bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic flux determination in perfused livers by mass balance analysis: Effect of fasting
Authors: Orman Mehmet A. , Arai Kosuke , Yarmush Martin L. , Androulakis Ioannis P. , Berthiaume Francois , Ierapetritou Marianthi G.
Published: July 2010

Isolated perfused livers from fasted rats have been extensively studied to understand the underlying mechanisms of injury‐induced acute and chronic changes in liver metabolism. In this study, we investigated the impact of fasting on perfused liver metabolism. The methodology we used combines a flux variability approach, sampling analysis and singular value decomposition (SVD) to analyze the data using the same metabolic reaction network for both fed and fasted livers. Considering both experimental observations and mathematical analysis, the results show that 24 h fasting results in a limited glucose production from glycogen and up‐regulation of gluconeogenic pathway. Glutamate metabolism and fatty acid oxidation are also slightly up‐regulated whereas aspartate metabolism is down‐regulated after fasting. Moreover, SVD analysis elucidates that glycogen breakdown mainly affects the pentose phosphate pathway in fasted state whereas co‐occurrence pattern associated with glycogen breakdown and glycolysis observed in flux samples of fed state is dominant. In conclusion, this analysis provides a detailed description of the metabolic changes in two different states, considering the entire steady state flux space and dominant flux patterns that capture the system variations within the flux space. Biotechnol. Bioeng. 2010;107: 825–835. © 2010 Wiley Periodicals, Inc.
Photodegradation as a mechanism for controlled drug delivery
Authors: Griffin Donald R. , Patterson Joseph T. , Kasko Andrea M.
Published: July 2010

A drug‐releasing model compound based on photosensitive acrylated ortho‐nitrobenzylether (o‐NBE) moiety and fluorescein was synthesized to demonstrate photolysis as a mechanism for drug release. Release of this model compound from a hydrogel network can be controlled with light intensity (5–20 mW/cm2), exposure duration (0–20 min) and wavelength (365, 405, 436 nm). Due to the high molar absorptivity of the compound (5,984 M−1 cm−1), light attenuation is significant in this system. Light attenuation can be used to self‐limit the dosing from a hydrogel, and allow subsequent release from the drug reservoir after equilibration, or attenuation can be utilized to create a chemical gradient within the hydrogel. A model of photodegradation that uses an integrated form of Beer–Lambert's law quantitatively predicts release from hydrophilic hydrogels with low crosslink density, but fails to quantitatively predict release from more hydrophobic systems, presumably due to partitioning of the hydrophobic model compound in the hydrogel. In contrast to other mechanisms of release (enzymolysis, hydrolysis), photolysis provides real‐time on demand control over drug release along with the unique ability to create chemical gradients within the hydrogel. Biotechnol. Bioeng. 2010;107: 1012–1019. © 2010 Wiley Periodicals, Inc.
Nature, causes and consequences of unintended events in surgical units
Authors: van Wagtendonk I , Smits M , Merten H , Heetveld M J , Wagner C
Published: July 2010

Background

Several studies have shown that the rate of unintended harm is higher in surgical than in non-surgical care. To improve patient safety in surgery, information about the underlying causes is needed. This observational study examined the nature, causes and consequences of unintended events in surgical units, and the completeness of event reporting.

Methods

Ten surgical units in the Netherlands participated. The study period per unit was 8–14 weeks, during which healthcare providers reported unintended events. Event reports were analysed with a root cause analysis tool (PRISMA). In addition, an independent surgeon reviewed about 40 patient records of patients in each surgical unit to examine whether an unintended event had occurred.

Results

A total of 881 unintended events were reported and analysed, of which 33·0 per cent were categorized as medication events. Most root causes were human (72·3 per cent), followed by organizational (16·1 per cent) and technical (5·7 per cent). More than half of the events had consequences for the patient. Sixty-four unintended events were identified in a review of 320 patient records. Only one of these events was also reported by a healthcare provider.

Conclusion

Event reporting and patient record review provide insight into diverse types of unintended events and complement each other. The information on unintended events from both sources may help target research and interventions to increase patient safety.
Functionalizing Mesoporous Bioglasses for Long‐Term Anti‐Osteoporotic Drug Delivery
Authors: López‐Noriega Adolfo , Arcos Daniel , Vallet‐Regí María
Published: July 2010

Mesoporous bioactive glasses (MBGs) associated with an anti‐osteoporotic drug (ipriflavone) have been prepared. With this aim, MBGs were functionalised with different organic groups by following a post‐grafting method, thus retaining the mesoporous network of the bioactive substrates. Drug‐delivery tests were carried out by using ipriflavone as a hydrophobic model drug. Our results revealed that by means of the proper functionalisation, most of the drug is retained in the mesoporous network. By tailoring the hydrophobicity of the surface with functional groups, the drug–material link can be tuned, thereby ensuring the long‐term delivery of ipriflavone. In vitro bioactive tests demonstrate that these systems exhibit the same excellent behaviour of non‐functionalised MBGs. The possibility to add a bone resorption inhibitor such as ipriflavone to highly bioactive materials confirms functionalised MBGs as very promising bone‐tissue regeneration systems.
3,4,5‐Trinitropyrazole‐Based Energetic Salts
Authors: Zhang Yanqiang , Guo Yong , Joo Young‐Hyuk , Parrish Damon A. , Shreeve Jean'ne M.
Published: July 2010

