bluuebunny/crossref_metadata_2025 huggingface dataset:
Supercapacitive transport of pharmacologic agents using nanoporous gold electrodes
Authors: Gittard Shaun D. , Pierson Bonnie E. , Ha Cindy M. , Wu Chung‐An Max , Narayan Roger J. , Robinson David B.
Published: January 2010

In this study, nanoporous gold supercapacitors were produced by electrochemical dealloying of gold‐silver alloy. Scanning electron microscopy and energy dispersive X‐ray spectroscopy confirmed completion of the dealloying process and generation of a porous gold material with ∼10 nm diameter pores. Cyclic voltammetry and chronoamperometry of the nanoporous gold electrodes indicated that these materials exhibited supercapacitor behavior. The storage capacity of the electrodes measured by chronoamperometry was ∼3 mC at 200 mV. Electrochemical storage and voltage‐controlled delivery of two model pharmacologic agents, benzylammonium and salicylic acid, was demonstrated. These results suggest that capacitance‐based storage and delivery of pharmacologic agents may serve as an alternative to conventional drug delivery methods.
Helical conformations of hexapeptides containing N‐terminus diproline segments
Authors: Kantharaju  , Raghothama Srinivasarao , Aravinda Subrayashastry , Shamala Narayanaswamy , Balaram Padmanabhan
Published: January 2010

The role of N‐terminus diproline segments in facilitating helical folding in short peptides has been investigated in a set of model hexapeptides of the type Piv‐Xxx‐Yyy‐Aib‐Leu‐Aib‐Phe‐OMe (Piv, pivaloyl). Nine sequences have been investigated with the following N‐terminus dipeptide segments: DPro‐Ala (4) and Pro‐ΨPro (5, Ψ, pseudoproline), Ala‐Ala (6), Ala‐Pro (7), Pro‐Ala (8), Aib‐Ala (9), Ala‐Aib (10). The analog sequences Piv‐Pro‐Pro‐Ala‐Leu‐Aib‐Phe‐OMe (2) and Piv‐Pro‐Pro‐Ala‐Aib‐Ala‐Aib‐OMe (3) have also been studied. Solid state conformations have been determined by X‐ray crystallography for peptides 4, 6, and 8 and compared with the previously determined crystal structure of peptide 1 (Boc‐Pro‐Pro‐Aib‐Leu‐Aib‐Val‐OMe); (Rai et al., JACS 2006, 128, 7916–7928). Peptides 1 and 6 adopt almost identical helical conformations with unfolding of the helix at the N‐terminus Pro (1) residue. Peptide 4 reveals the anticipated DPro‐Ala type II' β‐turn, followed by a stretch of 310‐helix. Peptide 8 adopts a folded conformation stabilized by four successive 4→1 intramolecular hydrogen bonds. Ala (2) adopts an αL conformation, resulting in a type II β‐turn conformation followed by a stretch of 310‐helix. Conformational properties in solution were probed using solvent perturbation of NH chemical shifts which permit delineation of hydrogen bonded NH groups and nuclear Overhauser effects (NOEs) between backbone protons, which are diagnostic of local residue conformations. The results suggest that, continuous helical conformations are indeed significantly populated for peptides 2 and 3. Comparison of the results for peptides 1 and 2, suggest that there is a significant influence of the residue that follows diproline segments in influencing backbone folding. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 360–370, 2010.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
ASIC verification: Integrating formal verification with HDL‐based courses
Authors: Massoumi Mehran , Sagahyroon Assim
Published: January 2010

The rapid progress of chip fabrication technology has paved the way to the design of complex ASICs containing several million transistors. According to published work, verification of these ASICs has emerged as a major bottleneck consuming up to three‐quarters of total pre‐silicon resources. This fact has tempted the scientific community to propose alternatives to the classical simulation approach. Recently, formal verification techniques have gained large attention and are becoming a key component in reducing the verification effort required to meet compressed design cycle times. In addition to the reliability factor, these techniques are proven to be cost effective since they help in reducing time allocated for test bench creation which is typically a time consuming and error prone activity. In this paper the formal or static approach is presented in a context that encourages its integration into HDL‐based courses at the senior or first year graduate level. Advantages of the static approach will be discussed by presenting property formulation for selected RTL designs. Moreover, the property language Property Specification Language (PSL), IEEE standard 1850, will be used in presenting property formulations. System Verilog Assertions (SVA) is another viable option for property specification and can be readily substituted for PSL. © 2010 Wiley Periodicals, Inc. Comput Appl Eng Educ 18: 269–276, 2010; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.20252
On the Mechanism of Action of Fullerene Derivatives in Superoxide Dismutation
Authors: Osuna Sílvia , Swart Marcel , Solà Miquel
Published: January 2010

