looped molecules unfold turns out to be a key determinant of filament number and filament length.
Effect of ciliary neurotrophic factor (CNTF) on motoneuron survival
Authors: Sendtner Michael , Arakawa Yoshihiro , Stockli Kurt A. , Kreutzberg Georg W. , Thoenen Hans
Published: May 2013

We have demonstrated that the extensive degeneration of motoneurons in the rat facial nucleus after transection of the facial nerve in newborn rats can be prevented by local ciliary neurotrophic factor (CNTF) administration. CNTF differs distinctly from known neurotrophic molecules such as NGF, BDNF and NT-3 in both its molecular characteristics (CNTF is a cytosolic rather than a secretory molecule) and its broad spectrum of biological activities. CNTF is expressed selectively by Schwann cells and astrocytes of the peripheral and central nervous system, respectively, but not by target tissues of the great variety of CNTF-responsive neurons. CNTF mRNA is not detectable by Northern blot or PCR analysis during embryonic development and immediately after birth. However, during the second post-natal week, a more than 30-fold increase in CNTF mRNA and protein occurs in the sciatic nerve. Since the period of low CNTF levels in peripheral nerves coincides with that of high vulnerability of motoneurons (i.e. axonal lesion results in degeneration of motoneuron cell boches), insufficient availability of CNTF may be the reason for the rate of lesion-induced cell death of early post-natal motoneurons. Highly enriched embryonic chick motoneurons in culture are supported at survival rates higher than 60 % by CNTF, even in single cell cultures, indicating that CNTF acts directly on motoneurons. In contrast to CNTF, the members of the neurotrophin gene family (NGF, BDNF and NT-3) do not support the survival of motoneurons in culture. However, aFGF and bFGF show distinct survival activities which are additive to those of CNTF, resulting in the survival of virtually all motoneurons cultured in the presence of CNTF and bFGF.
Coordination of trophic interactions by separate developmental programs in sensory neurons and their target fields
Authors: Davies Alun M. , Larmet Yves , Wright Edwina , Vogel Kristine S.
Published: May 2013

In the developing vertebrate nervous system the survival of sensory neurons becomes dependent on neurotrophic factors when their axons reach their target fields, and the synthesis of nerve growth factor (NGF) by target field cells commences with the arrival of the earliest axons. The timing of NGF synthesis and the onset of neurotrophic factor dependence are not, however, reliant on innervation. NGF synthesis occurs on time in developing target fields in which innervation is prevented, and sensory neurons cultured before innervating their targets become dependent on neurotrophic factors for survival after a certain length of time in culture. The length of time neurons survive in culture before becoming neurotrophic factor-dependent is related to the time they would normally contact their targets in vivo-, populations of neurons that have nearby targets which are innervated early respond to neurotrophic factors before neurons that have more distant targets which are innervated later. The timing of target field innervation is governed not only by the distance axons have to grow but by the rate at which they grow. Axonal growth rate is also regulated in accordance with target distance: neurons with distant targets extend axons faster than neurons with nearby targets. In addition to reviewing evidence for separate developmental programs that control the timing of neurotrophic factor synthesis in the target field and the onset of neurotrophic factor dependence in early sensory neurons, we will consider the mechanisms that might play a role in regulating the survival of neurons during the phase of neurotrophic factor independence.
Growth factors and transcription factors in oligodendrocyte development
Authors: Collarini Ellen J. , Pringle Nigel , Mudhar Hardeep , Stevens Georgina , Kuhn Rainer , Monuki Edwin S. , Lemke Greg , Richardson William D.
Published: May 2013

