Cloning and characterization of a novel human gene related to vascular endothelial growth factor

This paper describes the cloning and characterization of a new member of the vascular endothelial growth factor (VEGF) gene family, which we have designated VRF for VEGF-related-factor. Sequencing of cDNAs from a human fetal brain library and RT-PCR products from normal and tumor tissue cDNA pools indicate two alternatively spliced messages with open reading frames of 621 and 564 bp, respectively. The predicted proteins differ at their carboxyl ends resulting from a shift in the open reading frame. Both isoforms show strong homology to VEGF at their amino termini, but only the shorter isoform maintains homology to VEGF at its carboxyl terminus and conserves all 16 cysteine residues of VEGF165. Similarity comparisons of this isoform revealed overall protein identity of 48% and conservative substitution of 69% with VEGF189. VRF is predicted to contain a signal peptide, suggesting that it may be a secreted factor. The VRF gene maps to the D11S750 locus at chromosome band 11q13, and the protein coding region, spanning approximately 5 kb, is comprised of 8 exons that range in size from 36 to 431 bp. Exons 6 and 7 are contiguous and the two isoforms of VRF arise through alternate splicing of exon 6. VRF appears to be ubiquitously expressed as two transcripts of 2.0 and 5.5 kb; the level of expression is similar among normal and malignant tissues.

Targeting mutant fibroblast growth factor receptors in cancer

Fibroblast growth factor receptors (FGFRs) play diverse roles in the control of cell proliferation, cell differentiation, angiogenesis and development. Activating the mutations of FGFRs in the germline has long been known to cause a variety of skeletal developmental disorders, but it is only recently that a similar spectrum of somatic FGFR mutations has been associated with human cancers. Many of these somatic mutations are gain-of-function and oncogenic and create dependencies in tumor cell lines harboring such mutations. A combination of knockdown studies and pharmaceutical inhibition in preclinical models has further substantiated genomically altered FGFR as a therapeutic target in cancer, and the oncology community is responding with clinical trials evaluating multikinase inhibitors with anti-FGFR activity and a new generation of specific pan-FGFR inhibitors.

Vertical growth and resonator properties of hexagonally shaped zinc oxide nanonails

We synthesized vertically aligned nail-shaped ZnO nanocrystal arrays on silicon substrates via a combination of a carbothermal reduction method and textured ZnO seeding layers that were precoated on silicon substrates by thermally decomposing zinc acetate, and studied their optical properties using cathodoluminescence (CL) and photoluminescence techniques. The ZnO nanonails show a sharp band-gap edge UV emission and a defect-related broad green emission. Monochromatic CL images of an individual ZnO nanonail show variations in spatial distributions of respective CL bands that had different origins. We attribute the spatial variation of CL images to an uneven distribution of luminescent defects and/or a structure-related light out-coupling from hexagonal ZnO nanostructures. The most distinct CL feature from the hexagonal head of an individual ZnO nanonail was the occurrence of a series of distinct resonant peaks within the visible wavelength range. It appeared that the head of a nanonail played the role of a hexagonal cavity so that polarizationdependent whispering gallery modes were stimulated by electron beam excitation.

Catalyst-free growth and optical properties of vertically aligned ZnO Nanorod Arrays on Si substrates covered with thin buffer layers

Vertically aligned ZnO nanorods have been grown on silicon substrates pre-coated with thin, less than 10 nm, textured ZnO seeding layers via a vapor-solid mechanism. The ZnO seeding layers, which were essential for vertical alignment of ZnO nanorods without using any metal catalyst, were prepared by decomposing zinc acetate. The structure and the luminescence properties of the ZnO nanorods synthesized onto ZnO seeding layers were investigated and their morphologies were compared with those of single-crystalline GaN substrates and silicon substrates covered with sputtered ZnO flms. Patterning of ZnO seed layers using photolithography allowed the fabrication of patterned ZnO-nanorod arrays.

