bluuebunny/crossref_metadata_2025 huggingface dataset:
Graphene‐Based Multifunctional Iron Oxide Nanosheets with Tunable Properties
Authors: Koo Hye Young , Lee Ha‐Jin , Go Hye‐Ah , Lee Young Boo , Bae Tae Sung , Kim Jun Kyung , Choi Won San
Published: December 2010

We report the synthesis of graphenes with tunable properties due to the growth of needlelike iron oxide (IO) nanoparticles on their surfaces. The electrical conductivity, flexibility, and magnetic properties of graphene nanosheets (GNSs) could be tuned on demand by fine controlling both the surface coverage and the length of the IO nanoneedles. The degree of coverage of the IO nanoparticles on the surface of the GNSs made it possible to control the resulting properties of the IO/GNSs on demand. As examples of their utility, paperlike materials were generated by simple filtration, and the resulting IO/GNS nanocomposites showed extraordinary removal capacity and fast adsorption rates for AsV and CrVI ions in water. Another possible application is the preparation of multifunctional films equipped with conductivity, flexibility, and magnetic properties. The fabrication process is easy to scale up at a low cost. In addition, both the colloidal solution and film forms of the resulting IO/GNSs were effective for removal of heavy metal ions, meaning this material could be utilized for actual industrial applications.
Designing Structural Motifs for Clickamers: Exploiting the 1,2,3‐Triazole Moiety to Generate Conformationally Restricted Molecular Architectures
Authors: Zornik Denise , Meudtner Robert M. , El Malah Tamer , Thiele Christina M. , Hecht Stefan
Published: December 2010

Noncovalent interactions, especially hydrogen‐bonding interactions as well as electrostatic forces, confined within one macromolecule are the key to designing foldamers that adopt well‐defined conformations in solution. In the context of significant recent activities in the area of triazole‐connected foldamers, so‐called clickamers, we present a fundamental study that compares various model compounds that bear adjacent N‐, O‐, or F‐heteroatom substituents. The interplay of attractive and repulsive interactions leads to rotational constraints around the single bonds attached to both the 1‐ and 4‐positions of the 1,2,3‐triazole moiety and should therefore be able to induce well‐defined conformational preferences in higher oligomers and polymers, that is, foldamers. Various compounds were synthesized and characterized with regard to their preferred conformations in all three aggregation states—that is, in the gas phase, in solution as well as in the solid state—by employing DFT calculations, NMR spectroscopic experiments, and X‐ray crystallography, respectively. On the basis of the thus‐obtained general understanding of the conformational behavior of the individual connection motifs, heterostructures were prepared from different motifs without affecting their distinct folding characteristics. Therefore, this work provides a kind of foldamer construction kit, which should enable the design of various clickamers with specific shape and incorporated functionality.
The Effect of Sulfoxides on the Stereoselective Construction of Tetrahydrofurans: Total Synthesis of (+)‐Goniothalesdiol
Authors: Hernández‐Torres Gloria , Carreño M. Carmen , Urbano Antonio , Colobert Françoise
Published: December 2010

Good to excellent stereoselectivities were achieved in the reductive cyclization (with Et3SiH/trimethylsilyl trifluoromethanesulfonate (TMSOTf)) of enantiopure hydroxy sulfinyl ketones en route to 2,5‐cis‐disubstituted tetrahydrofuran skeletons. Electrostatic effects of the exocyclic sulfoxide, which stabilized the reactive intermediate oxocarbenium conformations, were responsible for the observed stereocontrol. A model is proposed to explain the results. The use of this reaction and the asymmetric β‐ketosulfoxide reduction as key steps facilitated the total enantioselective synthesis of the natural β‐C‐aryl glycoside (+)‐goniothalesdiol.
Effects of Statin Treatment on Cardiac Function in Patients With Chronic Heart Failure: A Meta‐Analysis of Randomized Controlled Trials
Authors: Zhang Lei , Zhang Shuning , Jiang Hong , Sun Aijun , Zou Yunzeng , Ge Junbo
Published: December 2010

Background

Whether additional benefit can be achieved with the use of statin treatment in patients with chronic heart failure (CHF) remains undetermined.

Hypothesis

Statin treatment may be effective in improving cardiac function and ameliorating ventricular remodeling in CHF patients.

Methods

The PubMed, MEDLINE, EMBASE, and EBM Reviews databases were searched for randomized controlled trials comparing statin treatment with nonstatin treatment in patients with CHF. Two reviews independently assessed studies and extracted data. Weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated using random effects models.

Results

Eleven trials with 590 patients were included. Pooled analysis showed that statin treatment was associated with a significant increase in left ventricular ejection fraction (WMD: 3.35%, 95% CI: 0.80 to 5.91%, P = 0.01). The beneficial effects of statin treatment were also demonstrated by the reduction of left ventricular end‐diastolic diameter (WMD: −3.77 mm, 95% CI: −6.24 to −1.31 mm, P = 0.003), left ventricular end‐systolic diameter (WMD: −3.57 mm, 95% CI: −6.37 to −0.76 mm, P = 0.01), B‐type natriuretic peptide (WMD: −83.17 pg/mL, 95% CI: −121.29 to −45.05 pg/mL, P < 0.0001), and New York Heart Association functional class (WMD: −0.30, 95% CI: −0.37 to −0.23, P < 0.00001). Meta‐regression showed a statistically significant association between left ventricular ejection fraction improvement and follow‐up duration (P = 0.03).

Conclusions

The current cumulative evidence suggests that use of statin treatment in CHF patients may result in the improvement of cardiac function and clinical symptoms, as well as the amelioration of left ventricular remodeling. Copyright © 2011 Wiley Periodicals, Inc.

