bluuebunny/crossref_metadata_2025 huggingface dataset:
EGFR ligand switch in late stage prostate cancer contributes to changes in cell signaling and bone remodeling
Authors: DeHaan Alyse M. , Wolters Natalie M. , Keller Evan T. , Ignatoski Kathleen M. Woods
Published: January 2009

BACKGROUND

Bone metastasis occurs frequently in advanced prostate cancer (PCa) patients; however, it is not known why this happens. The epidermal growth factor receptor (EGFR) ligand EGF is available to early stage PCa; whereas, TGF‐α is available when PCa metastasizes. Since the microenvironment of metastases has been shown to play a role in the survival of the tumor, we examined whether the ligands had effects on cell survival and proliferation in early and late PCa.

METHODS

We used LNCaP cells as a model of early stage, non‐metastatic PCa and the isogenic C4‐2B cells as a model of late stage, metastatic PCa.

RESULTS

We found that the proliferation factor MAPK and the survival factor AKT were differentially activated in the presence of different ligands. TGF‐α induced growth of C4‐2B cells and not of the parental LNCaP cells; however, LNCaP cells expressing a constitutively active AKT did proliferate with TGF‐α. Therefore, AKT appeared to be the TGF‐α‐responsive factor for survival of the late stage PCa cells. LNCaP cells exposed to EGF produced more osteoprotegerin (OPG), an inhibitor of bone remodeling, than C4‐2B cells with TGF‐α, which had increased expression of RANKL, an activator of bone remodeling. In concordance, TGF‐α‐treated C4‐2B conditioned medium was able to differentiate an osteoclast precursor line to a greater extent than EGF‐treated C4‐2B or TGF‐α‐treated LNCaP conditioned media.

CONCLUSION

The switch in EGFR ligand availability as PCa progresses affects cell survival and contributes to bone remodeling. Prostate 69:528–537, 2009. © 2009 Wiley‐Liss, Inc.
Comprehensive mutational analysis and mRNA isoform quantification of TP63 in normal and neoplastic human prostate cells
Authors: Parsons J. Kellogg , Saria Elizabeth A. , Nakayama Masashi , Vessella Robert L. , Sawyers Charles L. , Isaacs William B. , Faith Dennis A. , Bova G. Steven , Samathanam Christina A. , Mitchell Rebecca , De Marzo Angelo M.
Published: January 2009

BACKGROUND

The role of TP63 in cancer remains controversial since both oncogenic and tumor suppressive actions have been reported. p63 protein is found in the nuclei of basal cells of the normal prostate, yet it is absent in the vast majority of prostate cancer nuclei. Since a complex array of TP63 mRNA transcripts encode polypeptides with distinct functional properties, it is important to determine which forms are expressed in normal and prostate cancer tissue.

METHODS

We used real‐time RT‐PCR to distinguish TP63 mRNA isoforms in prostate cancer cell lines (n = 7), and samples from prostate cancer patients. We sequenced all TP63 exons from 20 primary tumors, 20 metastases, 28 tumor xenografts, and 7 prostate cancer cell lines.

RESULTS

TP63 mRNA isoforms were present in all tumors, albeit at levels lower than in normal prostate. The most abundant N‐terminal variant was ΔN; the most abundant C‐terminal variant was the α form. The prostate tumor cell line CWR22Rv1 contained a single G to T substitution in exon 8 that is identical to a dominant‐negative DNA binding inactivation mutation occurring in patients with a congenital TP63 deficiency syndrome. One patient tumor contained a somatic mutation in exon 11.

CONCLUSIONS

The pattern of TP63 mRNA expression in normal prostate tissue is retained in reduced amounts in prostate cancer, and a potentially functional TP63 mutation was identified in one prostate tumor. Thus, if TP63 is a prostate cancer gene it likely functions as a tumor suppressor. Further study of the role of TP63 isoforms in regulating stem cell functions of normal and neoplastic prostate epithelial cells is needed. Prostate 69:559–569, 2009. © 2009 Wiley‐Liss, Inc.
Suppression of prostate cancer in a transgenic rat model via γ‐tocopherol activation of caspase signaling
Authors: Takahashi Satoru , Takeshita Kentaro , Seeni Azman , Sugiura Satoshi , Tang Mingxi , Sato Shin‐ya , Kuriyama Hiroki , Nakadate Masao , Abe Koichi , Maeno Yoshitaka , Nagao Masataka , Shirai Tomoyuki
Published: January 2009

BACKGROUND

Epidemiological data indicate that intake of one form of vitamin E, γ‐tocopherol, may reduce prostate cancer risk, and several in vitro studies have demonstrated that γ‐tocopherol can inhibit prostate cancer cell growth. The purpose of the present study was to confirm effects of γ‐tocopherol on prostate cancer in the transgenic rat for adenocarcinoma of prostate (TRAP) model established in our laboratory.

METHODS

In Experiment 1, heterozygous male TRAP rats 5 weeks of age received α‐tocopherol at the concentration of 50 mg/kg in the diet, or γ‐tocopherol at 50 or 100 mg/kg for 10 weeks. In Experiment 2, TRAP rats of 3 weeks of age were given γ‐tocopherol at 50, 100, or 200 mg/kg diet for 7 weeks.

RESULTS

γ‐Tocopherol did not affect body weight gain, organ weights or serum levels of either testosterone or estradiol. However, quantitative evaluation of prostatic lesions demonstrated significantly suppression of sequential progression from PIN to adenocarcinoma in a dose‐dependent manner, along with clear activation of caspases 3 and 7 in the ventral lobe in both experiments.