We have studied the mechanism of the antioxidant activity of C60 derivatives at the BP86/TZP level with inclusion of solvent effects (DMSO) by using the COSMO approach. The reaction studied here involves degradation of the biologically relevant superoxide radical (O2.−), which is linked to tissue damage in several human disorders. Several fullerene derivatives have experimentally been shown to be protective in cell culture and animal models of injury, but precisely how these compounds protect biological systems is still unknown. We have investigated the activity of tris‐malonyl C60 (also called C3), which efficiently removes the superoxide anion with an activity in the range of several biologically effective, metal‐containing superoxide dismutase mimetics. The antioxidant properties of C3 are attributed to the high affinity of C60 to accept electrons. Our results show that once the superoxide radical is in contact with the surface of C3, its unpaired electron is transferred to the fullerene. This process, which converts the damaging O2.− to neutral oxygen O2, is the rate‐determining step of the reaction. Afterwards, another superoxide radical reacts with C3.− to form hydrogen peroxide and in the process takes up the additional electron that was transferred in the first step. The overall process is clearly exothermic and, in general, involves reaction steps with relatively low activation barriers. The capability of C3 to degrade a highly reactive oxygen species that is linked to several human diseases is of immediate interest for future applications in the field of biology and medicine.
Highly Uniform YBO3 Hierarchical Architectures: Facile Synthesis and Tunable Luminescence Properties
Authors: Jia Guang , You Hongpeng , Liu Kai , Zheng Yuhua , Guo Ning , Jia Junjiao , Zhang Hongjie
Published: January 2010

Highly uniform pancake‐like YBO3 hierarchical architectures have been successfully prepared by a designed two‐step hydrothermal method. Yttrium precursor microprisms were first synthesized according to a simple hydrothermal route. Subsequently, nearly monodisperse multilayered YBO3 products with a pancake‐like shape were synthesized at the expense of the precursor during the hydrothermal process. The whole process was carried out under aqueous conditions without the use of any organic solvent, surfactant, or catalyst. The conversion process from the precursor to YBO3 products has been investigated by time‐dependent XRD experiments. Extending this method, other LnBO3 (Ln=Ho, Er, Tm, Yb) samples with well‐defined shape and dimensionality have also been obtained by a similar synthetic process. The luminescence colors of YBO3 samples co‐doped with Eu3+ and Tb3+ under ultraviolet or low‐voltage electron beam excitation can be tuned from red, through yellow and green‐yellow, to green by simply adjusting the relative doping concentrations of the activator ions. This merit of multicolor emissions in the visible region endows materials of this kind with potential application in the fields of light‐display systems and optoelectronic devices.
Experiments in the Chemistry Teacher Training Program
Authors: Janzen Margot , Wentorf Wilfried
Published: January 2010

Die Diskussion zur Professionalisierung der Lehrerbildung war der Auslöser für eine kritische Überprüfung des an der Universität Kiel im Rahmen der Chemielehrerausbildung durchgeführten Unterrichtsversuche‐Praktikums für die Sekundarstufe I. Als Aufgabenfelder für eine Neugestaltung wurde die stärkere Einbindung fachdidaktischer Fragestellungen, die Berücksichtigung berufsorientierter Handlungskompetenzen und die Gestaltung und Reflexion von Lehr‐Lern‐Prozessen identifiziert. Daraus wurden drei Module entwickelt, die während des Praktikumszeitraumes aufeinander aufbauend durchgeführt wurden. Die im Folgenden vorgestellte Konzeption des Praktikums wird seit Wintersemester 2006/2007 durchgeführt.
Should all patients with melanoma between 1 and 2 mm Breslow thickness undergo sentinel lymph node biopsy?
Authors: Mays Michael P. , Martin Robert C. G. , Burton Alison , Ginter Brooke , Edwards Michael J. , Reintgen Douglas S. , Ross Merrick I. , Urist Marshall M. , Stromberg Arnold J. , McMasters Kelly M. , Scoggins Charles R.
Published: January 2010

BACKGROUND:

Sentinel lymph node (SLN) biopsy generally is recommended for patients who have melanoma with a Breslow thickness ≥1 mm. Most patients with melanoma between 1 mm and 2 mm thick have tumor‐negative SLNs and an excellent long‐term prognosis. The objective of the current study was to evaluate prognostic factors in this subset of patients and determine whether all such patients require SLN biopsy.

METHODS:

Patients with melanoma between 1 mm and 2 mm in Breslow thickness were evaluated from a prospective multi‐institutional study of SLN biopsy for melanoma. Disease‐free survival (DFS) and overall survival (OS) were evaluated by Kaplan‐Meier analysis to compare patients with melanoma that measured from 1.0 mm to 1.59 mm (Group A) versus patients with melanoma that measured from ≥1.6 mm to 2.0 mm thick (Group B). Univariate and multivariate analyses were performed to evaluate factors predictive of tumor‐positive SLN status, DFS, and OS.

RESULTS:

The current analysis included 1110 patients with a median follow‐up of 69 months. SLN status was tumor‐positive in 133 of 1110 patients (12%) including 66 of 762 patients (8.7%) in Group A and 67 of 348 patients (19.3%) in Group B (P < .0001). On multivariate analysis, age, Breslow thickness, and lymphovascular invasion were independently predictive of a tumor‐positive SLN (P < .05). DFS (P < .0001) and OS (P = .0001) were significantly better for Group A than for Group B. When tumor thickness was treated as either a continuous variable (P < 0.0001) or a categorical variable (P < .0001), it was significantly predictive of DFS and OS. On multivariate analysis, Breslow thickness, age, ulceration, histologic subtype, regression, Clark level, and SLN status were significant factors predicting DFS; and Breslow thickness, age, primary tumor location, sex, ulceration, and SLN status were significant factors predicting OS (P < .05). A subgroup of patients who had tumors <1.6 mm in Breslow thickness, had no lymphovascular invasion, and were aged ≥59 years had a low risk (5%) of tumor‐positive SLN.

