bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual‐Luminophore‐Labeled Gold Nanoparticles with Completely Resolved Emission for the Simultaneous Imaging of MMP‐2 and MMP‐7 in Living Cells under Single Wavelength Excitation
Authors: Wang Xu , Xia Yanqing , Liu Yuanyuan , Qi Wenxue , Sun Qianqian , Zhao Qian , Tang Bo
Published: April 2012

Although considerable effort has been devoted to the design of various nanoprobes for the fluorescent detection of multiple biomarkers in a single assay, they often suffer from emission‐overlapping, owing to small Stokes shifts and wide emission spectra, which results in cross‐talk and inaccurate quantification. Herein, we report the design and synthesis of a new nanoprobe for multienzyme detection with completely resolved emission peaks under single‐wavelength excitation. The probe was assembled by attaching a cleavable peptide spacer, which was comprised from a matrix metalloproteinase‐2 (MMP‐2) substrate and a MMP‐7 substrate, onto the surface of gold nanoparticles (AuNPs) through cysteine residues. A lanthanide complex, BCTOT‐EuIII (BCTOT=1,10‐bis(5′‐chlorosulfo‐thiophene‐2′‐yl)‐4,4,5,5,6,6,7,7‐octafluorodecane‐1,3,8,10‐tetraone), and 7‐amino‐4‐methylcoumarin (AMC) were attached to the N terminus and the C terminus of the peptide, respectively. In the presence of one or both targeting enzymes, the substrate was cleaved and fluorescence resonance energy transfer (FRET) between the dyes and AuNPs was prohibited, thereby resulting in the dramatic fluorescence emission of dyes. Importantly, there was no emission cross‐talk between the two dyes, thereby ensuring accurate detection of each enzyme. Based on this, the simultaneous fluorescence image of MMP‐2 and MMP‐7 was accomplished in living cells under single wavelength excitation. The apparent differences in the fluorescence imaging indicated distinct differences between the expression levels of MMPs between the human normal liver cells and the human hepatoma cells.
Chromatographic comparison of atenolol separation in reaction media on cellulose tris‐(3,5‐dimethylphenylcarbamate) chiral stationary phase using ultra fast liquid chromatography
Authors: Agustian Joni , Kamaruddin Azlina Harun , Aboul‐Enein Hassan Y.
Published: April 2012

Because chiral liquid chromatography (LC) could become a powerful tool to estimate racemic atenolol quantity, excellent enantiomeric separation should be produced during data acquisition for satisfactory observation of atenolol concentrations throughout the racemic resolution processes. Selection of chiral LC column and analytical protocol that fulfill demands of the ultra fast LC analysis is essential. This article describes the characteristics of atenolol chromatographic separation that resulted from different resolution media and analytical protocols with the use of a Chiralcel® OD column. The chromatograms showed quite different characteristics of the separation process. The single enantiomer and racemic atenolol could be recognized by the Chiralcel® OD column in less than 20 min. Symmetrical peaks were obtained; however, several protocols produced peaks with wide bases and slanted baselines. Observations showed that efficient enantioresolution of racemic atenolol was obtained at slow mobile phase flow rate, decreased concentration of amine‐type modifier but increased alcohol content in mobile phase and highest ultraviolet detection wavelength were required. The optimal ultra fast LC protocol enables to reduce and eliminate the peaks of either the atenolol solvent or the buffers and provided the highest peak intensities of both atenolol enantiomers. Chirality 24:356–367, 2012. © 2012 Wiley Periodicals, Inc.
Synthesis of 2‐(3‐(3,5‐bis(trifluoromethyl)phenyl)thioureido)‐3‐((dimethylamino)methyl)camphor organocatalysts
Authors: Grošelj Uroš , Ričko Sebastjan , Svete Jurij , Stanovnik Branko
Published: April 2012

In a stereo‐divergent synthesis, three novel camphor‐derived bifunctional thiourea organocatalysts 7, 8, 9 have been prepared in five steps starting from (+)‐camphor. In addition, borneol‐derived bifunctional thiourea organocatalysts 19/19’ have been prepared in three steps from (1S)‐(+)‐camphorquinone. Novel organocatalysts 7, 8, 9, 19/19’ have been evaluated in a model reaction of Michael addition of dimethyl malonate to trans‐β‐nitrostyrene with low to moderate enantioselectivities (20%–60% ee). Configuration of all novel compounds has been meticulously determined using nuclear magnetic resonance (NMR) techniques. Chirality 24:412–419, 2012. © 2012 Wiley Periodicals, Inc.
Evaluation of residual CD34+Ph+ progenitor cells in chronic myeloid leukemia patients who have complete cytogenetic response during first‐line nilotinib therapy
Authors: Defina Marzia , Ippoliti Micaela , Gozzetti Alessandro , Abruzzese Elisabetta , Castagnetti Fausto , Crupi Rosaria , Tiribelli Mario , Breccia Massimo , Salvucci Marzia , Aprile Lara , Baratè Claudia , Gozzini Antonella , Rosti Gianantonio , Lauria Francesco , Bocchia Monica
Published: April 2012

BACKGROUND:

Compared with imatinib, nilotinib is a potent breakpoint cluster region/v‐abl Abelson murine leukemia viral oncogene (bcr‐abl) kinase inhibitor, and it induces higher rate and rapid complete cytogenetic response (CCyR), yet no clinical data are available regarding its efficacy against chronic myeloid leukemia (CML) stem cells. Earlier studies demonstrated that clusters of differentiation 34–positive, Philadelphia chromosome–positive (CD34+Ph+) cells are detectable in about 45% of patients with CML, despite being on long‐term imatinib therapy and having achieved sustained CCyR.