CONCLUSIONS

The present study clearly demonstrated that γ‐tocopherol suppresses prostate tumor progression in an in vivo TRAP model, and could be a candidate chemopreventive agent for human prostate cancer. Prostate 69:644–651, 2009. © 2009 Wiley‐Liss, Inc.
Bone turnover markers as predictive tools for skeletal complications in men with metastatic prostate cancer treated with zoledronic acid
Authors: Lein Michael , Miller Kurt , Wirth Manfred , Weißbach Lothar , May Christoph , Schmidt Katja , Haus Ulrike , Schrader Mark , Jung Klaus
Published: January 2009

BACKGROUND

Bone turnover markers are helpful to diagnose bone metastases. The aim of this study was to evaluate the usefulness of these markers in prostate cancer patients with bone metastases before and during the treatment with zoledronic acid as predictive and monitoring tools of skeletal‐related events (SRE).

METHODS

One hundred seventeen prostate cancer patients with bone metastases and treated with zoledronic acid (4 mg every 4 weeks) were examined. Fifty‐six patients were with and 61 patients without SRE during a 60‐week study. Total and bone‐specific alkaline phosphatase, and amino‐terminal procollagen propeptides of type‐I‐collagen (PINP), cross‐linked N‐terminal (NTx), cross‐linked C‐terminal telopeptides of type‐I‐collagen (ICTP), and C‐terminal telopeptides of type‐I‐collagen as well as prostate‐specific antigen (PSA) were measured before and 12, 24, 36, 48, and 60 weeks after starting treatment.

RESULTS

Higher baseline concentrations were observed in the SRE group. The bone markers except for ICTP and tALP decreased to 20–80% of the baseline values at week 12 after the drug administration showing a generally higher decline in the non‐SRE group except for NTx. At all time points during treatment higher and increasing concentrations of bone markers were observed in the SRE group compared with non‐SRE group. Cox regression models with clinical data and bone markers showed the baseline NTx concentration as predictor of SREs. During the study, percentage changes of PINP and ICTP were most indicative for SREs.

CONCLUSIONS

Bone markers are useful tools to predict and diagnose SRE in prostate cancer patients with bone metastases under receiving zoledronic acid therapy. Prostate 69:624–632, 2009. © 2009 Wiley‐Liss, Inc.
Dysplasia of human prostate CD133hi sub‐population in NOD‐SCIDS is blocked by c‐myc anti‐sense
Authors: Goodyear S.M. , Amatangelo M.D. , Stearns M.E.
Published: January 2009

BACKGROUND

The CD133hi sub‐population of prostate epithelial cells has been demonstrated to possess tumor‐initiating capacity consistent with that of the cancer stem cell theory. However, the involvement of oncogenes such as c‐myc has not been fully elucidated in the CD133hi sub‐population.

METHODS

We have isolated primary prostate cell strains (IBC‐10a) and immortalized them by transfection with hTERT. The in vitro and in vivo tumorigenic capacity of isolated CD133hi and CD133lo cells was evaluated with respect to c‐myc expression using specific sense and anti‐sense oligonucleotides.

RESULTS

Freshly immortalized cells consisted of <3.3% CD133hi/CD24hi sub‐population (SP). “Prostaspheres” generated from single CD133hi cells in the presence of EGF consisted of ∼10% CD133hi SPs in 12–21 day cultures. A single Prostasphere generated from single CD133hi cells (6–10 cell stage at day 6 injected i.t) produced dysplastic lesions in NOD‐SCID mice (n = 4/5). Treatment of Prostaspheres from CD133hi SPs in vitro with c‐myc or cyclin D1 anti‐sense oligonucleotides totally blocked colony forming ability and growth. Furthermore, treatment of fully formed, 6‐day Prostaspheres for 48 hr with c‐myc anti‐sense significantly reduced c‐myc expression and their ability to generate lesions in NOD‐SCIDs (n = 10 Prostaspheres injected i.t./mouse).

CONCLUSIONS

These data demonstrate for the first time that a single CD133hi cell is competent to generate Prostaspheres in vitro and that CD133hi Prostaspheres require c‐myc to grow and form dysplastic lesions in vivo. Prostate 69: 689–698, 2009. © 2009 Wiley‐Liss, Inc.
Staying in school: assessing the role of access, availability, and economic opportunities – the case of Tajikistan
Authors: Baschieri Angela , Falkingham Jane
Published: January 2009

At independence in 1991, Tajikistan enjoyed almost universal literacy, reflecting the legacy of social development achieved during the Soviet period. However, since then the country has undergone immense economic, political and social upheaval, including civil war. As a consequence, the gains of the past are quickly being eroded. Recent evidence suggests that school attendance rates are declining, the gender gap is widening, and there is increasing geographical variation. This paper uses a unique source of data to investigate the relative roles of individual, household, and contextual factors to determine whether or not a child attends basic education in Tajikistan. Applying multilevel modelling and geographical information system techniques, the results show that contextual factors have a strong effect on school attendance. In particular, the accessibility and availability of school services and the quality of education have a positive effect. However, the level of economic development of the community in which the child lives exerts a negative effect on school attendance, reflecting the influence of higher opportunity costs of education in terms of the opportunities for income‐generating activities forgone. This has implications for educational policy, highlighting that a joined‐up approach is necessary to foster local economic development and to lower school dropout rates. Copyright © 2009 John Wiley & Sons, Ltd.
Ageing and temperature‐dependent behaviour of CdS nanoparticles
Authors: Bhattacharya Bhaskar , Tomar Sandeep Kumar , Saxena Amit , Lee Jun Young , Park Jung‐Ki
Published: January 2009

