bluuebunny/crossref_metadata_2025 huggingface dataset:
Rational bioprocess design for human pluripotent stem cell expansion and endoderm differentiation based on cellular dynamics
Authors: Ungrin Mark D. , Clarke Geoff , Yin Ting , Niebrugge Sylvia , Nostro M. Cristina , Sarangi Farida , Wood Geoffrey , Keller Gordon , Zandstra Peter W.
Published: December 2011

We present a predictive bioprocess design strategy employing cell‐ and molecular‐level analysis of rate‐limiting steps in human pluripotent stem cell (hPSC) expansion and differentiation, and apply it to produce definitive endoderm (DE) progenitors using a scalable directed‐differentiation technology. We define a bioprocess optimization parameter (L; targeted cell Loss) and, with quantitative cell division tracking and fate monitoring, identify and overcome key suspension bioprocess bottlenecks. Adapting process operating conditions to pivotal parameters (single cell survival and growth rate) in a cell‐line‐specific manner enabled adherent‐equivalent expansion of hPSCs in feeder‐ and matrix‐free defined‐medium suspension culture. Predominantly instructive differentiation mechanisms were found to underlie a subsequent 18‐fold expansion, during directed differentiation, to high‐purity DE competent for further commitment along pancreatic and hepatic lineages. This study demonstrates that iPSC expansion and differentiation conditions can be prospectively specified to guide the enhanced production of target cells in a scale‐free directed differentiation system. Biotechnol. Bioeng. 2012; 109:853–866. © 2011 Wiley Periodicals, Inc.
From intervention informatics to prevention informatics
Authors: Fuller Sherrilynne
Published: December 2011

The contributions of the information science community to health care are significant, especially through systems supporting clinical care for individual patients, an intervention informatics approach. Though valuable, this strategy is reactive, fails to account for numerous environmental factors affecting personal health and falls short of enhancing human health on a broader scale. An unmet challenge with abundant opportunity lies in prevention informatics, a proactive approach drawing on information science and technologies to deliver greater health gains at a population level. Prevention informatics is marked by a high degree social interactivity in real time, with technologies to bring together disparate data and represent it in an integrated and meaningful way as the basis for action. The approach relies on standards for classifying information, systematic knowledge management and improved methods to collect, mine and visualize data. Tools and software are already in use in locations around the world, relying on smartphone technology and geographic information systems to share community health information and location data. Further advances in prevention informatics will require adoption of common terminologies, visualization tools and GIS mapping, and optimized data exchange to support rapid prevention response.
Glycine Fluoromethylketones as SENP‐Specific Activity Based Probes
Authors: Dobrotă Cristian , Fasci Domenico , Hădade Niculina D. , Roiban Gheorghe‐Doru , Pop Cristina , Meier Veronika M. , Dumitru Ioana , Matache Mihaela , Salvesen Guy S. , Funeriu Daniel P.
Published: December 2011

We report here the synthesis and biochemical properties of a new peptidyl activity‐based probe 1 for SUMO proteases, SENPs. The activity‐based probe has at its C terminus a glycine‐derived fluoromethylketone moiety as a reactive group designed to target the active‐site cysteine of SENPs. Based on a study of the interactions between SENPs and SUMOs, we introduced further design elements that allow the activity‐based probe to selectively target SENPs at low micromolar to high nanomolar concentrations. Moreover, 1 out‐competes SUMO1 from the reversible SUMO1–SENP1 complex, thus suggesting that 1 and SUMO1 share a common binding site on SENP1.
Photocrosslinking between Peptide–Peptide or Peptide–Oligonucleotide by RuII–TAP Complexes
Authors: Ghesquière Jonathan , Gauthier Nicolas , De Winter Julien , Gerbaux Pascal , Moucheron Cécile , Defrancq Eric , Kirsch‐De Mesmaeker Andrée
Published: December 2011

RuII–TAP complexes have been shown to be very attractive compounds in the frame of developments of new anticancer drugs targeting the genetic material. This increasing interest originates from observations of covalent bond formations, triggered by photo‐induced electron transfer (PET) between RuII–TAP complexes and guanine bases of DNA. This photoreaction has recently been extended to the tryptophan (Trp) amino acid for future applications involving peptides. Thus, a double photo‐addition of Trp residues of peptides on RuII complexes is demonstrated by mass spectrometry with some structural issues. Such bi‐adduct formations offer the possibility of photocrosslinking two Trp‐containing biomolecules, which is investigated in this study. Thus, photocrosslinking between two complementary oligonucleotides (ODNs) derivatized by Trp‐containing tripeptides is demonstrated by polyacrylamide gel electrophoresis (PAGE) in the presence of RuII–TAP complexes. Both PAGE and MS indicate that such photocrosslinkings arise from two reaction pathways: either via the double addition of Trp residues on the Ru complex or from dimerization of Trp radicals. The competition between these two pathways depends on the experimental conditions. Heterobridgings between guanine bases and tryptophan residues mediated by RuII–TAP complexes is also examined, opening the way to ODN–peptide photocrosslinkings.
Is the Conventional Interpretation of the Anisotropic Effects of CC Double Bonds and Aromatic Rings in NMR Spectra in Terms of the π‐Electron Shielding/Deshielding Contributions Correct?
Authors: Baranac‐Stojanović Marija , Koch Andreas , Kleinpeter Erich
Published: December 2011