Lei Zhang, MD, Shuning Zhang, MD, and Hong Jiang, MD, contributed equally to this work. This study was supported by the Key Projects in the National Science and Technology Pillar Program in the Eleventh Five‐year Plan Period (No. 2006BAI01A04), National Natural Science Foundation of China (No. 30871073), National High‐Tech Research and Development Program of China (No. 2006AA02A406), and Outstanding Youth Grant from National Natural Science Foundation of China (No. 30725036). This work was not funded by an industry sponsor. The authors have no other funding, ﬁnancial relationships, or conﬂicts of interest to disclose.

Additional Supporting Information may be found in the online version of this article.
Flybrain neuron database: A comprehensive database system of the Drosophila brain neurons
Authors: Shinomiya Kazunori , Matsuda Keiji , Oishi Takao , Otsuna Hideo , Ito Kei
Published: December 2010

The long history of neuroscience has accumulated information about numerous types of neurons in the brain of various organisms. Because such neurons have been reported in diverse publications without controlled format, it is not easy to keep track of all the known neurons in a particular nervous system. To address this issue we constructed an online database called Flybrain Neuron Database (Flybrain NDB), which serves as a platform to collect and provide information about all the types of neurons published so far in the brain of Drosophila melanogaster. Projection patterns of the identified neurons in diverse areas of the brain were recorded in a unified format, with text‐based descriptions as well as images and movies wherever possible. In some cases projection sites and the distribution of the post‐ and presynaptic sites were determined with greater detail than described in the original publication. Information about the labeling patterns of various antibodies and expression driver strains to visualize identified neurons are provided as a separate sub‐database. We also implemented a novel visualization tool with which users can interactively examine three‐dimensional reconstruction of the confocal serial section images with desired viewing angles and cross sections. Comprehensive collection and versatile search function of the anatomical information reported in diverse publications make it possible to analyze possible connectivity between different brain regions. We analyzed the preferential connectivity among optic lobe layers and the plausible olfactory sensory map in the lateral horn to show the usefulness of such a database. J. Comp. Neurol. 519:807‐833, 2011. © 2010 Wiley‐Liss, Inc.
Differential expression of SNAP‐25 family proteins in the mouse brain
Authors: Yamamori Saori , Itakura Makoto , Sugaya Daichi , Katsumata Osamu , Sakagami Hiroyuki , Takahashi Masami
Published: December 2010

Soluble N‐ethylmaleimide‐sensitive factor attachment protein (SNAP)‐25 is a neuronal SNARE protein essential for neurotransmitter release from presynaptic terminals. Three palmitoylated SNAP‐25 family proteins: SNAP‐25a, SNAP‐25b, and SNAP‐23, are expressed in the brain, but little is known about their distributions and functions. In the present study, we generated specific antibodies to distinguish these three homologous proteins. Immunoblot and immunohistochemical analyses revealed that SNAP‐25b was distributed in synapse‐enriched regions throughout almost the entire brain, whereas SNAP‐25a and SNAP‐23 were expressed in relatively specific brain regions with partially complementary expression patterns. SNAP‐25a and SNAP‐25b, but not SNAP‐23, were also present in the axoplasm of nerve fibers. The intracellular localization was also different, and although SNAP‐25b and SNAP‐23 were found primarily in membrane and lipid raft‐enriched fractions of mouse brain homogenates, a substantial amount of SNAP‐25a was recovered in soluble fractions. In PC12 cells, SNAP‐25b was localized to the plasma membrane, but SNAP‐25a and SNAP‐23 were distributed throughout the cytoplasm. The expression and distribution of these three proteins were also differentially regulated in the early postnatal period. These results indicate that the three SNAP‐25 family proteins display a differential distribution in the brain as well as in neuronal cells, and possibly play distinct roles. J. Comp. Neurol. 519:916–932, 2011. © 2010 Wiley‐Liss, Inc.
Patient‐specific computational biomechanics for simulating adolescent scoliosis surgery: Predicted vs clinical correction for a preliminary series of six patients
Authors: Little J. Paige , Adam Clayton
Published: December 2010

Scoliosis is a spinal deformity that requires surgical correction in progressive cases. In order to optimize surgery outcomes, patient‐specific finite element models are being developed by our group. In this paper, a single rod anterior correction procedure is simulated for a group of six scoliosis patients. For each patient, personalized model geometry was derived from low‐dose CT scans, and clinically measured intra‐operative corrective forces were applied. However, tissue material properties were not patient‐specific, being derived from existing literature. Clinically, the patient group had a mean initial Cobb angle of 47.3 ∘, which was corrected to 17.5 ∘ after surgery. The mean simulated post‐operative Cobb angle for the group was 18.1 ∘. Although this represents good agreement between clinical and simulated corrections, the discrepancy between clinical and simulated Cobb angle for individual patients varied between − 10.3 and + 8.6∘, with only three of the six patients matching the clinical result to within accepted Cobb measurement error of ±5∘. The results of this study suggest that spinal tissue material properties play an important role in governing the correction obtained during surgery, and that patient‐specific modelling approaches must address the question of how to prescribe patient‐specific soft tissue properties for spine surgery simulation. Copyright © 2010 John Wiley & Sons, Ltd.
Quantification of testosterone and metabolites released after alkaline treatment in human urine
Authors: Fabregat Andreu , Pozo Oscar J. , Marcos Josep , Segura Jordi , Ventura Rosa
Published: December 2010