Nanoparticles of inorganic semiconductors in the form of colloids have attracted researchers due to their interesting optical properties. We report the process of the controlled coalescence of the nanoparticles in a colloid with time and also with temperature. Cadmium sulfide (CdS) nanoparticles were prepared in ethylene glycol (EG). The size of the particles was estimated by X‐ray diffraction and transmission electron microscopy and matched with the optical absorption data. The particles in the EG matrix were subjected to controlled annealing and the shift in the absorption edge towards its bulk value (∼2.4 eV) was monitored. The change in the band‐gap value has been used to calculate the increasing particle radii using the effective‐mass model. A similar effect is also reported with ageing of these particulates. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Optical orientation of electron and nuclear spins in strain free GaAs quantum dots grown by droplet epitaxy
Authors: Belhadj Thomas , Kuroda Takashi , Simon Claire‐Marie , Amand Thierry , Mano Takaaki , Sakoda Kazuaki , Koguchi Nobuyuki , Marie Xavier , Urbaszek Bernhard
Published: January 2009

We report optical orientation experiments in individual, strain free GaAs quantum dots in AlGaAs grown by modified droplet epitaxy. Circularly polarized optical excitation yields strong circular polarization of the resulting photoluminescence at 4 K. Optical injection of spin polarized electrons into the dot gives rise to dynamical nuclear polarization that considerably changes the exciton Zeeman splitting (Overhauser shift). We show that the created nuclear polarization is bistable and present a direct measurement of the build‐up time of the nuclear polarization in a single GaAs dot in the order of a second. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Polarization of emission from self‐assembled quantum dots and its application to the optical characterization of structure
Authors: Sheng Weidong
Published: January 2009

We revisit the optical anisotropy in quantum dots by using a tight‐binding approach. The mechanisms how shape anisotropy and strain field lead to optical anisotropy are identified. As the anisotropic structure of quantum dots imposes stronger confinement for the localized p‐orbitals aligning along the short axis, the valence‐band electrons prefer to occupy the orbitals aligning along the long axis, which leads to partially linear‐polarized interband emission. For intersubband transitions, the symmetry of those minor components from the valence bands in the electronic states is shown to account for the linear‐polarized absorption, which presents a picture different from that by the single‐band effective‐mass approximation. The dependence of polarization of the primary interband transition on the lateral aspect ratio of the structures is found to be insensitive to the random intermixing effects, which make it an appropriate tool for structure characterization. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Study of growth behaviour and microstructure of epitaxially grown self‐assembled Ge quantum dots on nanometer‐scale patterned SiO2/Si(001) substrates
Authors: Yoon Tae‐Sik , Kim Hyun‐Mi , Kim Ki‐Bum , Ryu Du Yeol , Russell Thomas P. , Zhao Zuoming , Liu Jian , Xie Ya‐Hong
Published: January 2009

The growth behaviour and microstructure of epitaxially grown self‐assembled Ge quantum dots on patterned SiO2/Si(001) substrates by molecular beam epitaxy were studied. The hexagonally ordered Si holes with 30 nm thick SiO2 mask layer having ∼25 nm diameter, ∼40 nm center‐to‐center distance, and density of ∼7 × 1010 cm–2, were formed using self‐assembled diblock copolymer, composed of polystyrene and poly(methyl methacrylate) (PS‐b ‐PMMA). The multiple Ge nuclei are selectively formed along the periphery of the individual Si holes and these nuclei subsequently coalesce forming single dot with an identical size of patterns. The strain of dots is relaxed up to 80%. The lattice planes of some Ge dots are found to be tilted from those of Si substrates. The Ge dots have dislocations at the interface with Si substrate even at the small size of ∼25 nm, resulting from the limited elastic relaxation in the confined patterned structure. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ordering of GaAs quantum dots by droplet epitaxy
Authors: Mano Takaaki , Kuroda Takashi , Noda Takeshi , Sakoda Kazuaki
Published: January 2009

Step‐edge‐induced ordering of GaAs QDs was achieved on GaAs(110) by droplet epitaxy in a lattice‐matched GaAs/AlGaAs system. After the growth of an AlGaAs barrier layer, step‐edges along the 〈113〉, 〈112〉, 〈111〉, and 〈221〉 directions were naturally formed. On these step‐edges, preferential nucleation of Ga droplets occurred, resulting in the formation of one‐dimensionally ordered Ga droplets. By irradiating intense As4 flux, we could form ordered GaAs QDs. Some of the arrays were longer than 1 μm and the QDs in the arrays were closely packed. After capping of the QDs followed by rapid thermal annealing, the ordered QD arrays exhibited strong photoluminescence emission. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Theory of electron–hole exchange interaction in double quantum dots
Authors: Ramirez Hanz Y. , Cheng Shun‐Jen , Chang Chih‐Pin
Published: January 2009

