bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of SHIP in the Development and Activation of Mouse Mucosal and Connective Tissue Mast Cells
Authors: Ruschmann Jens , Antignano Frann , Lam Vivian , Snyder Kim , Kim Connie , Essak Martha , Zhang Angela , Lin Ann Hsu-An , Mali Raghuveer Singh , Kapur Reuben , Krystal Gerald
Published: March 2012

Although SHIP is a well-established suppressor of IgE plus Ag-induced degranulation and cytokine production in bone marrow-derived mast cells (BMMCs), little is known about its role in connective tissue (CTMCs) or mucosal (MMCs) mast cells. In this study, we compared SHIP’s role in the development as well as the IgE plus Ag and TLR-induced activation of CTMCs, MMCs, and BMMCs and found that SHIP delays the maturation of all three mast cell subsets and, surprisingly, that it is a positive regulator of IgE-induced BMMC survival. We also found that SHIP represses IgE plus Ag-induced degranulation of all three mast cell subsets and that TLR agonists do not trigger their degranulation, whether SHIP is present or not, nor do they enhance IgE plus Ag-induced degranulation. In terms of cytokine production, we found that in MMCs and BMMCs, which are poor producers of TLR-induced cytokines, SHIP is a potent negative regulator of IgE plus Ag-induced IL-6 and TNF-α production. Surprisingly, however, in splenic or peritoneal derived CTMCs, which are poor producers of IgE plus Ag-induced cytokines, SHIP is a potent positive regulator of TLR-induced cytokine production. Lastly, cell signaling and cytokine production studies with and without LY294002, wortmannin, and PI3Kα inhibitor-2, as well as with PI3K p85α−/− BMMCs and CTMCs, are consistent with SHIP positively regulating TLR-induced cytokine production via an adaptor-mediated pathway while negatively regulating IgE plus Ag-induced cytokine production by repressing the PI3K pathway.
The FcRβ- and γ-ITAMs Play Crucial but Distinct Roles in the Full Activation of Mast Cells Induced by IgEκ and Protein L
Authors: Nunomura Satoshi , Kawakami Yuko , Kawakami Toshiaki , Ra Chisei
Published: March 2012

Previous studies suggested that Protein L (PpL), the bacterial Ig-binding protein, activates mast cells. PpL presumably performs the activation by interacting with membrane-bound IgEκ, but the underlying mechanisms behind the process remain unclear. In the current study, we found that cell-surface FcεRI expression is a critical factor participant in PpL-mediated full activation of murine mast cells, which includes cytokine production, the degranulation response, and leukotriene C4 (LTC4) release, and that engagement of the FcεRI with IgEκ and PpL is enough to induce tyrosine phosphorylation of ITAM in the FcRβ- and γ-signaling subunits. Introduction of mutations in two canonical tyrosine residues (Y47F/Y58F) of the FcRγ–ITAM completely abolished the above-mentioned mast cell functions, with the exception of LTC4 release. Importantly, the FcRβ–ITAM acts as a signal transducer that is responsible for LTC4 release independently of the FcRγ–ITAM. Taken together, our results suggest crucial and distinct functions for the FcRβ- and γ-ITAMs in the FcεRI-dependent full activation of mast cells induced by IgEκ and PpL.
Risk management as a social defence against anxiety
Authors: Geldenhuys Dirk J. , Levin Madia M. , Van Niekerk Annelize
Published: March 2012

Orientation: This article deals with the unconscious role of risk management in an African country.Research purpose: The aim of the study is to describe how risk management unconsciously influences behaviour when doing business in an African country.Motivation for the study: Operational risk management is a rational management imperative. However, this does not take cognisance of the unconscious role of risk management. A systems-psychodynamic perspective might be particularly relevant if the anxiety implied in risk management is not appropriately contained. Awareness of these dynamics may provide an opportunity for addressing them and allow for a more holistic way of managing risk.Research design, approach and method: The researchers conducted the study as a qualitative case study in an African country. They used purposive sampling and analysed the data using qualitative content analysis.Main findings: Viewing risk management from a systems-psychodynamic perspective allowed the researchers to identify the influence of risk management on the behaviour of people. The emerging hypothesis was that, if businesses do not address the anxiety underlying risk management, managing risk becomes a social defence against the anxiety.Practical/managerial implications: Awareness of the anxiety involved in risk management may assist businesses to manage risk in a more realistic way, making provision for, and even capitalising on, the human element.Contributions/value-add: The article provides a systems-psychodynamic, and hence a more complete, perspective of operational risk management when doing business in an African country.
The Robben Island diversity experience. An exploration of South African diversity dynamics
Authors: Pretorius Marius , Cilliers Frans , Michelle May
Published: March 2012