O-2A progenitor cells, the precursors of oligodendrocytes in the central nervous system (CNS), probably originate in the subventricular germinal zones of the developing CNS, and subsequently migrate away from there to populate the rest of the CNS with oligodendrocytes. We are trying to understand how the O-2A progenitor cells interact with their changing environment as they migrate, and how this influences each stage of their development into mature, myelinating oligodendrocytes. In this article we summarize evidence that platelet-derived growth factor (PDGF) is important for stimulating O-2A progenitor cell proliferation in vivo, and describe our efforts to map the distribution of PDGF and its receptors in the developing rat CNS by in situ hybridization and immunohistochemistry. These studies suggest that, in the CNS, PDGF a-receptor subunits may be restricted to O-2A lineage cells that have started to migrate away from the subventricular zones towards their final destinations. Many neurons express the A and/or B chains of PDGF, and astrocytes express the A chain, but it is not yet clear which of these cell types might be the major source of PDGF for O-2A lineage cells in vivo. O-2A progenitor cells can be purified and maintained in a proliferating state in vitro by culturing in the presence of PDGF and bFGF. Under these conditions, the POU transcription factor SCIP/Tst-1 is expressed at a high level; when oligodendrocyte differentiation is initiated by withdrawing the growth factors, SCIP/Tst-1 mRNA is rapidly down-regulated, followed by a decline in SCIP/Tst-1 protein and sequential activation of myelin-specific genes. These observations suggest that SCIP/Tst-1 may be mechanistically involved in the transition from proliferation to differentiation in the 0-2A lineage. By in situ hybridization, SCIP/Tst-1 appears also to be expressed in developing neurons, so perhaps it fulfils a similar function in several different cell lineages in the CNS.
The contrasting roles of N-CAM and N-cadherin as neurite outgrowthpromoting molecules
Authors: Doherty Patrick , Walsh Frank S.
Published: May 2013

The neural cell adhesion molecule (N-CAM) is a prominent member of the immunoglobulin gene superfamily of recognition molecules. It operates in a calcium-independent manner to promote cell-cell adhesion. Alternative splicing of a single gene generates more than twenty N-CAM isoforms and these can be further modified by the differential addition of complex N- and O-linked carbohydrates. In contrast, N-cadherin is a major calcium-dependent adhesion molecule in the brain; it is not a member of the immunoglobulin gene superfamily and, as far as we know, exists as a single gene product with no evidence of differential post-translational modification. Both molecules are believed to operate through a homophilic binding mechanism and both are expressed at key developmental times in a number of tissues including the brain. Antibody perturbation experiments suggest that both of the above cell adhesion molecules (CAMs) can support neurite outgrowth over complex cellular substrata such as astrocytes and Schwann cells. In the present review we discuss the use of a molecular genetic approach to study the neurite outgrowth-promoting activity of these molecules. Using this approach we have found that both CAMs are potent inducers of neurite outgrowth from a variety of neurons. However, whereas a critical value of N-CAM expression is required for increased neurite outgrowth, with small increases above this value having substantial effects, N-cadherin promotes neurite outgrowth in a highly linear manner. In addition, whereas N-CAM promotes chick retinal ganglion cell (RGC) neurite outgrowth at E6 but not Ell, N-cadherin does so throughout this developmental period. These studies show fundamental differences in neuronal responsiveness to CAMs, and suggest a more dynamic regulation for N-CAM-dependent neurite outgrowth than for N-cadherin-dependent neurite outgrowth.
On the cytomechanics and fluid dynamics of growth cone motility
Authors: Heidemann Steven R. , Lamoureux Phillip , Buxbaum Robert E.
Published: May 2013

Following a brief review of the controversy concerning the physical mechanism of growth cone advance, we present cytomechanical data to support a version of the classic model of growth cone motility. In this model, the growth cone is pulled forward by filopodial tension. Observations of growth cone behavior and axonal guidance suggest that this model should include fluid flow mechanisms as well as the original solid, elastic mechanism. Recent data are reviewed on the similarity of the fluid behavior of cytoplasm and of suspensions of cytoskeletal filaments. The thixotropic behavior of cytoplasm is used to develop a model for lamellipodial protrusion caused by filopodial tension.
Control of microtubule assembly in growth cones
Authors: Gordon-Weeks Phillip R.
Published: May 2013