CONCLUSIONS:

The current findings indicated that there is significant diversity in the biologic behavior of melanoma between 1 mm and 2 mm in Breslow thickness. SLN biopsy is recommended for all such patients to identify those with lymph node metastasis who are at the greatest risk of recurrence and mortality. Cancer 2010. © 2010 American Cancer Society.
5‐Aminolevulinic acid is a promising marker for detection of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement
Authors: Widhalm Georg , Wolfsberger Stefan , Minchev Georgi , Woehrer Adelheid , Krssak Martin , Czech Thomas , Prayer Daniela , Asenbaum Susanne , Hainfellner Johannes A. , Knosp Engelbert
Published: January 2010

BACKGROUND:

Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5‐Aminolevulinic acid (5‐ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5‐ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling.

METHODS:

5‐ALA was administered in 17 patients with diffusely infiltrating gliomas with nonsignificant contrast enhancement. During glioma resection, positive fluorescence was noted by a modified neurosurgical microscope. Intraoperative topographic correlation of focal 5‐ALA fluorescence with maximum 11C‐methionine positron emission tomography uptake (PETmax) was performed. Multiple tissue samples were taken from areas of positive and/or negative 5‐ALA fluorescence. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 criteria. Cell proliferation was assessed for multiregional samples by MIB‐1 labeling index (LI).

RESULTS:

Focal 5‐ALA fluorescence was observed in 8 of 9 patients with WHO grade III diffusely infiltrating gliomas. All 8 of 8 WHO grade II diffusely infiltrating gliomas were 5‐ALA negative. Focal 5‐ALA fluorescence correlated topographically with PETmax in all patients. MIB‐1 LI was significantly higher in 5‐ALA–positive than in nonfluorescent areas within a given tumor.

CONCLUSIONS:

The data indicate that 5‐ALA is a promising marker for intraoperative visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Unaffected by intraoperative brain shift, 5‐ALA may increase the precision of tissue sampling during tumor resection for histopathological grading, and therefore optimize allocation of patients to adjuvant treatments. Cancer 2010. © 2010 American Cancer Society.
Mucinous but not clear cell histology is associated with inferior survival in patients with advanced stage ovarian carcinoma treated with platinum‐paclitaxel chemotherapy
Authors: Bamias Aristotle , Psaltopoulou Theodora , Sotiropoulou Maria , Haidopoulos Dimitrios , Lianos Evangelos , Bournakis Evangelos , Papadimitriou Christos , Rodolakis Alexandros , Vlahos George , Dimopoulos Meletius A.
Published: January 2010

BACKGROUND:

Mucinous and clear cell histology have been associated with adverse prognosis in ovarian carcinomas. The authors compared the outcome of these subtypes with that of serous tumors in patients who were treated with combination paclitaxel/platinum at their center.

METHODS:

Four hundred twenty patients with histologically confirmed, serous (n = 367), mucinous (n = 24), or clear cell (n = 29) ovarian carcinomas, International Federation of Gynecology and Obstetrics stage III or IV disease, and who were treated with paclitaxel/platinum after cytoreductive surgery were included in this analysis.

RESULTS:

The median overall survival for each histological subtype was 47.7 months (95% confidence interval [CI], 37.7‐57.7 months) for serous, 15.4 months (95% CI, 4.2‐26.6 months) for mucinous, and 36.6 months (95% CI, 22.7‐50.5 months) for clear cell carcinomas. Cox regression analysis showed that mucinous histology was an independent predictor of poor prognosis compared with serous tumors (hazard ratio, 0.360; 95% CI, 0.215‐0.603; P = .001). In contrast, such a difference between clear cell and serous carcinomas was not found (P = .337). Median survival of patients with mucinous tumors and residual disease >2 cm was poor, averaging 7.1 months (95% CI, 4.6‐9.6 months).

CONCLUSIONS:

Mucinous but not clear cell histology is associated with significantly worse prognosis in advanced ovarian cancer treated with combination platinum/paclitaxel. Different therapeutic strategies should be studied in this entity. Cancer 2010. © 2010 American Cancer Society.
Weekly docetaxel, cisplatin, and 5‐fluorouracil as initial therapy for patients with advanced gastric and esophageal cancer
Authors: Overman Michael J. , Kazmi Syed M. , Jhamb Jagriti , Lin E , Yao James C. , Abbruzzese James L. , Ho Linus , Ajani Jaffer , Phan Alexandria
Published: January 2010

BACKGROUND:

Docetaxel, cisplatin, and 5‐flurouracil (DCF) administered every 3 weeks produces a high rate of treatment‐related adverse events. The objective of the current study was to evaluate the efficacy and tolerability of a weekly formulation of DCF.

METHODS:

Data from 117 patients treated at The University of Texas M. D. Anderson Cancer Center from 2002 to 2006 with a weekly formulation of DCF were retrospectively collected. A total of 95 patients received front‐line therapy with 20 mg/m2 of cisplatin, 350 mg/m2 of 5‐fluorouracil, and 20 mg/m2 of docetaxel administered once weekly for 6 consecutive weeks followed by a 2‐week break.

RESULTS:

Ninety‐five patients (median age, 62 years [range, 33 to 87 years], with an Eastern Cooperative Oncology Group performance status of 1 or 2 in 67%) received a median of 10 weeks of DCF treatment (range, 3‐41 weeks). Grade 3 or 4 hematologic toxicity (assessed according to National Cancer Institute Common Toxicity Criteria [version 3.0]) included granulocytopenia (4 patients) and anemia (9 patients). None of the patients developed a febrile neutropenic infection, but grade 3 or 4 non‐neutropenic infections occurred in 8 patients. Eighty patients had measurable disease with an objective response rate determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria of 34% (95% confidence interval [95% CI], 24‐45%). The median follow‐up was 9 months, with a median time to disease progression of 4.1 months (95% CI, 3.6‐5.7 months) and a median overall survival of 8.9 months (95% CI, 7.7‐10.8 months).