A rapid, accurate, and sensitive method based on liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) for the quantification of the testosterone (T) fraction released under basic conditions and its metabolites 1,4‐androstadien‐3,17‐dione (1,4‐AD), 4,6‐androstadien‐3,17‐dione (4,6‐AD) and 4,6‐androstadien‐17β‐ol‐3‐one (6‐T) obtained in the same way has been developed and validated. Urine samples (5 ml) were alkalinized and the released analytes were extracted by liquid‐liquid extraction. The chromatographic separation was performed in 8 min. MS/MS determination was performed under selected reaction monitoring mode using electrospray ionization in positive mode. The method was shown to be linear from 0.05 to 50 ng/ml for 1,4‐AD, 6‐T and T while for 4,6‐AD the linearity from 0.5 to 500 ng/ml was demonstrated (r > 0.99). Limits of detection below 0.05 ng/ml were obtained for all analytes. Intra‐assay precision and accuracies, evaluated at three concentrations levels (0.1, 1 and 20 ng/ml) were below 20%. The applicability of the analytical method was confirmed by analysis of several samples collected from healthy volunteers and samples collected after oral testosterone undecanoate administration. The analytical method was found to be able to quantify the metabolites either at the low concentrations levels present in the urine from untreated volunteers or at the high concentrations found after T administration. Short analysis time, simple sample preparation, and satisfactory quantitative parameters make this method potentially useful for anti‐doping control purposes. Copyright © 2010 John Wiley & Sons, Ltd.
Chemiluminescence and electrochemiluminescence detection of controlled drugs
Authors: Adcock Jacqui L. , Barrow Colin J. , Barnett Neil W. , Conlan Xavier A. , Hogan Conor F. , Francis Paul S.
Published: December 2010

We review the determination of various controlled drugs (opioids, tranquilizers, stimulants, and hallucinogens) using flow‐analysis methodologies (flow injection analysis, high performance liquid chromatography, capillary electrophoresis, and microfluidic devices) with chemiluminescence and electrochemiluminescence reagents such as luminol, diaryloxalates, tris(2,2′‐bipyridine)ruthenium(II), permanganate, manganese(IV), and sulfite, for industrial, clinical, pharmaceutical, and forensic science applications. Copyright © 2010 John Wiley & Sons, Ltd.
Severe anorexia nervosa: Outcomes from a medical stabilization unit
Authors: Gaudiani Jennifer L. , Sabel Allison Lee , Mascolo Margherita , Mehler Philip S.
Published: December 2010

Objective:

We report data from the medical stabilization and refeeding of patients with severe anorexia nervosa admitted over a 15‐month period.

Method:

Through chart review and computerized data collection, we evaluated demographic and clinical data from 25 consecutive patients admitted to our medical stabilization unit from October 2008 to January 2010.

Results:

In this adult‐patient population with a median body mass index (BMI) of 13.1 kg/m2 (interquartile range, 11.0–14.4), 44% developed hypoglycemia, 76% had abnormal liver function, 83% had abnormal bone density, 45% developed refeeding hypophosphatemia, and 92% were hypothermic. Severe liver function abnormality predicted the development of hypoglycemia (p = 0.02, OR 9.78, CI: 1.55–61.65). No clinical features predicted hypophosphatemia, including admission BMI (p = 0.19), serum glucose level (p = 0.21), elevated liver function tests (p = 0.39 for AST), or initial amount of kilocalories consumed (p = 0.06).

Discussion:

Patients with the most severe cases of anorexia nervosa have a high prevalence of serious medical complications during initial refeeding. © 2010 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)
New Chlorido(dimethyl sulfoxide)iridium(III) Complexes with N6‐Substituted Adenines – Kinetic N(7) versus Thermodynamic N(9) Coordinated Adenine Isomers (Eur. J. Inorg. Chem. 36/2010)
Authors: García‐Raso Angel , Fiol Juan J. , Albertí Francisca M. , Lagos Yolanda , Torres Marta , Barceló‐Oliver Miquel , Prieto María J. , Moreno Virtudes , Mata Ignasi , Molins Elies , Estarellas Carolina , Frontera Antonio , Quiñonero David , Deyà Pere M.
Published: December 2010

The cover picture shows two IrIII complexes with adenine derivatives that have been synthesized and characterized by spectroscopic techniques and by single‐crystal X‐ray diffraction studies. The interaction of IrIII‐adenine complexes and plasmidic DNA pBR322 has been analyzed. In all cases, iridium shows an octahedral geometry and is coordinated to four chlorido ligands, dimethyl sulfoxide (DMSO‐κS) and an adenine derivative. Two different coordination modes for adenine are observed, one through the N7 (kinetic product, right side of the picture) and the other one through the N9 atom (thermodynamic product, left side of the picture). Both mechanisms, which yield the different coordination products, have been studied by means of theoretical DFT calculations. Details are discussed in the article by A. García‐Raso, A. Frontera et al. on p. 5617 ff. The Christmas tree, which symbolizes the activation energy, is decorated with the crystal structure of an IrIII‐adenine complex, where the iridium atoms represent the Christmas ball ornaments.
Highly sensitive detection of melamine and its derivatives by capillary electrophoresis coupled with online preconcentration techniques
Authors: Jin Yue , Meng Lingchen , Li Meixian , Zhu Zhiwei
Published: December 2010