Orientation: Because of its historic, symbolic and psychological representation, presenting a diversity event on Robben Island posed invaluable opportunities to form an in-depth understanding of South African diversity dynamics. This research focussed on such an event interpreted from the systems psychodynamic perspective.Research purpose: The purpose of the research was to describe the experiences of participants attending the Robben Island Diversity Experience (RIDE) in order to understand South African diversity dynamics from a depth psychology perspective.Motivation for the study: Of the many and different diversity events presented in South African organisations, RIDE is the only annual systems psycho-dynamically designed and presented event. This research was an effort to explore the nature of these dynamics which manifest themselves from below the surface.Research design, approach and method: Qualitative and descriptive research from a hermeneutic phenomenology paradigm was used. The 15 participants who attended a RIDE event formed a case study. The data from an unstructured interview was content-analysed and interpreted using the systems psychodynamic perspective. The themes were integrated into a research hypothesis.Main findings: Five themes manifested themselves, namely, crossing boundaries, engaging the brave new world, ties that bind, being imprisoned and the struggle.Practical/managerial implications: The research highlighted the importance of understanding unconscious dynamics in the context of diversity in order to inform consultants about diversity management interventions in organisations.Contribution/value-add: The research contributed towards how South African diversity dynamics manifest themselves and how that can be addressed in organisations.
Service reliability assessment using failure mode and effect analysis (FMEA): survey and opportunity roadmap
Authors: Sutrisno A , Lee TJ
Published: March 2012

Despite Failure Mode and Effect Analysis (FMEA) being a strategic technique for creation of error free service operation, detailed survey study and development of opportunity roadmap for FMEA application in service operation is limited in literature. We presented a preliminary literature survey between 1994 and 2010 that covers 20 journals from 8 different literature databases. The result of our preliminary survey indicated that majority of previous service FMEA studies focused on profit and supply chain-oriented service business practices. New service FMEA research opportunities relating to enhancement in Risk Priority Number (RPN), reprioritization, versatility of its application in service supply chain framework and non-profit service sector as well as combination with other quality control tools are proposed for further investigations.
A design for Six Sigma case Study: Creating an IT change management system for a mid-size accounting firm
Authors: Long P , Kovach J , Ding D
Published: March 2012

Accounting firms provide financial services, such as bookkeeping, tax returns, and audit services. Unfortunately, employees sometimes encounter problems with Information Technology (IT) systems that interrupt their work. While the IT department is responsible for fixing these problems, their ability to do so is often hindered by the lack of a formal IT change management system. Such a system would improve the timely identification of prior changes to IT systems that may be related to current problems faced by the IT department, thereby reducing unplanned downtime and IT staff frustration. This work describes a case study that used the Design for Six Sigma methodology to establish a process for effectively managing IT system changes for a mid-size accounting firm. This structured design approach provided an underlying framework for this organization to translate users’ needs/expectations into the design of a new system that helped to improve the communication and awareness of system changes within the IT department.
The use of continuous improvement techniques: A survey-based study of current practices
Authors: Kovach JV , Cudney EA , Elrod CC
Published: March 2012

Today, the long-term health of any organization depends on their commitment to continuous improvement. Prior research has focused mainly on the effect of continuous improvement practices on performance. In contrast, this research collected data through a survey administered across multiple industries throughout the U.S. and identified the continuous improvement techniques (i.e., lean and quality improvement methods) that practitioners have successfully implemented within their organizations. It also examined the perceived effectiveness and the challenges/reasons for failure associated with these techniques, as well as determined whether implementation and effectiveness differ between types of operations (i.e., manufacturing versus service). Hence, this research provides a starting point for deploying lean and/or quality initiatives throughout an organization. It also provides guidance for practitioners about what tools are effective in a given situation and what problems they should try to anticipate/overcome when implementing continuous improvement techniques.
Spatial and temporal variations of dissolved organic carbon and inorganic carbon concentrations and δ13C in a peatland-stream continuum: implications of peatland invasion by vascular plants
Authors: Gogo S. , Albéric P. , Laggoun-Défarge F. , Binet S. , Aurouet A.
Published: March 2012

Abstract. Dissolved fluxes of C which are an important component of the global C budget of peatlands may be affected by global change in different ways. The evolution of peatland vegetation is an issue caused by the indirect effect of global change that still needs to be addressed. The aim of this study was to study the temporal and spatial variations in the quantity and the characteristics of dissolved C within in a peatland stream continuum, the peatland being invaded by Molinia caerulea and Betula spp. The study highlighted the following key points: (i) Vegetation change tends to increase the DOC concentration of peat surface water. (ii) DOC exports were in the range of those found in the literature, and it was clearly established that peatland DOC can reach second order streams. (iii) Peat water was supersaturated in CO2 especially in summer during the peak of microbial activity. (iv) the CO2 critical layer at the surface of the soil may promote CO2 excess build-up in the peat water. This critical layer may promote CO2 export out of the peatland. The effect of vegetation change on the DOC content of peat water deserves further attention as it may have a deep impact on downstream river water quality. In particular, it is necessary to clarify whether the concentration of C dynamics is affected by the invading species. More attention should be paid to hydrological processes (e.g. pumping capacity of the different plants) and the microbial activity in the rhizosphere of the invading plants. Also, the relation between the CO2 critical zone at the surface of the soil and the CO2 concentration in water should be studied in detail.
Effect of biostimulation on biodegradation of dissolved organic carbon in biological granular activated carbon filters
Authors: Tihomirova K. , Briedis A. , Rubulis J. , Juhna T.
Published: March 2012

