bluuebunny/crossref_metadata_2025 huggingface dataset:
A survey of image‐guided radiation therapy use in the United States
Authors: Simpson Daniel R. , Lawson Joshua D. , Nath Sameer K. , Rose Brent S. , Mundt Arno J. , Mell Loren K.
Published: May 2010

BACKGROUND:

Image‐guided radiation therapy (IGRT) is a novel array of in‐room imaging modalities that are used for tumor localization and patient setup in radiation oncology. The prevalence of IGRT use among US radiation oncologists is unknown.

METHODS:

A random sample of 1600 radiation oncologists was surveyed by Internet, e‐mail and fax regarding the frequency of IGRT use, clinical applications, and future plans for use. The definition of IGRT included imaging technologies that are used for setup verification or tumor localization during treatment.

RESULTS:

Of 1089 evaluable respondents, 393 responses (36.1%) were received. The proportion of radiation oncologists using IGRT was 93.5%. When the use of megavoltage (MV) portal imaging was excluded from the definition of IGRT, the proportion using IGRT was 82.3%. The majority used IGRT rarely (in <25% of their patients; 28.9%) or infrequently (in 25%‐50% of their patients; 33.1%). The percentages using ultrasound, video, MV‐planar, kilovoltage (kV)‐planar, and volumetric technologies were 22.3%, 3.2%, 62.7%, 57.7%, and 58.8%, respectively. Among IGRT users, the most common disease sites treated were genitourinary (91.1%), head and neck (74.2%), central nervous system (71.9%), and lung (66.9%). Overall, 59.1% of IGRT users planned to increase use, and 71.4% of nonusers planned to adopt IGRT in the future.

CONCLUSIONS:

IGRT is widely used among radiation oncologists. On the basis of prospective plans of responders, its use is expected to increase. Further research will be required to determine the safety, cost efficacy, and optimal applications of these technologies. Cancer 2010. © 2010 American Cancer Society.
Breast cancer in men in the United States
Authors: Harlan Linda C. , Zujewski Jo Anne , Goodman Marc T. , Stevens Jennifer L.
Published: May 2010

BACKGROUND:

Breast cancer in men is rare, so clinical trials are not practical. Recommendations suggest treating men who are diagnosed with breast cancer using the guidelines for postmenopausal women; however, to date, no population‐based studies have evaluated patterns of care.

METHODS:

To examine characteristics, treatment, and survival among men with newly diagnosed breast cancer, in 2003 and 2004, 512 men were identified from the Surveillance, Epidemiology and End Results Program. Data were reabstracted and therapy was verified through the patients' treating physicians.

RESULTS:

The majority of men (79%) were diagnosed through discovery of a breast lump or other signs/symptoms. Among men who had invasive disease, 86% underwent mastectomy, 37% received chemotherapy, and 58% received hormone therapy. In multivariate analysis, tumor size (P = .01) and positive lymph node status (P < .0001) were associated positively with the use of chemotherapy, whereas age group (P < .0001) and current unmarried status (P = .01) had negative associations. Among men who had invasive, estrogen receptor (ER)‐positive/borderline tumors, the use of tamoxifen or aromatase inhibitors (AIs) was associated with age group (P = .05). Among men who had invasive disease, cancer mortality was associated with tumor size (P < .0001). Among men with ER‐positive/borderline disease, increased cancer mortality was associated with tumor size (P < .0001), current unmarried status (P = .04), and decreased mortality with tamoxifen (P = .04).

CONCLUSIONS:

Tumor characteristics and marital status were the primary predictors of therapy and cancer mortality among men with breast cancer. Although AIs are not currently recommended, they are commonly prescribed. However, their use did not result in a decrease in cancer mortality. Research must examine the efficacy of AIs with and without gonadotropin‐releasing hormone analogues. Cancer 2010. © 2010 American Cancer Society.
Readability of Corporate Social Responsibility communication in Malaysia
Authors: Abu Bakar Aishah Sheikh , Ameer Rashid
Published: May 2010