High‐density energetic salts that are comprised of nitrogen‐rich cations and the 3,4,5‐trinitropyrazolate anion were synthesized in high yield by neutralization or metathesis reactions. The resulting salts were fully characterized by 1H, 13C NMR, and IR spectroscopy; differential scanning calorimetry; and elemental analysis. Additionally, the structures of the 3,5‐diaminotriazolium and triaminoguanidinium 3,4,5‐trinitropyrazolates were confirmed by single‐crystal X‐ray diffraction. Based on the measured densities and calculated heats of formation, the detonation performances (pressure: 23.74–31.89 GPa; velocity: 7586–8543 ms−1; Cheetah 5.0) of the 3,4,5‐trinitropyrazolate salts are comparable with 1,3,5‐triamino‐2,4,6‐trinitrobenzene (TATB; 31.15 GPa and 8114 ms−1). Impact sensitivities were determined to be no less than 35 J by hammer tests, which places these salts in the insensitive class.
Delayed embryonic development and impaired cell growth and survival in Actg1 null mice
Authors: Bunnell Tina M. , Ervasti James M.
Published: July 2010

Actins are among the most highly expressed proteins in eukaryotes and play a central role in nearly all aspects of cell biology. While the intricate process of development undoubtedly requires a properly regulated actin cytoskeleton, little is known about the contributions of different actin isoforms during embryogenesis. Of the six actin isoforms, only the two cytoplasmic actins, βcyto‐ and γcyto‐actin, are ubiquitously expressed. We found that γcyto‐actin null (Actg1−/−) mice were fully viable during embryonic development, but most died within 48 h of birth due to respiratory failure and cannibalization by the parents. While no morphogenetic defects were identified, Actg1−/− mice exhibited stunted growth during embryonic and postnatal development as well as delayed cardiac outflow tract formation that resolved by birth. Using primary mouse embryonic fibroblasts, we confirm that γcyto‐actin is not required for cell migration. The Actg1−/− cells, however, exhibited growth impairment and reduced cell viability, defects which perhaps contribute to the stunted growth and developmental delays observed in Actg1−/− embryos. Since the total amount of actin protein was maintained in Actg1−/− cells, our data suggests a distinct requirement for γcyto‐actin in cell growth and survival. © 2010 Wiley‐Liss, Inc.
Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors
Authors: Blay Jean‐Yves , von Mehren Margaret , Blackstein Martin E.
Published: July 2010

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and present predominantly in middle‐aged and older individuals. Historically, the outlook for patients with GISTs was very poor because of the general lack of efficacy of conventional chemotherapy and the often limited surgical options. However, the recognition of the role of mutations of the v‐kit Hardy/Zuckerman 4 feline sarcoma viral oncogene homolog KIT and the platelet derived growth factor receptor alpha gene PDGFRα in the development of GISTs led to the evaluation of potential antitumor effects of the tyrosine kinase inhibitors imatinib and, more recently, sunitinib. Consequently, these molecularly targeted therapies were introduced into clinical practice, and the outcome for patients with GISTs improved considerably. In the last few years, the European Society of Medical Oncology, the National Comprehensive Cancer Network, and the Canadian Advisory Committee on GIST each published a major set of guidelines or practice recommendations for the management of patients with GIST. In the current review, the latest recommendations from each organization are summarized in terms of diagnosis and risk assessment, tumor staging, surgical and/or drug treatment of primary resectable and recurrent metastatic disease, and patient follow‐up and assessment. In addition, areas of consensus and points of divergence among the guidelines are highlighted along with any unresolved issues. Cancer 2010. © 2010 American Cancer Society
Quantitative HER2 protein levels predict outcome in fluorescence in situ hybridization‐positive patients with metastatic breast cancer treated with trastuzumab
Authors: Lipton Allan , Köstler Wolfgang J. , Leitzel Kim , Ali Suhail M. , Sperinde Jeff , Weidler Jodi , Paquet Agnes , Sherwood Thomas , Huang Weidong , Bates Michael ,   the Trastuzumab Response Biomarker Group
Published: July 2010

BACKGROUND:

Only a portion of breast cancer patients currently selected for trastuzumab therapy respond.

METHODS:

Using a novel assay (HERmark) to quantify total human epidermal growth factor receptor 2 (HER2) expression, the authors examined outcomes in 102 trastuzumab‐treated metastatic breast cancer patients previously assessed as immunohistochemistry (IHC) 3+ by local but not central IHC, or fluorescence in situ hybridization (FISH) positive, and then retested by central FISH.

RESULTS:

Of 102 MBC patients previously scored as IHC 3+ or 2+/FISH‐positive and treated with trastuzumab‐containing regimens, 98 had both central FISH and HER2 total expression values. Sixty‐six of 76 central FISH‐positive patients (87%) had high HER2 total expression levels (concordant positive), and 19 of 22 central FISH‐negative patients (86%) were HER2 total expression low (concordant negative). Fourteen percent (3 of 22) of central FISH‐negative patients were HER2 total expression high (discordant HER2 total expression high), and 13% (10 of 76) of central FISH‐positive patients were HER2 total expression low (discordant HER2 total expression low). The concordant positive group had a significantly longer time to progression (TTP, median = 11.3 months) compared with the concordant negative group (median TTP, 4.5 months; hazard ratio [HR] = 0.42, P < .001), and also compared with the discordant HER2 total expression low group (median TTP, 3.7 months; HR = 0.43, P = .01). The discordant HER2 total expression low group behaved similarly compared with concordant negatives (HR = 1, P = .99). In analyses restricted to central FISH‐positive patients only (n = 77), Cox proportional hazards multivariate regression identified HER2 total expression as an independent predictor of TTP (HR = 0.29, P = .0015) and overall survival (HR = 0.19, P < .001).