CONCLUSIONS:

In patients with advanced gastric and esophageal cancer who were not candidates for every‐3‐week DCF, a weekly formulation of DCF demonstrated modest activity with minimal hematologic toxicity, suggesting that weekly DCF is a reasonable treatment option for such patients. Cancer 2010. © 2010 American Cancer Society.
The heterogeneity of epithelial ovarian cancer
Authors: Gershenson David M.
Published: January 2010

Epithelial ovarian cancer is heterogeneous and comprises 4 major rare subtypes—mucinous, clear cell, low‐grade serous, and endometrioid—all distinct from the more common high‐grade serous carcinoma. Women with uncommon histotypes should be triaged to separate clinical trials.
Radiation versus resection for Merkel cell carcinoma
Authors: Bichakjian Christopher K. , Coit Daniel G. , Wong Sandra L.
Published: January 2010

A report by Fang et al on lymph node disease in patients with Merkel cell carcinoma suggests that radiation monotherapy is an effective modality for regional disease control compared with lymphadenectomy. However, the selection bias inherent in retrospective studies must be considered before changing practice patterns.
Investigations of impurity striations in potassium bichromate crystals
Authors: Szurgot M.
Published: January 2010

Impurity striations in potassium bichromate crystals (KBC, lopezite) formed during crystal growth from aqueous solution were revealed by chemical etching and analyzed. Striations were revealed as etch grooves, as rows of dislocation etch pits and as rows of flat‐bottomed etch pits. Various types and groups of striations have been visualized. Some striations were due to lateral segregation of impurities caused by convection flow of the mother solution, other were formed during growth stoppages whereas induced striations were generated by changes in hydrodynamical conditions. Growth rates changes resulted in zonal distribution of impurities, formation of planar lattice strain, rows of clusters of point defects and rows of dislocations. Generation of striations with different intensities in various sectors is a proof of the selective capture of impurities. Ratios of growth rates of various faces of KBC crystals growing in forced and free convection regimes were determined by induced striations. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The influence of concentration and supersaturation ratio of CuI·HI on CuI crystal growth by decomplexation method
Authors: Gu Mu , Gao Pan , Liu Xiao‐Lin , Huang Shi‐Ming , Liu Bo , Ni Chen , Xu Rong‐Kun , Ning Jia‐Min
Published: January 2010

The fundamental role of solubility and supersaturation of solute for crystal growth from solution has been widely realized. In order to optimize the process of CuI crystal growth by CuI·HI decomplexation in HI acid, the solubility and supersaturation curves of CuI in HI‐H2O mixed solvent were measured, and then a modified concentration programming scheme was designed, which could grow high quality CuI single crystals of 2.5 mm on edge successfully. In this scheme, the concentration distribution of CuI·HI complex and HI acid in silica gel along their diffused direction were measured with spectrophotometer, and the evolution of CuI·HI complex supersaturation ratio was analysed. It was found that the excess CuI·HI complex concentration would lead to the high supersaturation ratio and the formation CuI dendrites. The condition for regular CuI single crystal growth in silica gel was measured as follow: when the crystal nuclei appears, the CuI·HI complex concentration in HI‐H2O solvent should be kept in the range of 0.033–0.050 mol/L and its corresponding supersaturation ratio is 1.24–1.45, and then they should be respectively declined to a range of 0.025–0.033 mol/L and 1.14–1.26 at the stage of crystal growth. The results may provide a useful clue for further improvement of the experimental scheme. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Development of criteria for the detection of adrenosterone administration by gas chromatography‐mass spectrometry and gas chromatography‐combustion‐isotope ratio mass spectrometry for doping control
Authors: Brooker Lance , Parr Maria Kristina , Cawley Adam , Flenker Ulrich , Howe Christopher , Kazlauskas Rymantas , Schänzer Wilhelm , George Adrian
Published: January 2010

Adrenosterone (androst‐4‐ene‐3,11,17‐trione, 11‐oxoandrostenedione) is an endogenous steroid hormone that has been promoted as a dietary supplement capable of reducing body fat and increasing muscle mass. It is proposed that adrenosterone may function as an inhibitor of the 11β‐hydroxysteroid dehydrogenase type 1 enzyme (11β‐HSD1), which is primarily responsible for reactivation of cortisol from cortisone. The urinary metabolism of adrenosterone was investigated, after a single oral administration in two male subjects, by gas chromatography‐mass spectrometry (GC‐MS) and gas chromatography‐combustion‐isotope ratio mass spectrometry (GC‐C‐IRMS). Substantially increased excretion of 11β‐hydroxyandrosterone, 11β‐hydroxyetiocholanolone, 11‐oxoandrosterone and 11‐oxoetiocholanolone was observed. Minor metabolites such as 3α,17β‐dihydroxy‐5β‐androstan‐11‐one, 3α‐hydroxyandrost‐4‐ene‐11,17‐dione and 3α,11β‐dihydroxyandrost‐4‐en‐17‐one were also identified. The exogenous origin of the most abundant adrenosterone metabolites was confirmed by GC‐C‐IRMS according to World Anti‐Doping Agency criteria. Through analysis of a reference population data set obtained from urine samples provided by elite athlete volunteers (n = 85), GC‐MS doping control screening criteria are proposed:

11β‐hydroxyandrosterone concentration greater than 10 000 ng/mL (specific gravity adjusted to 1.020) or

11β‐hydroxyandrosterone/11β‐hydroxyetiocholanolone ratio greater than 20.