This study examines the readability of Corporate Social Responsibility (CSR) communication (disclosure) for a sample of listed companies in Malaysia. The study employs Readability Formulae and finds that the extent of syntactic complexity making it difficult to comprehend the CSR communication of the listed companies varies from very difficult to fairly difficult. There is a relationship between the readability of the CSR communication and companies' performance. Our findings imply that management of poorly performing companies deliberately choose difficult language in CSR communication which supports the obfuscation hypothesis. Our study contributes significantly to research in CSR literature by enumerating the syntactical difficulties in the corporate annual CSR communications. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
Application of a fuzzy hierarchical model to the assessment of corporate social and environmental sustainability
Authors: Kouikoglou Vassilis S. , Phillis Yannis A.
Published: May 2010

Corporate responsibility has many facets. A corporation should organize its operations so that its environmental impact is minimal, its economic state is viable, labor conditions are good, and compliance with laws and regulations is satisfactory, among others. Corporate responsibility is intimately connected to corporate sustainability which expresses the economic, environmental, and social standing of a company. A responsible corporation embraces the principle of transparency of data pertaining to its performance and its policies and strives for strategies that enhance its sustainability. A model is presented that uses hierarchical fuzzy reasoning to assess corporate sustainability, given a number of inputs, called basic indicators. Inputs are normalized according to their sustainability status and then combined to obtain a sustainability index on [0, 1] for each facet of the corporation. A sensitivity analysis pinpoints the most important indicators affecting sustainability. Two case studies of multinational cement companies are presented in detail. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
Preparation and Li Storage Properties of Hierarchical Porous Carbon Fibers Derived from Alginic Acid
Authors: Wu Xing‐Long , Chen Li‐Li , Xin Sen , Yin Ya‐Xia , Guo Yu‐Guo , Kong Qing‐Shan , Xia Yan‐Zhi
Published: May 2010

One‐dimensional (1D) hierarchical porous carbon fibers (HPCFs) have been prepared by controlled carbonization of alginic acid fibers and investigated with scanning electron microscopy (SEM), transmission electron microscopy (TEM), X‐ray diffraction (XRD), X‐ray photoelectron spectroscopy (XPS), Raman spectroscopy, nitrogen adsorption–desorption isotherms, and electrochemical tests toward lithium storage. The as‐obtained HPCFs consist of a 3D network of nanosized carbon particles with diameters less than 10 nm and exhibit a hierarchical porous architecture composed of both micropores and mesopores. Electrochemical measurements show that HPCFs exhibit excellent rate capability and capacity retention compared with commercial graphite when employed as anode materials for lithium‐ion batteries. At the discharge/charge rate of 45 C, the reversible capacity of HPCFs is still as high as 80 mA h g−1 even after 1500 cycles, which is about five times larger than that of commercial graphite anode. The much improved electrochemical performances could be attributed to the nanosized building blocks, the hierarchical porous structure, and the 1D morphology of HPCFs.
Estimation of the location of dielectrics using a capacitor with widely spaced parallel electrodes and additional electrodes
Authors: Ohchi Masashi , Heigaku Sai , Tokushima Hisao , Furukawa Tatsuya
Published: May 2010

We have investigated the estimation of the location of a dielectric from the capacitance measured with widely spaced measurement electrodes provided with a shield and additional electrodes. In order to investigate the estimation method, a numerical technique was developed for calculating the capacitance between widely spaced measurement electrodes by finite element analysis. We discuss the new method for estimation of the locations of two dielectrics by using a capacitor with widely spaced parallel electrodes and additional electrodes. © 2010 Wiley Periodicals, Inc. Electr Eng Jpn, 172(3): 8–17, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20938
Decrease of primary electron number by NO, CO2, and SF6 mixing at breakdown in high‐pressure nitrogen
Authors: Kobayashi Fuminori , Hamano Syuichi , Iwao Toru , Yumoto Motoshige
Published: May 2010

It is reported that metastable excited particles affect the breakdown properties of nitrogen gas under low pressure extended over a long period. The purpose of this study is to confirm the influence of excited particles with the high‐pressure condition and to reduce the influence by excited particles. In the experiment, the delay time was measured and the number of primary electrons was evaluated. The test was carried out in N2/NO, N2/CO, N3/SP6, and N2/NO/SF6. The decrease rate of the primary electron number supplied by excited particles is higher in N2/NO than in N2/CO2. In N2/NO/SF6, it was more effective than two mixture gases. © 2010 Wiley Periodicals, Inc. Electr Eng Jpn, 172(3): 1–7, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20939
Modeling method for lead‐acid battery simulation using step changing current
Authors: Shimada Takae , Kurokawa Kosuke
Published: May 2010