METHODS:

CD34+ cells from bone marrow of de novo CML patients in the chronic phase (n = 24) treated with nilotinib (median duration of therapy, 22 months) were isolated and scored for BCR‐ABL by fluorescent in situ hybridization (FISH) analysis. Similar analysis was also performed in 5 de novo CML chronic phase patients who achieved CCyR within 3 months of nilotinib therapy.

RESULTS:

FISH evaluation of a median of 100 CD34+ nuclei per patient revealed that only 1 of 20 (5%) evaluable patients showed residual Ph+ progenitor cells. In this patient, just 1 of 140 (0.7%) CD34+ interphase nuclei was found to be positive for BCR‐ABL. Surprisingly, no CD34+Ph+ cells were found even in those 5 patients evaluated after 3 months of nilotinib treatment.

CONCLUSIONS:

This study assessed for the first time the persistence of CD34+Ph+ cells during nilotinib first‐line treatment. Preliminary results showed that in patients in CCyR, even after short‐term nilotinib therapy, residual leukemic progenitors are very rarely detected compared with imatinib‐treated CCyR patients. It is yet to be determined if these findings will have an impact in the path to a cure of CML with tyrosine kinase inhibitors. Cancer 2012. © 2012 American Cancer Society.
Reverse phase protein array profiling reveals distinct proteomic signatures associated with chronic myeloid leukemia progression and with chronic phase in the CD34‐positive compartment
Authors: Quintás‐Cardama Alfonso , Qiu Yi Hua , Post Sean M. , Zhang Yiqun , Creighton Chad J. , Cortes Jorge , Kornblau Steven M.
Published: April 2012

BACKGROUND:

Chronic myeloid leukemia (CML) is a clonal stem cell malignancy whose pathogenesis is driven by constitutive activation of the breakpoint cluster region–v‐abl Abelson murine leukemia viral oncogene homolog 1 (BCR‐ABL1) kinase. Although BCR‐ABL1 activation is present in all patients with CML, patients can present in 3 different phases characterized by an increasingly worse prognosis and diminished responsiveness to tyrosine kinase inhibitors: chronic phase, accelerated phase, or blastic phase. The biologic basis for progression from chronic phase to blastic phase and for regulating the homeostasis of tyrosine kinase inhibitor‐resistant CML stem cells is not entirely understood.

METHODS:

To shed some light into these aspects of CML biology, the authors used reverse phase protein arrays probed with 112 individual monoclonal antibodies to compare protein expression patterns in 40 samples of leukemia‐enriched fractions from patients with CML (25 in chronic phase, 5 in accelerated phase, and 10 in phase).

RESULTS:

An analysis of variance (significance cutoff, P < .01) unveiled a set of proteins that were overexpressed in blastic phase, including heat‐shock protein 90 (hsp90); retinoblastoma (Rb); apoptosis‐inducing factor (AIF); serine/threonine‐protein phosphatase 2A (PP2A); B‐cell leukemia 2 (Bcl‐2); X‐linked inhibitor of apoptosis protein (Xiap); human homolog of Drosophila Mad (mothers against decapentaplegic) and related Caenorhabditis elegans gene Sma, family member 1 (Smad1); single‐stranded DNA binding protein 2 alpha (SSBP2α); poly(adenosine diphosphate‐ribose) polymerase (PARP); GRB2‐associated binding protein 2 (Gab2); and tripartite motif containing 24 (Trim24). It is noteworthy that several of these proteins also were overexpressed in the CD34‐positive compartment, which putatively contains the CML stem cell population.

CONCLUSIONS:

The results from this study indicated that reverse phase protein array analysis can unveil differentially expressed proteins in advanced phase CML that can be exploited therapeutically with targeted approaches. Cancer 2012. © 2012 American Cancer Society.
Thyroid cancer incidence by histological type and related variants in a mildly iodine‐deficient area of Northern Italy, 1998 to 2009
Authors: Ceresini Graziano , Corcione Luigi , Michiara Maria , Sgargi Paolo , Teresi Giulio , Gilli Annalisa , Usberti Elisa , Silini Enrico , Ceda Gian Paolo
Published: April 2012

BACKGROUND:

The incidence of thyroid cancer is increasing in several countries. However, the issue of whether this applies to all different histological types and related variants is poorly addressed.

METHODS:

All incident thyroid cancers diagnosed between 1998 and 2009 in a mildly iodine‐deficient area in northern Italy were derived from a population‐based tumor registry. Stage of disease, size of the tumor, focality, and histological variants were recorded from a review of pathology reports and slides. The mean annual increase (MAI) of the standardized incidence rate was calculated over the entire 12‐year period of observation and a standardized rate ratio was evaluated to compare the mean standardized incidence between 2 periods of 6 years each (1998‐2003 vs 2004‐2009).

RESULTS:

In total, 980 cases were considered. An increase in the incidence trend for all thyroid tumors was demonstrated; the increase was found to be continuous from 1998 to 2002 but not afterward. The cancer incidence increased in both male and female subjects. Papillary thyroid carcinoma (PTC), the follicular variant of PTC, the tall cell variant of PTC (TCV‐PTC), and Hurthle cell carcinoma (HC) showed the most relevant changes in incidence whereas follicular carcinoma was not found to be significantly affected. TCV‐PTC was the only histological type to demonstrated a significant (P < .01) proportional increase in the second 6‐year period of observation. Only TCV‐PTC and HC were found to display a significant MAI after 2002.