A theory of electron–hole exchange interaction in vertically stacked double quantum dots is developed. This theory was built up from the full interacting Hamiltonian of two coupled dots, taking into account both of the macroscopic and microscopic natures of particle wave functions. In the basis of S‐type Fock–Darwin orbitals, compact formulations for electron–hole exchange terms responsible for the fine structure splitting of spin exciton states as functions of material parameters, geometric structure of dots, and the strength of external field are explicitly derived. Significant reduction of the splitting, down to 50% of the magnitude of such energy in single dot cases, is observed as the system is switched into the near‐resonance regime. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Ellagitannin (BJA3121), an anti‐proliferative natural polyphenol compound, can regulate the expression of MiRNAs in HepG2 cancer cells
Authors: Wen Xiao‐Yun , Wu Shao‐Yu , Li Zhi‐Qin , Liu Zhong‐qiu , Zhang Jia‐Jie , Wang Guang‐Fa , Jiang Zhi‐Hong , Wu Shu‐Guang
Published: January 2009

MicroRNAs (miRNAs) play an important role in cancers. A number of miRNA expression‐profiling studies have been done to identify the miRNA signatures of cancers from different cellular origin. There is, however, relatively little information on how anticancer agents regulate miRNA expression. Ellagitannin (BJA3121), 1,3‐Di‐O‐galloyl‐4,6‐(s)‐HHDP‐b‐D‐glucopyranose, is a new natural polyphenol compound isolated from Balanophora Japonica MAKINO. Our preliminary results have shown that BJA3121 had antiproliferative effect and modified the expression of different genes in human HepG2 cancer cells. In this study, we further evaluate whether this antineoplastic compound is able to alter miRNA expression in HepG2 cells. We demonstrated for the first time that BJA3121 can regulate the expression of 25 miRNAs, including 17 upregulated and 8 downregulated miRNAs in HepG2 cells. Our results suggested that BJA3121‐modifed miRNA expression can mediate, at least in part, the antiproliferative and multigene regulatory action induced by the compound on HepG2 cancer cells. Copyright © 2009 John Wiley & Sons, Ltd.
Anti inflammatory effect of natural honey on bovine thrombin‐induced oxidative burst in phagocytes
Authors: Ahmad Asif , Khan Rafeeq Alam , Mesaik M. Ahmed
Published: January 2009

Thrombin, hyperglycemia and reactive oxygen species (ROS) have been discovered to play a pivotal role in the pathogenesis of cardiovascular disease (CVD). The aim of the study was to evaluate the direct effect of bovine thrombin (BTh) on ROS production by human neutrophils and rodent macrophages and to investigate the effect of honey on BTh‐induced ROS production from phagocytes.

Professional phagocytes, i.e. neutrophils and macrophages, were stimulated by BTh and ROS production was measured in luminol/lucigenin enhanced chemiluminescence (CL) assays. In another experiment the effects of honey treatment on BTh‐induced ROS production by phagocytes was tested using a CL assay.

The results indicate that BTh directly activates phagocytes. A significant generation of ROS was noted with the luminol/lucigenin enhanced chemiluminescence (CL) system. Honey treatment of phagocytes activated by bovine thrombin showed effective suppression of oxidative respiratory burst monitored by the CL assay.

In conclusion, it can be assumed that this direct action of BTh on phagocytes causing ROS production might exaggerate the inflammatory response at the site of atheromatous plaques. The suppressive activity of honey towards thrombin‐induced ROS production by phagocytes could be beneficial in the interruption of the pathological progress of CVD and may play a cardioprotective role. Copyright © 2009 John Wiley & Sons, Ltd.
Improved effect of Pycnogenol® on impaired spatial memory function in partial androgen deficiency rat model
Authors: Hasegawa Noboru , Mochizuki Miyako
Published: January 2009

The improved effect of Pycnogenol® on impaired spatial memory function was studied in orchidectomized rats. Endogenous testosterone levels were decreased by approximately one‐half for 3 months after castration. In the radial arm maze, castration significantly impaired working and reference memory function without lowering motor function. Pycnogenol® increased the NGF content in the hippocampus and cortex, and improved the spatial memory impairment. These observations confirmed that diagnostic accuracy can be improved by Pycnogenol® in androgen‐deficient rats. Copyright © 2009 John Wiley & Sons, Ltd.
A systematic review on the effectiveness of willow bark for musculoskeletal pain
Authors: Vlachojannis J. E. , Cameron M. , Chrubasik S.
Published: January 2009

Since ancient times preparations from Salix species have been used to alleviate pain. The aim of this study was to update the evidence of the effectiveness of willow bark products in the treatment of musculoskeletal pain. OVID(MEDLINE), PUBMED, Silverplatter, and CENTRAL and manual searches were used to identify clinical trials investigating Salix preparations. Authors SC and JEV extracted the data independently and discussed disagreements.

Seven manuscripts were identified, reporting four trials with confirmatory and four with exploratory study designs. Three manuscripts presented the same trial data: repetitious reports were excluded. One confirmatory and two exploratory studies indicate a dose‐dependent analgesic effect not inferior to rofecoxib in patients with low back pain. In one exploratory and one confirmatory study conflicting results were achieved in participants with osteoarthritis. No significant effect was seen in a confirmatory study in patients with rheumatoid arthritis, but this study was grossly underpowered. All studies investigated ethanolic extracts with daily doses up to 240 mg salicin over periods of up to six weeks. Minor adverse events occurred during treatment.