Growth cones are transient structures present at the tips of growing axons and dendrites (neurites). They are crucial to neuronal development because of their pathfinding ability and their role in synaptogenesis (reviewed by Dodd and Jessell, 1988). In the last few years it has become apparent that growth cones are also involved in the assembly of the cytoskeleton of the elongating neurite (reviewed by Gordon-Weeks, 1989, 1991). We are particularly interested in the assembly of microtubules in the growth cone and its importance for neurite advance. The microtubules in the neurite are bundled into fascicles, presumably by the cross-linking action of microtubule-associated proteins (MAPs), and on entering the growth cone they splay out like the ribs of a fan with their ‘plus’ ends, the ends at which assembly takes place preferentially, oriented distally. Within the growth cone there is a large pool of assembly competent tubulin that provides subunits for microtubule elongation. Several observations point to the existence of precise mechanisms controlling assembly of this soluble tubulin pool. If the control mechanisms are disrupted the ability of the neurite to advance is severely compromised. We have examined the possibility that MAPs are important components in this control mechanism. Many of the known MAPs are present within growth cones, including MAP IB, MAP 2 and tau. Experiments with neuronal cultures and growth cones isolated as a subcellular fraction from developing rat brain point particularly toward the phosphorylated form of MAP IB as an essential component in the concerted assembly of microtubules at the growth cone and in particular in the bundling of microtubules in the neurite.
The bicoid and dorsal morphogens use a similar strategy to make stripes in the Drosophila embryo
Authors: Ip Y. Tony , Levine Michael , Small Stephen J.
Published: May 2013

The anterior-posterior (A-P) and dorsal-ventral (D-V) axes of the early Drosophila embryo are established by two key maternal morphogens: bicoid (bed) and dorsal (dl), respectively. The bed protein is expressed in a broad concentration gradient along the A-P axis, with peak levels present at the anterior pole, while dl is expressed in a gradient along the D-V axis with peak levels along the ventral surface. The two morphogens are unrelated and their gradients are formed by distinct processes. Nonetheless, we have obtained evidence that they generate sharp on/off stripes of target gene expression through a similar mechanism. Both morphogens establish overlapping patterns of transcriptional activators and repressors in the early embryo. The activators and repressors bind to closely linked sites within short (300 to 500 bp) target promoter elements that have the properties of on/off switches. The activators act in concert with the morphogen to define a broad region where target genes can be initiated. Borders of target gene expression are established by the repressors, resulting in the formation of stripes.
Molecular mechanisms leading to loss of differentiation and gain of invasiveness in epithelial cells
Authors: Birchmeier Walter , Weidner K. Michael , Behrens Jurgen
Published: May 2013

It has been realized for some time that the loss of epithelial differentiation in carcinomas, which is accompanied by higher mobility and invasiveness of the tumor cells, is a consequence of reduced intercellular adhesion. A variety of recent reports have indicated that the primary cause for the ‘scattering’ of the cells in invasive carcinomas is a loss of the integrity of intercellular junctions. Thus, defects in expression or structure of several components of the epithelial adherens junctions (e.g. E-cadherin, a-catenin) can occur, and our increased knowledge about the molecules of the junctions allows an explanation of these defects in molecular terms in some of the cases. Furthermore, tyrosine phosphorylation of junctional components (e.g. p-catenin) appears to play a role in the assembly and disassembly of cell-cell contacts. Some of the effectors of epithelial junction formation are tyrosine protein kinases, e.g. the scatter factor/hepatocyte growth factor receptor c-Met, the FGF receptors and the pp6Osre kinase. The importance of tyrosine phosphorylation in junctions during tumor development is becoming increasingly evident.
Distribution and role of heterotrimeric G proteins in the secretory pathway of polarized epithelial cells
Authors: Stow Jennifer L. , Almeida J. Bruno de
Published: May 2013