CONCLUSIONS:

The incidence of thyroid cancer has increased within the last decade, an increase that is accounted for mostly by differentiated tumors. The most significant increases were documented for aggressive variants of basic histotypes. Cancer 2012. © 2012 American Cancer Society.
Detection of fluticasone propionate in horse plasma and urine following inhaled administration
Authors: Gray Bobby P. , Biddle Simon , Pearce Clive M. , Hillyer Lynn
Published: April 2012

Fluticasone propionate (FP) is an anti‐inflammatory agent with topical and inhaled applications commonly used in the treatment of asthma in steroid‐dependent individuals. The drug is used in racehorses to treat Inflammatory Airway Disease; this work was performed in order to advise on its use and detect potential misuse close to racing. Methods were developed for the extraction and analysis of FP from horse plasma and a carboxylic acid metabolite (FP‐17βCOOH) from horse urine. The methods utilize ultra high performance liquid chromatography coupled to tandem mass spectrometry (UPLC‐MS/MS) in order to detect the extremely low concentrations of analyte present in both matrices. The developed methods were used to analyse plasma and urine samples collected following inhaled administration of FP to six thoroughbred horses. FP was detected in plasma for a minimum of 72 h post‐administration and FP‐17βCOOH was detected in urine for approximately 18 h post‐administration. The results show that it is possible to detect FP in the horse following inhaled administration. Copyright © 2012 John Wiley & Sons, Ltd.
Study of polycyclic aromatic hydrocarbons in atmospheric particulate matter of an urban area with iron and steel mills
Authors: Menezes Helvécio C. , Cardeal Zenilda L.
Published: April 2012

Polycyclic aromatic hydrocarbons (PAHs) were analyzed from ambient air particulate matter <10 µm (PM10) and the total suspended particulate (TSP) phase continuously for a period of six months (May–October 2010) at five sampling sites located in the urban area of Divinópolis (Minas Gerais), southeastern Brazil, near iron and steel mills. The carcinogenic potency of priority PAHs relative to benzo[a]pyrene was estimated for a period of six months. Benzo[a]pyrene equivalents were 7.52 ng/m3 for the study period. The estimated risk of lifetime lung cancer was 6.5 × 10−4. A model based on the diagnostic ratio and principal component analysis was applied for source apportionment. Considering the entire study period, the burning of biomass and fuel oil accounted for about 70% of the PAH profile. An inventory was performed during the monitoring period, with 37 companies representing major industries located in the urban area. The observations were consistent with the distribution of sources and indicated that the iron and steel sector was the largest contributor. Environ. Toxicol. Chem. 2012; 31: 1470–1477. © 2012 SETAC
Current emergency restoration practices show need for more automated systems
Authors: Singer Jason
Published: April 2012

According to the National Oceanic and Atmospheric Administration National Weather Service data, in an average year, the United States is hit by 5–10 Nor'easters, 20–30 killer tornadoes, and 13–17 named storms, half of which potentially will become major hurricanes attaining strength status of Category 3 or higher. Clearly, these weather events threaten significant disruptions to electric utilities' provision of uninterrupted electric service and high power quality, critical requirements mandated by the electric customer.
Differential TERT promoter methylation and response to 5‐aza‐2′‐deoxycytidine in acute myeloid leukemia cell lines: TERT expression, telomerase activity, telomere length, and cell death
Authors: Pettigrew Kerry A. , Armstrong Richard N. , Colyer Hilary A. A. , Zhang Shu‐Dong , Rea Irene Maeve , Jones Rhiannon E. , Baird Duncan M. , Mills Ken I.
Published: April 2012

The catalytic subunit of human telomerase (TERT) is highly expressed in cancer cells, and correlates with complex cytogenetics and disease severity in acute myeloid leukemia (AML). The TERT promoter is situated within a large CpG island, suggesting that expression is methylation‐sensitive. Studies suggest a correlation between hypermethylation and TERT overexpression. We investigated the relationship between TERT promoter methylation and expression and telomerase activity in human leukemia and lymphoma cell lines. DAC‐induced demethylation and cell death were observed in all three cell lines, as well as telomere shortening in HL‐60 cells. DAC treatment reduced TERT expression and telomerase activity in OCI/AML3 and HL‐60 cells, but not in U937 cells. Control U937 cells expressed lower levels of TERT mRNA, carried a highly methylated TERT core promoter, and proved more resistant to DAC‐induced repression of TERT expression and cell death. AML patients had significantly lower methylation levels at several CpGs than “well elderly” individuals. This study, the first to investigate the relationship between TERT methylation and telomerase activity in leukemia cells, demonstrated a differential methylation pattern and response to DAC in three AML cell lines. We suggest that, although DAC treatment reduces TERT expression and telomerase activity, this is unlikely to occur via direct demethylation of the TERT promoter. However, further investigations on the regions spanning CpGs 7–12 and 14–16 may reveal valuable information regarding transcriptional regulation of TERT. © 2012 Wiley Periodicals, Inc.
Buried and Submerged Greek Archaeological Coastal Structures and Artifacts as Gauges to Measure Late Holocene Seafloor Subsidence off Calabria, Italy
Authors: Stanley Jean‐Daniel , Bernasconi Maria Pia
Published: April 2012