The review provides moderate evidence of effectiveness for the use of ethanolic willow bark extract in low back pain. Further studies are required to find out if treatment of osteoarthritis and rheumatoid arthritis requires extract with higher doses than 240 mg salicin per day. Copyright © 2009 John Wiley & Sons, Ltd.
Aircraft‐based observations of air–sea fluxes over Denmark Strait and the Irminger Sea during high wind speed conditions
Authors: Petersen G. N. , Renfrew I. A.
Published: January 2009

During the Greenland Flow Distortion experiment (GFDex), aircraft‐based observations of air–sea fluxes were obtained over Denmark Strait and the Irminger Sea. High‐frequency observations of velocity, temperature and water vapour have been used to calculate turbulent fluxes of momentum, heat and moisture using the eddy covariance method. These are the first direct air–sea flux observations in this region, and add to the relatively small collection of direct air–sea flux observations made in high wind speed conditions. The aircraft‐based turbulence legs were flown at remarkably low levels, only 30–50 m above the sea‐surface and so within the atmospheric surface layer. Results are presented for 145 flux runs, each of 2 min (approximately 12 km), 131 over open water and 14 over sea ice and the marginal ice zone. The flux data were obtained in 10 m neutral wind speeds of up to 25 m s−1, with 80% of the flux data in the range 15–19 m s−1.

Over open water, the wind stress varied from 0.2 to 1.9 N m−2 and the surface sensible and latent heat fluxes from 50 to 300 W m−2, resulting in total surface heat fluxes of up to 600 W m−2. The exchange coefficients are at the upper end of those previously observed. Mean values for the 15–19 m s−1 range are CDN = 2.04 × 10−3, CHN = 1.63 × 10−3 and CEN = 1.57 × 10−3 for momentum, heat and moisture, respectively. The value of the momentum exchange coefficient is in line with previous studies; however, both the heat and moisture exchange coefficients are higher than in previous studies. Values of CDN over sea ice and the marginal ice zone were in the range 1.67–6.29 × 10−3 and were, for these conditions, generally higher than CDN over adjacent open water areas. No significant spatial patterns in the exchange coefficients over open water have been detected, although there is some suggestion of higher exchange coefficients immediately downwind of the sea ice. Copyright © 2009 Royal Meteorological Society
The impact of a mesoscale convective system cold pool on the northward propagation of the intertropical discontinuity over West Africa
Authors: Flamant C. , Knippertz P. , Parker D. J. , Chaboureau J.‐P. , Lavaysse C. , Agusti‐Panareda A. , Kergoat L.
Published: January 2009

The interaction between a mesoscale convection system cold pool and the intertropical discontinuity (ITD) is investigated on two consecutive days (5 and 6 June 2006), in the framework of the African Monsoon Multidisciplinary Analysis Special Observing Period (SOP 1a). Satellite imagery and surface meteorological observations are used to track the movement of the ITD prior to and after its interaction with the cold pool. The impact of the northward propagating cold pool on the Sahelo‐Saharan planetary boundary layer (PBL) thermodynamics and aerosol vertical distribution is analyzed by means of airborne and ground‐based measurements over the two‐day period. Complementary European Centre for Medium‐range Weather Forecasts (ECMWF) analyses are also used. The influence of the cold pool persists as a coherent dynamic and thermodynamic structure over these two study days, influencing a front at least 1000 km long and approximately 200 km wide, spreading across southern Mali. Dropsonde measurements revealed that the cold pool was bringing moisture quite far north over the northern Sahel and to the southern fringes of the Sahara, as well as cooling the desert surface. As a result, the vertical development of the Sahelo‐Saharan PBL was found to be delayed on 6 June compared with 5 June. Further north, over the part of the Sahara not impacted by the propagating cold pool, the airborne measurements suggest that the large amounts of dust in the upper part of the Saharan aerosol layer, as observed by lidar, may also have had an impact on the Saharan PBL, by reducing the insolation in this region. The airborne observations were also used to assess the quality of the ECMWF analyses at 1200 UTC on 5 and 6 June, as well as + 36 h, + 24 h and + 12 h forecasts valid at 1200 UTC on 6 June. A quantitative improvement was seen in the 6 June forecast valid at 1200 UTC once information relevant to the propagation of the ITD was assimilated, i.e. for the + 24 h and + 12 h forecasts. The analyses were able to reproduce the northward surge of moisture associated with the cold pool, suggesting that ECMWF analyses may be used to analyze the role of propagating density currents on the so‐called monsoon onset mechanism. Copyright © 2009 Royal Meteorological Society
Fourier transform ion cyclotron resonance mass spectral characterization of metal‐humic binding
Authors: Stenson Alexandra C.
Published: January 2009

The interaction between metals and naturally occurring humic substances and the thereby induced issues of bioavailability and hydrogeochemical turnover of metal ions in natural waters have been the subject of intense study for decades. Traditional bulk techniques to investigate metal‐humic binding (e.g. potentiometry and inductively coupled plasma mass spectrometry (ICP‐MS)) can provide quantitative results for the relative abundance and distribution of metal species in humic samples and/or overall binding constants. The shortcoming of these bulk techniques is the absence of structural detail. Ultra‐high‐resolution mass spectrometry, currently the only technique demonstrated to resolve individual humic ions, is not generally employed to provide the missing qualitative information primarily because the identification of metal complexes within the already complex mixtures of humic substances is non‐trivial and time‐consuming to the extent of eliminating any possibility for real‐time manipulation of chelated analytes. Here, it is demonstrated that with tailored selection of the metal ion, it is possible to visually identify large numbers of metal‐humic complexes (∼500 for Be2+, ∼1100 for Mn2+, and ∼1500 for Cr3+) in real‐time as the spectra are being acquired. Metal ions are chosen so that they form primarily even‐m/z complexes with humic ions. These even‐m/z complexes stand out in the spectrum and can readily be characterized based on molecular formulae, which here revealed for example that Suwannee River fulvic acid (SRFA) complexes encompassed primarily highly oxygenated fulvic acids of relatively low double‐bond equivalence. Facile, real‐time identification of even‐m/z metal‐humic complexes additionally allows for the specific selection of metal‐humic complexes for MSn analysis and in‐trap ion‐neutral reactions enabling investigation of metal‐humic complex structure. MS/MS data were collected to demonstrate the potential of the technique as well as highlight some of the remaining challenges. Copyright © 2009 John Wiley & Sons, Ltd.
A recycling framework for the construction of Bonferroni‐based multiple tests
Authors: Burman C.‐F. , Sonesson C. , Guilbaud O.
Published: January 2009