CONCLUSIONS:

A subset of patients with HER2 gene amplification by FISH express low levels of HER2 protein and have reduced response to trastuzumab‐containing therapy, similar to FISH‐negative patients. This cohort represents a training dataset, and the observed relationships and derived cutoffs require validation in an independent cohort of trastuzumab‐treated metastatic breast cancer patients. Cancer 2010. © 2010 American Cancer Society.
Asymmetric distribution of cadherin 23 and protocadherin 15 in the kinocilial links of avian sensory hair cells
Authors: Goodyear Richard J. , Forge Andy , Legan P. Kevin , Richardson Guy P.
Published: July 2010

Cadherin 23 and protocadherin 15 are components of tip links, fine filaments that interlink the stereocilia of hair cells and are believed to gate the hair cell's mechanotransducer channels. Tip links are aligned along the hair bundle's axis of mechanosensitivity, stretching obliquely from the top of one stereocilium to the side of an adjacent, taller stereocilium. In guinea pig auditory hair cells, tip links are polarized with cadherin 23 at the upper end and protocadherin 15 at the lower end, where the transducer channel is located. Double immunogold labeling of avian hair cells was used to study the distribution of these two proteins in kinocilial links, a link type that attaches the tallest stereocilia of the hair bundle to the kinocilium. In the kinocilial links of vestibular hair bundles, cadherin 23 localizes to the stereocilium and protocadherin 15 to the kinocilium. The two cadherins are therefore asymmetrically distributed within the kinocilial links but of a polarity that is, within those links that are aligned along the hair bundle's axis of sensitivity, reversed relative to that of tip links. Conventional transmission electron microscopy of hair bundles fixed in the presence of tannic acid reveals a distinct density in the 120–130 nm long kinocilial links that is located 35–40 nm from the kinociliary membrane. The location of this density is consistent with it being the site at which interactions occur in an in trans configuration between the opposing N‐termini of homodimeric forms of cadherin 23 and protocadherin 15. J. Comp. Neurol. 518:4288–4297, 2010. © 2010 Wiley‐Liss, Inc.
Topographic arrangement of the rotundo‐entopallial projection in the pigeon (Columba livia)
Authors: Fredes Felipe , Tapia Sebastian , Letelier Juan Carlos , Marín Gonzalo , Mpodozis Jorge
Published: July 2010

The tectofugal pathway (retina – optic tectum – nucleus rotundus – entopallium) is a prominent route mediating visual discrimination in diurnal birds. Several lines of evidence have shown that at the tecto‐rotundal stage this pathway is composed of multiple parallel channels. Anatomical studies show that the nucleus rotundus is composed of at least four subdivisions, according to differences in cytoarchitectonic, histochemical, and hodological properties. Each of these subdivisions is in receipt of a highly convergent, nontopographic tectal projection, originating from a distinct subset of tecto‐rotundal neurons. Physiological studies show that neurons of different subdivisions respond specifically to different visual dimensions, such as color, luminance, two‐dimensional motion, and in‐depth motion. At present it is less clear whether or to what extent this channel segregation is preserved at the telencephalic stage of the tectofugal pathway. The entopallium shows no obvious subdivisions or laminations. Nevertheless, tract‐tracing experiments show that separate portions of the entopallium receive efferent projections from different rotundal subdivisions, in a way that maintains the rostrocaudal order of these subdivisions. In the present study we investigate in detail the topography of the rotundo‐entopallial projection by means of anterograde and retrograde neuronal tracers. Our results confirm the zonal topography proposed by previous studies and indicate that each zone in the entopallium receives a direct and topographically organized projection from its corresponding rotundal subdivision. These results suggest that the spatial arrangement of the different rotundal functional modules is preserved at the entopallial level. J. Comp. Neurol. 518:4342–4361, 2010. © 2010 Wiley‐Liss, Inc.
Comparative studies of diurnal and nocturnal rodents: Differences in lifestyle result in alterations in cortical field size and number
Authors: Campi Katharine L. , Krubitzer Leah
Published: July 2010

In this study we examine and describe the neuroanatomical organization of sensory cortex in four rodents: laboratory Norway rats (Long Evans; Rattus norvegicus), wild‐caught Norway rats (Rattus norvegicus), wild‐caught California ground squirrels (Spermophilus beecheyi), and wild‐caught Eastern gray squirrels (Sciurus carolinensis). Specifically, we examined the myeloarchitecture and cytochrome oxidase reactivity for several well‐identified areas in visual cortex (areas 17, 18, and 19), somatosensory cortex (areas S1, S2 and PV), and auditory cortex [areas A1 + AAF (R) and TA] and compared the percentage of dorsolateral cortex devoted to each of these areas. Our results demonstrate that squirrels have a larger mean percentage of dorsolateral cortex devoted to visual areas than rats. The difference is due to the greater percentage of cortex devoted to known areas such as area 17 and area 18 and not simply to a difference in the number of visual areas, which ultimately makes this distinction even more pronounced. Furthermore, both rat groups have a larger percentage of the dorsolateral cortex devoted to somatosensory and auditory cortical areas. Differences within groups were also observed. The arboreal squirrel had a larger mean percentage of dorsolateral cortex devoted to areas 17 and 18 compared with the terrestrial squirrel. The laboratory Norway rat had a larger percentage of dorsolateral cortex devoted to both somatosensory and auditory areas than the wild‐caught Norway rat. Our results indicate that differences in sensory apparatus, use of sensory systems, and niche are reflected in the organization and size of cortical areas. J. Comp. Neurol. 518:4491–4512, 2010. © 2010 Wiley‐Liss, Inc.
BMP2 expression in the adult rat brain
Authors: Sato Tomonori , Mikawa Sumiko , Sato Kohji
Published: July 2010