Based on the nucleus‐independent chemical shift (NICS) concept, isotropic magnetic shielding values have been computed along the three Cartesian axes for ethene, cyclobutadiene, benzene, naphthalene, and benzocyclobutadiene, starting from the molecular/ring center up to 10 Å away. These through‐space NMR spectroscopic shielding (TSNMRS) values, which reflect the anisotropic effects, have been broken down into contributions from localized‐ and canonical molecular orbitals (LMOs and CMOs); these contributions revealed that the proton NMR spectroscopic chemical shifts of nuclei that are spatially close to the CC double bond or the aromatic ring should not be explained in terms of the conventionally accepted π‐electron shielding/deshielding effects. In fact, these effects followed the predictions only for the antiaromatic cyclobutadiene ring.
General Bottom‐Up Construction of Spherical Particles by Pulsed Laser Irradiation of Colloidal Nanoparticles: A Case Study on CuO
Authors: Wang Hongqiang , Kawaguchi Kenji , Pyatenko Alexander , Li Xiangyou , Swiatkowska‐Warkocka Zaneta , Katou Yukiko , Koshizaki Naoto
Published: December 2011

The development of a general method to fabricate spherical semiconductor and metal particles advances their promising electrical, optical, magnetic, plasmonic, thermoelectric, and optoelectric applications. Herein, by using CuO as an example, we systematically demonstrate a general bottom‐up laser processing technique for the synthesis of submicrometer semiconductor and metal colloidal spheres, in which the unique selective pulsed heating assures the formation of spherical particles. Importantly, we can easily control the size and phase of resultant colloidal spheres by simply tuning the input laser fluence. The heating–melting–fusion mechanism is proposed to be responsible for the size evolution of the spherical particles. We have systematically investigated the influence of experimental parameters, including laser fluence, laser wavelength, laser irradiation time, dispersing liquid, and starting material concentration on the formation of colloidal spheres. We believe that this facile laser irradiation approach represents a major step not only for the fabrication of colloidal spheres but also in the practical application of laser processing for micro‐ and nanomaterial synthesis.
Rare‐Earth Metal Allyl and Hydrido Complexes Supported by an (NNNN)‐Type Macrocyclic Ligand: Synthesis, Structure, and Reactivity toward Biomass‐Derived Furanics
Authors: Abinet Elise , Martin Daniel , Standfuss Sabine , Kulinna Heiko , Spaniol Thomas P. , Okuda Jun
Published: December 2011

The preparation and characterization of a series of neutral rare‐earth metal complexes [Ln(Me3TACD)(η3‐C3H5)2] (Ln=Y, La, Ce, Pr, Nd, Sm) supported by the 1,4,7‐trimethyl‐1,4,7,10‐tetraazacyclododecane anion (Me3TACD−) are reported. Upon treatment of the neutral allyl complexes [Ln(Me3TACD)(η3‐C3H5)2] with Brønsted acids, monocationic allyl complexes [Ln(Me3TACD)(η3‐C3H5)(thf)2][B(C6X5)4] (Ln=La, Ce, Nd, X=H, F) were isolated and characterized. Hydrogenolysis gave the hydride complexes [Ln(Me3TACD)H2]n (Ln=Y, n=3; La, n=4; Sm). X‐ray crystallography showed the lanthanum hydride to be tetranuclear. Reactivity studies of [Ln(Me3TACD)R2]n (R=η3‐C3H5, n=0; R=H, n=3,4) towards furan derivatives includes hydrosilylation and deoxygenation under ring‐opening conditions.
Oxygen Atom Transfer from a trans‐Dioxoruthenium(VI) Complex to Nitric Oxide
Authors: Man Wai‐Lun , W. Y. Lam William , Ng Siu‐Mui , Y. K. Tsang Wenny , Lau Tai‐Chu
Published: December 2011

In aqueous acidic solutions trans‐[RuVI(L)(O)2]2+ (L=1,12‐dimethyl‐3,4:9,10‐dibenzo‐1,12‐diaza‐5,8‐dioxacyclopentadecane) is rapidly reduced by excess NO to give trans‐[Ru(L)(NO)(OH)]2+. When ≤1 mol equiv NO is used, the intermediate RuIV species, trans‐[RuIV(L)(O)(OH2)]2+, can be detected. The reaction of [RuVI(L)(O)2]2+ with NO is first order with respect to [RuVI] and [NO], k2=(4.13±0.21)×101 M−1 s−1 at 298.0 K. ΔH≠ and ΔS≠ are (12.0±0.3) kcal mol−1 and −(11±1) cal mol−1 K−1, respectively. In CH3CN, ΔH≠ and ΔS≠ have the same values as in H2O; this suggests that the mechanism is the same in both solvents. In CH3CN, the reaction of [RuVI(L)(O)2]2+ with NO produces a blue‐green species with λmax at approximately 650 nm, which is characteristic of N2O3. N2O3 is formed by coupling of NO2 with excess NO; it is relatively stable in CH3CN, but undergoes rapid hydrolysis in H2O. A mechanism that involves oxygen atom transfer from [RuVI(L)(O)2]2+ to NO to produce NO2 is proposed. The kinetics of the reaction of [RuIV(L)(O)(OH2)]2+ with NO has also been investigated. In this case, the data are consistent with initial one‐electron O− transfer from RuIV to NO to produce the nitrito species [RuIII(L)(ONO)(OH2)]2+ (k2>106 M−1 s−1), followed by a reaction with another molecule of NO to give [Ru(L)(NO)(OH)]2+ and NO2− (k2=54.7 M−1 s−1).
Removal efficiency of heavy oil by free and immobilised microorganisms on laboratory‐scale
Authors: Bao Mutai , Chen Qingguo , Gong Yuanjiao , Li Yiming , Wang Haifeng , Jiang Guancheng
Published: December 2011

This study explored free and immobilised microorganisms to degrade heavy oil. Two oil‐degrading bacterial strains (W‐1 and W‐2) were isolated from heavy oil wastewater samples collected from Shengli Oil Field in China. W‐1 and W‐2, identified as Rhosococcus sp. and Bacillus cereus sp., respectively, were tested for their growth behaviour and optimal growth conditions in the laboratory. The obtained results showed that the optimal growth conditions for W‐1 and W‐2 were identified as pH of 8, temperature of 40°C, and salinity of 2% and 4%, respectively. The environmental conditions affecting oil‐degrading efficiency by W‐1 and W‐2 were optimised in the media containing 0.3% heavy oil. The results showed that the optimal degradation and optimal growth conditions were similar, and the oil degradation rates of W‐1 and W‐2 were about 34.6% and 45.3%, respectively after 5 days.