In this paper we describe Bonferroni‐based multiple testing procedures (MTPs) as strategies to split and recycle test mass. Here, ‘test mass’ refers to (parts of) the nominal level α at which the family‐wise error rate is controlled. Briefly, test mass is split between different null hypotheses, and whenever a null hypothesis is rejected, the part of α allocated to it may be recycled to the testing of other hypotheses. These recycling MTPs are closed testing procedures based on raw p‐values associated with testing the individual null hypotheses, and the class of such MTPs includes, for example, serial and parallel gatekeeping, fallback and Holm procedures. Graphical displays and a concise algebraic notation are provided for such MTPs. This recycling approach has pedagogical advantages and may facilitate the tailoring of MTPs for different purposes. Copyright © 2009 John Wiley & Sons, Ltd.
Flexibility in internationalization: is it valuable during an economic crisis?
Authors: Lee Seung‐Hyun , Makhija Mona
Published: January 2009

This study investigates the value of the strategic flexibility provided by firms' international investments during an economic crisis, defined here as an unanticipated significant downturn in the economy. To avoid below‐par performance, firms need to adapt quickly to this significant change in their environment, making real options very valuable to them. Although firms' international investments can potentially provide such flexibility, this issue has not been empirically examined in a context of such dramatic negative change. We consider two types of international investments by firms in this regard, foreign direct investments and export‐related international investments, developing two measures that directly assess the flexibility derived from each that are new to the literature. Based on these measures, we find evidence that both types of international investments provided valuable flexibility for Korean firms during the economic crisis conditions. This study contributes to the literature by showing that firms with real options investments in place have a greater ability to flexibly adapt their overall operations in line with unforeseen negative environmental change, in contrast to firms without such investments. Copyright © 2009 John Wiley & Sons, Ltd.
From crisis to opportunity: environmental jolt, corporate acquisitions, and firm performance
Authors: Wan William P. , Yiu Daphne W.
Published: January 2009

This study incorporates the external environmental context into the study of corporate acquisitions by examining the performance implications of corporate acquisitions during an environmental jolt that alters the levels of environmental munificence. We posit that compared to the periods before and after an environmental jolt, corporate acquisitions during a jolt would be positively related to firm performance. Furthermore, we suggest that organizational slack would improve firm performance and accentuate the positive relationship between corporate acquisitions and firm performance during an environmental jolt; however, it would have negative impact on firm performance and make the acquisition‐performance relationship more negative before and after a jolt. Using the Asian Economic Crisis as a natural experiment, we found general support for our core arguments based on a sample of firms from Hong Kong and Singapore. Our work demonstrates that firms can capitalize on the opportunities created by the changes in an environmental jolt. Copyright © 2009 John Wiley & Sons, Ltd.
Single photon emission computed tomography experience with (S)‐5‐[123I]iodo‐3‐(2‐azetidinylmethoxy)pyridine in the living human brain of smokers and nonsmokers
Authors: Brašić James Robert , Zhou Yun , Musachio John L. , Hilton John , Fan Hong , Crabb Andrew , Endres Christopher J. , Reinhardt Melvin J. , Dogan Ahmet S. , Alexander Mohab , Rousset Olivier , Maris Marika A. , Galecki Jeffrey , Nandi Ayon , Wong Dean F.
Published: January 2009

(S)‐5‐[123I]iodo‐3‐(2‐azetidinylmethoxy)pyridine (5‐[123I]IA), a novel potent radioligand for high‐affinity α4β2* neuronal nicotinic acetylcholine receptors (nAChRs), provides a means to evaluate the density and the distribution of nAChRs in the living human brain. We sought in healthy adult smokers and nonsmokers to (1) evaluate the safety, tolerability, and efficacy of 5‐[123I]IA in an open nonblind trial and (2) to estimate the density and the distribution of α4β2* nAChRs in the brain. Single photon emission computed tomography (SPECT) was performed for 5 h after the i.v. administration of ∼0.001 μg/kg (∼10 mCi) 5‐[123I]IA. Blood pressure, heart rate, and neurobehavioral status were monitored before, during, and after the administration of 5‐[123I]IA to 12 healthy adults (8 men and 4 women) (6 smokers and 6 nonsmokers) ranging in age from 19 to 46 years (mean = 28.25, standard deviation = 8.20). High plasma‐nicotine level was significantly associated with low 5‐[123I]IA binding in: (1) the caudate head, the cerebellum, the cortex, and the putamen, utilizing both the Sign and Mann–Whitney U‐tests; (2) the fusiform gyrus, the hippocampus, the parahippocampus, and the pons utilizing the Mann–Whitney U‐test; and (3) the thalamus utilizing the Sign test. We conclude that 5‐[123I]IA is a safe, well‐tolerated, and effective pharmacologic agent for human subjects to estimate high‐affinity α4/β2 nAChRs in the living human brain. Synapse 63:339–358, 2009. © 2009 Wiley‐Liss, Inc.
Ferritin nanoparticles as magnetic resonance reporter gene
Authors: Cohen Batya , Ziv Keren , Plaks Vicki , Harmelin Alon , Neeman Michal
Published: January 2009