Bone morphogenetic protein‐2 (BMP2) is a member of the transforming growth factor‐β (TGF‐β) superfamily and plays important roles in multiple biological events. Although BMP2 expression has been well described in the early development of the central nervous system (CNS), little information is available on its expression in the adult CNS. We thus investigated BMP2 expression in the adult rat CNS by using immunohistochemistry. Here we show that BMP2 is widely expressed throughout the adult CNS. In addition, besides intense BMP2 expression in almost all neurons, we found BMP2 expression in astrocytes and ependymal cells. Interestingly, we found that the axons of olfactory sensory neurons express BMP2. In addition, in the glomerular layer, BMP2 was very strongly expressed in some glomeruli, whereas the other glomeruli were weakly stained, suggesting that the variations in BMP2 expression level in each glomerus might be cues for each axon to find its adequate target and to keep its identity. Furthermore, we compared the expression patterns of BMP2 and BMP4. Interestingly, BMP4 was preferentially expressed in the dendrites of several neurons, whereas BMP2 was basically not expressed in the dendrites; however, it was detected in the axons. This means that in a single neuron the localizations of BMP2 and BMP4 are differentially regulated. These data indicate that BMP2 is more widely expressed throughout the adult CNS than previously reported, and its continued abundant expression in the adult brain strongly supports the idea that BMP2 also plays pivotal roles in the adult brain. J. Comp. Neurol. 518:4513–4530, 2010. © 2010 Wiley‐Liss, Inc.
Ovarian hormone‐induced reorganization of oxytocin‐labeled dendrites and synapses lateral to the hypothalamic ventromedial nucleus in female rats
Authors: Griffin Gerald D. , Ferri‐Kolwicz Sarah L. , Reyes Beverly A.S. , Van Bockstaele Elisabeth J. , Flanagan‐Cato Loretta M.
Published: July 2010

Central oxytocin (OT) modulates many social behaviors, including female rat sexual receptivity, quantified as the copulatory stance known as lordosis. The expression of the lordosis response is modulated by OT action in the ventromedial nucleus of the hypothalamus (VMH), as demonstrated by behavioral pharmacology experiments. However, the subcellular localization of OT in this brain region has been unclear. We tested the hypothesis that ovarian hormones reorganize OT‐labeled pre‐ or postsynaptic elements in the fiber complex lateral to the VMH by using immunoelectron microscopy. OT immunolabeling occurred in axonal boutons identified by the presence of small, clear synaptic vesicles and double labeling with the presynaptic markers synaptophysin and vesicular glutamate transporter 2. OT immunoreactivity also was observed in dendritic profiles, verified with double labeling for the dendrite‐specific marker microtubule‐associated protein 2. Ovarian hormones did not alter the density of axonal boutons; however, estradiol treatment reduced the density of dendritic profiles by 34%. This effect was reversed when progesterone was given subsequent to estradiol. The effect of estradiol treatment was specific to dendrites that lacked OT immunostaining; the density of OT‐labeled dendritic profiles remained constant during estradiol treatment. With the estradiol‐induced exit of non‐OT‐labeled dendritic profiles, the remaining OT‐labeled dendritic profiles experienced an increase in their number of synaptic contacts. Thus, hormone treatments that mimic the 4‐day rat estrous cycle provoke a chemically coded reorganization of dendrite innervation in the fiber plexus lateral to the VMH that may underlie the hormone‐specific effect of OT on reproductive behavior. J. Comp. Neurol. 518:4531–4545, 2010. © 2010 Wiley‐Liss, Inc.
Cellobiose Dehydrogenase: A Versatile Catalyst for Electrochemical Applications
Authors: Ludwig Roland , Harreither Wolfgang , Tasca Federico , Gorton Lo
Published: July 2010

Cellobiose dehydrogenase catalyses the oxidation of aldoses—a simple reaction, a boring enzyme? No, neither for the envisaged bioelectrochemical applications nor mechanistically. The catalytic cycle of this flavocytochrome is complex and modulated by its flexible cytochrome domain, which acts as a built‐in redox mediator. This intramolecular electron transfer is modulated by the pH, an adaptation to the environmental conditions encountered or created by the enzyme‐producing fungi. The cytochrome domain forms the base from which electrons can jump to large terminal electron acceptors, such as redox proteins, and also enables by that path direct electron transfer from the catalytically active flavodehydrogenase domain to electrode surfaces. The application of electrochemical techniques to the elucidation of the molecular and catalytic properties of cellobiose dehydrogenase is discussed and compared to biochemical methods. The results lead to valuable insights into the function of this cellulose‐bound enzyme, but also form the basis of exciting applications in biosensors, biofuel cells and bioelectrocatalysis.
Directional Study of the Optical Properties of Tb3+‐ and Eu3+‐Doped Nanoparticles Embedded in Silica Photonic Crystals
Authors: Bovero Enrico , Yano Kazuhisa , Nakamura Tadashi , Yamada Yuri , van Veggel Frank C. J. M.
Published: July 2010