Urine samples fulfilling these screening criteria may be subjected to GC‐C‐IRMS analysis for confirmation of adrenosterone administration. Copyright © 2010 John Wiley & Sons, Ltd.
Pbx1 is essential for growth of zebrafish swim bladder
Authors: Teoh Pick‐Har , Shu‐Chien Alexander Chong , Chan Woon‐Khiong
Published: January 2010

pbx1, a TALE (three–amino acid loop extension) homeodomain transcription factor, is involved in a diverse range of developmental processes. We examined the expression of pbx1 during zebrafish development by in situ hybridization. pbx1 transcripts could be detected in the central nervous system and pharyngeal arches from 24 hpf onwards. In the swim bladder anlage, pbx1 was detected as early as 28 hpf, making it the earliest known marker for this organ. Morpholino‐mediated gene knockdown of pbx1 revealed that the swim bladder failed to inflate, with eventual lethality occurring by 8 dpf. The knockdown of pbx1 did not perturb the expression of prdc and foxA3, with both early swim bladder markers appearing normally at 36 and 48 hpf, respectively. However, the expression of anxa5 was completely abolished by pbx1 knockdown at 60 hpf suggesting that pbx1 may be required during the late stage of swim bladder development. Developmental Dynamics 239:865–874, 2010. © 2010 Wiley‐Liss, Inc.
Roles for netrin signaling outside of axon guidance: A view from the worm
Authors: Ziel Joshua W. , Sherwood David R.
Published: January 2010

The Netrin family of extracellular ligands and their receptors were the first identified signaling pathway regulating axon guidance. Subsequent work across model systems has begun to reveal the interactions that take place downstream of Netrin reception to facilitate growth cone migration. Though intensely studied, many aspects of this signaling system remain unclear. Even less understood are the growing number of contexts in which Netrin signaling influences cells beyond axon guidance and even outside the nervous system. Genetic and cell‐biological studies in C. elegans have played an instrumental role in identifying critical functions for Netrin ligands in setting up specialized and potentially adhesive membrane‐associated domains within a broad range of cell types. Here we review recent literature implicating Netrin or its receptors in morphogenetic processes outside of growth cone regulation with a special focus on studies in C. elegans that suggest cell biological mechanisms for Netrin signaling. Developmental Dynamics 239:1296–1305, 2010. © 2010 Wiley‐Liss, Inc.
Movers and shakers or anchored: Caenorhabditis elegans nuclei achieve it with KASH/SUN
Authors: Zhou Kang , Hanna‐Rose Wendy
Published: January 2010

The invariant cell division patterns that characterize Caenorhabditis elegans development make it an ideal system to study the mechanisms that control nuclear movement and positioning. Forward genetic screens in this system allowed identification of the key molecular machinery for connecting the nucleus to the cytoskeleton; pairs of protein partners, consisting of a KASH domain protein and a SUN domain protein, bridge the nuclear envelope to connect the nucleus to cytoskeletal components. The C. elegans genome encodes several KASH/SUN pairs, and mutant phenotypes as well as tissue‐specific expression patterns suggest a diversity of functions. These functions include moving the nucleus but have been extended to effects on the chromosomes inside the nucleus as well. We review the impact of the C. elegans system in pioneering this field as well as the functions of these KASH/SUN protein pairs across spatial and temporal C. elegans development. Developmental Dynamics 239:1352–1364, 2010. © 2010 Wiley‐Liss, Inc.
C. elegans as a model organism to investigate molecular pathways involved with Parkinson's disease
Authors: Harrington Adam J. , Hamamichi Shusei , Caldwell Guy A. , Caldwell Kim A.
Published: January 2010

Parkinson's disease (PD) is an age‐related movement disorder resulting, in part, from selective loss of dopaminergic neurons. Both invertebrate and mammalian models have been developed to study the cellular mechanisms altered during disease progression; nevertheless there are limitations within each model. Mammalian models remain invaluable in studying PD, but are expensive and time consuming. Here, we review genetic and environmental factors associated with PD, and describe how the nematode roundworm, Caenorhabditis elegans, has been used as a model organism for studying various aspects of this neurodegenerative disease. Both genetic and chemical screens have been conducted in C. elegans to identify molecular pathways, proteins, and small molecules that can impact PD pathology. Lastly, we highlight future areas of investigation, in the context of emerging fields in biology, where the nematode can be exploited to provide mechanistic insights and potential strategies to accelerate the path toward possible therapeutic intervention for PD. Developmental Dynamics 239:1282–1295, 2010. © 2010 Wiley‐Liss, Inc.
Diphenoxido‐Bridged CoII and ZnII Complexes of Tripodal N2O2 Ligands: Stabilisation of MII‐Coordinated Phenoxyl Radical Species
Authors: Mukherjee Atasi , Lloret Francesc , Mukherjee Rabindranath
Published: January 2010