Abstract. The addition of labile organic carbon (LOC) to enhance the biodegradation rate of dissolved organic carbon (DOC) in biological columns was studied. Acetate standard solution (NaAc) and LB (Luria Bertrani) medium were used as LOC as biostimulants in glass column system used for measurements of biodegradable dissolved organic carbon (BDOC). The addition of LOC related with the increase of total DOC in sample. The concentration of BDOC increased up to 7 and 5 times and was utilized after 24 min. contact time. The biodegradation rate constant was increased at least 8 times during adaptation-biostimulation period. There was a strong positive correlation between the biodegradation rate constant and the concentration of BDOC. Biostimulation period ranged from 24 to 53 h for NaAc biostimulant and from 20 to 168 h for LB. The study has shown that LOC could be used as stimulator to enhance the biodegradation rate of DOC during biofiltration.
On the sources of hydrological prediction uncertainty in the Amazon
Authors: Paiva R. C. D. , Collischonn W. , Bonnet M. P. , Gonçalves L. G. G.
Published: March 2012

Abstract. Recent extreme events in the Amazon River basin and the vulnerability of local population motivate the development of hydrological forecast systems (HFSs) using process based models for this region. In this direction, the knowledge of the source of errors in HFSs may guide the choice on improving model structure, model forcings or developing data assimilation (DA) systems for estimation of initial model states. We evaluate the relative importance of hydrologic initial conditions (ICs) and model meteorological forcings (MFs) errors (precisely precipitation) as sources of stream flow forecast uncertainty in the Amazon River basin. We used a hindcast approach developed by Wood and Lettenmaier (2008) that contrasts Ensemble Streamflow Prediction (ESP) and a reverse Ensemble Streamflow Prediction (reverse-ESP). Simulations were performed using the physically-based and distributed hydrological model MGB-IPH, comprising surface energy and water balance, soil water, river and floodplain hydrodynamics processes. Model was forced using TRMM 3B42 precipitation estimates. Results show that uncertainty on initial conditions play an important role for discharge predictability even for large lead times (~1 to 3 months) on main Amazonian Rivers. ICs of surface waters state variables are the major source of hydrological forecast uncertainty, mainly in rivers with low slope and large floodplains. ICs of groundwater state variables are important mostly during low flow period and southeast part of the Amazon, where lithology and the strong rainfall seasonality with a marked dry season may be the explaining factors. Analyses indicate that hydrological forecasts based on a hydrological model forced with historical meteorological data and optimal initial conditions, may be feasible. Also, development of DA methods is encouraged for this region.
Short-term use of inhaled and intranasal corticosteroids is not associated with glaucoma progression on optical coherence tomography
Authors: Johnson Lenworth N. , Soni Chetan R. , Johnson Meredith A.J. , Madsen Richard W.
Published: March 2012

Purpose

To compare the changes in retinal nerve fiber layer (RNFL) thickness and optic nerve cup/disc ratio on optical coherence tomography (OCT) between users and nonusers of inhaled and intranasal corticosteroids (ICS).

Methods

Retrospective study of participants with glaucoma or glaucoma suspect having 2 or more OCTs during a 6-year period. The rates of change in Stratus OCT fast RNFL thickness scan and fast optic disc scan data were compared between ICS users and nonuser controls using random coefficient models.

Results

A total of 170 participants met the inclusion criteria, of whom 42 (25%) were ICS users and 128 (75%) were controls. The mean duration of follow-up was 3.2 years. There were no significant differences in the mean rates of change in superior RNFL (−0.8874 µm/y ICS users; −0.8592 µm/y controls; p=0.943), nasal RNFL (−0.0529 µm/y ICS users; −0.3577 µm/y controls; p=0.419), inferior RNFL (0.2703 µm/y ICS users; −0.1910 µm/y controls; p=0.165), and temporal RNFL (−0.3618 µm/y ICS users; −0.3612 µm/y controls; p=0.998) between ICS users and controls. There were no significant differences in the mean rates of change in horizontal cup/disc ratio (−0.0047 µm/y ICS users; 0.0002 µm/y controls; p=0.212) and vertical cup/disc ratio (0.0013 µm/y ICS users; 0.0029 µm/y; p=0.717) between ICS users and controls.

Conclusions

We found no significant difference in the rates of RNFL or optic nerve cup/disc ratio progression among individuals with glaucoma or glaucoma suspect following short-term ICS use.
Elevation of CA 125 and CA 19–9 in patients with end-stage liver disease
Authors: Singhal Ashish , Lander Elaine , Karachristos Andreas , Daly Ellen , Dowling Phyllis , Patel Vishal , Maloo Manoj , Jain Ashokkumar
Published: March 2012

Background

The serum tumor markers CA 19–9 and CA 125 are the serologic markers used for the monitoring of biliopancreatic and ovarian cancer, respectively. They are reported to be elevated in a variety of nonneoplastic clinical situations, including end-stage liver disease (ESLD). However, their prevalence and degree of elevation in patients with ESLD remained unclear.

Aim

To examine the prevalence and degree of elevation of CA 19–9 and CA 125 in patients with ESLD and to determine their association with severity of liver disease.

Methods

Retrospective analysis of 161 patients with ESLD that were evaluated for liver transplantation at our institution between March 2009 and December 2010. The mean age was 55.15 ± 8.75 years and 107 (66.4%) of the patients were men. Serum CA 19–9 and CA 125 levels were determined during evaluation of their candidacy for liver transplantation.

Results

Eighty-three (51.5%) patients had elevated CA 125 and 44 (53%) of them had a serum concentration >5 times the upper limit of normal (ULN). Elevated CA 125 was associated with alcoholic liver disease, high Model for End-Stage Liver Disease (MELD) score, and presence of ascites. Similarly, 37 (23%) patients had elevated CA 19–9 and 8 (21.6%) of them had a serum concentration >5 times ULN. Elevation of CA 19–9 was associated with high MELD score.