This paper proposes a new simulation model of lead‐acid battery characteristics and a modeling method using step changing current. Battery simulation model is necessary to simulate the photovoltaic systems with batteries. The proposed model considers the nonlinearity of internal resistance and includes 36 constants that can be determined by only four cycles of charge–discharge tests. This paper offers a detailed description of the measurement method and modeling procedures of the battery characteristics. Results of verification tests using charge–discharge patterns of a hypothetical photovoltaic system show 1.0% of mean absolute error ratio of the simulated power at a battery temperature of $17 \ ^{\circ}\hbox{C}$. © 2010 Wiley Periodicals, Inc. Electr Eng Jpn, 172(3): 18–27, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20980
Nondaily behavior detection monitoring system for elderly people based on bayesian network representation of omnidirectional vision sensor
Authors: Seki Hirokazu , Tadakuma Susumu
Published: May 2010

This paper describes an unusual behavior detection system based on an omnidirectional vision sensor, as one of the important elements in realizing “Sensing and Robotic Support Rooms” for elderly people. Such support rooms are expected to be further developed in the future with advanced abilities to automatically recognize elderly people's actions and behavior patterns, to detect unusual patterns by using sensors, and to support their daily motions by using robotic manipulator control systems. The proposed monitoring system using an omnidirectional vision sensor automatically learns daily behavior patterns and detects unusual behavior patterns and actions by using the Bayesian network approach. The Bayesian network is constructed by using image feature values such as area and center‐of‐gravity values extracted from a captured image sequence, and the respective behavior patterns are represented as conditional probabilities. Unusual behavior patterns can be automatically detected on the basis of the low generation probability values. Experiments based on the investigation of elderly people's typical daily behavior patterns have shown the effectiveness of the proposed system. © 2010 Wiley Periodicals, Inc. Electr Eng Jpn, 172(3): 42–51, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20990
Fundamental characteristics of laboratory scale model DC microgrid to exchange electric power from distributed generators installed in residential houses
Authors: Kakigano Hiroaki , Hashimoto Takuya , Matsumura Yohei , Kurotani Takashi , Iwamoto Wataru , Miura Yushi , Ise Toshifumi , Momose Toshinari , Hayakawa Hideki
Published: May 2010

The DC microgrid is a novel power system using DC distribution in order to provide superhigh‐quality power. This DC system is suitable for DC‐output distributed generation and energy storage. In this research, we assumed one type of DC microgrid for residential houses (apartment house or housing complex). Each residence has a distributed generation facility such as a gas engine or fuel cell. These cogeneration facilities are connected to the DC power line, and the electricity from the cogeneration facilities can be shared among the residences. The hot water from the cogeneration facility is used in each residence. We constructed an experimental system based on this concept in our laboratory. We have studied the fundamental characteristics and the quality of the power supplied to the loads against several fluctuations or faults. The experimental results demonstrated that the system could supply high‐quality power to the loads despite sudden load variations and voltage sags of the utility grid. Afterwards, we moved the experimental system to an experimental apartment house (NEXT21). We studied the quality of power supply by using practical power lines, and confirmed that the system was also able to supply power to home appliances stably. © 2010 Wiley Periodicals, Inc. Electr Eng Jpn, 172(3): 28–41, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20996
Biosorption study of anionic dyes from aqueous solutions using Bacillus amyloliquefaciens
Authors: Yenikaya Cengiz , Atar Emrah , Olgun Asim , Atar Necip , İlhan Semra , Çolak Ferdağ
Published: May 2010