Two kinds of online preconcentration techniques including large‐volume sample stacking‐sweeping and selective‐exhaustive injection‐sweeping (SEI‐S) were employed in CE to develop a rapid, simple and sensitive method for determination of melamine (MM) and its derivatives such as ammeline (AMN), ammelide (AMD) and cyanuric acid (CA) in liquid milk products. Though the sensitivity of large‐volume sample stacking‐sweeping is not particularly high, it can be used to detect all the four compounds simultaneously. However, it is very difficult to improve the sensitivity of these four compounds by using single SEI‐S method directly, owing to their completely different extents of protonation or deprotonation. Grouping can solve this problem perfectly. After the four compounds are divided into two groups (MM/AMN and AMD/CA), cation‐SEI‐S or anion‐SEI‐S can be applied for their online stacking. In cation‐SEI‐S, the detection limits for MM and AMN were both 0.01 ng/mL based on the signal‐to‐noise ratio of 3. In anion‐SEI‐S, the detection limits were 0.05 and 0.02 ng/mL for CA and AMD, respectively. Results of this study show a great potential for the SEI‐S method to be a useful tool for the rapid and sensitive determination of MM and its derivatives in liquid milk products.
CZE separation of amitrol and triazine herbicides in environmental water samples with acid‐assisted on‐column preconcentration
Authors: Arribas Alberto Sánchez , Moreno Mónica , Bermejo Esperanza , Zapardiel Antonio , Chicharro Manuel
Published: December 2010

A simple analytical scheme for the detection and quantification of amitrol and triazine herbicides (atrazine, ametryn and atraton) and degradation product (2‐hydroxyatrazine) in environmental water samples by CZE is reported. On‐column preconcentration of analytes from untreated water samples (mineral, spring, tap and river water) is accomplished by introducing an acid plug (200 mM citrate of pH 2.0) after the sample and then proceeding with the CZE separation, using 100 mM formiate buffer of pH 3.5 as running buffer and 25.0 KV as separation voltage. UV detection at 200 nm provides LODs from 50 to 300 nM in untreated samples and they were lowered tenfold by sample preconcentration by evaporation. Calculated recoveries were typically higher than 90%. Minimal detectable concentration of the electroactive amitrol could be decreased about 20‐fold when electrochemical detection was employed by monitoring the amperometric signal at +800 mV using a carbon paste electrode (LOD of 9.6 nM, 0.81 μg/L, versus 170 nM, 14.3 μg/L, using amperometric and UV detection, respectively) in untreated water samples.
Relating the sediment phase speciation of arsenic, cadmium, and chromium with their bioavailability for the deposit-feeding polychaete Nereis succinea
Authors: Baumann Zofia , Fisher Nicholas S
Published: December 2010

We studied the influence of sediment geochemistry on bioavailability of As, Cd, and Cr in deposit-feeding polychaetes. Metal phase speciation in sediments was determined with a sequential extraction scheme, and assimilation efficiencies (AEs) of ingested metals were determined by pulse-chase feeding experiments using γ-emitting isotopes. Worms were fed sediments collected from geochemically diverse estuaries that were labeled by sorbing dissolved radiotracers or mixing with radiolabeled algae. Uptake of sediment-bound metals was compared with that from labeled algae or goethite. Metal AEs showed a positive relationship with the exchangeable and carbonate sedimentary fractions, whereas metals in iron and manganese oxides and acid-volatile sulfides, or in pyrite and other refractory material, were inversely correlated with AEs. Arsenic was most bioavailable from algae (72%), less from sediments mixed with algae (24–70%) and least from sediments labeled directly (1–12%). Arsenic AEs in sediments labeled directly showed a positive correlation with sedimentary Mn and Al and negative correlation with Fe. Cadmium AEs were positively correlated with salinity and negatively correlated with sedimentary organic C. The AEs of Cr from sediments or algae were less than 5%, but they were 34% from pure goethite. By quantifying the relationship of metal speciation in sediments with their bioavailability for deposit-feeding polychaetes, the present study provides new insight into understanding metal bioaccumulation in benthic invertebrates. Environ. Toxicol. Chem. 2011; 30:747–756. © 2011 SETAC
ℋ︁‐LU factorization in preconditioners for augmented Lagrangian and grad‐div stabilized saddle point systems
Authors: Börm Steffen , Le Borne Sabine
Published: December 2010

The (mixed finite element) discretization of the linearized Navier–Stokes equations leads to a linear system of equations of saddle point type. The iterative solution of this linear system requires the construction of suitable preconditioners, especially in the case of high Reynolds numbers. In the past, a stabilizing approach has been suggested which does not change the exact solution but influences the accuracy of the discrete solution as well as the effectiveness of iterative solvers. This stabilization technique can be performed on the continuous side before the discretization, where it is known as ‘grad‐div’ (GD) stabilization, as well as on the discrete side where it is known as an ‘augmented Lagrangian’ (AL) technique (and does not change the discrete solution). In this paper, we study the applicability of ℋ︁‐LU factorizations to solve the arising subproblems in the different variants of stabilized saddle point systems. We consider both the saddle point systems that arise from the stabilization in the continuous as well as on the discrete setting. Recently, a modified AL preconditioner has been proposed for the system resulting from the discrete stabilization. We provide a straightforward generalization of this approach to the GD stabilization. We conclude the paper with numerical tests for a variety of problems to illustrate the behavior of the considered preconditioners as well as the suitability of ℋ︁‐LU factorization in the preconditioners. Copyright © 2010 John Wiley & Sons, Ltd.
A linearity‐preserving cell‐centered scheme for the heterogeneous and anisotropic diffusion equations on general meshes
Authors: Gao Zhiming , Wu Jiming
Published: December 2010