Dynamic imaging of gene expression in live animals is among the exciting challenges of molecular imaging. To achieve that, one of the approaches is to use reporter genes that encode for the synthesis of easily detectable products. Such reporter genes can be designed to be expressed under the control of the regulatory elements included in a promoter region of a gene of interest, thus allowing the use of the same reporter gene for the detection of multiple genes. The most commonly used reporter genes include the firefly light‐generating enzyme luciferase and the green fluorescent protein detectable by bioluminescence and fluorescence optical imaging, respectively. Over the last years a number of studies demonstrated the ability to use the iron‐binding protein ferritin as a reporter gene that allows the detection of gene expression by magnetic resonance imaging (MRI). MRI provides high spatial resolution and soft tissue contrast for deep tissues along with a large arsenal of functional and anatomical contrast mechanisms that can be correlated with gene expression, and can potentially be translated into clinical use Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
In vivovisualization of macrophage infiltration and activity in inflammation using magnetic resonance imaging
Authors: Beckmann Nicolau , Cannet Catherine , Babin Anna Louise , Blé François‐Xavier , Zurbruegg Stefan , Kneuer Rainer , Dousset Vincent
Published: January 2009

Because macrophages play a key role on host defense, visualization of the migration of these cells is of high relevance for both diagnostic purposes and the evaluation of therapeutic interventions. The present article addresses the use of iron oxide and gadolinium‐based particles for the noninvasivein vivodetection of macrophage infiltration into inflamed areas by magnetic resonance imaging (MRI). A general introduction on the functions and general characteristics of macrophages is followed by a discussion of some of the agents and acquisition schemes currently used to track the cellsin vivo. Attention is then devoted to preclinical and clinical applications in the following disease areas: atherosclerosis and myocardial infarction, stroke, multiple sclerosis, rheumatoid arthritis, and kidney transplantation Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Using nanoparticles to push the limits of detection
Authors: Wittenberg Nathan J. , Haynes Christy L.
Published: January 2009

The size‐dependent chemical and physical properties of nanoparticles inspire the design of unique assays and the use of new detection schemes while also offering the opportunity to vastly improve the results achieved when using traditional signal transduction methods. Herein, the most commonly exploited nanoparticle amplification schemes are organized and reviewed on the basis of the detection methods used to monitor the nanoparticle property of interest. The topics covered include the improved signal photostability and brightness of semiconductor quantum dots, the increased extinction coefficient of noble metal nanoparticles, the advantages of having a magnetic label on individual target molecules to facilitate separation, the multiplexing that is enabled with ‘barcoded’ nanoparticles, and the greatly amplified signals that can be achieved on the basis of conductivity changes, generated current, or simply by adding a ‘massive’ nanoparticle onto a small molecule target. Common approaches emerge among different nanoparticle materials and detection schemes, and it is also clear that there is still significant opportunity to use nanoparticles in as‐yet‐unimagined ways to further improve assay and sensor limits of detection Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Nanotechnology Approaches to Biology > Cells at the Nanoscale
Occupational exposure to nanomedical applications
Authors: Murashov Vladimir
Published: January 2009

Applications of nanotechnology in medicine such as cancer treatment drugs, imaging agents, and sensors promise to save people's lives and improve quality of life. Although only a limited number of nano‐enabled medical applications are commercially available at this time, many are in the final stages of approval by regulatory agencies overseeing medical applications. Workers' exposure to nano‐enabled medical applications in research and development laboratories and manufacturing facilities can already occur. This article reviews the information available on exposure to nano‐enabled medical applications in occupational settings such as manufacturing and health care facilities. First, this report reviews monitoring exposure to conventional medical applications. Next, it describes monitoring exposure to nanomaterials. And, finally, it summarizes monitoring exposure to nano‐enabled medical applications highlighting their unique aspects Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
In vivo fluorescence imaging: a personal perspective
Authors: Ghoroghchian P. Peter , Therien Michael J. , Hammer Daniel A.
Published: January 2009

In vivo fluorescence imaging with near‐infrared (NIR) light holds enormous potential for a wide variety of molecular diagnostic and therapeutic applications. Because of its quantitative sensitivity, inherent biological safety, and relative ease of use (i.e., with respect to cost, time, mobility, and its familiarity to a diverse population of investigators), fluorescence‐based imaging techniques are being increasingly utilized in small‐animal research. Moreover, there is substantial interest in the translation of novel optical techniques into the clinic, where they will prospectively aid in noninvasive and quantitative screening, disease diagnosis, and post‐treatment monitoring of patients. Effective deep‐tissue fluorescence imaging requires the application of exogenous NIR‐emissive contrast agents. Currently, available probes fall into two major categories: organic and inorganic NIR fluorophores (NIRFs). In the studies reviewed herein, we utilized polymersomes (50 nm to 50 µm diameter polymer vesicles) for the incorporation and delivery of large numbers of highly emissive oligo (porphyrin)‐based, organic NIRFs Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies
Current status of nanotechnology approaches for cardiovascular disease: a personal perspective
Authors: Buxton Denis B
Published: January 2009