The movement of newly synthesized proteins in the constitutive secretory pathway, from their site of synthesis in the endoplasmic reticulum to the cell surface or to intracellular destinations, requires an orderly sequence of transport steps between membrane-bound compartments. Until recently, the trafficking and secretion of proteins through this pathway was thought to occur as a relatively automatic, unregulated series of events. Recent studies show that protein trafficking in the constitutive secretory pathway requires GTP hydrolysis by families of GTP-binding proteins (G proteins), which at multiple steps potentially provide regulation and specificity for protein trafficking. Many monomeric G proteins are known to be localized and functional on membrane compartments in the constitutive secretory pathway. Now, members of the heterotrimeric G protein family have also been localized on intracellular membranes and compartments such as the Golgi complex. We have studied the localization and targeting of Gα subunits to distinct membrane domains in polarized epithelial cells. The distribution of different Gα subunits on very specific membrane domains in cultured epithe-liai cells and in epithelial cells of the kidney cortex, is highly suggestive of roles for these G proteins in intracellular trafficking pathways. One of these G protein subunits, Gαi-3, was localized on Golgi membranes. Studies on LLC-PK 1 cells overexpressing Gαi-3 provided evidence for its functional role in regulating the transport of a constitutively secreted heparan sulfate proteoglycan through the Golgi complex. Inhibition or activation of heterotrimeric G proteins by pertussis toxin or by aluminium fluoride respectively, have provided further evidence for regulation of intracellular transport by pertussis toxin-sensitive G proteins. Although the functions of Golgi-associated G proteins are not yet understood at the molecular level, heterotrimeric G proteins have been implicated in the binding of cytosolic coat proteins and vesicle formation on Golgi membranes. Future studies will elucidate how multiple G proteins, of both the heterotrimeric and monomeric families, are involved in the regulation of Golgi function and protein trafficking in the secretory pathway.
Molecular analysis of the coiled body
Authors: Bohmann Kerstin , Ferreira João , Santama Niovi , Weis Karsten , Lamond Angus I.
Published: May 2013

There is increasing interest in studying how specific metabolic activities within the nucleus are organised into functional domains. The best known example is the nucleolus where rRNA genes are transcribed and rRNA processed and assembled into ribosomal subunits. Other subnuclear domains have been known for many years through morphological studies but are only recently being analysed at the molecular level. Here we focus on an evolutionarily conserved nuclear domain, called the coiled body, which contains splicing snRNPs. We review recent literature on the coiled body and discuss a possible model for its biological function.
Amphiphilic Star Polymers Bearing a Triphenylene Core for Novel Dispersants of Carbon Nanotubes in Polar Media
Authors: Motoyanagi Jin , Matsumoto Tomoyuki , Shiotani Takumi , Miki Sadao , Minoda Masahiko
Published: May 2013

Well-defined six-armed amphiphilic star polymers (TP-C0-PMAPEG)s and (TP-C5-PMAPEG)s bearing a triphenylene core were designed as dispersants of carbon nanotubes, and synthesized via controlled radical polymerization. It was found that these star polymers were capable of forming stable dispersions of single-walled and multiwalled carbon nanotubes in polar media such as MeOH and water.
Control over Flexibility of Entangled Porous Coordination Frameworks by Molecular and Mesoscopic Chemistries
Authors: Furukawa Shuhei , Sakata Yoko , Kitagawa Susumu
Published: May 2013

Entangled porous coordination frameworks, wherein two or more distinct frameworks are catenated over an entire crystal, are known to demonstrate unique structural flexibilities in response to the accommodation of molecules in the voids between the frameworks. In this highlight review, we introduce key functions of entangled frameworks based on two principles of their dynamic features: shearing and displacement. We further describe strategies to control the flexibilities; one is a molecular chemistry approach to functionalize frameworks by chemical modification, and the other is a mesoscopic chemistry approach to change the physical form, in particular, the crystal size.
Technology is becoming a Hypercortext
Authors: Neuman Yair
Published: May 2013

A review of The Semantic Sphere 1: Computation, Cognition and Information Economy, by Pierre Lévy. ISTE Ltd. and John Wiley and Sons Inc., 2011; 381 pages.
Szanse i perspektywy Polski w latach 1989-1990 widziane przez pryzmat opinii „polskiego Londynu”
Authors: Pyłat Joanna
Published: May 2013

Hopes, Opportunities and Perspectives. Poland 1989‑1990 seen through the Prism of “Polish London”

The article discusses the approach of the Polish émigré community in London to the transformation of Poland towards democracy throughout 1989‑1990. The article focuses on journalists and activists who debated the issues in: “Dziennik Polski i Dziennik Żołnierza”, “Rzeczpospolita Polska” and “Orzeł Biały”. Research focuses on the topics surrounding the events, observations, predictions and very often fears towards the character of the political transformation as well as the direction which new elites would take. Important for contemporary commentators was also the role of the Polish Diaspora in the processes and its future place within the new structures of the new Polish Republic. Research was conducted through the analysis of majority of the sources discussing the situation in Poland as well as ongoing transition which occurred during 1989‑1990, supported by historical evidence and opinions and thoughts of émigré community leaders including: last remaining Presidents in Exile Kazimierz Sabbat and Ryszard Kaczorowski as well as the prime minister of the Government of the Republic of Poland in exile prof. Edward Szczepanik.
Effectiveness of the Polish, Danish and Cypriot Presidencies in the Field of Enlargement Policy – ‘a Project Assessment Perspective’
Authors: Dulak Michał
Published: May 2013