In this paper a finite volume scheme for the heterogeneous and anisotropic diffusion equations is proposed on general, possibly nonconforming meshes. This scheme has both cell‐centered unknowns and vertex unknowns. The vertex unknowns are treated as intermediate ones and are expressed as a linear weighted combination of the surrounding cell‐centered unknowns, which reduces the scheme to a completely cell‐centered one. We propose two types of new explicit weights which allow arbitrary diffusion tensors, and are neither discontinuity dependent nor mesh topology dependent. Both the derivation of the scheme and that of new weights satisfy the linearity‐preserving criterion which requires that a discretization scheme should be exact on linear solutions. The resulting new scheme is called as the linearity‐preserving cell‐centered scheme and the numerical results show that it maintain optimal convergence rates for the solution and flux on general polygonal distorted meshes in case that the diffusion tensor is taken to be anisotropic, at times heterogeneous, and/or discontinuous. Copyright © 2010 John Wiley & Sons, Ltd.
An improved progressive preconditioning method for steady non‐cavitating and sheet‐cavitating flows
Authors: Esfahanian Vahid , Akbarzadeh Pooria , Hejranfar Kazem
Published: December 2010

An improved progressive preconditioning method for analyzing steady inviscid and laminar flows around fully wetted and sheet‐cavitating hydrofoils is presented. The preconditioning matrix is adapted automatically from the pressure and/or velocity flow‐field by a power‐law relation. The cavitating calculations are based on a single fluid approach. In this approach, the liquid/vapour mixture is treated as a homogeneous fluid whose density is controlled by a barotropic state law. This physical model is integrated with a numerical resolution derived from the cell‐centered Jameson's finite volume algorithm. The stabilization is achieved via the second‐and fourth‐order artificial dissipation scheme. Explicit four‐step Runge–Kutta time integration is applied to achieve the steady‐state condition. Results presented in the paper focus on the pressure distribution on hydrofoils wall, velocity profiles, lift and drag forces, length of sheet cavitation, and effect of the power‐law preconditioning method on convergence speed. The results show satisfactory agreement with numerical and experimental works of others. The scheme has a progressive effect on the convergence speed. The results indicate that using the power‐law preconditioner improves the convergence rate, significantly. Copyright © 2010 John Wiley & Sons, Ltd.
Mental and psychological conditions, medical comorbidity and functional limitation: differential associations in older adults with cognitive impairment, depressive symptoms and co‐existence of both
Authors: Millán‐Calenti José C. , Maseda Ana , Rochette Sophie , Vázquez Gustavo A. , Sánchez Alba , Lorenzo Trinidad
Published: December 2010

Objective

Cognitive impairment and depressive symptoms are common among the geriatric population but the co‐occurrence of both is rarely studied. The purpose of this study was to identify and compare the factors associated with three groups of elderly people: those assessed with cognitive impairment alone (COG), depressive symptoms alone (DEP) or co‐existence of both (COG‐DEP).

Methods

The cross‐sectional study included 600 community‐dwellers ages 65 and older. All participants underwent a comprehensive evaluation. Global cognition was measured by the Mini‐Mental State Examination (MMSE) and depressive symptoms were defined by the Geriatric Depression Scale (GDS). Specific chronic illnesses relevant to the Charlson comorbidity index (CCI) were self‐reported. Functional status was evaluated by the Katz' basic (ADL) and Lawton's instrumental (IADL) activities of daily living scales.

Results

COG‐DEP was explained by IADL dependence (OR: 11.9, 95% CI: 4.59–30.78), ADL dependence (OR: 11.5, 95% CI: 5.59–23.69), cerebrovascular disease (OR: 3.6, 95% CI: 1.48–8.68), congestive heart failure (OR: 3.4, 95% CI: 1.77–6.59) and diabetes (OR: 2.6, 95% CI: 1.30–5.18), but it was best predicted by functional limitations in the adjusted model. Being functionally dependent and medically ill with shorter life expectancy was shown to significantly increase the odds of being DEP. Functional limitation in IADL was without distinction associated to COG, DEP and COG‐DEP.

Conclusion

The present results on COG, DEP and COG‐DEP show the particular relevance of certain medical comorbidities and functional limitations to those three distinct groups of elderly people. Copyright © 2010 John Wiley & Sons, Ltd.
Limitation of physical performance in a muscle fatiguing handgrip exercise is mediated by thalamo‐insular activity
Authors: Hilty Lea , Jäncke Lutz , Luechinger Roger , Boutellier Urs , Lutz Kai
Published: December 2010

In this study, we investigated central/supraspinal processes mediating cessation of a muscle fatiguing exercise. Fifteen male subjects performed 39 intermittent, isometric handgrip contractions (13 s on, 5–6 s off) with the dominant right hand while brain activation was assessed by means of functional magnetic resonance imaging (fMRI). An adaptive, partly stochastic protocol was designed such that in approximately 50% of the contraction trials the required force could not be held until the end of the trial (task failure trial). Trials performed in compliance with the force requirements (succeeded trial) were compared with task failure trials concerning neural activity during a small time window before task failure occurred. The data revealed significantly increased activation contralaterally in both the mid/anterior insular cortex and the thalamus during the investigated time window in the case of subsequent task failure. In accordance with other studies investigating sensations that alert the organism to urgent homeostatic imbalance such as air hunger, hunger for food, and pain, we assume that an increased thalamo‐insular activation in the context of a fatigue‐induced handgrip exercise could reflect increased homeostatic disturbance in the exercising muscle and may be of essential importance by mediating task failure to maintain the integrity of the organism. Hum Brain Mapp, 2011. © 2010 Wiley Periodicals, Inc.
3,3′‐diindolylmethane enhances taxotere‐induced growth inhibition of breast cancer cells through downregulation of FoxM1
Authors: Ahmad Aamir , Ali Shadan , Wang Zhiwei , Ali Ashhar S. , Sethi Seema , Sakr Wael A. , Raz Avraham , Rahman KM Wahidur
Published: December 2010