In this study, the biosorption of two commonly used dyes, namely Acid Blue 225 (AB 225) and Acid Blue 062 (AB 062), from aqueous solutions by Bacillus amyloliquefaciens biomass was studied in a batch system with respect to initial dye concentration, pH, adsorbent dosage, and contact time. The biomass exhibited maximum uptake at pH 1 due to its positive nature at acidic pH and the anionic nature of the dyes. Kinetic studies showed that the biosorption of dyes on biomass was a gradual process. An equilibrium was reached in 90 min for both dyes. The kinetic studies indicated that a pseudo‐second‐order rate equation was able to provide a realistic description of biosorption kinetics of the dyes. The constants obtained from the pseudo‐second‐order kinetic model at different temperatures were evaluated and the activation energies for the biosorption of AB 225 and AB 062 were found to be 13.52 and 13.62 kJ/mol, respectively. Isotherm studies pointed out that biosorption of dyes on biomass followed the Langmuir isotherm model. The adsorption capacity of biomass for AB 225 and AB 062 were 111.15 and 112.19 mg/g, respectively. Thermodynamic quantities that characterize the biosorption phenomena, i.e. enthalpy, entropy, and free energy change of the adsorption, were calculated leading to a conclusion on the efficiency of the properties of the biosorbent‐dye systems.
Impaired reelin processing and secretion by Cajal–Retzius cells contributes to granule cell dispersion in a mouse model of temporal lobe epilepsy
Authors: Duveau Venceslas , Madhusudan Amrita , Caleo Matteo , Knuesel Irene , Fritschy Jean‐Marc
Published: May 2010

Cajal–Retzius cells play a crucial role during ontogeny in regulating cortical lamination via release of reelin. In adult brain, they comprise small calretinin‐positive interneurons located in the marginal zone of the cerebral cortex and in the hippocampal fissure. Alterations of reelin signaling or expression have been involved in major neurological disorders, and they underlie granule cell dispersion (GCD) in mesial temporal lobe epilepsy (TLE). Here, we investigated in a mouse model of TLE the contribution of Cajal–Retzius cells to reelin production in epileptic hippocampus and the molecular mechanisms underlying GCD. Following unilateral intrahippocampal Kainic acid injection in adult mice to induce an epileptic focus, we observed that Cajal–Retzius cells gradually became strongly immunopositive for reelin, due to intracellular accumulation. This phenotype resembled the morphology of Cajal–Retzius cells in reeler Orleans (relnorl/orl) mice, which express a secretion‐deficient 310‐kDa reelin fragment. The possibility that GCD might result from abnormal reelin processing in Cajal–Retzius cells, leading to a lack of reelin secretion, was confirmed by KA injection in relnorl/+ mice, which induced severe GCD. Furthermore, Western blot analysis in KA‐treated wildtype mice revealed increased production of ∼300‐kDa reelin fragments, confirming abnormal proteolytic processing. This effect was not seen upon treatment with Botulinum neurotoxin E (BoNT/E), which prevents GCD in KA‐lesioned hippocampus by chronic blockade of synaptic transmission. Furthermore, BoNT/E blocked upregulation of TrkB in Cajal–Retzius cells, suggesting that production of truncated reelin in KA‐treated hippocampus is activity‐dependent and regulated by BDNF. Altogether, these data reveal that GCD results from abnormal reelin processing in Cajal–Retzius cells under the control of BDNF. Our findings highlight the critical role played by Cajal–Retzius cells for hippocampal neuronal reorganization in TLE. © 2010 Wiley‐Liss, Inc.
Preserved hippocampus activation in normal aging as revealed by fMRI
Authors: Persson Jonas , Kalpouzos Grégoria , Nilsson Lars‐Göran , Ryberg Mats , Nyberg Lars
Published: May 2010

The hippocampus is deteriorated in various pathologies such as Alzheimer's disease (AD) and such deterioration has been linked to memory impairment. By contrast, the structural and functional effects of normal aging on the hippocampus is a matter of debate, with some findings suggesting deterioration and others providing evidence of preservation. This constitutes a crucial question since many investigations on AD are based on the assumption that the deterioration of the hippocampus is the breaking point between normal and pathological aging. A growing number of fMRI studies specifically aimed at investigating hippocampal engagement in various cognitive tasks, notably memory tasks, but the results have been inconclusive. Here, we optimized the episodic face‐name paired‐associates task in order to test the functioning of the hippocampus in normal aging. Critically, we found no difference in the activation of the hippocampus between the young and a group of older participants. Analysis of individual patterns of activation substantiated this impression. Collectively, these findings provide evidence of preserved hippocampal functioning in normal aging. © 2010 Wiley‐Liss, Inc.
Damage of GABAergic neurons in the medial septum impairs spatial working memory and extinction of active avoidance: Effects on proactive interference
Authors: Pang Kevin C.H. , Jiao Xilu , Sinha Swamini , Beck Kevin D. , Servatius Richard J.
Published: May 2010