The effects of the stop band (SB) in colloidal photonic crystals composed of silica spheres containing Eu3+‐ and Tb3+‐doped yttria nanoparticles are analysed. Reflection and transmission spectra indicate movement of the stop band, due to the 111 series of planes, towards shorter wavelengths with increasing angle of observation. The profile of the emission spectra is modified by the presence of the SB depending on the angle of measurement. Such a modification is more effective for a narrow emission band and it is thus more evident in the case of Tb3+ than Eu3+. An angular effect is also observed in the lifetime, which presents two maxima and one minimum. In the case of Tb3+ the maxima are at observation angles of 35 and 50°, and the minimum at 45°. We attribute this behaviour to penetration of the excitation beam at 475 nm modulated by the stop band. The ions excited in this way emit from different depths in the crystal, and therefore their lifetime will be affected differently by the same stop band, depending on the thickness of the crystal that must be crossed. Eu3+ shows a similar but less pronounced effect for two reasons: first, the main stop band (due to the 111 planes) is not effective at the excitation wavelength of 392 nm; second, the broadness of the Eu3+ emission is comparable to the width of the SB, and a decrease in the transition rate at the wavelength of the SB maximum is compensated by an increase at the sides of the SB.
Detection of molecular targets on the surface of CD34+CD38− bone marrow cells in myelodysplastic syndromes
Authors: Xie Wei , Wang Xuhua , Du Wen , Liu Wei , Qin Xiaoming , Huang Shiang
Published: July 2010

Myelodysplastic syndrome (MDS) is a kind of clonal stem‐cell disorder in which aberration within a hematopoietic stem cell (HSC) gives rise to the entire disease as in acute myeloid leukemia (AML). Studies have showed that contrasting normal stem cells, AML stem cells express CD96 and CD123, but lack of CD90, although both of them reside within the CD34+CD38− population. So far, little is known about expression of the markers on MDS HSC. In this study, we analyzed the immunophenotypic characteristics of CD34+CD38− bone marrow (BM) cells by multicolor flow cytometry in 38 patients with MDS and 10 control patients. We found that CD34+CD38− BM cells coexpressed CD13, CD33, CD117, CD133, and HLA‐DR almost in all patients, but in MDS they expressed higher amounts of CD13 (79% ± 16% vs. 36% ± 13%, P < 0.05) and CD133 (66% ± 20% vs. 25% ± 13%, P < 0.05). CD90 was expressed in all control patients but just in 63% of patients with MDS. No control patients had an expression of CD2, CD5, CD7, CD44, CD96, and CD123, which expressed variable amounts in 17–53% of patients with MDS. The level of CD13 in RCMD (89% ± 7%), RAEB‐1 (88% ± 11%), and RAEB‐2 (81% ± 13%) were obviously higher than that of RA (63% ± 16%, P < 0.05). CD2, CD5, and CD7 were more frequently observed in RAEB or INT and HIGH‐R cases. Taken together, we demonstrate MDS stem cells display deranged phenotypic abnormalities that may make them particularly difficult to eradicate using therapies targeted against surface antigens, and the percentage of cells expressing CD13 is notably higher in patients with high‐grade MDS that may be a potential prognostic indicator of MDS in the future. © 2010 International Society for Advancement of Cytometry
Digital analysis and sorting of fluorescence lifetime by flow cytometry
Authors: Houston Jessica P. , Naivar Mark A. , Freyer James P.
Published: July 2010

Frequency‐domain flow cytometry techniques are combined with modifications to the digital signal‐processing capabilities of the open reconfigurable cytometric acquisition system (ORCAS) to analyze fluorescence decay lifetimes and control sorting. Real‐time fluorescence lifetime analysis is accomplished by rapidly digitizing correlated, radiofrequency (RF)‐modulated detector signals, implementing Fourier analysis programming with ORCAS' digital signal processor (DSP) and converting the processed data into standard cytometric list mode data. To systematically test the capabilities of the ORCAS 50 MS/sec analog‐to‐digital converter (ADC) and our DSP programming, an error analysis was performed using simulated light scatter and fluorescence waveforms (0.5–25 ns simulated lifetime), pulse widths ranging from 2 to 15 μs, and modulation frequencies from 2.5 to 16.667 MHz. The standard deviations of digitally acquired lifetime values ranged from 0.112 to >2 ns, corresponding to errors in actual phase shifts from 0.0142° to 1.6°. The lowest coefficients of variation (<1%) were found for 10‐MHz modulated waveforms having pulse widths of 6 μs and simulated lifetimes of 4 ns. Direct comparison of the digital analysis system to a previous analog phase‐sensitive flow cytometer demonstrated similar precision and accuracy on measurements of a range of fluorescent microspheres, unstained cells, and cells stained with three common fluorophores. Sorting based on fluorescence lifetime was accomplished by adding analog outputs to ORCAS and interfacing with a commercial cell sorter with a RF‐modulated solid‐state laser. Two populations of fluorescent microspheres with overlapping fluorescence intensities but different lifetimes (2 and 7 ns) were separated to ∼98% purity. Overall, the digital signal acquisition and processing methods we introduce present a simple yet robust approach to phase‐sensitive measurements in flow cytometry. The ability to simply and inexpensively implement this system on a commercial flow sorter will allow both better dissemination of this technology and better exploitation of the traditionally underutilized parameter of fluorescence lifetime. Published 2010 Wiley‐Liss, Inc.
IL‐10 produced by activated human B cells regulates CD4+ T‐cell activation in vitro
Authors: Bouaziz Jean‐David , Calbo Sebastien , Maho‐Vaillant Maud , Saussine Anne , Bagot Martine , Bensussan Armand , Musette Philippe
Published: July 2010

IL‐10‐producing regulatory B cells have been identified in mice and shown to downregulate inflammation, making them potentially important for maintenance of tolerance. In this study, we isolated B cells from human blood and spleen, and showed that after a short period of ex vivo stimulation a number of these cells produced IL‐10. The IL‐10‐producing B cells did not fall within a single clearly defined subpopulation, but were enriched in both the memory (CD27+) and the transitional (CD38high) B‐cell compartments. Combined CpG‐B+anti‐Ig stimulation was the most potent IL‐10 stimulus tested. B cells stimulated in this way inhibited CD4+CD25− T‐cell proliferation in vitro by a partially IL‐10‐dependent mechanism. These findings imply that manipulating IL‐10 production by human B cells could be a useful therapeutic strategy for modulating immune responses in humans.
Metal‐Free Synthesis of Imido Derivatives by Direct Oxidation of α‐Amido Sulfones
Authors: Martinelli Fabio , Palmieri Alessandro , Petrini Marino
Published: July 2010