This article concerns the evaluation of the Polish, Danish and Cypriot presidencies in the field of the European Union enlargement policy. In order to assess an effectiveness of both countries he uses a project assessment perspective, which theoretical model was initially developed in the book Skuteczność polskiej prezydencji w Unii Europejskiej (trans.: The effectiveness of the Polish presidency in the European Union). A thesis standing behind this approach says that after the treaty of Lisbon has come into force, and has changed crucial functions of each presidency, we can’t any more consider a country chairing the Council neither as honest broker nor as representative of own national interests. A project assessment perspective delivers more adequate categories based on project management theory and practice. In the empirical part of the study the author focuses on the effects of Polish, Danish and Cypriot activities in the field of relations with six candidate countries since 1 July 2011 till 31 December 2012.
Kłopoty pojęciowe z demokracją
Authors: Łojek Stanisław
Published: May 2013

Conceptual problems with democracy. Descriptive, semantic and normative approaches

The conceptual confusion makes it difficult to provide a convincing answer to the question of what democracy is. One reason of this, which I would like to analyze below, is a intermingling of the descriptive, normative and semantic elements in almost each theory of democracy. I will show that a pure description is probably impossible, and that any attempt to approach the actual functioning of any regime necessarily contains normative assessment and expectations. In conclusion, I point out that a fair comparison of democratic models and practices requires a special effort to separate the normative and descriptive elements. I also note that the study of normative assumptions underlying some commonly accepted views of democracy allows a better understanding of their theoretical and practical circumstances and consequences, which in turn can contribute to their revision.
Returns Policies Between Channel Partners for Durable Products
Authors: Gümüş Mehmet , Ray Saibal , Yin Shuya
Published: May 2013

Many durable products with relatively short selling seasons have been using returns policies between manufacturers and retailers as the contractual protocol for some time. Recently, these sectors have witnessed the growing popularity of peer-to-peer Web-based used goods markets as important transaction channels between buyers and sellers. Given that these two issues are critically linked from both supply and demand perspectives, in this paper we study the role that consumer valuation of used products plays in shaping a manufacturer's incentive to offer a returns policy option to a retailer when used goods might be devalued compared to new ones as a result of physical deterioration (or obsolescence). We do so through a two-period dyadic channel framework where the retailer faces uncertain demand for a durable product from a renewable set of customers who are impatient but forward looking. The manufacturer, on the other hand, needs to decide whether or not to offer a returns contract to the retailer. We first characterize the necessary and sufficient condition under which a returns contract is the equilibrium strategy as well as the corresponding channel decisions. Further analysis of this condition reveals that a higher consumer valuation of used products increases the likelihood of a returns contract being the equilibrium strategy. This result seems to be robust except when the potential demands for the two periods are quite deterministic and uncorrelated. However, it contradicts the burgeoning managerial trend to replace returns contracts with price-only ones in sectors where used goods are valued relatively highly by the consumers. We also discuss how used goods markets affect the equilibrium channel decisions as well as how demand uncertainty and logistics costs associated with returns influence the equilibrium contracting strategy.
A Joint Model of Usage and Churn in Contractual Settings
Authors: Ascarza Eva , Hardie Bruce G. S.
Published: May 2013

As firms become more customer-centric, concepts such as customer equity come to the fore. Any serious attempt to quantify customer equity requires modeling techniques that can provide accurate multiperiod forecasts of customer behavior. Although a number of researchers have explored the problem of modeling customer churn in contractual settings, there is surprisingly limited research on the modeling of usage while under contract. The present work contributes to the existing literature by developing an integrated model of usage and retention in contractual settings. The proposed method fully leverages the interdependencies between these two behaviors even when they occur on different time scales (or “clocks”), as is typically the case in most contractual/subscription-based business settings.