Conclusions

CA 125 and CA 19–9 concentrations were elevated in 51.5% and 23% of patients with ESLD, respectively. Although the definite etiology remained unclear, their elevation was associated with the pathological conditions associated with advanced liver disease. Further studies are needed to clarify the underlying mechanism(s) responsible for their increased levels.
Murine Double Minute Clone 2 309T/G and 285G/C Promoter Single Nucleotide Polymorphism as a Risk Factor for Breast Cancer: A Polish Experience
Authors: Piotrowski Piotr , Lianeri Margarita , Rubis Blazej , Knula Hanna , Rybczynska Maria , Grodecka-Gazdecka Sylwia , Jagodzinski Pawel P.
Published: March 2012

Background

Breast cancer is a multifactorial disease caused by complex interactions between genetic and environmental factors. Recently, a functional polymorphism, MDM2 285G>C (rs117039649), has been discovered. This polymorphism antagonizes the effect of the 309T>G (rs2279744) polymorphism on the same gene, resulting in decreased MDM2 transcription.

Methods

The MDM2 285G>C and 309T>G polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing analysis in women with breast cancer (n=468) and controls (n=550).

Results

The odds ratio (OR) for breast cancer patients with the MDM2 285C/C and 285G/C genotypes was 0.4768 (95% confidence interval [CI] 0.2906–0.7824; p=0.0033, pcorr=0.0066). We also found a significantly lower frequency of the MDM2 285C allele in patients with breast cancer than in controls: the OR for the C allele in patients with breast cancer was 0.4930 (95% CI=0.3059–0.7947, p=0.0031, pcorr=0.0062). The p value of the chi-square test for the trend observed for the MDM2 285G>C polymorphism was statistically significant (ptrend=0.0036). The statistical power of this study amounted to 85% for the G/C or C/C genotypes and 85% for the C allele. However, we did not observe significant differences between the distribution of MDM2 309T>G genotypes and alleles in patients with breast cancer and healthy controls.

Conclusion

In a sample of the Polish population, we observed that the MDM2 285C gene variant may be a significant protective factor against breast cancer.
Cytokeratin-19 fragments, nucleosomes and neuron-specific enolase as early measures of chemotherapy response in non-small cell lung cancer
Authors: Alm El-Din Mohamed A. , Farouk Gihan , Nagy Hala , Elzaher Ayman Abd , El-Magd Gehan H. Abo
Published: March 2012

Aim

To investigate the reduction in the serum level of cytokeratin-19 fragments (CYFRA 21–1), nucleosomes and neuron-specific enolase (NSE) as early measures of the response to chemotherapy in non-small cell lung cancer (NSCLC).

Methods

Forty-two consecutive patients with locally advanced NSCLC were included. All patients received platinum-based chemotherapy. Staging investigations and quantification of CYFRA 21–1, nucleosomes and NSE (using enzyme-linked immunosorbent assay, ELISA) were performed before the start of treatment and after the second cycle of chemotherapy. According to the response to chemotherapy, patients were classified into 3 groups: (I) disease regression, (II) stable disease, and (III) progressive disease. The reduction in the levels of tumor markers was correlated with the response to chemotherapy.

Results

After the second cycle of chemotherapy, groups I and II had significantly decreased serum levels of CYFRA 21–1 (p<0.05). Similarly, the concentration of nucleosomes was significantly lower than the baseline levels in groups I (p=0.0008) and II (p=0.003). The reduction of both CYFRA 21–1 and nucleosome levels was not significant for patients in group III. In all groups the reduction of NSE levels in response to chemotherapy was not significant. As a marker of response to chemotherapy, CYFRA 21–1 showed the highest sensitivity (88.9%) and specificity (77.4%) compared with nucleosomes (77.8% and 58.1% respectively) and NSE (66.7% and 51.8% respectively).

Conclusion

The reduction in the serum level of CYFRA 21–1 and nucleosomes may be used for early identification of NSCLC patients with good response to chemotherapy.
Determining the age of Qatari Jabal Jassasiyah Petroglyphs
Authors: Hassiba Raid , Cieslinski Gerald Benjamin , Chance Brandon , Abdulla Al-Naimi Faisal , Pilant Michael , Rowe Marvin W.
Published: March 2012

The petroglyph site in Jabal Jassasiyah Qatar is located approximately 60 km northeast of the capital city of Doha and has over 900 different types of petroglyphs. The most commonly found petroglyphs are cupules, which are almost always arranged in geometric patterns. A number of petroglyphs of boats are also found, usually seen from above, with a few seen in profile. As there is little evidence of what age to assign to these petroglyphs, samples of the calcium oxalate containing layers covering the petroglyphs were sent for radiocarbon dating to determine the minimum age they were created. The minimum ages of nine samples taken for analysis were found to be very short, the oldest minimum age being only 235 years BP (before present). No evidence was found for the petroglyphs dating back a few millennia as was previously postulated. Due to the lack of chronological data for Qatar’s archaeological past, the study data cannot completely rule out the petroglyphs dating back to ancient times.
Synthesis and characterization of PMMA‐cellulose nanocomposites by in situ polymerization technique
Authors: Sain Sunanda , Ray Dipa , Mukhopadhyay Anirudhha , Sengupta Suparna , Kar Tanusree , Ennis Christopher J. , Rahman Pattanathu K. S. M.
Published: March 2012