Oxidation of α‐amidoaryl sulfones with m‐chloroperoxybenzoic acid under mild conditions readily provides the corresponding imides in satisfactory yields. The overall process probably involves formation of an N‐acyliminium ion intermediate, which by attack of the peroxyacid anion generates the final imido derivatives.
Quantification of Sub‐Nanomolar Levels of Aluminum by Adsorptive Stripping Voltammetry Using Rubeanic Acid as a Selective Chelating Agent
Authors: Abbasi Shahryar , Bahiraei Atusa , Farmany Abbas
Published: July 2010

A novel, sensitive and selective adsorptive stripping procedure for determination of aluminum is presented. The method is based on the adsorptive accumulation of dithiooxamide (Rubeanic acid) complex of aluminum onto a hanging mercury drop electrode, followed by reduction of adsorbed species by voltammetric scan using differential pulse modulation. The influences of control variables on the sensitivity of the proposed method for the determination of aluminum were studied. The optimum analytical conditions were found to be Rubeanic acid (RA) concentration of 8.0×10−5 M, ammonia buffer (NH3NH4Cl) pH of 6.5, and accumulation potential at −50 mV vs. Ag/AgCl with an accumulation time of 60 s. The peak currents are proportional to the concentration of aluminum over the 0.3–70 ng mL−1 ranges with detection limit of 0.012 ng mL−1. The procedure was applied to the determination of aluminum in the Lab. Water, HCl of Merck and potato samples with satisfactory results.
Analysis of E. coli soluble proteins by non‐denaturing micro 2‐DE/3‐DE and MALDI‐MS‐PMF
Authors: Manabe Takashi , Jin Ya
Published: July 2010

Escherichia coli (strain K‐12)‐soluble proteins were analyzed by nondenaturing micro 2‐DE and MALDI‐MS‐PMF. The reported conditions of nondenaturing IEF in agarose column gels [Jin, Y., Manabe, T., Electrophoresis 2009, 30, 939–948] were modified to optimize the resolution of cellular soluble proteins. About 300 CBB‐stained spots, the apparent molecular masses of which ranged from ca. 6000 to 10 kDa, were detected. All the spots on two reference 2‐DE gels (one for wide mass range and one for low‐molecular‐mass range) were numbered and subjected to MALDI‐MS‐PMF for the assignment of constituting polypeptides. Most of the spots (310 spots out of 329) provided significant match (p<0.05) with polypeptides in Swiss‐Prot database and totally 228 polypeptide species were assigned. Activity staining of enzymes such as alkaline phosphatase and catalases was performed on the 2‐DE gels and the locations of the activity spots matched well with those of the MS‐assigned polypeptides of the enzymes. Most of the polypeptides with subunit information in Swiss‐Prot (119 polypeptides as homo‐multimers and 25 as hetero‐multimers out of the 228), such as pyruvate dehydrogenase complex which is composed of three enzymatic components, were detected at the apparent mass positions of their polymers, suggesting that the proteins were separated retaining their subunit structures. When a nondenaturing 2‐DE gel was vertically cut into 2 mm strips and one of the strips was subjected to a third‐dimension micro SDS‐PAGE (micro 3‐DE), about 190 CBB‐stained spots were detected. The assignment of the polypeptides separated on the 3‐DE gel would further provide information on protein/polypeptide interactions.
Protective effect of high protein and calcium intake on the risk of hip fracture in the framingham offspring cohort
Authors: Sahni Shivani , Cupples L Adrienne , Mclean Robert R , Tucker Katherine L , Broe Kerry E , Kiel Douglas P , Hannan Marian T
Published: July 2010

The effect of protein on bone is controversial, and calcium intake may modify protein's effect on bone. We evaluated associations of energy-adjusted tertiles of protein intake (ie, total, animal, plant, animal/plant ratio) with incident hip fracture and whether total calcium intake modified these associations in the Framingham Offspring Study. A total of 1752 men and 1972 women completed a baseline food frequency questionnaire (1991–1995 or 1995–1998) and were followed for hip fracture until 2005. Hazard ratios (HRs) were estimated using Cox proportional hazards regression adjusting for confounders. Baseline mean age was 55 years (SD 9.9 years, range 26 to 86 years). Forty-four hip fractures occurred over 12 years of follow-up. Owing to significant interaction between protein (total, animal, animal/plant ratio) and calcium intake (p interaction range = .03 to .04), stratified results are presented. Among those with calcium intakes less than 800 mg/day, the highest tertile (T3) of animal protein intake had 2.8 times the risk of hip fracture [HR = 2.84, 95% confidence interval (CI) 1.20–6.74, p = .02] versus the lowest tertile (T1, p trend = .02). In the 800 mg/day or more group, T3 of animal protein had an 85% reduced hip fracture risk (HR = 0.15, 95% CI 0.02–0.92, p = .04) versus T1 (p trend = .04). Total protein intake and the animal/plant ratio were not significantly associated with hip fracture (p range = .12 to .65). Our results from middle-aged men and women show that higher animal protein intake coupled with calcium intake of 800 mg/day or more may protect against hip fracture, whereas the effect appears reversed for those with lower calcium intake. Calcium intake modifies the association of protein intake and the risk of hip fracture in this cohort and may explain the lack of concordance seen in previous studies. © 2010 American Society for Bone and Mineral Research.
Relativistic effects in HgHe and HgXe CCSD(T) ground state potential curves. Low‐density viscosity simulations of Hg:Xe mixture
Authors: Bučinský Lukáš , Biskupič Stanislav , Ilčin Michal , Lukeš Vladimír , Laurinc Viliam
Published: July 2010