We propose a model in which usage and renewal are modeled simultaneously by assuming that both behaviors reflect a common latent variable that evolves over time. We capture the dynamics in the latent variable using a hidden Markov model with a heterogeneous transition matrix and allow for unobserved heterogeneity in the associated usage process to capture time-invariant differences across customers.

The model is validated using data from an organization in which an annual membership is required to gain the right to buy its products and services. We show that the proposed model outperforms a set of benchmark models on several important dimensions. Furthermore, the model provides several insights that can be useful for managers. For example, we show how our model can be used to dynamically segment the customer base and identify the most common “paths to death” (i.e., stages that customers go through before churn).
National Brand's Response to Store Brands: Throw In the Towel or Fight Back?
Authors: Nasser Sherif , Turcic Danko , Narasimhan Chakravarthi
Published: May 2013

Nearly a quarter of all products purchased in U.S. supermarkets and drug stores are store brands (SBs). Although the presence of SBs benefits both consumers and retailers, it is a threat to the dominance of the incumbent national brand manufacturers (NBMs). When considering the potential threat of an SB, an NBM generally pursues one of three strategies: accommodate, displace, or buffer. Under the accommodation strategy, the NBM repositions the products in his existing product line. Under the displacement strategy, the NBM elects to supply the SB to preempt the entry of the SB supplier. Under the buffering strategy, the NBM adds a defender product, which competes with his own product offering and the new SB. Using a game-theoretic model, we consider a market where consumers are heterogeneous in their valuation of product quality and analyze an NBM's response to an SB threat. We focus on two important drivers: the NBM's ability to differentiate on the quality dimensions and his cost advantage over the outside supplier of SB. To completely characterize the NBM's response, we consider two regimes. In the first regime, the NBM is a monopolist producer. In the second regime, the retailer has the added option of procuring an SB product from an independent, nonstrategic SB manufacturer. By comparing the results from both regimes, we develop a descriptive theory that clarifies the incentives of the NBM to accommodate, displace, or buffer. In doing this, we determine how the NBM's whole product portfolio should be designed, i.e., the positioning (quality levels) and prices of all its offerings.
Photo-click chemistry strategies for spatiotemporal control of metal-free ligation, labeling, and surface derivatization
Authors: Arumugam Selvanathan , Orski Sara V. , Mbua Ngalle Eric , McNitt Christopher , Boons Geert-Jan , Locklin Jason , Popik Vladimir V.
Published: May 2013

Three photo-click ligation strategies described in this account provide scientists with efficient and selective tools for derivatization of various molecules, polymers, and surfaces. Fast photochemical reactions that are utilized in these techniques permit spatiotemporal control of the process. The absence of activating reagents and catalysts, as well as compatibility with aqueous media, makes photo-click ligations suitable for biomedical applications. The first of these approaches relies on the photochemical decarbonylation of cyclopropenones to produce cyclooctynes. The latter undergo rapid catalyst-free strain-promoted azide–alkyne cycloaddition (SPAAC) to azide-tagged substrates. The second method is based on a very fast (>104M–1s–1) light-triggered hetero-Diels–Alder reaction and permits efficient derivatization of substrates bearing vinyl ether moiety. An even faster reaction between photochemically generated naphthoquinone methides (oNQMs) and thiols (~2 × 105M–1s–1) serves as a basis for a third method. This thiol photo-click chemistry allows for the selective derivatization of thiol-functionalized substrates or labeling of free cysteine residues in proteins. The thioether linkage produced by the reaction ofoNQMs and a thiol is stable under ambient conditions, but can be cleaved by UV irradiation, regenerating free thiol. This feature permits the removal or replacement of immobilized compounds, as well as traceless substrate release.
Extended family history of autoimmune diseases and phenotype and genotype of children with newly diagnosed type 1 diabetes
Authors: Parkkola Anna , Härkönen Taina , Ryhänen Samppa J , Ilonen Jorma , Knip Mikael , _ _
Published: May 2013

Objective

Based on the concept of clustering autoimmunity, children with a positive family history of autoimmunity could be expected to have a different pathogenetic form of type 1 diabetes (T1D) and thus a stronger autoimmune reactivity against β-cells and an increased prevalence of the HLA-DR3-DQ2 haplotype.