Emerging evidence suggests that the transcription factor Forkhead Box M1 (FoxM1) is associated with aggressive human carcinomas, including breast cancer. Because elevated expression of FoxM1 has been observed in human breast cancers, FoxM1 has attracted much attention in recent years as a potential target for the prevention and/or therapeutic intervention in breast cancer. However, no information is currently available regarding how downregulation of FoxM1 could be achieved for breast cancer prevention and therapy. Here, we report for the first time that 3,3′‐diindolylmethane (DIM), a nontoxic dietary chemopreventive agent could effectively downregulate FoxM1 in various breast cancer cell lines. Using gene transfection, real‐time reverse transcription‐PCR, Western blotting, invasion and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays, we found that DIM could enhance Taxotere‐induced growth inhibition of breast cancer cells, and decreased invasive capacity of breast cancer cells was observed after either treatment alone or the combination. These effects were associated with downregulation of FoxM1. We also found that knock down of FoxM1 expression by small interfering RNA (siRNA) transfection increased DIM‐induced cell growth inhibition, whereas over‐expression of FoxM1 by cDNA transfection attenuated DIM‐induced cell growth inhibition, suggesting the mechanistic role of FoxM1. Most importantly, the combination treatment significantly inhibited tumor growth in severe combined immunodeficiency (SCID) mice, and the results were correlated with the downregulation of FoxM1 in tumor remnants. We conclude that inactivation of FoxM1 and its target genes by DIM could enhance the therapeutic efficacy of Taxotere in breast cancer, which could be a useful strategy for the prevention and/or treatment of breast cancer.
Checkpoint kinase inhibitor synergizes with DNA‐damaging agents in G1 checkpoint‐defective neuroblastoma
Authors: Xu Hong , Cheung Irene Y. , Wei Xiao X. , Tran Hoa , Gao Xiaoni , Cheung Nai‐Kong V.
Published: December 2010

Checkpoint kinase inhibitors can enhance the cancer killing action of DNA‐damaging chemotherapeutic agents by disrupting the S/G2 cell cycle checkpoints. The in vitro and in vivo effects of the Chk1/2 inhibitor AZD7762 when combined with these agents were examined using neuroblastoma cell lines with known p53/MDM2/p14ARF genomic status. Four of four p53 mutant lines and three of five MDM2/p14ARF abnormal lines were defective in G1 checkpoint, correlating with failure to induce endogenous p21 after treatment with DNA‐damaging agents. In cytotoxicity assays, these G1 checkpoint‐defective lines were more resistant to DNA‐damaging agents when compared to G1 checkpoint intact lines, yet becoming more sensitive when AZD7762 was added. Moreover, AZD7762 abrogated DNA damage‐induced S/G2 checkpoint arrest both in vitro and in vivo. In xenograft models, a significant delay in tumor growth accompanied by histological evidence of increased apoptosis was observed, when AZD7762 was added to the DNA‐damaging drug gemcitabine. These results suggest a therapeutic potential of combination therapy using checkpoint kinase inhibitor and chemotherapy to reverse or prevent drug resistance in treating neuroblastomas with defective G1 checkpoints.
Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: Leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma
Authors: Mahmood S. Tariq , Agresta Samuel , Vigil Carlos E. , Zhao Xiuhua , Han Gang , D'Amato Gina , Calitri Ciara E. , Dean Michelle , Garrett Christopher , Schell Michael J. , Antonia Scott , Chiappori Alberto
Published: December 2010

Soft tissue sarcomas (STS) represent a diverse group of histologic subtypes with targetable molecular alterations, often treated as a single disease. Sunitinib malate is a multitargeted receptor tyrosine kinase inhibitor active in other solid tumors carrying similar alterations (i.e., imatinib mesylate‐refractory gastrointestinal stromal tumors). This single‐institution phase II study investigated the safety and efficacy of sunitinib malate in three common STS subtypes. Patients with documented unresectable or metastatic STS (liposarcoma, leiomyosarcoma and malignant fibrous histiocytoma [MFH]), measurable disease, and 3 or less prior lines of therapy were eligible. Treatment consisted of sunitinib malate, 50 mg daily, for 4 weeks every 6 weeks. Forty‐eight patients were enrolled, and 35% were heavily pretreated (≥2 prior lines of chemotherapy). The safety profile resembled previously known sunitinib malate toxicities. Median progression‐free and overall survivals for liposarcoma, leiomyosarcoma, and MFH were 3.9 and 18.6, 4.2 and 10.1 and 2.5 and 13.6 months, respectively. The 3‐month progression‐free rates in the untreated and pretreated (chemotherapy) patients with liposarcoma, leiomyosarcoma and MFH were 75% and 69.2%, 60%, and 62.5% and 25% and 44.4%, respectively. With the caveats that a minority of patients with potentially indolent or low‐grade disease could have been included and the small numbers, a 3‐month progression‐free rate of >40% suggests activity for sunitinib malate at least in liposarcomas and leiomyosarcomas. Thus, we believe that further investigation in these susceptible STS subtypes is warranted.
High‐frequency microwave ablation method for enhanced cancer treatment with minimized collateral damage
Authors: Yoon Jeonghoon , Cho Jeiwon , Kim Namgon , Kim Dae‐Duk , Lee Eunsook , Cheon Changyul , Kwon Youngwoo
Published: December 2010