Cellulose nanoparticles (CNPs) were prepared from jute fiber by acid hydrolysis followed by high‐speed homogenization. The CNPs were used as fillers in the production of polymethylmethacrylate (PMMA) nanocomposites by in situ suspension polymerization technique. The suspension polymerization of MMA was carried out in the presence of CNPs, which were dispersed in water medium and in situ PMMA/cellulose nanocomposite granules were formed. PMMA polymer, without any filler, was also prepared by similar suspension polymerization technique. PMMA and PMMA/cellulose nanocomposite films were prepared by solution casting method. Viscosity average molecular weights of neat PMMA and the PMMA extracted from PMMA/cellulose nanocomposite granules were determined by viscometric method and average molecular mass of PMMA extracted from PMMA/cellulose nanocomposites was found to be reduced than that of neat PMMA. Attenuated total reflectance Fourier transform infrared spectroscopy was performed to find out any chemical interaction between polymer matrix and the CNPs. X‐ray diffraction study and differential scanning calorimetry were done to investigate the structures of the nanocomposite films and the glass transition temperature was found to be lower in the nanocomposite than that in the virgin polymer. Field emission scanning electron microscopy and atomic force microscopy were done to examine the morphology of the films. Such an in situ suspension polymerization technique for the preparation of PMMA/cellulose nanocomposites can be very useful to prepare tailor‐made materials. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
Semi‐dynamic traffic assignment model with mode and route choices under stochastic travel times
Authors: Nakayama Sho‐ichiro , Takayama Jun‐ichi , Nakai Junya , Nagao Kazuki
Published: March 2012

Transportation network conditions vary significantly during the course of a day. In many urban areas, public transit and (private) automobiles constitute the actual forms of transportation that use such networks. Public transportation by rail is more reliable than by automobiles or buses; therefore, ordinary static and deterministic traffic assignment models with combined mode and route choices may not be suitable to assess a transportation network that includes public railways. Moreover, within‐day dynamics and reliability need to be incorporated in such a model. In this paper, we use a semi‐dynamic traffic assignment model that considers within‐day dynamics by improving the static traffic assignment model. In addition, stochastic travel times are incorporated into the model. Thus, we propose a semi‐dynamic traffic assignment model with mode choice between public transit and automobiles, route choice with stochastic travel times, and an accompanying computing algorithm. This model enables us to assess within‐day dynamics of transportation networks and travel time reliability of public railways. Copyright © 2012 John Wiley & Sons, Ltd.
Systematic review of total pancreatectomy and islet autotransplantation for chronic pancreatitis
Authors: Bramis K , Gordon-Weeks A N , Friend P J , Bastin E , Burls A , Silva M A , Dennison A R
Published: March 2012

Background

Total pancreatectomy and islet autotransplantation (TP/IAT) is a treatment option in a subset of patients with chronic pancreatitis. A systematic review of the literature was performed to evaluate the outcome of this procedure, with an attempt to ascertain when it is indicated.

Methods

MEDLINE (1950 to present), Embase (1980 to present) and the Cochrane Library were searched to identify studies of outcomes in patients undergoing TP/IAT. Cohort studies that reported the outcomes following the procedure were included. The MOOSE guidelines were used as a basis for this review.

Results

Five studies met the inclusion criteria. The techniques reported for pancreatectomy and islet cell isolation varied between studies. TP/IAT was successful in reducing pain in patients with chronic pancreatitis. Comparing morphine requirements before and after the procedure, two studies recorded significant reductions. Concurrent IAT reduced the insulin requirement after TP; the rate of insulin independence ranged from 46 per cent of patients at 5 years' mean follow-up to 10 per cent at 8 years. The impact on quality of life was poorly reported. The studies reviewed did not provide evidence for optimal timing of TP/IAT in relation to the evolution of chronic pancreatitis.

Conclusion

This systematic review showed that TP/IAT had favourable outcomes with regard to pain reduction. Concurrent IAT enabled a significant proportion of patients to remain independent of insulin supplementation.
The potential usage of caffeic acid phenethyl ester (CAPE) against chemotherapy‐induced and radiotherapy‐induced toxicity
Authors: Akyol Sumeyya , Ginis Zeynep , Armutcu Ferah , Ozturk Gulfer , Yigitoglu M. Ramazan , Akyol Omer
Published: March 2012

Protection of the patients against the side effects of chemotherapy and radiotherapy regimens has attracted increasing interest of clinicians and practitioners. Caffeic acid phenethyl ester (CAPE), which is extracted from the propolis of honeybee hives as an active component, specifically inhibits nuclear factor κB at micromolar concentrations and show ability to stop 5‐lipoxygenase‐catalysed oxygenation of linoleic acid and arachidonic acid. CAPE has antiinflammatory, antiproliferative, antioxidant, cytostatic, antiviral, antibacterial, antifungal and antineoplastic properties. The purpose of this review is to summarize in vivo and in vitro usage of CAPE to prevent the chemotherapy‐induced and radiotherapy‐induced damages and side effects in experimental animals and to develop a new approach for the potential usage of CAPE in clinical trial as a protective agent during chemotherapy and radiotherapy regimens. Copyright © 2012 John Wiley & Sons, Ltd.
Nanostructured Manganese Oxide Supported on Carbon Nanotubes for Electrocatalytic Water Splitting
Authors: Mette Katharina , Bergmann Arno , Tessonnier Jean‐Philippe , Hävecker Michael , Yao Lide , Ressler Thorsten , Schlögl Robert , Strasser Peter , Behrens Malte
Published: March 2012