This synthesis integrates recently acquired archaeological and geological data with earlier documented observations to shed light on the subsidence of ancient Greek coastal facilities in southern Italy. These are now positioned between former shorelines and inner shelf sectors at five Calabrian margin localities. Submergence of coastal to inner shelf facilities has resulted in part from sea‐level rise by about 2 m associated with glacio‐hydro‐isostatic factors since archaic to classic Greek time. This phenomenon alone, however, does not explain the wide variation of measured subsidence rates from site‐to‐site. The marked lowering of coastal site substrates by seismo‐tectonic activity (including extensional fault motion), stratal readjustments at depth, and compaction of underlying sediment sequences is significant. Four of the subsided facilities are positioned near emerged Calabrian areas where prevailing Holocene average annual land uplift rates range to ˜1.0 mm/yr; at the fifth, near Hipponion, terrains have risen by nearly 2 mm/yr. In marked contrast, submerged and/or buried structures record the following late Holocene long‐term average rates of coastal margin subsidence: Sybaris‐Thuri on the Taranto Gulf margin (˜0.5–1.0 mm/yr); Hipponion‐Vibo Valentia along the Tyrrhenian coast (˜0.8 to ˜3.2 mm/yr); and Locri‐Epizefiri, Kaulonia, and Capo Colonna on Calabria's Ionian margin (˜1.6, ˜1.6–2.4, and ˜4.0 mm/yr, respectively). © 2012 Wiley Periodicals, Inc.
Constraining saturated hydraulic transmissivity values by means of maximum saturated area mapping and maximum subsurface discharge: long‐term simulation in the Amazon basin
Authors: da Silva Roberto Valmir , Yamashiki Yosuke , Takara Kaoru
Published: April 2012

Although saturated hydraulic conductivity (K0) and saturated hydraulic transmissivity (T0) are physically based parameters, quite often, their calibrated values lie out of the physically based range, driving modellers to increased K0 values in some orders of magnitude, from field measured values, in order to fit observed discharge data. Therefore, calibration is a necessary process in hydrological modelling. Within a hydrological model, K0 or T0 plays an important role. They allow the model to represent the hydrograph separation through estimates of subsurface discharges. Simulating different flow components in hydrological modelling is an increasing need for basin management and water quality predictions. The present study has the objective to develop two criteria to constrain T0 values using a TOPMODEL multi‐velocity approach in order to represent the hydrograph separation in a more realistic way. The method was (i) applied to three sub‐basins in the Amazon basin (the Óbidos, the Humaita and Santo Antônio basins), (ii) evaluated by means of a combined objective function and uncertainty bounds and (iii) validated in a long‐term simulation. Because the constraint criteria were applied, it has verified a significant reduction in subsurface uncertainty for all the basins. The constraint criteria reduced the number of simulations to 11%, 42% and 23% for the Óbidos basin, the Humaita basin and the Santo Antônio basin, respectively. This means that a large number of simulations were rejected in the sense they represented unrealistic hydrograph separation. Copyright © 2012 John Wiley & Sons, Ltd.
High‐frequency observations of melt effects on snowpack stratigraphy, Kahiltna Glacier, Central Alaska Range
Authors: Winski Dominic , Kreutz Karl , Osterberg Erich , Campbell Seth , Wake Cameron
Published: April 2012

With an increased volume of melt on many of the world's glaciers, study of how meltwater affects the properties of glacial snowpack becomes essential to our understanding of how glaciers will respond to climate change. We address this problem by studying how snow properties changed on sub‐daily timescales on the Kahiltna Glacier, Alaska, between May 26 and June 10, 2010. During this period, we dug 1.8‐m‐deep snow pits twice daily to record the stratigraphy of melt layers, snow hardness, grain size, and density and sampled for hydrogen isotopic composition (δD) on four occasions. From these data, we show that 65% of the melted surface snow infiltrates and refreezes in the snowpack. This leads to a densification of the snow, a 729% increase in volume of melt layers, and a homogenization of isotopic and physical snow properties. From visual and stratigraphic observations, we show that meltwater flow within the snowpack is conducted primarily along lenses and pipes, where melt layers later form, but that more homogeneous capillary‐based flow is also important. Finally, we show using isotope ratios that post‐depositional alteration is exacerbated with increased melt extent, using the δD profile below a volcanic ash layer as a case study. In the future, similar studies would benefit from this high‐frequency monitoring approach to assessing snowpack evolution, as it allows for a greater understanding of short duration processes. New directions for study would include longer‐term monitoring efforts over a wider spatial snow pit network. Copyright © 2012 John Wiley & Sons, Ltd.
Synthesis of biodegradable poly(ε‐caprolactone)‐organosiloxane hybrid with carboxylate groups
Authors: Song Sang‐Hoon , Lee Seung Jin , Rhee Sang‐Hoon
Published: April 2012