W‐1 and W‐2 capable of degrading oil was immobilised in calcium alginate gel beads containing active carbon and used for degradation of heavy oil. The heavy oil biodegradability of immobilised bacteria improved dramatically, compared with that of the free ones. The heavy oil biodegradation rates of immobilised W‐2 were found to be maximal at the same optimal growth conditions of pH, temperature, and salinity as the free ones. The best biodegradation rate of immobilised W‐2 reached above 78%, which is 33% than that of the free W‐2. © 2011 Canadian Society for Chemical Engineering
Effects of basic calponin on the flexural mechanics and stability of F‐actin
Authors: Jensen Mikkel Herholdt , Watt James , Hodgkinson Julie L. , Gallant Cynthia , Appel Sarah , El‐Mezgueldi Mohammed , Angelini Thomas E. , Morgan Kathleen G. , Lehman William , Moore Jeffrey R.
Published: December 2011

The cellular actin cytoskeleton plays a central role in the ability of cells to properly sense, propagate, and respond to external stresses and other mechanical stimuli. Calponin, an actin‐binding protein found both in muscle and non‐muscle cells, has been implicated in actin cytoskeletal organization and regulation. In this work, we studied the mechanical and structural interaction of actin with basic calponin, a differentiation marker in smooth muscle cells, on a single filament level. We imaged fluorescently labeled thermally fluctuating actin filaments and found that at moderate calponin binding densities, actin filaments were more flexible, evident as a reduction in persistence length from 8.0 to 5.8 μm. When calponin‐decorated actin filaments were subjected to shear, we observed a marked reduction of filament lengths after decoration with calponin, which we argue was due to shear‐induced filament rupture rather than depolymerization. This increased shear susceptibility was exacerbated with calponin concentration. Cryo‐electron microscopy results confirmed previously published negative stain electron microscopy results and suggested alterations in actin involving actin subdomain 2. A weakening of F‐actin intermolecular association is discussed as the underlying cause of the observed mechanical perturbations. © 2011 Wiley Periodicals, Inc
Retrospective analysis of antitumor effects of zoledronic acid in breast cancer patients with bone‐only metastases
Authors: Niikura Naoki , Liu Jun , Hayashi Naoki , Palla Shana L. , Tokuda Yutaka , Hortobagyi Gabriel N. , Ueno Naoto T. , Theriault Richard L.
Published: December 2011

BACKGROUND:

Bisphosphonates have been used successfully in the treatment of hypercalcemia and to reduce skeletal complications of bone metastasis, but have not been shown to prevent bone metastasis or to prolong survival time in metastatic breast cancer patients. The aim of this study was to determine whether the progression‐free survival (PFS) and overall survival (OS) of patients with bone‐only breast cancer metastasis differed based on whether patients received zoledronic acid, pamidronate, or no bisphosphonate upon diagnosis of their metastases.

PATIENTS AND METHODS:

We retrospectively identified 314 patients diagnosed with bone‐only metastasis at the time of initial staging or who developed bone metastasis as the first recurrence site during follow‐up from January 1, 1997 to December 31, 2008, at The MD Anderson Cancer Center. Univariate and multivariate Cox hazards models were used to assess the effects of each treatment on PFS and OS.

RESULTS:

Patients who had more than 1 bone metastasis and Eastern Cooperative Oncology Group (ECOG) performance status of 2 and 3 were more likely to receive zoledronic acid in this analysis. Compared with no bisphosphonate use, the use of zoledronic acid was not significantly associated with longer PFS (hazard ratio [HR] = 0.72, P = .058 in univariate analysis, and HR = 0.80, P = .235 in multivariate analysis) nor with longer OS (HR = 1.04, P = .863 in univariate analysis and HR = 1.34, P = .192 in multivariate analysis).

CONCLUSION:

Our study demonstrates that for patients with bone‐only metastases, zoledronic acid did not prolong PFS or OS. In patients with bone‐only metastasis, we could not demonstrate antitumor effects of zoledronic acid. Cancer 2012. © 2011 American Cancer Society.
The prognostic difference of monoallelic versus biallelic deletion of 13q in chronic lymphocytic leukemia
Authors: Garg Ravin , Wierda William , Ferrajoli Alessandra , Abruzzo Lynne , Pierce Sherry , Lerner Susan , Keating Michael , O'Brien Susan
Published: December 2011

BACKGROUND:

Fluorescence in situ hybridization can detect genomic abnormalities in up to 80% of cases and provides prognostic information on patients with chronic lymphocytic leukemia (CLL). Although 13q deletion as the sole abnormality has been found to confer a favorable prognosis, there are little data as to whether there is a difference in prognostic value between monoallelic versus biallelic deletion of 13q.

METHODS:

The authors reviewed the electronic database for patients with CLL who carried the 13q deletion as the sole abnormality and presented to The University of Texas MD Anderson Cancer Center (MDACC). Untreated patients were separated into 2 groups: those having monoallelic versus those with biallelic deletion of 13q. Using Mann‐Whitney, chi‐square, and Kaplan‐Meier analysis, the baseline quantitative and qualitative variables for each group, along with the time from presentation to MDACC to treatment, were compared.