Three new tripodal ligands with an N2O2 donor set, namely2‐tert‐butyl‐6‐({(2‐hydroxybenzyl)[2‐(2‐pyridyl)ethyl]amino}methyl)‐4‐methylphenol (H2L1), 2‐tert‐butyl‐6‐({(2‐hydroxybenzyl)[2‐(2‐pyridyl)ethyl]amino}methyl)‐4‐methoxyphenol (H2L2) and 2‐tert‐butyl‐6‐({[2‐(dimethylamino)ethyl](2‐hydroxybenzyl)amino}methyl)‐4‐methoxyphenol (H2L3) have been synthesised. Treatment of the ligands with Co(CH3CO2)2·4H2O or [Zn(H2O)6][ClO4]2 in the presence of Et3N provides the corresponding CoII and ZnII complexes of composition [MII2(L1)2] [M = Co (1) (single‐crystals are a solvate with the composition [CoII2(L1)2]·2CHCl3, i.e. 1·2CHCl3); M = Zn (2)], [MII2(L2)2] [M = Co (3); Zn (4)] and [CoII2(L3)2] (5). Crystallographic analyses reveal that the complexes have closely similar diphenoxido‐bridged structures. Each metal centre assumes MIIN2O3 coordination. The geometry around each metal ion in 1·2CHCl3 (τ = 0.76), 2 (τ = 0.77), 3 (τ = 0.74), 4 (τ = 0.76) and 5 [one CoII (τ = 0.49) and the other CoII (τ = 0.63)] is intermediate between ideal square‐pyramidal (τ = 0) and trigonal‐bipyramidal (τ = 1). Temperature‐dependent magnetic studies reveal weak intramolecular antiferromagnetic exchange couplings for all the three CoII complexes(–J = 1.84, 1.32 and 5.70 cm–1 for 1, 3 and 5, respectively). Spectroscopic properties of the complexes have also been investigated. Cyclic voltammetric (CV) measurements of 1 and 2 show an irreversible oxidative response at Epa (anodic peak potential) in the range 0.60–0.75 V relative to the SCE (saturated calomel electrode), whereas two successive quasi‐reversible oxidative responses can be observed for 3–5 at E1/2 values in the range 0.40–0.53 V relative to the SCE. Oxidative responses are due to the formation of MII‐coordinated phenoxyl radical species. The metal‐coordinated phenoxyl radical species, generated by two‐electron coulometric oxidation of 3–5, were characterised by CV and by adsorption and EPR spectroscopy. The stability of such species was determined by measuring the decay constant (absorption spectroscopy), which reveals that the phenoxyl radical species of 5 is more stable than that of 3 and 4. EPR spectroscopic studies (120 K) of coulometrically generated two‐electron oxidised species of 4 in CH2Cl2 (containing 0.1 M TBAP) at 298 K reveal a combination of an isotropic S = ${1 \over 2}$ signal at g = 2 [(phenolato)(phenoxyl radical)‐coordinated dizinc(II) complex] and a spin‐triplet resonance (S = 1) that gives rise to the symmetric split‐line pattern [bis(phenoxyl radical)‐cordinated dizinc(II) complex]. To pinpoint the site of oxidation (metal‐ or ligand‐centred) in each case, DFT calculations were performed at the B3LYP level of theory.
Bioconjugates of 1′‐Aminoferrocene‐1‐carboxylic Acid with (S)‐3‐Amino‐2‐methylpropanoic Acid and L‐Alanine
Authors: Semenčić Mojca Čakić , Heinze Katja , Förster Christoph , Rapić Vladimir
Published: January 2010

Formal CH2 insertion in bioconjugates composed of 1′‐aminoferrocene‐1‐carboxylic acid (Fca) and alanine Boc‐Ala‐Fca‐Ala‐OCH3 gives Fca bioconjugates with the β‐amino acid (S)‐3‐amino‐2‐methylpropanoic acid (Aib). The novel homologous conjugates of ferrocene were fully characterized by spectroscopic and analytical methods. NMR, CD and IR spectroscopy in concert with DFT calculations suggest that the formal “L‐Ala–to–(S)‐β‐Aib mutations” can exert ferrocene helix inversion due to the different stereogenic carbon atoms of L‐Ala and (S)‐β‐Aib. Furthermore, the mutation (de‐)stabilizes the conserved secondary structure with two intramolecular hydrogen bonds, depending on the “mutation site”. The systematic work presented provides a firm basis for understanding the factors that determine folding in bioconjugates of ferrocene and β‐amino acids and will guide the rational design of metallocene peptidomimetics incorporating β‐amino acids.
Digital quantification of gene expression using emulsion PCR
Authors: Shi Xiaolong , Tang Chao , Wang Wei , Zhou Dequan , Lu Zuhong
Published: January 2010

Here we describe a single‐molecule quantitative assay of mRNA levels based on mRNA mediate‐ligation and BEAMing (beads, emulsion, amplification, and magnetics) technique, which allows accurate and parallel measurement of multiple genes from a small amount of cells. In this method, a pair of oligos complementary target mRNA was used to probe transcripts for each gene of interest. The ligated products of oligos pair were clonally amplified on beads in millions of parallel compartmentalized droplets in a water‐in‐oil emulsion. The levels of each transcript within a sample were measured by counting the number of the correspondingly amplified beads which were immobilized on a glass surface. To demonstrate its utility, this method has been applied to the quantitation of the mRNA levels for two transcription factors, Klf4 and Sox5, and a housekeeping gene, Gapdh, in human leukemia K562 cells before and after induction with phorbol 12‐myristate 13‐acetate. Interestingly, we found a significant downregulation of the mRNA level of Sox5 after phorbol 12‐myristate 13‐acetate treatment. The mRNA mediate‐ligation and BEAMing technique provides an accurate and sensitive way to quantify the amount of multiple specific mRNA in a very small number of cells, which may be valuable in the studies requiring precise and parallel quantization of multiple mRNA in the defined cell populations.
Preparative divergent flow IEF without carrier ampholytes for separation of complex biological samples
Authors: Stastna Miroslava , Slais Karel
Published: January 2010