To overcome the limits of conventional microwave ablation, a new frequency spectrum above 6 GHz has been explored for low‐power and low collateral damage ablation procedure. A planar coaxial probe‐based applicator, suitable for easy insertion into the human body, was developed for our study to cover a wideband frequency up to 30 GHz. Thermal ablations with small input power (1–3 W) at various microwave frequencies were performed on nude mice xenografted with human breast cancer. Comparative study of ablation efficiencies revealed that 18‐GHz microwave results in the largest difference in the temperature rise between cancer and normal tissues as well as the highest ablation efficiency, reaching 20 times that of 2 GHz. Thermal profile study on the composite region of cancer and fat also showed significantly reduced collateral damage using 18 GHz. Application of low‐power (1 W) 18‐GHz microwave on the nude mice xenografted with human breast cancer cells resulted in recurrence‐free treatment. The proposed microwave ablation method can be a very effective process to treat small‐sized tumor with minimized invasiveness and collateral damages.
Vascular effects dominate solid tumor response to treatment with combretastatin A‐4‐phosphate
Authors: Jane Lunt Sarah , Akerman Simon , Hill Sally A. , Fisher Matthew , Wright Victoria J. , Reyes‐Aldasoro Constantino C. , Tozer Gillian M. , Kanthou Chryso
Published: December 2010

Vascular‐targeted therapeutics are increasingly used in the clinic. However, less is known about the direct response of tumor cells to these agents. We have developed a combretastatin‐A‐4‐phosphate (CA4P) resistant variant of SW1222 human colorectal carcinoma cells to examine the relative importance of vascular versus tumor cell targeting in the ultimate treatment response. SW1222Res cells were generated through exposure of wild‐type cells (SW1222WT) to increasing CA4P concentrations in vitro. Increased resistance was confirmed through analyses of cell viability, apoptosis and multidrug‐resistance (MDR) protein expression. In vivo, comparative studies examined tumor cell necrosis, apoptosis, vessel morphology and functional vascular end‐points following treatment with CA4P (single 100 mg/kg dose). Tumor response to repeated CA4P dosing (50 mg/kg/day, 5 days/week for 2 weeks) was examined through growth measurement, and ultimate tumor cell survival was studied by ex vivo clonogenic assay. In vitro, SW1222Res cells showed reduced CA4P sensitivity, enhanced MDR protein expression and a reduced apoptotic index. In vivo, CA4P induced significantly lower apoptotic cell death in SW1222Res versus SW1222WT tumors indicating maintenance of resistance characteristics. However, CA4P‐induced tumor necrosis was equivalent in both lines. Similarly, rapid CA4P‐mediated vessel disruption and blood flow shut‐down were observed in both lines. Cell surviving fraction was comparable in the two tumor types following single dose CA4P and SW1222Res tumors were at least as sensitive as SW1222WT tumors to repeated dosing. Despite tumor cell resistance to CA4P, SW1222Res response in vivo was not impaired, strongly supporting the view that vascular damage dominates the therapeutic response to this agent.
Biology of Krüppel‐like factor 6 transcriptional regulator in cell life and death
Authors: Andreoli Verónica , Gehrau Ricardo C. , Bocco Jose Luis
Published: December 2010

An essential role for the Krüppel‐like transcription factor family has been determined in the regulation of remarkable processes including cell proliferation, differentiation, signal transduction, oncogenesis, and cell death. A member of this group, Krüppel‐like factor 6 (KLF6), identified on the basis of its ability to regulate a group of genes belonging to the carcinoembryonic antigen gene family, has been involved in human carcinogenesis. Early studies proposed a tumor suppressor function for KLF6 because of its ability to reduce cell proliferation through several biochemical mechanisms including regulation of cell cycle components, oncogene products, and apoptosis. Mutations within the klf6 gene, decreased expression and/or loss‐of‐heterozygosity were associated with the development of different human malignancies, and, hence, further supporting the tumor suppressor function of KLF6. This view has been challenged by other studies in distinct types of human cancers describing infrequent genetic alterations of klf6 gene or even enhanced expression in some tumors. The scenario about KLF6 function became still more complex as the description of oncogenic KLF6 splice variant 1 (SV1) with dominant negative activity against the wild type KLF6 (wtKLF6) protein. Additionally, increased evidence is suggesting that KLF6 is a bonafide target of several signaling cascades, which ultimate regulatory effect on this protein could drive decisions of cell life and death, facing the dilemma about how wtKLF6 could be involved in both processes. These apparently conflicting situations, emerged by apparently opposite effects mediated by wtKLF6, may be related, at least in part, to the biological cross‐talk with the c‐Jun oncoprotein. Depending on the stimulus received by the cell, wtKLF6 interaction with c‐Jun determines different cell outcomes such as proliferation control or apoptosis. Thus, KLF6 responsiveness represents a kind of cell warning signal on receiving different stimuli, including oncogenic activation and microbial infections, orchestrating the implementation of proliferation and apoptotic programs. © 2010 IUBMB IUBMB Life, 62(12): 896–905, 2010
MicroRNAs and other small silencing RNAs in cancer
Authors: Rovira Carlos , Güida Maria C. , Cayota Alfonso
Published: December 2010

Small noncoding RNAs are key controllers of cellular function, and their deregulation can lead to cancer development and metastatic evolution. This review summarizes the most important examples of small RNAs involved in human cancer and discusses their clinical use as biomarkers and drug targets for diagnosis, prognosis, and treatment of cancer. We also describe the possible mechanisms underlying small RNA‐mediated transformation and outline the future describing new small RNA families with great potential in cancer biology. © 2010 IUBMB IUBMB Life, 62(12): 859–968
Protective effects of 1,3‐diaryl‐2‐propen‐1‐one derivatives against H2O2‐induced damage in SK‐N‐MC cells
Authors: Bayati Samaneh , Yazdanparast Razieh , Majd Soraya Sajadi , Oh Seikwan
Published: December 2010