The comparison of coupled cluster with single and double excitations and with perturbative correction of triple excitations [CCSD(T)] ground state potential curves of mercury with rare gases (RG): HgHe and HgXe, at several levels of theory is presented. The scalar relativistic (REL) effects and spin‐orbit coupling effects in the ground state potential curves of these weakly bounded dimers are considered. The CCSD(T) ground state potential curves at the level of the Dirac‐Coulomb Hamiltonian (DCH) are compared with CCSD(T) curves at the level of 4‐component spin‐free modified DCH, the scalar 2nd order Douglas‐Kroll‐Hess (DKH2) and the nonrelativistic (NR‐LL) (Lévy‐Leblond) Hamiltonian. In addition, London‐Drude formula and SCF interaction energy curves are employed in the analysis of different contributions of REL effects in dissociation energies of HgRG and Hg2 dimers. Moreover, the large anharmonicity of the HgHe ground state potential curve is highlighted. The computationally less demanding scalar DKH2 Hamiltonian is employed to calculate the HgXe, Hg2, and Xe2 all electron CCSD(T) ground state potential curves in highly augmented quadruple zeta basis sets. These potential curves are used to simulate the shear viscosity of mercury, xenon, and mercury‐xenon (Hg:Xe) mixture. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011
A convenient one‐pot procedure for the synthesis of 2‐aryl quinazolines using active MnO2 as oxidant
Authors: Peng Yi‐Yuan , Zeng Yuyun , Qiu Ganyinsheng , Cai Lisheng , Pike Victor W.
Published: July 2010

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A variety of 2‐aryl quinazolines were synthesized from the condensation of 2‐aminobenzylamines and aryl aldehydes to form 2‐aryl‐1,2,3,4‐tetrahydroquinazolines and subsequent oxidation of the intermediates with MnO2. J. Heterocyclic Chem., (2010).
Soil amendment with agro‐industrial byproducts: molecular‐chemical compositions and effects on soil biochemical activities and phosphorus fractions
Authors: Negassa Wakene , Baum Christel , Leinweber Peter
Published: July 2010

Environmental pollution by agro‐industrial byproducts in developing countries can be alleviated by recycling into soils. However, little is known about their chemical composition and impact on soil fertility. Therefore, the objectives of the present study were (1) to characterize the molecular‐chemical composition of dry (COD) and wet (COW) coffee, sisal (SIS), barley malt of brewery (BEB), and sugarcane processing (FIC) byproducts, and filter cakes of linseed (LIC) and niger seed (NIC) and (2) to evaluate their effects on respiration, pH, enzyme activities, and P fractions of a tropical soil. The agro‐industrial byproducts significantly differed in their concentrations of plant nutrients and organic‐matter compositions. The highest proportions of lipids, phenols + lignin monomers, and alkylaromatics were observed in COD, N‐containing compounds in COW, sterols in FIC, peptides in LIC, suberin in SIS, and fatty acid in COW and FIC. The application of the byproducts at the rate of 40 kg P ha–1 (1.1 to 13.2 g C [kg soil]–1) significantly (p < 0.05) increased the rate and cumulative soil respiration, soil pH, acid phosphatase and urease activities, and labile inorganic P over the control treatment. Ranking the qualities of the agro‐industrial byproducts for soil amendment based on their composition and effects on soil properties revealed the order NIC > LIC > BEB > COW > SIS > FIC > COD.
Carotenoid content impacts flavor acceptability in tomato (Solanum lycopersicum)
Authors: Vogel Jonathan T , Tieman Denise M , Sims Charles A , Odabasi Asli Z , Clark David G , Klee Harry J
Published: July 2010

BACKGROUND: Tomatoes contain high levels of several carotenoids including lycopene and β‐carotene. Beyond their functions as colorants and nutrients, carotenoids are precursors for important volatile flavor compounds. In order to assess the importance of apocarotenoid volatiles in flavor perception and acceptability, we conducted sensory evaluations of near‐isogenic carotenoid biosynthetic mutants and their parent, Ailsa Craig.

RESULTS: The carotenoid contents of these tomatoes were extremely low in the r mutant, increased in lycopene in old gold, and higher in tetra‐cis‐lycopene and ζ‐carotene in tangerine. The volatiles derived from these carotenoids (β‐ionone, geranylacetone and 6‐methyl‐5‐hepten‐2‐one) were proportionally altered relative to their precursors. Fruits were also analyzed for soluble solids, sugars, acids and flavor volatiles. Consumer panels rated the r mutant lowest for all sensory attributes, while Ailsa Craig was generally rated highest. Old gold and tangerine were rated intermediate in two of the three harvests.

CONCLUSIONS: Several chemicals were negatively correlated with at least one of the hedonic scores while several others were positively correlated with tomato flavor acceptability. The results permitted identification of positive and negative interactions of volatiles with tomato flavor. Copyright © 2010 Society of Chemical Industry
The influence of monoacylglycerol and L‐glutamic acid on the viscoelastic properties of wheat flour dough and sensory characteristics of French loaf product
Authors: Pečivová Pavlína , Burešová Iva , Bílková Hana
Published: July 2010

BACKGROUND: The influence of monoacylglycerol Rimulsoft Super(V) and L‐glutamic acid added to wheat flour dough was studied. Properties of the doughs were evaluated on the basis of chemical analysis and rheological measurements on a farinograph. Bakery products made from these doughs were subsequently subjected to sensory analyses.