Efficient separation method is a crucial part of the process in which components of highly complex biological sample are identified and characterized. Based on the principles of recently newly established electrophoretic method called divergent flow IEF (DF IEF), we have tested the DF IEF instrument which is able to operate without the use of background carrier ampholytes. We have verified that during separation and focusing of sample consisting of high numbers of proteins (yeast lysate and wheat flour extract), the pH gradient of preparative DF IEF can be created by autofocusing of the sample components themselves without any addition of carrier ampholytes. In DF IEF, the proteins are separated, desalted and concentrated in one step. The fractions of yeast lysate sample, collected at the DF IEF output and subjected to gel IEF, contained the zones of proteins gradually covering the pI values from 3.7 to 8.5. In our experimental arrangement, the highest number of proteins has been found in fractions with pI values around 5.3 as detected by polyacrylamide gel IEF with CBB staining. During DF IEF, the selected protein bands have been concentrated up to 16.8‐fold.
SDS‐PAGE and two‐dimensional maps in a radial gel format
Authors: Millioni Renato , Miuzzo Manuela , Antonioli Paolo , Sbrignadello Stefano , Iori Elisabetta , Dosselli Ryan , Puricelli Lucia , Kolbe Markus , Tessari Paolo , Righetti Pier Giorgio
Published: January 2010

A novel method for performing 2‐D map analysis is here reported, consisting in a modification of the second dimension run, which is performed not in a conventional square‐ or rectangular‐size gel, but in a radial surface. This has the advantage of permitting resolution of closely adjacent bands, representing strings of isoforms of similar or identical mass but of closely spaced isoelectric points. When used in a mono‐dimensional, SDS‐PAGE format, this system allows the simultaneous running of 62 sample tracks. Examples are given of separation of plasma and urinary proteins.
ACE applied to the quantitative characterization of benzo‐18‐crown‐6‐ether binding with alkali metal ions in a methanol–water solvent system
Authors: Ehala Sille , Makrlík Emanuel , Toman Petr , Kašička Václav
Published: January 2010

ACE was applied to the quantitative evaluation of noncovalent binding interactions between benzo‐18‐crown‐6‐ether (B18C6) and several alkali metal ions, Li+, Na+, K+, Rb+ and Cs+, in a mixed binary solvent system, methanol–water (50/50 v/v). The apparent binding (stability) constants (Kb) of B18C6–alkali metal ion complexes in the hydro‐organic medium above were determined from the dependence of the effective electrophoretic mobility of B18C6 on the concentration of alkali metal ions in the BGE using a nonlinear regression analysis. Before regression analysis, the mobilities measured by ACE at ambient temperature and variable ionic strength of the BGE were corrected by a new procedure to the reference temperature, 25°C, and the constant ionic strength, 10 mM. In the 50% v/v methanol–water solvent system, like in pure methanol, B18C6 formed the strongest complex with potassium ion (log Kb=2.89±0.17), the weakest complex with cesium ion (log Kb=2.04±0.20), and no complexation was observed between B18C6 and the lithium ion. In the mixed methanol–water solvent system, the binding constants of the complexes above were found to be about two orders lower than in methanol and about one order higher than in water.
Uniform hazard versus uniform risk bases for performance‐based earthquake engineering of light‐frame wood construction
Authors: Li Yue , Yin Yuejun , Ellingwood Bruce R. , Bulleit William M.
Published: January 2010

This paper investigates the implications of designing for uniform hazard versus uniform risk for light‐frame wood residential construction subjected to earthquakes in the United States. Using simple structural models of one‐story residences with typical lateral force‐resisting systems (shear walls) found in buildings in western, eastern and central regions of the United States as illustrations, the seismic demands are determined using nonlinear dynamic time‐history analyses, whereas the collapse capacities are determined using incremental dynamic analyses. The probabilities of collapse, conditioned on the occurrence of the maximum considered earthquakes and design earthquakes stipulated in ASCE Standard 7‐05, and the collapse margins of these typical residential structures are compared for typical construction practices in different regions in the United States. The calculated collapse inter‐story drifts are compared with the limits stipulated in FEMA 356/ASCE Standard 41‐06 and observed in the recent experimental testing. The results of this study provide insights into residential building risk assessment and the relation between building seismic performance implied by the current earthquake‐resistant design and construction practices and performance levels in performance‐based engineering of light‐frame wood construction being considered by the SEI/ASCE committee on reliability‐based design of wood structures. Further code developments are necessary to achieve the goal of uniform risk in earthquake‐resistant residential construction. Copyright © 2010 John Wiley & Sons, Ltd.
Dynamic interactions of life and its landscape: feedbacks at the interface of geomorphology and ecology
Authors: Reinhardt Liam , Jerolmack Douglas , Cardinale Brad J. , Vanacker Veerle , Wright Justin
Published: January 2010