Biodegradable poly(ε‐caprolactone)‐organosiloxane hybrid with carboxylate groups was newly synthesized by a sol–gel method with the capacity to conjugate cell adhesion ligands for the potential applications as a bone tissue engineering scaffold material. An intermediate hybrid contained positively charged amine groups was synthesized by end‐capping α,ω‐hydroxyl poly(ε‐caprolactone) with (3‐isocyanatopropyl)triethoxysilane and a subsequent sol–gel reaction with (3‐aminopropyl)triethoxysilane. This resulted in a new hybrid composed of biodegradable organic poly(ε‐caprolactone) segments connected by inorganic siloxane linkages containing positively charged amine groups. The successive succinlylation of amine groups created amide bonds and converted the cationic sites of succinic anhydride into negatively charged carboxylate groups. New formations of amine and carboxylate groups could be directly and indirectly confirmed using Fourier transformed infrared spectrometry, zeta potentials, and atomic force microscopy. Biodegradability of hybrid with carboxylate groups was also examined by weight loss in phosphate buffered saline, and it was about 14 wt % after 8 weeks. Conjugating capacity of a cell adhesion ligand was examined by comparing the relative fluorescent intensities of covalently and noncovalently immobilized synthetic GGGGRGDASSK‐FITC oligopeptides onto the carboxylated groups of the hybrid using confocal laser scanning microscopy; the relative fluorescent intensity of covalently conjugated RGD peptide was about three times higher than that of noncovalently coated RGD peptide. The hybrid covalently conjugated by GGGGRGDASSK oligopeptides improved proliferation and differentiation activities of preosteoblastic MC3T3‐E1 cells. The results suggest that this hybrid possesses an encouraging potential to be used as a bone tissue engineering scaffold material due to its biodegradability and high capacity for conjugating cell adhesion ligands. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2012.
Evaluation of epoxy resin sealer after three root canal filling techniques by confocal laser scanning microscopy
Authors: Kok Daniela , Duarte Marco Antônio Húngaro , Da Rosa Ricardo Abreu , Wagner Márcia Helena , Pereira Jefferson Ricardo , Só Marcus Vinícius Reis
Published: April 2012

The aim of this study was to evaluate the penetration of endodontic sealer into the dentin tubules, the integrity of the sealer layer perimeter, and the sealer area at the apical third after different filling techniques by confocal laser scanning microscopy (CLSM). Forty‐five mandibular premolars were mechanically prepared with ProTaper files, until F5 file. Thereafter, they were filled with an epoxy‐resin sealer (AH Plus) mixed with Rhodamine B dye (0.1% proportion) and allocated in three groups: Group 1, single master cone; Group 2, cold lateral compaction; and Group 3, Thermafil. For confocal laser scanning microscopy analysis, the specimens were transversely sectioned at 4 mm from the apex. The images at ×10 and ×40 were analyzed by Imagetool 3.0 software. Significant differences were not found among the three experimental groups according the dentin‐impregnate area by the sealer (P = 0.68) and between the sealer and root canal perimeter (P = 0.18). However, root canal filling techniques were significantly different when apical sealer areas were compared (P = 0.001). Thermafil group showed smaller sealer areas (8.09%) while cold lateral compaction and gutta‐percha master cone showed similar areas (17.37 and 21.18%, respectively). The dentin‐impregnated area was not dependent on the root canal filling technique. Single master cone, cold lateral condensation and Thermafil techniques presented integrity of the sealer perimeter close to 100% and Thermafil resulted in a significantly thinner sealer layer. Microsc. Res. Tech. 75:1277–1280, 2012. © 2012 Wiley Periodicals, Inc.
Free‐breathing 3D whole‐heart black‐blood imaging with motion sensitized driven equilibrium
Authors: Srinivasan Subashini , Hu Peng , Kissinger Kraig V. , Goddu Beth , Goepfert Lois , Schmidt Ehud J. , Kozerke Sebastian , Nezafat Reza
Published: April 2012

Purpose:

To assess the efficacy and robustness of motion sensitized driven equilibrium (MSDE) for blood suppression in volumetric 3D whole‐heart cardiac MR.

Materials and Methods:

To investigate the efficacy of MSDE on blood suppression and myocardial signal‐to‐noise ratio (SNR) loss on different imaging sequences, seven healthy adult subjects were imaged using 3D electrocardiogram (ECG)‐triggered MSDE‐prep T1‐weighted turbo spin echo (TSE), and spoiled gradient echo (GRE), after optimization of MSDE parameters in a pilot study of five subjects. Imaging artifacts, myocardial and blood SNR were assessed. Subsequently, the feasibility of isotropic spatial resolution MSDE‐prep black‐blood was assessed in six subjects. Finally, 15 patients with known or suspected cardiovascular disease were recruited to be imaged using a conventional multislice 2D double inversion recovery (DIR) TSE imaging sequence and a 3D MSDE‐prep spoiled GRE.

Results:

The MSDE‐prep yielded significant blood suppression (75%–92%), enabling a volumetric 3D black‐blood assessment of the whole heart with significantly improved visualization of the chamber walls. The MSDE‐prep also allowed successful acquisition of black‐blood images with isotropic spatial resolution. In the patient study, 3D black‐blood MSDE‐prep and DIR resulted in similar blood suppression in left ventricle and right ventricle walls but the MSDE‐prep had superior myocardial signal and wall sharpness.

Conclusion:

MSDE‐prep allows volumetric black‐blood imaging of the heart. J. Magn. Reson. Imaging 2012;36:379–386. © 2012 Wiley Periodicals, Inc.
Temporal profile of molecular signatures associated with circulating endothelial progenitor cells in human ischemic stroke
Authors: Sobrino Tomás , Pérez‐Mato María , Brea David , Rodríguez‐Yáñez Manuel , Blanco Miguel , Castillo José
Published: April 2012