Incipient wetness impregnation and a novel deposition symproportionation precipitation were used for the preparation of MnOx/CNT electrocatalysts for efficient water splitting. Nanostructured manganese oxides have been dispersed on commercial carbon nanotubes as a result of both preparation methods. A strong influence of the preparation history on the electrocatalytic performance was observed. The as‐prepared state of a 6.5 wt. % MnOx/CNT sample could be comprehensively characterized by comparison to an unsupported MnOx reference sample. Various characterization techniques revealed distinct differences in the oxidation state of the Mn centers in the as‐prepared samples as a result of the two different preparation methods. As expected, the oxidation state is higher and near +4 for the symproportionated MnOx compared to the impregnated sample, where +2 was found. In both cases an easy adjustability of the oxidation state of Mn by post‐treatment of the catalysts was observed as a function of oxygen partial pressure and temperature. Similar adjustments of the oxidation state are also expected to happen under water splitting conditions. In particular, the 5 wt. % MnO/CNT sample obtained by conventional impregnation was identified as a promising catalytic anode material for water electrolysis at neutral pH showing high activity and stability. Importantly, this catalytic material is comparable to state‐of‐art MnOx catalyst operating in strongly alkaline solutions and, therefore, offers advantages for hydrogen production from waste and sea water under neutral, hence, environmentally benign conditions.
Double Stereodifferentiation in the Catalytic Asymmetric Aziridination of Imines Prepared from α‐Chiral Amines
Authors: Huang Li , Zhang Yu , Staples Richard J. , Huang Rui H. , Wulff William D.
Published: March 2012

The catalytic asymmetric aziridination of imines and diazo compounds (AZ reaction) mediated by boroxinate catalysts derived from the VANOL and VAPOL ligands was investigated with chiral imines derived from five different chiral, disubstituted, methyl amines. The strongest matched and mismatched reactions with the two enantiomers of the catalyst were noted with disubstituted methyl amines that had one aromatic and one aliphatic substituent. The synthetic scope for the AZ reaction was examined in detail for α‐methylbenzyl amine for cis‐aziridines from α‐diazo esters and for trans‐aziridines from α‐diazo acetamides. Optically pure aziridines could be routinely obtained in good yields and with high diastereoselectivity and the minor diastereomer (if any) could be easily separated. The matched case for cis‐aziridines involved the (R)‐amine with the (S)‐ligand, but curiously, for trans‐aziridines the matched case involved the (R)‐amine with the (R)‐ligand for imines derived from benzaldehyde and n‐butanal, and the (R)‐amine with the (S)‐ligand for imines derived from the bulkier aliphatic aldehydes pivaldehyde and cyclohexane carboxaldehyde.
Bistable Cucurbituril Rotaxanes Without Stoppers
Authors: Sinha Mantosh K. , Reany Ofer , Yefet Maayan , Botoshansky Mark , Keinan Ehud
Published: March 2012

Bistable rotaxanes are important design elements of molecular devices for a broad range of applications, such as controlled drug release, molecular rotary motors, and chemical sensors. The host–guest complexes of cucurbit[6]uril and 1,4‐bis(alkylaminomethyl)benzene were found to exhibit two stable binding modes with an unexpectedly high barrier between them. Their structural and dynamic properties, kinetic and thermodynamic parameters, as well as different chemical reactivity towards the azide–alkyne [3+2] cycloaddition reaction (click chemistry), were discovered by NMR spectroscopy, X‐ray crystallography, and isothermal titration microcalorimetry. The highly stable 2:1 complex, which is formed at room temperature, was found to be a kinetic product, which may be converted to the thermodynamic 1:1 complex upon prolonged heating to 100 °C. The latter is a very stable rotaxane despite the fact that it lacks bulky end groups.
Label‐Free Detection of Nanomolar Unmodified Single‐ and Double‐Stranded DNA by Using Surface‐Enhanced Raman Spectroscopy on Ag and Au Colloids
Authors: Papadopoulou Evanthia , Bell Steven E. J.
Published: March 2012

Unlabelled single‐ and double‐stranded DNA (ssDNA and dsDNA, respectively) has been detected at concentrations ≥10−9 M by surface‐enhanced Raman spectroscopy. Under appropriate conditions the sequences spontaneously adsorbed to the surface of both Ag and Au colloids through their nucleobases; this allowed highly reproducible spectra with good signal‐to‐noise ratios to be recorded on completely unmodified samples. This eliminated the need to promote absorption by introducing external linkers, such as thiols. The spectra of model ssDNA sequences contained bands of all the bases present and showed systematic changes when the overall base composition was altered. Initial tests also showed that small but reproducible changes could be detected between oligonucleotides with the same bases arranged in a different order. The spectra of five ssDNA sequences that correspond to different strains of the Escherichia coli bacterium were found to be sufficiently composition‐dependent so that they could be differentiated without the need for any advanced multivariate data analysis techniques.
Relative and Absolute Configuration of Vatiparol (1 mg): A Novel Anti‐inflammatory Polyphenol
Authors: Ge Hui Ming , Sun Han , Jiang Nan , Qin Yan Hua , Dou Huan , Yan Tong , Hou Ya Yi , Griesinger Christian , Tan Ren Xiang
Published: March 2012