There appears to be no single axis of causality between life and its landscape, but rather, each exerts a simultaneous influence on the other over a wide range of temporal and spatial scales. These influences occur through feedbacks of differing strength and importance with co‐evolution representing the tightest coupling between biological and geomorphological systems. The ongoing failure to incorporate these dynamic bio‐physical interactions with human activity in landscape studies limits our ability to predict the response of landscapes to human disturbance and climate change. This limitation is a direct result of the poor communication between the ecological and geomorphological communities and consequent paucity of interdisciplinary research. Recognition of this failure led to the organization of the Meeting of Young Researchers in Earth Science (MYRES) III, titled ‘Dynamic Interactions of Life and its Landscape’. This paper synthesizes and expands upon key issues and findings from that meeting, to help chart a course for future collaboration among Earth surface scientists and ecologists: it represents the consensus view of a competitively selected group of 77 early‐career researchers. Two broad themes that serve to focus and motivate future research are identified: (1) co‐evolution of landforms and biological communities; and (2) humans as modifiers of the landscape (through direct and indirect actions). Also outlined are the state of the art in analytical, experimental and modelling techniques in ecological and geomorphological research, and novel new research avenues that combine these techniques are suggested. It is hoped that this paper will serve as an interdisciplinary reference for geomorphologists and ecologists looking to learn more about the other field. Copyright © 2010 John Wiley & Sons, Ltd.
Reduced functional coupling in the default‐mode network during self‐referential processing
Authors: van Buuren Mariët , Gladwin Thomas E. , Zandbelt Bram B. , Kahn René S. , Vink Matthijs
Published: January 2010

Activity within the default‐mode network (DMN) is thought to be related to self‐referential processing, such as thinking about one's preferences or personality traits. Although the DMN is generally considered to function as a network, evidence is starting to accumulate that suggests that areas of the DMN are each specialized for different subfunctions of self‐referential processing. Here, we address the issue of functional specialization by investigating changes in coupling between areas of the DMN during self‐referential processing. To this aim, brain activity was assessed during a task in which subjects had to indicate whether a trait adjective described their own personality (self‐referential, Self condition), that of another person (other‐referential, Other condition), or whether the trait was socially desirable (nonreferential, Control condition). To exclude confounding effects of cardiorespiratory processes on activity and functional coupling, we corrected the fMRI signal for these effects. Activity within areas of the DMN was found to be modulated by self‐referential processing. More specifically, during the Self condition compared to the Other and Control condition, activity within the dorsal medial prefrontal cortex, ventral medial prefrontal cortex, and posterior cingulate cortex was increased. Moreover, coupling between areas of the DMN was reduced during the Self condition compared to the Other and Control condition, while coupling between regions of the DMN and regions outside the network was increased. As such, these results provide an indication for functional specialization within the DMN and support the notion that each area of the DMN is involved in different subfunctions of self‐referential processing. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Atlas‐based segmentation of developing tissues in the human brain with quantitative validation in young fetuses
Authors: Habas Piotr A. , Kim Kio , Rousseau Francois , Glenn Orit A. , Barkovich A. James , Studholme Colin
Published: January 2010

Imaging of the human fetus using magnetic resonance (MR) is an essential tool for quantitative studies of normal as well as abnormal brain development in utero. However, because of fundamental differences in tissue types, tissue properties and tissue distribution between the fetal and adult brain, automated tissue segmentation techniques developed for adult brain anatomy are unsuitable for this data. In this paper, we describe methodology for automatic atlas‐based segmentation of individual tissue types in motion‐corrected 3D volumes reconstructed from clinical MR scans of the fetal brain. To generate anatomically correct automatic segmentations, we create a set of accurate manual delineations and build an in utero 3D statistical atlas of tissue distribution incorporating developing gray and white matter as well as transient tissue types such as the germinal matrix. The probabilistic atlas is associated with an unbiased average shape and intensity template for registration of new subject images to the space of the atlas. Quantitative whole brain 3D validation of tissue labeling performed on a set of 14 fetal MR scans (20.57–22.86 weeks gestational age) demonstrates that this atlas‐based EM segmentation approach achieves consistently high DSC performance for the main tissue types in the fetal brain. This work indicates that reliable measures of brain development can be automatically derived from clinical MR imaging and opens up possibility of further 3D volumetric and morphometric studies with multiple fetal subjects. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Neural representation of abstract and concrete concepts: A meta‐analysis of neuroimaging studies
Authors: Wang Jing , Conder Julie A. , Blitzer David N. , Shinkareva Svetlana V.
Published: January 2010

A number of studies have investigated differences in neural correlates of abstract and concrete concepts with disagreement across results. A quantitative, coordinate‐based meta‐analysis combined data from 303 participants across 19 functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) studies to identify the differences in neural representation of abstract and concrete concepts. Studies that reported peak activations in standard space in contrast of abstract > concrete or concrete > abstract concepts at a whole brain level in healthy adults were included in this meta‐analysis. Multilevel kernel density analysis (MKDA) was performed to identify the proportion of activated contrasts weighted by sample size and analysis type (fixed or random effects). Meta‐analysis results indicated consistent and meaningful differences in neural representation for abstract and concrete concepts. Abstract concepts elicit greater activity in the inferior frontal gyrus and middle temporal gyrus compared to concrete concepts, while concrete concepts elicit greater activity in the posterior cingulate, precuneus, fusiform gyrus, and parahippocampal gyrus compared to abstract concepts. These results suggest greater engagement of the verbal system for processing of abstract concepts and greater engagement of the perceptual system for processing of concrete concepts, likely via mental imagery. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.