Alzheimer's disease (AD) is an age‐related neurodegenerative disorder of the central nervous system resulting in memory loss and dementia. Some of the associated pathogenic changes are amyloid peptide aggregation, excitotoxicity, oxidative stress and inflammation. Oxidative stress plays an indispensable role in the pathophysiology of AD. Therefore, antioxidant therapies appear to be promising approaches in dealing with AD patients. In that line, we evaluated the free radical scavenging capabilities of 13 different chalcones (1,3‐diphenyl‐2‐propen‐1‐one) derivatives against the free‐radical damaging effects of hydrogen peroxide (H2O2) on the SK‐N‐MC neuroblastoma cell line. Pretreatment of the cells for 3 h with 20 µ m of each of these derivatives (compounds 8–20) followed by exposure to 300 µ m H2O2 for 24 h indicated that all compounds, except compound 20, were capable of restoring the viabilities of cells relative to the control (H2O2–treated) cells. The destructive effect of H2O2 on the adhesive behavior of the cells was almost totally restored by each of the derivatives. In addition, each of the derivatives except compounds 20 and 14 significantly reduced the extent of lipofuscin formation among the cells time‐dependently. Despite these activities, some of the derivatives, such as compounds 12 and 19, did not reduce the H2O2‐induced intracellular ROS (reactive oxygen species) levels, meaning that these two derivatives act through a different mechanism other than free‐radical scavenging activity. On the other hand, for those derivatives acting as anti‐oxidants, structure–activity evaluation clearly revealed that the hydroxyl group of vanillin ring is required for their free‐radical scavenging activities. Copyright © 2010 John Wiley & Sons, Ltd.
Colloidal platinum nanoparticles increase mitochondrial stress induced by resin composite components
Authors: Kachi Hanako , Noda Mamoru , Wataha John C. , Nakaoki Yasuko , Sano Hidehiko
Published: December 2010

Components of dental composites have been implicated as metabolic and oxidative stressors in cells. Antioxidant colloidal platinum nanoparticles (CPtN) could be useful as nanofillers that reduce cellular stress caused during placement and exposure to unpolymerized composite components. Yet, CPtN may have pro‐ or anti‐oxidative properties depending on the chemical environment in which they are used. This study investigated the ability of CPtN to mitigate mitochondrial or oxidative stress induced by camphorquinone (CQ) and dimethylaminoethyl methacrylate (DMAEM), two components of dental composites that initiate light‐activated addition polymerization. THP‐1 human monocytic cells were exposed to subtoxic concentrations of CQ and DMAEM, then blue light for 0–60 s. Mitochondrial and oxidative stress were estimated 0, 6, or 24 h after irradiation by measuring cellular ATP or GSH levels, respectively. CPtN (0–20 ppm) were added prior to blue light irradiation. Statistically significant effects were determined by ANOVA with Tukey post‐hoc analysis (α = 0.05). Light alone did not alter THP‐1 activity, but CQ and DMAEM induced 120% increases in cell ATP levels, which was increased further (50%) by CPtN. Blue light irradiation caused a 50% drop in ATP levels, which increased to 75% when CPtN were added. GSH levels were suppressed by CQ/DMAEM and blue light, and CPtN increased suppression by 20–30%. CPtN did not mitigate mitochondrial or oxidative stress in THP‐1, but amplified these stresses under the conditions tested. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Oxygen tension affects terminal differentiation of corneal limbal epithelial cells
Authors: Li Cheng , Yin Tingting , Dong Nuo , Dong Fei , Fang Xiaowei , Qu Yang‐Luowa , Tan Yehui , Wu Huping , Liu Zuguo , Li Wei
Published: December 2010

Oxygen concentration has been shown to be crucial in the proliferation and differentiation of various types of cells, while the impact of oxygen tension on the lineage commitment of epithelial cells remains elusive. In this study, we investigated the effect of hypoxia on the differentiation of corneal limbal epithelium using an ex vivo squamous metaplasia model. Under normoxic conditions when exposed to air, the hyperproliferation and abnormal epidermal‐like differentiation of human corneal limbal epithelium was induced, whereas when exposed to air under hypoxic conditions, although we observed augmented proliferation, the abnormal differentiation was inhibited. The Notch signaling pathway was activated in hypoxic cultures, whereas the p38 MAPK signaling pathway was downregulated. The addition of Notch inhibitor under hypoxic conditions restored the activation of p38 MAPK and resulted in the recidivation of limbal epithelial cells to epidermal‐like differentiation. Moreover, the epidermal‐like differentiation of rabbit limbal epithelial cells was also blocked under hypoxic conditions in corneal epithelial cell sheets engineered ex vivo. We concluded that hypoxia can prevent abnormal differentiation while enhancing the proliferation of corneal limbal epithelial cells. Hypoxia coupled with air exposure can be used in the tissue engineering of corneal limbal epithelium. J. Cell. Physiol. 226: 2429–2437, 2011. © 2010 Wiley‐Liss, Inc.
SNAr reaction of 2,5‐dinitrofuran: A mild and efficient method for the preparation of 2‐aryloxy‐5‐nitrofuran
Authors: Gavade Sandip , Padiya Kamlesh , Bajare Swapnil , Balaskar Ravi , Mane Dhananjay
Published: December 2010

2,5‐Dinitrofuran which can be easily prepared by nitration of 2‐nitrofuran, on phase transfer catalysed SNAr reaction with phenol gave good yield of 2‐aryloxy‐5‐nitrofuran. J. Heterocyclic Chem., (2011).