RESULTS:

A total of 176 patients were identified; 143 patients had a monoallelic deletion of 13q, whereas 33 patients had a biallelic deletion. The only significantly different values between the groups were albumin (4.5 g/dL vs 4.4 g/dL; P = .01) and zeta‐chain‐associated protein kinase 70 (ZAP70) expression (1.7% vs 4.8%; P = .010). The median time from fluorescence in situ hybridization analysis to treatment in both the monoallelic and biallelic groups had not been reached (P = not significant).

CONCLUSIONS:

Except for inconsequential differences in albumin and ZAP70 expression, there was no difference in the baseline characteristics between patients with CLL who had monoallelic or biallelic deletion of 13q. In addition, there was no significant difference in endpoints, including time to treatment. Cancer 2012;3531–3537. © 2011 American Cancer Society.
Creating and Modulating Microdomains in Pore‐Spanning Membranes
Authors: Orth Alexander , Johannes Ludger , Römer Winfried , Steinem Claudia
Published: December 2011

The architecture of the plasma membrane is not only determined by the lipid and protein composition, but is also influenced by its attachment to the underlying cytoskeleton. Herein, we show that microscopic phase separation of “raft‐like” lipid mixtures in pore‐spanning bilayers is strongly determined by the underlying highly ordered porous substrate. In detail, lipid membranes composed of DOPC/sphingomyelin/cholesterol/Gb3 were prepared on ordered pore arrays in silicon with pore diameters of 0.8, 1.2 and 2 μm, respectively, by spreading and fusion of giant unilamellar vesicles. The upper part of the silicon substrate was first coated with gold and then functionalized with a thiol‐bearing cholesterol derivative rendering the surface hydrophobic, which is prerequisite for membrane formation. Confocal laser scanning fluorescence microscopy was used to investigate the phase behavior of the obtained pore‐spanning membranes. Coexisting liquid‐ordered‐ (lo) and liquid‐disordered (ld) domains were visualized for DOPC/sphingomyelin/cholesterol/Gb3 (40:35:20:5) membranes. The size of the lo‐phase domains was strongly affected by the underlying pore size of the silicon substrate and could be controlled by temperature, and the cholesterol content in the membrane, which was modulated by the addition of methyl‐β‐cyclodextrin. Binding of Shiga toxin B‐pentamers to the Gb3‐doped membranes increased the lo‐phase considerably and even induced lo‐phase domains in non‐phase separated bilayers composed of DOPC/sphingomyelin/cholesterol/Gb3 (65:10:20:5).
Carbonyl‐Functionalized Quaterthiophenes: A Study of the Vibrational Raman and Electronic Absorption/Emission Properties Guided by Theoretical Calculations
Authors: Aragó Juan , Ponce Ortiz Rocío , Nieto‐Ortega Belén , Hernández Víctor , Casado Juan , Facchetti Antonio , Marks Tobin J. , Viruela Pedro M. , Ortí Enrique , López Navarrete Juan T.
Published: December 2011

This work investigates the evolution of the molecular, vibrational, and optical properties within a family of carbonyl‐functionalized quaterthiophenes: 5,5′′′‐diheptanoyl‐2,2′:5′,2′′:5′′,2′′′‐quaterthiophene (1), 5,5′′′‐diperfluorohexylcarbonyl‐2,2′:5′,2′′:5′′,2′′′‐quaterthiophene (2), and 2,7‐[bis(5‐perfluorohexylcarbonylthien‐2‐yl)]‐4H‐cyclopenta[2,1‐b:3,4‐b′]‐dithiophene‐4‐one (3). The analysis is performed by Raman and UV/Vis absorption/excitation/fluorescence spectroscopy in combination with density functional calculations. Theoretical calculations show that substitution with carbonyl groups and perfluorohexyl chains induces progressive quinoidization of the π‐conjugated backbone in comparison to the carbonyl‐free compound 5,5′′′‐dimethyl‐2,2′:5′,2′′:5′′,2′′′‐quaterthiophene (DM‐4T) used as reference. Raman spectra are dominated by a strong Raman line which mainly corresponds to a combination of CC/CC stretching vibrations spreading over the whole thiophene core. This band undergoes a remarkable downshift as a consequence of the structural changes induced by the electron‐withdrawing groups on the π‐conjugated backbone. The band splitting on incorporation of a central carbonyl bridge evidences the formation of two structural domains in the molecule. The excitation and fluorescence spectra recorded at low temperature show well‐resolved vibronic structures associated with the most intense collective CC/CC stretching mode. Optical absorption and fluorescence bands exhibit remarkable bathochromic dispersion on carbonyl functionalization, indicative of extension of π conjugation. TDDFT calculations enable a detailed description of the trends observed in the absorption spectra. Resonance Raman spectra reflect the structural changes predicted for the S0→S1 electronic transition and evidence the cross‐conjugated character that the central carbonyl group confers on 3.
Low temperature photoluminescence studies on semiorganic tris thiourea copper (I) chloride single crystal
Authors: Ariponnammal S. , Chandrasekaran S. , Sanjeeviraja C.
Published: December 2011

Semiorganic tris thiourea copper (I) chloride (TTCC) single crystals have been synthesized from copper (II) chloride via slow evaporation technique. The stoichiometry of the grown anhydrous complex crystal has been confirmed by elemental CHNS (C, H, N and S) and atomic absorption spectrophotometric (AAS) analysis. The crystal structure with space group has been confirmed by single crystal and powder X‐ray diffraction (XRD) studies. The FTIR study assigned the presence of functional groups and confirmed the co‐ordination of metal ions with thiourea. It also confirmed the transition from Cu2+ to Cu+ when thiourea combined with Copper (II) chloride. The optical transparency of the crystal has been studied by UV‐Vis spectrum and deduced the energy gap. The room temperature Photoluminescence (PL) spectrum reported maximum emission line at 410.92 nm and Stokes shift has been determined as 75 nm or 16.5 eV. Low temperature luminescence study from 300 K to 77 K exhibited three blue emission peaks and one green emission peak. The green emission band has been assigned to recombination of an electron in a shallow trap and Cu2+. Blue emission has been attributed to S2‐ vacancies. The interesting hysteresis loop has been exhibited by the variation of energy gap with low temperature. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Nitrogen‐Doped Carbon Nanotubes as a Highly Active Metal‐Free Catalyst for Selective Oxidation
Authors: Chizari Kambiz , Deneuve Adrien , Ersen Ovidiu , Florea Ileana , Liu Yu , Edouard David , Janowska Izabela , Begin Dominique , Pham‐Huu Cuong
Published: December 2011