Nanotechnology is poised to have an increasing impact on cardiovascular health in coming years. Diagnostically, multiplexed point‐of‐care devices will enable rapid genotyping and biomarker measurement to optimize and tailor therapies for the individual patient. Nanoparticle‐based molecular imaging agents will take advantage of targeted agents to provide increased insight into disease pathways rather then simply providing structural and functional information. Drug delivery will be impacted by targeting of nanoparticle‐encapsulated drugs to the site of action, increasing the effective concentration and decreasing systemic dosage and side effects. Controlled and tailored release of drugs from polymers will improve control of pharmacokinetics and bioavailability. The application of nanotechnology to tissue engineering will facilitate the fabrication of better tissue implants in vitro, and provide scaffolds to promote regeneration in vivo taking advantage of the body's own repair mechanisms. Medical devices will benefit from the development of nanostructured surfaces and coatings to provide better control of thrombogenicity and infection. Taken together, these new technologies have enormous potential for improving the diagnosis and treatment of cardiovascular diseases Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease
Anti‐angiogenic perfluorocarbon nanoparticles for diagnosis and treatment of atherosclerosis
Authors: Caruthers Shelton D. , Cyrus Tillmann , Winter Patrick M. , Wickline Samuel A. , Lanza Gregory M.
Published: January 2009

Complementary developments in nanotechnology, genomics, proteomics, molecular biology and imaging offer the potential for early, accurate diagnosis. Molecularly‐targeted diagnostic imaging agents will allow noninvasive phenotypic characterization of pathologies and, therefore, tailored treatment close to the onset. For atherosclerosis, this includes anti‐angiogenic therapy with specifically‐targeted drug delivery systems to arrest the development of plaques before they impinge upon the lumen. Additionally, monitoring the application and effects of this targeted therapy in a serial fashion will be important. This review covers the specific application of ανβ3‐targeted anti‐angiogenic perfluorocarbon nanoparticles in (1) the detection of molecular markers for atherosclerosis, (2) the immediate verification of drug delivery with image‐based prediction of therapy outcomes, and (3) the serial, noninvasive observation of therapeutic efficacy Copyright © 2009 John Wiley & Sons, Inc.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease
Complexes of N‐Thiophosphorylthiourea α‐NaphthylNHC(S)NHP(S)(OiPr)2 (HL) with Copper(I). Crystal Structures of HL and Cu(PPh3)2L
Authors: Babashkina Maria G. , Safin Damir A. , Szyrwiel Łukasz , Kubiak Maria , Sokolov Felix D. , Starikov Yuri V. , Kozlowski Henryk
Published: January 2009

Reaction of the potassium salt of N‐thiophosphorylated thiourea α‐naphthylNHC(S)NHP(S)(OiPr)2 (HL) with Cu(PPh3)3I in aqueous EtOH/CH2Cl2 leads to the mononuclear complex [Cu(PPh3)2L–S,S′]. By using copper(I) iodide instead ofCu(PPh3)3I, the polynuclear complex [Cun(L–S,S′)n] was obtained. The structures of these compounds were investigated by elemental analysis, 1H and 31P{1H} NMR and IR spectroscopy. The crystal structures of HL and Cu(PPh3)2L were determined by single‐crystal X‐ray diffraction.
Luminol/H2O2/KSCN/CuSO4 Oscillating Chemiluminescence System in the Presence of Complexing Agents
Authors: Samadi‐Maybodi Abdolraouf , Akhoondi Reza
Published: January 2009

The oscillating system luminol/H2O2/KSCN/CuSO4 with (2‐hydroxyethyl)trimethylammoniumhydroxide (2‐HETMAOH) was investigated by using luminometry technique. Temperature and solvent effects on the behavior of the oscillating system were studied. The influences of complexing agents such as ethylenediaminetetraacetic acid (EDTA) and methionine were also investigated for this system. All experiments were performed by using the luminometer technique in a batch reactor.
The thickness of the intestinal mucous layer in the colon of rats fed various sources of non-digestible carbohydrates is positively correlated with the pool of SCFA but negatively correlated with the proportion of butyric acid in digesta
Authors: Hedemann Mette S. , Theil Peter K. , Bach Knudsen K. E.
Published: January 2009

The present experiment aimed to study the influence of six sources of non-digestible carbohydrates (NDC) on the mucous layer in the colon of rats. The NDC sources used were as follows: cellulose (C); pectin (P); inulin; resistant starch (RS); barley hulls. The diets contained 108–140 g NDC/kg DM. A fibre-free (FF) diet served as a control. The diets were fed to forty-eight rats for 34–41 d. The thickness of the total mucous layer in the colon was increased (P < 0·05) in rats fed C, P and RS when compared with rats fed a FF diet. In the colon, positive correlations were observed between the total thickness of the mucous layer and the area of neutral mucins, the pool of SCFA and the pool of acetic acid, while it was negatively correlated with the proportion of butyrate. The total thickness of the mucous layer was not correlated with the MUC gene transcription. The transcription of the gene MUC2 was negatively correlated (P = 0·04), whereas the transcription of MUC3 was positively correlated (P = 0·05) with the butyrate pool in the caecum. No correlations between the MUC2 or MUC3 transcription and SCFA were found in the colon. Hence, the regulation of the MUC genes differs between the compartments of the hindgut and, within compartments, the MUC genes may be regulated differently. In conclusion, a diet providing a large pool of SCFA with a low proportion of butyrate in the colon stimulates the formation of a thick mucous layer, which probably benefits intestinal health.