Bioactive natural products offer multiple opportunities for the discovery of novel chemical entities with potential pharmaceutical, nutraceutical and agrochemical applications. Many new organic compounds with novel scaffolds are isolated in small quantities and established methods often fail to determine the structure and bioactivity of such novel natural products. To meet this challenge, we present here a new methodology combining RDC (residual dipolar coupling)‐based NMR spectroscopy in microtubes, with a motif‐inspired biological assessment strategy. Using only one milligram (ca. 1.5 μmol) of sample, the new protocol established the bioactivity as well as the relative and absolute configuration of vatiparol obtained from Vatica parvifolia. Vatiparol is unique in its unprecedented carbon skeleton and selective inhibitory effect on the expression of monocyte chemo‐attractant protein‐1 (MCP‐1, also known as CCL2). The plausible biosynthetic pathway of vatiparol is briefly discussed. The approach introduced here promises to be widely applicable to the determination of the structure and bioactivity of structurally unknown organic samples available in very limited amounts.
Comparison of the Prognostic Value of Peak Creatine Kinase‐MB and Troponin Levels Among Patients With Acute Myocardial Infarction: A Report from the Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines
Authors: Chin Chee Tang , Wang Tracy Y. , Li Shuang , Wiviott Stephen D. , deLemos James A. , Kontos Michael C. , Peterson Eric D. , Roe Matthew T.
Published: March 2012

Background:

Although peak creatine kinase‐myocardial band (CK‐MB) and troponin levels have been correlated with mortality among patients with acute myocardial infarction (AMI), the independent prognostic implications of these markers have not been compared.

Hypothesis:

We hypothesized that in patients with AMI, peak troponin levels (as compared to peak CK‐MB levels) would have greater prognostic value.

Methods:

We examined AMI patients in the National Cardiovascular Data Registry ACTION Registry–GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines) with CK‐MB and troponin I levels recorded, excluding patients who were transferred in or out. Peak marker levels, standardized by the local laboratory upper limit of normal and assay standard deviation, were fitted into the previously validated ACTION Registry–GWTG mortality model to compare prognostic value.

Results:

Between January 2007 and March 2009, 16 009 ST‐segment elevation myocardial infarction (STEMI) and 26854 non–ST‐segment elevation myocardial infarction (NSTEMI) patients were identified. Peak marker ratios were directly associated with in‐hospital mortality in both STEMI and NSTEMI patients. Peak CK‐MB had slightly greater discrimination compared with peak troponin I in predicting mortality in both STEMI (model C‐statistic 0.881 vs 0.877, P = 0.011) and NSTEMI (C‐statistic 0.831 vs 0.824, P = 0.001) patients.

Conclusions:

Both peak CK‐MB and peak troponin I levels are independently associated with in‐hospital mortality in this large contemporary database of AMI patients treated in routine practice. Peak marker values slightly improved model performance in prognosticating in‐hospital mortality; the incremental value was higher with CK‐MB than with troponin I. These findings may help to guide future risk stratification algorithms and contribute to more efficient use of serial cardiac marker measurements in clinical practice. Clin. Cardiol. 2011 DOI: 10.1002/clc.21980

This project was supported by grant number U18HS016964 from the Agency for Healthcare Research and Quality (AHRQ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHRQ. The funding source had no role in the design or implementation of the study, or in the decision to seek publication. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Novel Gd(III)‐based probes for MR molecular imaging of matrix metalloproteinases
Authors: Gringeri Concetta V. , Menchise Valeria , Rizzitelli Silvia , Cittadino Evelina , Catanzaro Valeria , Dati Gabriele , Chaabane Linda , Digilio Giuseppe , Aime Silvio
Published: March 2012

Two novel Gd‐based contrast agents (CAs) for the molecular imaging of matrix metalloproteinases (MMPs) were synthetized and characterized in vitro and in vivo. These probes were based on the PLG*LWAR peptide sequence, known to be hydrolyzed between Gly and Leu by a broad panel of MMPs. A Gd–DOTA chelate was conjugated to the N‐terminal position through an amide bond, either directly to proline (compd Gd–K11) or through a hydrophilic spacer (compd Gd–K11N). Both CA were made strongly amphiphilic by conjugating an alkyl chain at the C‐terminus of the peptide sequence. Gd–K11 and Gd–K11N have a good affinity for β‐cyclodextrins (KD 310 and 670 µ m respectively) and for serum albumin (KD 350 and 90 µ m respectively), and can be efficiently cleaved in vitro at the expected site by MMP‐2 and MMP‐12. Upon MMP‐dependent cleavage, the CAs lose the C‐terminal tetrapeptide and the alkyl chain, thus undergoing to an amphiphilic‐to‐hydrophilic transformation that is expected to alter tissue pharmacokinetics. To prove this, Gd–K11 was systemically administered to mice bearing a subcutaneous B16.F10 melanoma, either pre‐treated or not with the broad spectrum MMP inhibitor GM6001 (Ilomastat). The washout of the Gd‐contrast enhancement in MR images was significantly faster for untreated subjects (displaying MMP activity) with respect to treated ones (MMP activity inhibited). The washout kinetics of Gd‐contrast enhancement from the tumor microenvironment could be then interpreted in terms of the local activity of MMPs. Copyright © 2012 John Wiley & Sons, Ltd.
An approach towards molecular imaging of activated platelets allows imaging of symptomatic human carotid plaques in a new model of a tissue flow chamber
Authors: von Elverfeldt Dominik , Meißner Mirko , Peter Karlheinz , Paul Dominik , Meixner Fabian , Neudorfer Irene , Merkle Annette , Harloff Andreas , Zirlik Andreas , Schöllhorn Joachim , Markl Michael , Hennig Jürgen , Bode Christoph , von zur Muhlen Constantin
Published: March 2012