Endothelial progenitor cells (EPC) have been associated with good functional outcome in ischemic stroke. From preclinical studies, it has been reported that EPC proliferation is mediated by several molecular markers, including vascular endothelial growth factor (VEGF), stromal cell‐derived factor‐1α (SDF‐1α), and the activity of matrix metalloproteinase‐9 (MMP‐9). Therefore, our aim was to study the role of these molecular factors in EPC proliferation in human ischemic stroke. Forty‐eight patients with first episode of nonlacunar ischemic stroke were prospectively included in the study within 12 hr of symptom onset. EPC colonies were classified as early‐outgrowth colony forming unit‐endothelial cell (CFU‐EC) and quantified at admission, at 24 and 72 hr, at day 7, and at 3 months. At the same time, serum levels of VEGF, SDF‐1α, and active MMP‐9 were measured by ELISA. The primary endpoint was EPC increment during the first week, which was defined as the difference in the number of CFU‐EC between day 7 and admission. We found that VEGF (r = 0.782), SDF‐1α (r = 0.828), and active MMP‐9 (r = 0.740) levels at 24 hr from stroke onset showed a strong correlation with EPC increment. Similar results were found for VEGF levels at 72 hr (r = 0.839) and at day 7 (r = 0.602) as well as for active MMP‐9 levels at 72 hr (r = 0.442) and at day 7 (r = 0.474). In the multivariate analyses, serum levels of VEGF at 72 hr (B: 0.074, P < 0.0001) and SDF‐1α at 24 hr (B: 0.049, P = 0.008) were independent factors for EPC increment during the first week of evolution. These findings suggest that VEGF and SDF‐1α may mediate EPC proliferation in human ischemic stroke. © 2012 Wiley Periodicals, Inc.
The Use of Cyclopenta[2,1‐b;3,4‐b′]dithiophene Analogues for the Development of Low‐Bandgap Materials
Authors: Willot Pieter , De Cremer Lieven , Koeckelberghs Guy
Published: April 2012

This paper presents the synthesis and characterization of low‐bandgap materials based on cyclopenta[1,2‐b;3,4‐b′]dithiophene (CPDT). An array of electron‐poor monomers is synthesized and used to prepare homo‐ and alternating donor–acceptor copolymers. This yields polymers with low bandgaps (Eg = 1.12–1.23 eV) and broad light absorption (400–1100 nm). The influence of the electron‐withdrawing substituent and the donor material on the polymer properties is studied. It is demonstrated that the low bandgap is not a result of intramolecular charge transfer, but of a transition localized in the electron‐poor CPDT monomer. The bandgap can be correlated with the substituent on the CPDT monomer and is relatively independent of other parameters, resulting in materials with an easily tunable bandgap.
Stimulation site within the MRI‐defined STN predicts postoperative motor outcome
Authors: Wodarg Fritz , Herzog Jan , Reese René , Falk Daniela , Pinsker Markus O. , Steigerwald Frank , Jansen Olav , Deuschl Günther , Mehdorn H. Maximillian , Volkmann Jens
Published: April 2012

High‐frequency stimulation of the subthalamic nucleus (STN‐HFS) is highly effective in treating motor symptoms in Parkinson's disease (PD) and medication side effects as well as in improving quality of life. Despite preoperative screening for patients as eligible candidates for this treatment, electrode position may furthermore influence treatment quality. Here, we investigated the relationship between the anatomical site of stimulation within the MRI‐defined STN and the outcome of PD patients after STN‐HFS. In 30 PD patients with bilateral STN stimulation, we retrospectively defined the boundaries of the STN within the axial target plane of the stereotactic T2‐weighted MRI and determined the position of the active electrode contact in relation to the border of the STN. The position of the active contact within the STN was the only variable to predict the outcome of STN stimulation. In contrast, covariates such as age, disease duration, symptom severity, and response to levodopa had no effect. The lateral position of the stimulation contact within the STN led to significantly better clinical improvement, lower stimulation parameters, and less need for postoperative dopaminergic medication. The outcome of patients with stimulation contacts within the medial region of the STN was significantly worse. Precise targeting of the lateral region of the STN is essential for achieving sufficient stimulation efficacy. Preoperative T2‐weighted MRI might be a useful component of the targeting procedure to improve the outcome of PD patients. © 2012 Movement Disorder Society
Tic‐induced gait dysfunction
Authors: Fasano Alfonso , Růžička Evžen , Bloem Bastiaan R.
Published: April 2012

Background:

Many neurological disorders impair gait, but only a few of them are episodic or paroxysmal, the most important ones being freezing of gait and paroxysmal dyskinesias.

Methods:

We describe 4 patients with tic disorders (3 with Tourette syndrome, and 1 with a tic disorder secondary to vascular disease) in whom intrusion of complex motor tics interfered with normal progression of stepping, thus producing an episodic gait disorder.

Results:

The involuntary movements that interfered with gait had features typical for tics, including their brief, sudden, irresistible, inapposite, and nonrhythmic recurrence. The motor behavior resembled tripping (n = 2), “blocking” of gait, or hip movements minimally interfering with gait.

Conclusions:

Tic‐induced gait disturbance is an episodic gait disorder occurring in patients with tics and should be recognized as a possible cause of episodic gait disturbances. © 2012 Movement Disorder Society
Hydroxyurea for the treatment of sickle cell disease: Efficacy, barriers, toxicity, and management in children
Authors: Strouse John J. , Heeney Matthew M.
Published: April 2012

Hydroxyurea is the only approved medication in the United States for the treatment of sickle cell anemia (HbSS) and is widely used in children despite an indication limited to adults. We review the evidence of efficacy and safety in children with reference to pivotal adult studies. This evidence and expert opinion form the basis for recommended guidelines for the use of hydroxyurea in children including indications, dosing, therapeutic and safety monitoring, and interventions to improve adherence. However, there are substantial gaps in our knowledge to be addressed by on‐going and planned studies in children. Pediatr Blood Cancer 2012;59:365–371. © 2012 Wiley Periodicals, Inc.
Assessment of medication knowledge and adherence among patients under oral chronic medication treatment in community pharmacy settings
Authors: Okuyan Betul , Sancar Mesut , Izzettin Fikret Vehbi
Published: April 2012

Purpose

This study aimed to determine whether there is a relationship between the lack of medication knowledge and the self‐reported rates of patient medication adherence.