Influence of internal fixator stiffness on murine fracture healing : two types of fracture healing lead to two distinct cellular events and FGF-2 expressions

This study aimed to clarify the relationship between the mechanical environment at the fracture site and endogenous fibroblast growth factor-2 (FGF-2). We compared two types of fracture healing with different callus formations and cellular events using MouseFix(TM) plate fixation systems for murine fracture models. Left femoral fractures were induced in 72 ten-week-old mice and then fixed with a flexible (Group F) or rigid (Group R) Mouse Fix(TM) plate. Mice were sacrificed on days 3, 5, 7, 10, 14, and 21. The callus volumes were measured by 3D micro-CT and tissues were histologically stained with hematoxylin & eosin or safranin-O. Sections from days 3, 5, and 7 were immunostained for FGF-2 and Proliferating Cell Nuclear Antigen (PCNA). The callus in Group F was significantly larger than that in Group R. The rigid plate allowed bone union without a marked external callus or chondrogenesis. The flexible plate formed a large external callus as a result of endochondral ossification. Fibroblastic cells in the granulation tissue on days 5 and 7 in Group F showed marked FGF-2 expression compared with Group R. Fibroblastic cells showed ongoing proliferation in granulation tissue in group F, as indicated by PCNA expression, which explained the relative granulation tissue increase in group F. There were major differences in early phase endogenous FGF-2 expression between these two fracture healing processes, due to different mechanical environments.

Hyaluronic acid : evaluation as a potential delivery vehicle for vitronectin:growth factor complexes in wound healing applications

We have previously reported that novel vitronectin:growth factor (VN:GF) complexes significantly increase re-epithelialization in a porcine deep dermal partial-thickness burn model. However, the potential exists to further enhance the healing response through combination with an appropriate delivery vehicle which facilitates sustained local release and reduced doses of VN:GF complexes. Hyaluronic acid (HA), an abundant constituent of the interstitium, is known to function as a reservoir for growth factors and other bioactive species. The physicochemical properties of HA confer it with an ability to sustain elevated pericellular concentrations of these species. This has been proposed to arise via HA prolonging interactions of the bioactive species with cell surface receptors and/or protecting them from degradation. In view of this, the potential of HA to facilitate the topical delivery of VN:GF complexes was evaluated. Two-dimensional (2D) monolayer cell cultures and 3D de-epidermised dermis (DED) human skin equivalent (HSE) models were used to test skin cell responses to HA and VN:GF complexes. Our 2D studies revealed that VN:GF complexes and HA stimulate the proliferation of human fibroblasts but not keratinocytes. Experiments in our 3D DED-HSE models showed that VN:GF complexes, both alone and in conjunction with HA, led to enhanced development of both the proliferative and differentiating layers in the DED-HSE models. However, there was no significant difference between the thicknesses of the epidermis treated with VN:GF complexes alone and VN:GF complexes together with HA. While the addition of HA did not enhance all the cellular responses to VN:GF complexes examined, it was not inhibitory, and may confer other advantages related to enhanced absorption and transport that could be beneficial in delivery of the VN:GF complexes to wounds.

Towards a controlled growth of self-assembled nanostructures: shaping, ordering and localization in Ge/Si heteroepitaxy.

The strain-induced self-assembly of suitable semiconductor pairs is an attractive natural route to nanofabrication. To bring to fruition their full potential for actual applications, individual nanostructures need to be combined into ordered patterns in which the location of each single unit is coupled with others and the surrounding environment. Within the Ge/Si model system, we analyze a number of examples of bottom-up strategies in which the shape, positioning, and actual growth mode of epitaxial nanostructures are tailored by manipulating the intrinsic physical processes of heteroepitaxy. The possibility of controlling elastic interactions and, hence, the configuration of self-assembled quantum dots by modulating surface orientation with the miscut angle is discussed. We focus on the use of atomic steps and step bunching as natural templates for nanodot clustering. Then, we consider several different patterning techniques which allow one to harness the natural self-organization dynamics of the system, such as: scanning tunneling nanolithography, focused ion beam and nanoindentation patterning. By analyzing the evolution of the dot assembly by scanning probe microscopy, we follow the pathway which leads to lateral ordering, discussing the thermodynamic and kinetic effects involved in selective nucleation on patterned substrates.

Relationship to the bereaved and perceptions of severity of trauma differentiate elements of posttraumatic growth

The field of bereavement and grief has been expanding to recognise the potential for growth following the loss of a loved one. This study sought to examine the effect of the relationship to the deceased and perceptions of the severity of the trauma on dimensions of posttraumatic growth. Participants were 146 people who had lost either: a) a first degree relative, b) a second degree relative, or c) a non-related friend. Results demonstrated that both severity and the relationship to the bereaved differentiate posttraumatic growth outcomes. For example, participants who had lost a first degree relative reported higher levels of growth than those who had lost a second degree relative. Consistent with previous research in general trauma populations, the more severe the loss was rated, the higher the levels of growth. Implications for practice are discussed.