Design and methods

We tested this hypothesis in a cross-sectional observational study from the Finnish Pediatric Diabetes Register. HLA class II genotypes and β-cell autoantibodies were analyzed, and data on the extended family history of autoimmunity and clinical markers at diagnosis were collected with a structured questionnaire from 1488 children diagnosed with T1D under the age of 15 years (57% males).

Results

Only 23 children (1.5%) had another autoimmune disease (AID) known at diagnosis, and they had a milder metabolic decompensation at diabetes presentation. One-third (31.4%) had at least one relative with an AID other than T1D with affected mothers being overrepresented (8.2%) compared with fathers (2.8%). The children with a positive family history of other AIDs had higher levels of islet cell antibodies (P=0.003), and the HLA-DR3-DQ2 haplotype in the children was associated with celiac disease in the extended family (P<0.001), but not with an increased frequency of autoimmune disorders, in general.

Conclusions

Approximately one-third of children with newly diagnosed T1D have a first- and/or second-degree relative affected by an AID. Our data do not consistently support the hypothesis of differential pathogenetic mechanisms in such children.
The early evolution of synapsids, and the influence of sampling on their fossil record
Authors: Brocklehurst Neil , Kammerer Christian F. , Fröbisch Jörg
Published: May 2013

Synapsids dominated the terrestrial realm between the late Pennsylvanian and the Triassic. Their early evolution includes some of the first amniotes to evolve large size, herbivory, and macro-predators. However, little research has focused on the changes in diversity occurring during this early phase in their evolutionary history, with more effort concentrating on later events such the Permo-Triassic extinction. Here we assess synapsid diversity, at both the species and genus levels, between the Carboniferous (Moscovian) and the Middle Permian (Capitanian). A raw, taxic diversity (richness) estimate is generated, and we use two separate methods to correct for sampling biases in this curve. To remove the effect of anthropogenic sampling bias, we apply a recently published modification of the residual diversity method, and then generate a supertree, using matrix representation with parsimony to infer ghost lineages and obtain a phylogenetic diversity estimate. The general diversity pattern reflects the initial diversification of synapsids in the late Pennsylvanian and early Cisuralian, which was followed by an extinction event during the Sakmarian. Diversity recovered during the Artinskian and Kungurian, coinciding with the radiation of Caseidae, although other families begin to decline. A second extinction event occurred across the Kungurian/Roadian boundary, in which Edaphosauridae and Ophiacodontidae died out although Caseidae and Therapsida diversified. The sampling-corrected curves reveal further extinction during the Roadian, although therapsids were again unaffected. Pelycosaurian-grade synapsids survived during the Wordian and Capitanian, but were a minor part of an otherwise therapsid-dominated fauna. Evidence of significant anthropogenic sampling bias calls into question previous diversity studies that have not employed sampling correction.
Future use of life-cycle assessment in civil engineering
Authors: Glass Jacqueline , Dyer Tom , Georgopoulos Costas , Goodier Chris , Paine Kevin , Parry Tony , Baumann Henrikke , Gluch Pernilla
Published: May 2013

A LimesNet mission to Chalmers University of Technology, in Sweden, is reported in this paper. The aim of the mission was to explore new ways of exploiting the untapped potential of life-cycle assessment, its application in the civil engineering and construction industries and, specifically, to debate the associated trade-off decisions for reinforced concrete structures (buildings and civil engineering). Life-cycle assessment is an important tool in sustainable design; engineers need robust life-cycle assessment data and must balance this with operational performance considerations (e.g. energy consumption, durability). Through the mission it was clear that much could be learned from the Swedish experience. The UK team noted the importance of life-cycle assessment studies which allow building performance and construction products to be benchmarked and the role of emerging European standards (e.g. product category rules for construction and the development of environmental product declarations). Valuable lessons exist for consulting engineers and materials manufacturers, and there is a need for the greater inclusion of life-cycle assessment skills in the civil engineering education curriculum.
Effects of Metformin, Metformin Plus Rosiglitazone, and Metformin Plus Lifestyle on Insulin Sensitivity and β-Cell Function in TODAY
Authors:   TODAY Study Group
Published: May 2013

OBJECTIVE

The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that combination therapy with metformin plus rosiglitazone provided superior durability of glycemic control compared with metformin alone, with significantly lower treatment failure rates (38.6 vs. 51.7%), and metformin plus lifestyle was intermediate. Herein we describe the temporal changes in measures of β-cell function and insulin sensitivity over a 4-year period among the three treatments.