Methods

Patients eligible to participate in the study had been taking oral medication at least once daily over the course of a minimum of three consecutive months before recruitment to the study. All participants were older than 18 years. The level of each patient's knowledge of his or her medication was randomly assessed by a trained fifth‐year pharmacy student through an adapted questionnaire. In addition, patient adherence was evaluated via utilization of the Morisky Medication Adherence Scale.

Results

Of the 765 study participants (mean ± SD age = 55.45 ± 15.05 years, range = 20–91 years, 56.2% women), 58.0% reported adherence to their medication regimen and 64.5% professed optimal knowledge of their medication. The mean duration of medication utilization was 26.77 ± 40.62 months (range = 3–504 years). A statistically significant correlation exists between the total medication knowledge score on the questionnaire and the level of medication adherence (r = −0.964, p < 0.001).

Conclusion

Improvement in the patient's knowledge of medications taken would bear a positive effect on medication adherence. Copyright © 2012 John Wiley & Sons, Ltd.
Thermal and electrical properties of glass fiber reinforced o‐cresol novolac epoxy composites cured with allylated phenol novolac hardener
Authors: Shin Seunghan , Lim Dong Guk , Kang Taeyoun , Chun Hyunaee , Cho Jin Ku
Published: April 2012

An allyl group was introduced into a phenol novolac hardener to improve the thermal and electrical properties of glass fiber reinforced o‐cresol novolac epoxy composites. Based on 1H NMR analysis, it was found that the degree of allylation was measured as 12.5% and 15.3% of allylated moieties underwent Claisen rearrangement. Thermal and electrical properties of the prepared composites were investigated by thermal mechanical analysis, dynamic mechanical analysis and dielectric measurements. Their thermal expansion coefficient and glass transition temperature measured by thermal mechanical analysis varied from 20.1 to 18.0 ppm K−1 and 132.5 to 170.9 °C, respectively, due to allylation of the phenol novolac hardener. From the storage modulus at the rubbery plateau, it was confirmed that these improvements were mainly caused by an increase in the crosslink density of the matrix resin owing to allyl groups. The electrical properties of the composites, however, showed no noticeable changes by allylation of the phenol novolac hardener. Copyright © 2012 Society of Chemical Industry
Refinement of protein structure homology models via long, all‐atom molecular dynamics simulations
Authors: Raval Alpan , Piana Stefano , Eastwood Michael P. , Dror Ron O. , Shaw David E.
Published: April 2012

Accurate computational prediction of protein structure represents a longstanding challenge in molecular biology and structure‐based drug design. Although homology modeling techniques are widely used to produce low‐resolution models, refining these models to high resolution has proven difficult. With long enough simulations and sufficiently accurate force fields, molecular dynamics (MD) simulations should in principle allow such refinement, but efforts to refine homology models using MD have for the most part yielded disappointing results. It has thus far been unclear whether MD‐based refinement is limited primarily by accessible simulation timescales, force field accuracy, or both. Here, we examine MD as a technique for homology model refinement using all‐atom simulations, each at least 100 μs long—more than 100 times longer than previous refinement simulations—and a physics‐based force field that was recently shown to successfully fold a structurally diverse set of fast‐folding proteins. In MD simulations of 24 proteins chosen from the refinement category of recent Critical Assessment of Structure Prediction (CASP) experiments, we find that in most cases, simulations initiated from homology models drift away from the native structure. Comparison with simulations initiated from the native structure suggests that force field accuracy is the primary factor limiting MD‐based refinement. This problem can be mitigated to some extent by restricting sampling to the neighborhood of the initial model, leading to structural improvement that, while limited, is roughly comparable to the leading alternative methods. Proteins 2012;. © 2012 Wiley Periodicals, Inc.
Forming interdisciplinary expertise: one organization's journey on the road to translational nanomedicine
Authors: Tsai‐hsuan Ku Sharon
Published: April 2012

This paper provides a sociological account of how researchers of different disciplines become experts in translational nanomedicine. Using a case study of the Nanotechnology Characterization Laboratory (NCL) at the National Cancer Institute (NCI), the author argues that the relationship between the different disciplines involved in translational nanomedicine should be understood in the broader sociopolitical context of the boundary politics between the academy, industry, and government. This study suggests that the process of training the nanobio expert is not simply a process of inculcating skills; it is also a process of institution building. In the case of the NCL, sustaining the laboratory's existence at the interface between the university, industry, and government informed how researchers practiced interdisciplinarity and cultivated their interdisciplinary expertise. It required mobilizing institutional resources through administrative/managerial strategies. Viewing the formation of a professional identity as a social process helps clarify the meaning of interdisciplinarity and provides insight in evaluating the performance of interdisciplinary collaboration and the design of nanoscience education. WIREs Nanomed Nanobiotechnol 2012, 4:366–377. doi: 10.1002/wnan.1172

This article is categorized under:

Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
Reduction of N-terminal methionylation while increasing titer by lowering metabolic and protein production rates in E. coli auto-induced fed-batch fermentation
Authors: Xu Jianlin , Qian Yueming , Skonezny Paul M , You Li , Xing Zizhuo , Meyers David S , Stankavage Robert J , Pan Shih-Hsie , Li Zheng Jian
Published: April 2012

A standard fed-batch fermentation process using 1 mM isopropyl-β-d-thiogalactopyranoside (IPTG) induction at 37 °C in complex batch and feed media had been developed for manufacturing of a therapeutic protein (TP) expressed in inclusion bodies (IBs) by E. coli BL21 (DE3) driven by T7 promoter. Six unauthentic TP N-terminal variants were identified, of which methionylated TP (Met-TP) ratio was predominant. We hypothesized that lowering metabolic and protein production rates would reduce the Met-TP ratio while improving TP titer. The standard process was surprisingly auto-induced without added IPTG due to galactose in the complex media. Without changing either the clone or the batch medium, a new process was developed using lower feed rates and auto-induction at 29 °C after glucose depletion while increasing induction duration. In comparison to the standard process, the new process reduced the unauthentic Met-TP ratio from 23.6 to 9.6 %, increased the TP titer by 85 %, and the specific production yield from 210 to 330 mg TP per gram of dry cell weight. Furthermore, the TP recovery yield in the purified IBs was improved by ~20 %. Adding together, ~105 % more TP recovered in the purified IBs from per liter of fermentation broth for the new process than the standard process. The basic principles of lowering metabolic and production rates should be applicable to other recombinant protein production in IBs by fed-batch fermentations.
Critical Micelle Concentration of Poly(Oxy‐1,2‐Ethanediyl), α‐Nonyl Phenol‐ω‐Hydroxy Ethers (C9H19C6H4Ei=6,10.5,12,17.5) by Surface Equations of State
Authors: Viades‐Trejo Josefina , Abascal‐González Dulce María , Gracia‐Fadrique Jesús
Published: April 2012

The analysis of surface tension variation versus surfactant concentration is the most usual method to estimate the critical micelle concentration (CMC). This parameter represents a fundamental thermodynamic boundary state where several surface properties, i.e. surface tension, surface pressure, surface concentration and surface coverage, simultaneously reach their limit values marking the conditions of the surface tension decrease. Thus the choice of the method used for CMC evaluation becomes of great importance, as the values depend on the principles from which the chosen method is derived. This paper presents CMC data from three surface equations of state: Gibbs, Langmuir and Volmer, modified to include the CMC among their constitutive parameters. Surface tension data of four nonyl phenol ethoxylates (6, 10.5, 12 and 17.5 ethylene oxide) along with ionic and non‐ionic surfactants from the literature were evaluated by the three surface equations of state; the following CMC × 107 values were obtained: for nonyl phenol 6 ethylene oxide 7.2, 7.2 and 6.8, for the 10.5 ethylene oxide 10, 12.4 and 9, for the 12 ethylene oxide 138.1, 147 and 137.4, and for the 17.5 ethylene oxide 4.9, 4.1 and 4.3 from Gibbs, Langmuir and Volmer equations respectively. These results compared with data from the literature, show the particular features of each equation, namely their predictive capabilities, and the thermodynamic parameters obtained besides the critical micelar concentration. It was found that for the critical micelle concentration determination in most cases Gibbs and Volmer models are equally satisfactory.
Influence of mouth guards on autonomic nervous system activities: A quantitative study of pupillary flash responses
Authors: Ishida Jun‐ichi , Wada Yoshiro , Imai Yuichiro , Hirata Yutaka , Yamashita Masayuki , Kirita Tadaaki
Published: April 2012

Background: Recently, it has been reported that mouth guards (MGs), which reduce the incidence and severity of traumatic oral injuries in contact sports, may actually affect sports performance. We have observed that a majority of subjects showed improved dynamic visual acuity during head rotation when using a MG, but subjects who were unwilling to use a MG showed the opposite effect. Thus, we hypothesized that unpleasant sensations due to MGs may decrease sports performance.

Methods: In this study, we measured autonomic nervous system activity to evaluate unpleasant sensations objectively and quantitatively by measuring the pupillary flash response (PFR) and heart rate variability (HRV), before, during, and after wearing 3‐ and 5‐mm‐thick custom‐made MGs in 10 healthy subjects.

Results: It was found that the 5‐mm MG had a higher incidence of unpleasant sensations (50% of subjects) than did the 3‐mm MG (10%). PFR (not HRV) analysis showed that both sympathetic and parasympathetic nervous system activities increased in subjects with unpleasant sensations.

Conclusions: We suggest that the unpleasant sensation induced this unusual autonomic nervous system response, which could not be detected by traditional methods such as HRV analysis. By using PFR analysis, it is possible to make MGs without unpleasant sensations for better sports performance.
FGFR3 targeting strategies for achondroplasia
Authors: Laederich Melanie B. , Horton William A.
Published: April 2012

Mutations that exaggerate signalling of the receptor tyrosine kinase fibroblast growth factor receptor 3 (FGFR3) give rise to achondroplasia, the most common form of dwarfism in humans. Here we review the clinical features, genetic aspects and molecular pathogenesis of achondroplasia and examine several therapeutic strategies designed to target the mutant receptor or its signalling pathways, including the use of kinase inhibitors, blocking antibodies, physiologic antagonists, RNAi and chaperone inhibitors. We conclude by discussing the challenges of treating growth plate disorders in children.