Comparison of Kenz Lifecorder EX and ActiGraph accelerometers in 10-yr-old children

A new accelerometer, the Kenz Lifecorder EX (LC; Suzuken Co. Ltd, Nagoya, Japan), offers promise as a feasible monitor alternative to the commonly used Actigraph (AG: Actigraph LLC, Fort Walton Beach, FL). Purpose: This study compared the LC and AG accelerometers and the Yamax SW-200 pedometer (DW) under free-living conditions with regard to children's steps taken and time in light-intensity physical activity (PA) and moderate to vigorous PA (MVPA). Methods: Participants (N = 31, age = 10.2 ± 0.4 yr) wore LC, AG, and DW monitors from arrival at school (7:45 a.m.) until they went to bed. Time in light and MVPA intensities were calculated using two separate intensity classifications for the LC (LC_4 and LC_5) and four classifications for the AG (AG_Treuth, AG_Puyau, AG_Trost, and AG_Freedson). Both accelerometers provided steps as outputs. DW steps were self-recorded. Repeated-measures ANOVA was used to assess overlapping monitor outputs. Results: There was no difference between DW and LC steps (Δ = 200 steps), but a nonsignificant trend was observed in the pairwise comparison between DW and AG steps (Δ = 1001 steps, P = 0.058). AG detected significantly greater steps than the LC (Δ = 801 steps, P = 0.001). Estimates of light-intensity activity minutes ranged from a low of 75.6 ± 18.4 min (LC_4) to a high of 309 ± 69.2 min (AG_Treuth). Estimates of MVPA minutes ranged from a low of 25.9 ± 9.4 min (LC_5) to a high of 112.2 ± 34.5 min (AG_Freedson). No significant differences in MVPA were seen between LC_5 and AG_Treuth (Δ = 4.9 min) or AG_Puyau (Δ = 1.7 min). Conclusion: The LC detected a comparable number of steps as the DW but significantly fewer steps than the AG in children. Current results indicate that the LC_5 and either AG_Treuth or AG_Puyau intensity derivations provide similar mean estimates of time in MVPA during-free living activity in 10-yr-old children.

Factors effecting motor vehicle growth in Dhaka

Dhaka’s traffic is heterogeneous, both motorized (MT) and non-motorized (NMT) transport are common. Traffic congestion has become a part of city dwellers’ lives. This paper explores the factors for motor vehicle growth in Dhaka. The scope of the paper will be limited to literature review...

The growth and international expansion of an emerging market retailer in Latin America

This study contributes to the literature on international retailing by addressing a gap in the literature as to how retailers from emerging markets expand internationally. This historical case study analyzes the growth and internationalization process of Chilean retailer Falabella, one of the largest in Latin America and has been able to compete with multinationals from developed countries. The research is based upon primary and secondary data sources including 33 oral interviews with company managers and family executives, as well as industry data, corporate reports, and trade journals. Drawing on institutional theory, the findings show that by belonging to a family conglomerate, engaging in networks and partnerships, organizational learning, and having an experienced management team helped Falabella gain legitimacy in all international markets.

A fibrocontractive mechanochemical model of dermal wound closure incorporating realistic growth factor kinetics

Fibroblasts and their activated phenotype, myofibroblasts, are the primary cell types involved in the contraction associated with dermal wound healing. Recent experimental evidence indicates that the transformation from fibroblasts to myofibroblasts involves two distinct processes: the cells are stimulated to change phenotype by the combined actions of transforming growth factor β (TGFβ) and mechanical tension. This observation indicates a need for a detailed exploration of the effect of the strong interactions between the mechanical changes and growth factors in dermal wound healing. We review the experimental findings in detail and develop a model of dermal wound healing that incorporates these phenomena. Our model includes the interactions between TGFβ and collagenase, providing a more biologically realistic form for the growth factor kinetics than those included in previous mechanochemical descriptions. A comparison is made between the model predictions and experimental data on human dermal wound healing and all the essential features are well matched.