Catalytic reactions are generally carried out on supported metals or oxides, which act as an active phase and require impregnation and thermal treatment steps. During tests, the metal or oxide nanoparticles could be further sintered, which would induces deactivation. Direct incorporation of the active phase into the matrix of a support could be an elegant alternative to prevent catalyst deactivation. Here, we report that nitrogen‐doped carbon nanotubes (N‐CNTs) can be efficiently employed as a metal‐free catalyst for oxidative reactions that allow the selective transformation of the harmful, gaseous H2S into solid sulfur. The catalyst exhibits a high stability during the test at high space velocity. The macroscopic shaping of the catalyst on the silicon carbide foam also increases its catalytic activity by improving the contact between the reactants and the catalyst. Such macroscopic shaping allows the avoidance of problems linked with transport and handling of nanoscopic materials and also reduces the pressure drop across the catalyst bed to a large extent.
High‐throughput screening for various classes of doping agents using a new ‘dilute‐and‐shoot’ liquid chromatography‐tandem mass spectrometry multi‐target approach
Authors: Guddat S. , Solymos E. , Orlovius A. , Thomas A. , Sigmund G. , Geyer H. , Thevis M. , Schänzer W.
Published: December 2011

A new multi‐target approach based on liquid chromatography – electrospray ionization tandem mass spectrometry (LC‐(ESI)‐MS/MS) is presented to screen for various classes of prohibited substances using direct injection of urine specimens. With a highly sensitive new generation hybrid mass spectrometer classic groups of drugs – for example, diuretics, beta2‐agonists – stimulants and narcotics are detectable at concentration levels far below the required limits.

Additionally, more challenging and various new target compounds could be implemented. Model compounds of stimulant conjugates were studied to investigate a possible screening without complex sample preparation. As a main achievement, the integration of the plasma volume expanders dextran and hydroxyethyl starch (HES), commonly analyzed in time‐consuming, stand‐alone procedures, is accomplished. To screen for relatively new prohibited compounds, a common metabolite of the selective androgen receptor modulator (SARMs) andarine, a metabolite of growth hormone releasing peptide (GHRP‐2), and 5‐amino‐4‐imidazolecarboxyamide ribonucleoside (AICAR) are analyzed. Following a completely new approach, conjugates of di(2‐ethylhexyl) phthalate (DEHP) metabolites are monitored to detect abnormally high levels of plasticizers indicating for illicit blood transfusion.

The assay was fully validated for qualitative purposes considering the parameters specificity, intra‐ (3.2–16.6%) and inter‐day precision (0.4–19.9%) at low, medium and high concentration, robustness, limit of detection (1–70 ng/ml, dextran: 30 µg/ml, HES: 10 µg/ml) and ion suppression/enhancement effects.

The analyses of post‐administration and routine doping control samples demonstrates the applicability of the method for sports drug testing. This straightforward and reliable approach accomplishes the combination of different screening procedures resulting in a high‐throughput method that increases the efficiency of the labs daily work. Copyright © 2011 John Wiley & Sons, Ltd.
The overlooked difference between human endogenous and recombinant erythropoietins and its implication for sports drug testing and pharmaceutical drug design
Authors: Reichel Christian
Published: December 2011

Sequential deglycosylation by exoglycosidase treatment (Reagent Array Analysis Method, RAAM) and subsequent sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) revealed a profound structural difference between human endogenous and recombinant erythropoietins. While both proteins behaved similarly upon digestion with Arthrobacter ureafaciens α‐sialidase and Steptococcus pneumoniae β‐D‐galactosidase, the action of N‐acetyl‐β‐D‐glucosaminidase from Steptococcus pneumoniae was partly blocked by endogenous but not recombinant erythropoietins. Consequently, further treatment with Jack bean α‐D‐mannosidase and Helix pomatia β‐D‐mannosidase led to only very limited additional deglycosylation of endogenous EPO, while rhEPO glycans continued to be degraded. The behaviour was visualized by SDS‐PAGE combined with Western blotting. While the apparent molecular masses of most endogenous glycoforms did not further decrease after treatment with the first three enzymes, masses of most rhEPO glycoforms continued to drop after digestion with the two mannosidases. Both, human urinary and serum EPO showed this blocking effect, and all of the tested 28 recombinant epoetins were accessible to further degradation by exo‐mannosidases. The majority of EPO pharmaceuticals is produced in Chinese hamster ovary (CHO) cell lines, few in other ones (i.e. baby hamster kidney (BHK) or human fibrosarcoma (HT‐1080) cells). Since human endogenous EPO is primarily produced by the kidneys, tissue specific glycosylation might explain the altered deglycosylation behaviour. This difference was overlooked since EPO was first isolated from human urine in 1977. The results might prove useful for anti‐doping testing and future EPO drug development. Copyright © 2011 John Wiley & Sons, Ltd.
Structural and functional response of methane‐consuming microbial communities to different flooding regimes in riparian soils
Authors: Bodelier Paul L.E. , Bär‐Gilissen Marie‐Jose , Meima‐Franke Marion , Hordijk Kees
Published: December 2011