RESULTS: It was found that L‐glutamic acid influenced the water absorption in dough more (50.0 g kg−1; water absorption 56.6%) than monoacylglycerol Rimulsoft Super(V) (50.0 g kg−1; water absorption 55.0%). Farinograph measurements showed that doughs with the addition of L‐glutamic acid resembled flour containing high‐quality gluten, but dough with the addition of monoacylglycerol Rimulsoft Super(V) corresponded to ‘weak’ flour.

Sensory analyses revealed that, in comparison with the control sample of French loaf, the saliva‐absorbing capacity increased in the French loaf with the highest addition of L‐glutamic acid (30.0 g kg−1). Deterioration in quality and texture in French loaf with addition of L‐glutamic acid (8.0 g kg−1, 30.0 g kg−1) was noted. No other statistically significant differences were found.

CONCLUSION: It is acceptable to add both additives to dough in order to modify its rheological properties. Copyright © 2010 Society of Chemical Industry
The influence of organic/integrated production on the content of phenolic compounds in apple leaves and fruits in four different varieties over a 2‐year period
Authors: Petkovsek Maja Mikulic , Slatnar Ana , Stampar Franci , Veberic Robert
Published: July 2010

BACKGROUND: Phenolics in fruit may be influenced by the fruit type, cultivation conditions of a plant, climatic conditions, growing season, storage conditions, and industrial processing. The aim of this study was to compare single phenolic compounds, total phenolics and antioxidant capacity of four varieties of apple grown under organic and integrated conditions over a 2‐year period.

RESULTS: Several different phenolic compounds belonging to the groups of hydroxycinnamic acids, flavanols, dihydrochalcones, flavonols and anthocyanins were quantified. The levels of all analysed groups of phenolics were higher (not always significantly) in the organically grown apple leaves and fruit than in the leaves or apples from integrated production. Leaves from organic trees had 10–20% higher content levels of total phenols than the leaves from trees in the integrated growing system. In both years, organic production affected the increase in the antioxidant activity of apple peel. Organic apples have higher total phenolic content than the integrated grown ones.

CONCLUSION: Cultivation type had an important influence on the polyphenolic level and antioxidant capacity of the apple fruits and leaves. Apples from organic production showed a higher content of hydroxycinnamic acids, flavanols, dihydrochalcones, quercetins and total phenolics than apples from integrated cultivation. Copyright © 2010 Society of Chemical Industry
Changes in phenolic compounds and Rancimat stability of olive oils from varieties of olives at different stages of ripeness
Authors: Nieto Leopoldo Martínez , Hodaifa Gassan , Lozano Peña Juan Luis
Published: July 2010

BACKGROUND: Recently, diets rich in natural foods and food‐derived components, such as phenolic compounds, have received a great deal of attention because they are perceived as ‘safe’ and ‘non‐medicinal’. In fact, some are known to function as chemopreventive agents against oxidative damage, cerebrovascular disease, and aging.

RESULTS: Phenolic compounds, natural antioxidants present in virgin olive oil, play an important role in oil quality by contributing significantly to protecting oil stability against oxidation. In addition, polyphenols are the main contributors to olive oil bitterness, astringency and pungency. The data were fit by linear regression, giving Rancimat stability (h) = 0.18× Total polyphenols (mg L−1) in the virgin olive oil.

CONCLUSIONS: The practice of harvesting ripe olives as soon as possible to produce oils of high phenolic contents and thus high oxidative stability implies bitter and piquant oils, this being admissible for oils of some varieties but detrimental to others appreciated in the market for being more fruity and sweeter. Copyright © 2010 Society of Chemical Industry
ADMET‐Polymerization of Dienes based on Sustainable Chemicals
Authors: Günther Stefan , Lamprecht Patrick , Luinstra Gerrit A.
Published: July 2010

Summary: Eugenol and isoeugenol were used as natural based starting materials to prepare unsaturated polyethers and polycarbonates. The polymerization was achieved in a two step procedure exploiting the orthogonal phenol and ene functionalities. Thus diene terminated ethers and organic carbonates were obtained from eugenol and isoeugenol, and subjected to ADMET polymerisation using Grubbs 2nd generation catalyst1. The obtained unsaturated polymers have molecular weights ranging from 2.700 to 32.000 g/mol. Molecular weight build up was partly restricted by the low solubility of the products.
Ring Closing Metathesis Using Chiral Template Consisting of Hard and Soft Parts
Authors: Siddiki Hakim S. M. A. , Sugimura Takashi
Published: July 2010

Summary: Macrocyclic compounds having 18‐, 19‐, 22‐, and 23‐membered rings were prepared quantitatively by ring closing metathesis of diene substrates consisting of a rigid o‐ or m‐phthalate group and flexible but geometrically regulated 2,4‐pentanediol tethers. From the p‐phthalate analogues, the ring closing metathesis and the cyclic dimmer formation were observed to give 24‐membered ring (70% yield) and 40‐membered ring (65% yield) respectively.
Mesoporous Molecular Sieves as Advanced Supports for Olefin Metathesis Catalysts
Authors: Balcar Hynek , Čejka Jiří
Published: July 2010

Summary: Siliceous mesoporous molecular sieves MCM‐41, MCM‐48 and SBA‐15 and organised mesoporous alumina represent progressive supports for new heterogeneous catalysts for olefin metathesis and metathesis polymerization. In combination with Mo and Re oxides they provide catalysts of considerably higher activity in comparison with those based on conventional silica and alumina. Immobilization of Mo and Ru alkylidenes on these materials led to the highly active and selective catalysts with negligible leaching of transition metal.