RESEARCH DESIGN AND METHODS

TODAY participants (699) were tested periodically with an oral glucose tolerance test to determine insulin sensitivity (1/fasting insulin [1/IF]), insulinogenic index (△I30/△G30) or C-peptide index (△C30/△G30), and β-cell function relative to insulin sensitivity (oral disposition index [oDI]).

RESULTS

During the first 6 months, metformin plus rosiglitazone exhibited a significantly greater improvement in insulin sensitivity and oDI versus metformin alone and versus metformin plus lifestyle; these improvements were sustained over 48 months of TODAY. Irrespective of treatment, those who failed to maintain glycemic control had significantly lower β-cell function (∼50%), higher fasting glucose concentration, and higher HbA1c at randomization compared with those who did not fail.

CONCLUSIONS

The beneficial change in insulin sensitivity and the resultant lower burden on β-cell function achieved in the first 6 months with metformin plus rosiglitazone appear to be responsible for its superior glycemic durability over metformin alone and metformin plus lifestyle. However, initial β-cell reserve and HbA1c at randomization are independent predictors of glycemic durability. Therefore, efforts to preserve β-cell function before significant loss occurs and to reduce HbA1c may be beneficial in the treatment of youth with type 2 diabetes.
Comments on the height reducing property
Authors: Akiyama Shigeki , Zaimi Toufik
Published: May 2013

A complex number α is said to satisfy the height reducing property if there is a finite subset, say F, of the ring ℤ of the rational integers such that ℤ[α] = F[α]. This property has been considered by several authors, especially in contexts related to self affine tilings and expansions of real numbers in non-integer bases. We prove that a number satisfying the height reducing property, is an algebraic number whose conjugates, over the field of the rationals, are all of modulus one, or all of modulus greater than one. Expecting the converse of the last statement is true, we show some theoretical and experimental results, which support this conjecture.
Inequality of Chances as a Symmetry Phase Transition
Authors: Rosenblatt Jorge
Published: May 2013

We propose a model for Lorenz curves. It provides two-parameter fits to data on incomes, electric consumption, life expectation and rate of survival after cancer. Graphs result from the condition of maximum entropy and from the symmetry of statistical distributions. Differences in populations composing a binary system (poor and rich, young and old, etc.) bring about chance inequality. Symmetrical distributions insure equality of chances, generate Gini coefficients Gi £ ⅓, and imply that nobody gets more than twice the per capita benefit. Graphs generated by different symmetric distributions, but having the same Gini coefficient, intersect an even number of times. The change toward asymmetric distributions follows the pattern set by second-order phase transitions in physics, in particular universality: Lorenz plots reduce to a single universal curve after normalisation and scaling. The order parameter is the difference between cumulated benefit fractions for equal and unequal chances. The model also introduces new parameters: a cohesion range describing the extent of apparent equality in an unequal society, a poor-rich asymmetry parameter, and a new Gini-like indicator that measures unequal-chance inequality and admits a theoretical expression in closed form.
The Role of Short-Chain Conjugated Poly-(R)-3-Hydroxybutyrate (cPHB) in Protein Folding
Authors: Reusch Rosetta
Published: May 2013

Poly-(R)-3-hydroxybutyrate (PHB), a linear polymer of R-3-hydroxybutyrate (R-3HB), is a fundamental constituent of biological cells. Certain prokaryotes accumulate PHB of very high molecular weight (10,000 to >1,000,000 residues), which is segregated within granular deposits in the cytoplasm; however, all prokaryotes and all eukaryotes synthesize PHB of medium-chain length (~100–200 residues) which resides within lipid bilayers or lipid vesicles, and PHB of short-chain length (<12 residues) which is conjugated to proteins (cPHB), primarily proteins in membranes and organelles. The physical properties of cPHB indicate it plays important roles in the targeting and folding of cPHB-proteins. Here we review the occurrence, physical properties and molecular characteristics of cPHB, and discuss its influence on the folding and structure of outer membrane protein A (OmpA) of Escherichia coli.