Climate change will lead to more extreme precipitation and associated increase of flooding events of soils. This can turn these soils from a sink into a source of atmospheric methane. The latter will depend on the balance of microbial methane production and oxidation. In the present study, the structural and functional response of methane oxidizing microbial communities was investigated in a riparian flooding gradient. Four sites differing in flooding frequency were sampled and soil‐physico‐chemistry as well as methane oxidizing activities, numbers and community composition were assessed. Next to this, the active community members were determined by stable isotope probing of lipids. Methane consumption as well as population size distinctly increased with flooding frequency. All methane consumption parameters (activity, numbers, lipids) correlated with soil moisture, organic matter content, and conductivity. Methane oxidizing bacteria were present and activated quickly even in seldom flooded soils. However, the active species comprised only a few representatives belonging to the genera Methylobacter, Methylosarcina, and Methylocystis, the latter being active only in permanently or regularly flooded soils.

This study demonstrates that soils exposed to irregular flooding harbor a very responsive methane oxidizing community that has the potential to mitigate methane produced in these soils. The number of active species is limited and dominated by one methane oxidizing lineage. Knowledge on the characteristics of these microbes is necessary to assess the effects of flooding of soils and subsequent methane cycling therein.
Impact of historical founder effects and a recent bottleneck on MHC variability in Commander Arctic foxes (Vulpes lagopus)
Authors: Ploshnitsa Anna I. , Goltsman Mikhail E. , Macdonald David W. , Kennedy Lorna J. , Sommer Simone
Published: December 2011

Populations of Arctic foxes (Vulpes lagopus) have been isolated on two of the Commander Islands (Bering and Mednyi) from the circumpolar distributed mainland population since the Pleistocene. In 1970–1980, an epizootic outbreak of mange caused a severe population decline on Mednyi Island. Genes of the major histocompatibility complex (MHC) play a primary role in infectious disease resistance. The main objectives of our study were to compare contemporary variation of MHC class II in mainland and island Arctic foxes, and to document the effects of the isolation and the recent bottleneck on MHC polymorphism by analyzing samples from historical and contemporary Arctic foxes. In 184 individuals, we found 25 unique MHC class II DRB and DQB alleles, and identified evidence of balancing selection maintaining allelic lineages over time at both loci. Twenty different MHC alleles were observed in mainland foxes and eight in Bering Island foxes. The historical Mednyi population contained five alleles and all contemporary individuals were monomorphic at both DRB and DQB. Our data indicate that despite positive and diversifying selection leading to elevated rates of amino acid replacement in functionally important antigen‐binding sites, below a certain population size, balancing selection may not be strong enough to maintain genetic diversity in functionally important genes. This may have important fitness consequences and might explain the high pathogen susceptibility in some island populations. This is the first study that compares MHC diversity before and after a bottleneck in a wild canid population using DNA from museum samples.
Locus‐specific view of flax domestication history
Authors: Fu Yong‐Bi , Diederichsen Axel , Allaby Robin G.
Published: December 2011

Crop domestication has been inferred genetically from neutral markers and increasingly from specific domestication‐associated loci. However, some crops are utilized for multiple purposes that may or may not be reflected in a single domestication‐associated locus. One such example is cultivated flax (Linum usitatissimum L.), the earliest oil and fiber crop, for which domestication history remains poorly understood. Oil composition of cultivated flax and pale flax (L. bienne Mill.) indicates that the sad2 locus is a candidate domestication locus associated with increased unsaturated fatty acid production in cultivated flax. A phylogenetic analysis of the sad2 locus in 43 pale and 70 cultivated flax accessions established a complex domestication history for flax that has not been observed previously. The analysis supports an early, independent domestication of a primitive flax lineage, in which the loss of seed dispersal through capsular indehiscence was not established, but increased oil content was likely occurred. A subsequent flax domestication process occurred that probably involved multiple domestications and includes lineages that contain oil, fiber, and winter varieties. In agreement with previous studies, oil rather than fiber varieties occupy basal phylogenetic positions. The data support multiple paths of flax domestication for oil‐associated traits before selection of the other domestication‐associated traits of seed dispersal loss and fiber production. The sad2 locus is less revealing about the origin of winter tolerance. In this case, a single domestication‐associated locus is informative about the history of domesticated forms with the associated trait while partially informative on forms less associated with the trait.
Dinuclear and Mononuclear Chromium Acetylide Complexes
Authors: Egler‐Lucas Carolina , Blacque Olivier , Venkatesan Koushik , López‐Hernández Alberto , Berke Heinz
Published: December 2011