The development of magnetic resonance imaging (MRI) contrast agents targeting epitopes in atherosclerosis is of general interest. In particular, early detection of activated platelets as key players in plaque rupture could provide improved triage of patients. However, so far the efficiency of contrast agents targeting human pathologies can only be examined in animal experiments, which do not necessarily reflect human in vivo conditions. We therefore describe application of a contrast agent targeting activated human platelets in an MRI tissue flow chamber, allowing detection and characterization of contrast agent binding. Microparticles of iron oxide (MPIO) were conjugated to an antibody targeting ligand‐induced binding sites (LIBS) on the activated platelet glycoprotein IIb/IIIa‐receptor or to control antibody, resulting in LIBS–MPIO or control–MPIO contrast agent. Human endarterectomy specimens from patients with acute stroke or transient ischemic attack were imaged ex vivo before and after contrast agent perfusion using a 9.4 T MRI system. Specimens were measured under static (n = 18) or flow conditions (n = 18) in a specially designed flow chamber setup, simulating physiological conditions in a stenosed vessel. A significant MPIO‐induced negative contrast was achieved in MRI by LIBS–MPIO in specimens under static and flow conditions (LIBS–MPIO vs control–MPIO: p < 0.01), and the location of LIBS–MPIO binding corresponded well between histology and MRI (p < 0.05). The number of MPIOs per platelet area on endarterectomy specimens in histology was significantly higher with LIBS–MPIO (p < 0.001). Furthermore, the intensity of contrast agent binding and signal change showed the potential to reflect the severity of clinical symptoms. LIBS–MPIO allows the detection of activated platelets on the surface of symptomatic atherosclerotic human plaques using molecular MRI. Furthermore, the MRI tissue flow chamber setup described could help to evaluate binding properties of contrast agents, and might therefore be an interesting tool for contrast agent development from animal experiments towards clinical application. Copyright © 2012 John Wiley & Sons, Ltd.
1H chemical shift magnetic resonance imaging probes with high sensitivity for multiplex imaging
Authors: Yang Yan , Schühle Daniel T. , Dai Guangping , Alford Jamu K. , Caravan Peter
Published: March 2012

Proton‐based chemical shift imaging probes were encapsulated inside nano‐carriers to increase the sensivitity of the reporters. Co‐encapsulation with a relaxation agent results in improved sensitivity and suppresses background signals. Simultaneous imaging of different chemical shift reporters allows multiplexed detection. Copyright © 2011 John Wiley & Sons, Ltd.
Development of 177Lu‐nanobodies for radioimmunotherapy of HER2‐positive breast cancer: evaluation of different bifunctional chelators
Authors: D'Huyvetter Matthias , Aerts An , Xavier Catarina , Vaneycken Ilse , Devoogdt Nick , Gijs Marlies , Impens Nathalie , Baatout Sarah , Ponsard Bernard , Muyldermans Serge , Caveliers Vicky , Lahoutte Tony
Published: March 2012

Nanobodies show favourable pharmacokinetic characteristics for tumor targeting, including high tumor‐to‐background‐ratios. Labelled with a therapeutic radionuclide, nanobodies could be used as an adjuvant treatment option for HER2‐overexpressing minimal residual disease. The therapeutic radionuclide Lutetium‐177 is linked to the nanobody using a bifunctional chelator. The choice of the bifunctional chelator could affect the in vivo behaviour of the radiolabeled nanobody. Consequently, we compared four different bifunctional chelators ‐ p‐SCN‐Bn‐DOTA, DOTA‐NHS‐ester, CHX‐A”‐DTPA or 1B4M‐DTPA ‐ in order to select the optimal chemical link between Lutetium‐177 and a HER2 targeting nanobody.

MS results revealed different degrees of chelator‐conjugation. High stability in time was observed, together with nanomolar affinities on HER2‐expressing tumor cells. Ex vivo biodistributions as well as SPECT/micro‐CT analyses showed high activities in tumors expressing medium HER2 levels with low background activity except for the kidneys. The 1B4M‐DTPA‐coupled conjugate was further evaluated in a high HER2‐expressing tumor model. Here, tumor uptake values of 5.99 ± 0.63, 5.12 ± 0.17, 2.83 ± 0.36 and 2.47 ± 0.38 %IA/g were obtained at 1, 3, 24 and 48h p.i., which coincided with exceptionally low background values, except for the kidneys, and unprecedented tumor‐to‐background ratios. No specific binding was observed in a HER2‐negative model.

In conclusion, the in‐house developed anti‐HER2 nanobody 2Rs15dHIS can be successfully labeled with 177Lu using different bifunctional chelators. Both macrocyclic and acyclic chelators show high stability in time. High specific tumor uptake combined with the lowest background uptake was measured using the 1B4M‐DTPA‐based conjugate. Copyright © 2012 John Wiley & Sons, Ltd.