Reaction of trans‐Cl2Cr(dmpe)2 (1) [dmpe = 1,2‐bis(dimethylphosphanyl)ethane] with 0.5 equiv. of Me3Sn–C≡C–C≡C–SnMe3 or Me3Sn–C≡C–C6H4–C≡C–SnMe3 afforded the dinuclear complexes trans‐[Cl(dmpe)2Cr≡C–C≡C–C≡Cr(dmpe)2Cl] (2), trans‐[Cl(dmpe)2Cr–C≡C–C≡C–Cr(dmpe)2Cl][SnMe3Cl2]2 (2[SnMe3Cl2]2), and trans‐[Cl(dmpe)2Cr–C≡C–C6H4–C≡C–Cr(dmpe)2Cl][SnMe3Cl2]2 (3[SnMe3Cl2]2), which could be transformed to the 2[PF6]2 and 3[BPh4]2 salts. Substitutions of the chloride groups in 2 were carried out to achieve the corresponding iodo (4) and (trimethylsilyl)alkynyl (5) complexes. Utilizing similar reactions and treatment with only 1 equiv. of the corresponding alkynyl ligand [Me3Sn–C≡C–R (R = –SnMe3, –C6H5), Me3Sn–C≡C–C≡C–R (R = –SiMe3, –SnMe3), and Me3Sn–C≡C–C6H4–C≡C–SnMe3] allowed us to prepare a series of mononuclear monoacetylide complexes: trans‐[Cl(dmpe)2Cr–C≡C–R] [R = –SnMe3(6),–C6H5(7)], trans‐[Cl(dmpe)2Cr–C≡C–C≡C–R] [R = –SiMe3(8),–SnMe3(9)], and trans‐[Cl(dmpe)2Cr–C≡C–C6H4–C≡C–SnMe3] (10), respectively. The complexes 2, 2[SnMe3Cl2]2, 2[PF6]2, 3[SnMe3Cl2]2, 3[BPh4]2, and 6–10 displayed paramagnetic behavior. Electrochemical studies performed on the dinuclear complexes (2), (2[SnMe3Cl2]2), (3[SnMe3Cl2]2), and (5) showed one two‐electron redox wave revealing a class‐I type behavior based on the Robin–Day classification, which is untypical for dinuclear complexes bridged by a butadiyne ligand. The complexes were characterized by NMR, ESI–MS, cyclic voltammetry, EPR spectroscopy, magnetic measurements, and exemplary single‐crystal X‐ray diffraction studies for 2, 2[SnMe3Cl2]2, 8, 9, and 10.
Hydrogen‐Bond‐Assisted Helical Folding of Propeller‐Shaped Molecules: Effects of Extended π‐Conjugation on Chiral Selection, Conformational Stability, and Exciton Coupling
Authors: Opsitnick Elizabeth A. , Jiang Xuan , Hollenbeck Andrew N. , Lee Dongwhan
Published: December 2011

Cooperative interaction between multiple chiral centers dictates the absolute handedness of structural folding. We have designed and prepared a series of chiral C3‐symmetric tris(N‐salicylidenamine) derivatives that adopt three‐blade propeller‐like conformations. Synthetic access to an expanded family of such constructs was aided by enzymatic resolution and C–C cross‐coupling reactions of aryl‐substituted chiral propargylic alcohol derivatives. These key structural components were integrated into molecular propellers of predetermined helical screw sense. Through comparative studies on a homologous set of molecules, we found that installation of phenylene‐ethynylene‐derived π‐conjugation profoundly affected the stabilities of the helically folded structures, as evidenced by UV/Vis and circular dichroism (CD) studies. Increasing the number of hydrogen bonds through additional substitution also enhanced the populations of the folded conformations in solution. In addition to introducing steric bias to control structural folding, linearly π‐conjugated groups function as spatially well‐defined chromophores that give rise to characteristic exciton‐coupled circular dichroism. Absolute configurations of chiral centers could thus be further confirmed by comparing the torsional relationships between pairs of chromophores on adjacent subunits, which are fully consistent with the computationally predicted structural models.
Electrochemical Aptasensor Based on a Macrocyclic Ligand Bearing Neutral Red
Authors: Evtugyn Gennady , Kostyleva Veronika , Sitdikov Rusal , Porfireva Anna , Savelieva Maria , Stoikov Ivan , Antipin Igor , Hianik Tibor
Published: December 2011

An amperometric aptasensor has been developed by immobilization of DNA aptamer with Neutral Red (NR) on polycarboxylated thiacalix[4]arene onto the electropolymerized NR layer at a glassy carbon electrode. The NR reduction current recorded after 10 min incubation decayed with increased thrombin concentration due to limitation of the electron exchange in the surface layer. The aptasensor makes it possible to determine 0.1–50 nM of thrombin (limit of detection 0.05 nM). The aptasensor can be used for the direct determination of thrombin in blood serum and does not exert any alteration of the response in the presence of 100 fold excess of serum proteins.
Ion‐Selective Optodes in a Sampling Capillary for Tear Fluid Analysis
Authors: Lindner Ernő , Bordelon Dwight , Kim Mariya D. , Dergunov Sergey A. , Pinkhassik Eugene , Chaum Edward
Published: December 2011

Plasticized PVC membrane‐based potassium or sodium ion‐selective optodes were incorporated into sampling capillaries in combination with sol‐gel‐based hydrogen ion‐selective optodes for the sampling and analysis of minute tear fluid samples. The performance characteristic of the K+/pH and Na+/pH sensor arrays were optimized for an adequate dynamic response range, sensitivity, stability, and response time. The precision and accuracy of the combined sampling/measurement system was evaluated both in stopped flow and continuous flow modes using aqueous standard solutions. By using a two point calibration protocol, with pH standards bracketing the sample, the pH of 20 µL pooled human tear samples could be determined with a precision less than ±0.03 pH units. Errors in the pH measurements have a significant influence on the attainable precision and accuracy of the ion‐exchange‐based K+ and Na+ optodes. Nevertheless, the results of the quantitative assessment of the K+ and Na+ concentrations in “check” standards and pooled human tear fluid samples were within ±5 % of the nominal values or of the results of the determinations with atomic absorption spectrophotometry. Cationic surfactants in artificial tear drops were found to interfere with the K+ and Na+ optode responses. No interference was detected in the presence of anionic and nonionic surfactants.
2‐D t‐ITP/CZE determination of clinical urinary proteins using a microfluidic‐chip capillary electrophoresis device
Authors: Wu Ruige , Yeung William S. B. , Fung Ying‐Sing
Published: December 2011

To replace the time‐consuming sample pretreatment procedure, a microfluidic chip‐CE device incorporating on‐chip sample desalting/preconcentration with transient isotachophoresis (ITP)/capillary zone electrophoresis (CZE) was fabricated to perform sequential on‐chip sample pretreatment and CE determination of four urinary proteins in clinical samples. On‐chip sample desalting, clean‐up and analyte preconcentration enable removing interfering sample matrix prior to transferring analytes to separation capillary for transient ITP/CZE determination. Four important urinary proteins transferrin, β2‐microglobulin, human serum albumin (HSA) and immunoglobulin G (IgG), investigated were shown to achieve quantitation limits sufficiently high to meet medical requirements, sensitivity enhancement up to 40‐fold and detection limits down to 0.3, 0.05, 0.6, 0.5 mg/L, respectively. Compared to the stacking effect, the use of a large sample size was found to be the major factor for sensitivity enhancement. The method reliability is established by close to 100% recoveries and statistical agreement of results from the method developed with currently used clinical radio‐immunoassay method for all four proteins investigated. Moreover, an assay time of less than 10 min is needed in the method developed as compared to 7 h for the radio‐immunoassay method.
Polyelectrolytes in multivalent salt solutions
Authors: Wu Kun‐Mao , Wei Yu‐Fu , Hsiao Pai‐Yi
Published: December 2011

We study conformational and electrophoretic properties of polyelectrolytes (PEs) in tetravalent salt solutions under the action of electric fields by means of molecular dynamics simulations. Chain conformations are found to have a sensitive dependence on the salt concentrationCs. AsCsis increased, the chains first shrink to a globular structure and subsequently re‐expand above a critical concentrationCs*. An external electric field can further alter the chain conformation. If the field strengthEis larger than a critical valueE*, the chains are elongated.E*is shown to be a function ofCsby using two estimatorsEI*andEII*through the study of the polarization energy and the onset point of chain unfolding, respectively. The electrophoretic mobility of the chains depends strongly onCs, and the magnitude increases significantly, accompanying the chain unfolding, whenE>EII*. We study the condensed ion distributions modified by electric fields and discuss the connection of the modification with the change of chain morphology and mobility. Finally,E*is studied by varying the chain lengthN. The inflection point is used as a third estimatorEIII*.EIII*scales asN−0.63(4)andN−0.76(2)atCs=0.0 andCs*, respectively.EII*follows a similar scaling law toEIII*but a crossover appears atCs=Cs*whenNis small. TheEI*estimator fails to predict the critical field, which is due to oversimplifying the critical polarization energy to the thermal energy. Our results provide valuable information to understand the electrokinetics of PE solutions at the molecular level and could be helpful in micro/nanofluidic applications.
Sedimentary architecture of abandoned channel fills
Authors: Toonen Willem H. J. , Kleinhans Maarten G. , Cohen Kim M.
Published: December 2011

Channel fills are common elements of Holocene river systems and older fluvial sequences, but surprisingly little is known about formation and their sedimentary build‐up. Abandoned channels result from channel shifting processes at various scales, including meander cutoff and channel‐belt avulsion. Channel‐fill sequences are of importance as containers of palaeoenvironmental proxy‐records, can be used to reconstruct palaeochannel dynamics and derive palaeoflood records, and contain materials that allow dating the abandonment. Integrated knowledge on the dynamic nature (geometrical and physical insights) of channel abandonment and resultant sedimentary recording is a necessity for comparing and collating records from a series of abandoned channel fills.

This paper intends to make channel‐fill sedimentological sequences more useful recorders of channel abandonment processes and palaeofloods, for which improved understanding is needed of the internal build‐up of channel fills. We review oxbow lake infilling along meandering rivers, and supplement this with highly detailed descriptions of two selected field examples of channel fills from the apex‐region of the Netherlands' Rhine delta. From these examples it becomes clear that regional setting and type of abandonment result in different channel‐fill end‐members; oxbow cutoffs generally produce thick laminated clayey fills as the channel entrance is plugged rapidly, avulsion‐abandoned channels are filled with coarse (proximal) deposits as a result of a maintained open river connection.

Field examples of channel fills are integrated with knowledge on channel abandonment dynamics in meander cutoff and bifurcating river situations, including insights from recent numerical modelling. We propose a sedimentary‐architecture descriptive scheme that distinguishes elements from two stages of channel‐fill development; (i) the abandonment stage with initial proximal fill, and (ii) the subsequent fully abandoned palaeochannel that collects distal fill. Copyright © 2011 John Wiley & Sons, Ltd.
Hydrological thresholds of soil surface properties identified using conditional inference tree analysis
Authors: Tighe Matthew , Muñoz‐Robles Carlos , Reid Nick , Wilson Brian , Briggs Sue V.
Published: December 2011

There has been limited success in determining critical thresholds of ground cover or soil characteristics that relate to significant changes in runoff or sediment production at the microscale (<1 m2), particularly in semi‐arid systems where management of ground cover is critical. Despite this lack of quantified thresholds, there is an increasing research focus on the two‐phase mosaic of vegetation patches and inter‐patches in semi‐arid systems. In order to quantify ground cover and soil related thresholds for runoff and sediment production, we used a data mining technique known as conditional inference tree analysis to determine statistically significant values of a range of measured variables that predicted average runoff, peak runoff, sediment concentration and sediment production at the microscale. On Chromic Luvisols across a range of vegetation states in semi‐arid south‐eastern Australia, large changes in runoff and sediment production were related to a hierarchy of different variables and thresholds, but the percentage of bare soil played a primary role in predicting runoff and sediment production in most instances. The identified thresholds match well with previous thresholds found in semi‐arid and temperate regions (including the approximate values of 30%, 50% and 70% total ground cover). The analysis presented here identified the critical role of soil surface roughness, particularly where total ground cover is sparse. The analysis also provided evidence that a two‐phase mosaic of patches and inter‐patches identified via rapid visual assessment could be further delineated into distinct groups of hydrological response, or a multi‐phase rather than a two‐phase system. The approach used here may aid in assessing scale‐dependent responses and address data non‐linearity in studies of semi‐arid hydrology. Copyright © 2012 John Wiley & Sons, Ltd.