The medial septum and diagonal band (MSDB) are important in spatial learning and memory. On the basis of the excitotoxic damage of GABAergic MSDB neurons, we have recently suggested a role for these neurons in controlling proactive interference. Our study sought to test this hypothesis in different behavioral procedures using a new GABAergic immunotoxin. GABA‐transporter‐saporin (GAT1‐SAP) was administered into the MSDB of male Sprague–Dawley rats. Following surgery, rats were trained in a reference memory water maze procedure for 5 days, followed by a working memory (delayed match to position) water maze procedure. Other rats were trained in a lever‐press avoidance procedure after intraseptal GAT1‐SAP or sham surgery. Intraseptal GAT1‐SAP extensively damaged GABAergic neurons while sparing most cholinergic MSDB neurons. Rats treated with GAT1‐SAP were not impaired in acquiring a spatial reference memory, learning the location of the escape platform as rapidly as sham rats. In contrast, GAT1‐SAP rats were slower than sham rats to learn the platform location in a delayed match to position procedure, in which the platform location was changed every day. Moreover, GAT1‐SAP rats returned to previous platform locations more often than sham rats. In the active avoidance procedure, intraseptal GAT1‐SAP impaired extinction but not acquisition of the avoidance response. Using a different neurotoxin and behavioral procedures than previous studies, the results of this study paint a similar picture that GABAergic MSDB neurons are important for controlling proactive interference. © 2010 Wiley‐Liss, Inc.
Synthesis and Characterization of Dendrimeric Bridged Salen/Saloph Complexes and Investigation of Their Magnetic and Thermal Behaviors
Authors: Erdem Koç Ziya , Uysal Şaban
Published: May 2010

Eight new multinuclear FeIII and CrIII complexes involving the tetradentate Schiff bases N,N′‐bis(salicylidene)ethylenediamine (salenH2) or N,N′‐bis(salicylidene)benzene‐1,2‐diamine (salophH2) and the two new ligands 4,4′,4″,4′′′,4′′′′,4′′′″‐[1,3,5‐triazine‐2,4,6‐triyltris(nitrilomethylidyne‐4,1‐phenyleneoxy‐1,3,5‐triazine‐6,2,4‐triyldiimino)]hexakis[benzoic acid] (4) or 5,5′,5″,5′′′,5′′′′,5′′′″‐[1,3,5‐triazine‐2,4,6‐triyltris(nitrilomethylidyne‐4,1‐phenyleneoxy‐1,3,5‐triazine‐6,2,4‐triyldiimino)]hexakis[benzene‐1,3‐dicarboxylic acid] (5) were synthesized (Schemes 1 and 2) and characterized by means of 1H‐NMR and FT‐IR spectroscopy, elemental analysis, LC/MS analysis, AAS (atomic‐absorption spectrum) analysis, thermal analyses, and magnetic‐susceptibility measurements. The complexes can also be characterized as low‐spin distorted‐octahedral FeIII and CrIII complexes bridged by carboxylato moieties.
Four New Nor‐Diterpenoid Alkaloids from Aconitum brachypodum
Authors: Shen Yong , Zuo Ai‐Xue , Jiang Zhi‐Yong , Zhang Xue‐Mei , Wang Hong‐Ling , Chen Ji‐Jun
Published: May 2010

Four new C19‐nor‐diterpenoid alkaloids, named brachyaconitines A–D (1–4), were isolated from the roots of Aconitum brachypodum Diels. Their structures were elucidated as 3‐O‐acetyl‐20‐deethyl‐20‐formylaconitine (1), 3‐O‐acetyl‐19,20‐didehydro‐20‐deethylaconitine (2), 3‐O‐acetyl‐8‐de(acetyloxy)‐7,8,17,20‐tetradehydro‐20‐deethyl‐7,17‐secoaconitine (3), and 1‐O‐methylflavaconitine (4) by means of MS, IR, 1D‐ and 2D‐NMR analyses. The structure of compound 1 was confirmed by an X‐ray diffraction experiment.
A New Isofuranonaphthalenone and Benzopyrans from the Endophytic Fungus Nodulisporium sp. A4 from Aquilaria sinensis
Authors: Wu Zheng‐Chao , Li Dong‐Li , Chen Yu‐Chan , Zhang Wei‐Min
Published: May 2010

A new isofuranonaphthalenone, (7R*,8S*)‐3,6,7,8‐tetrahydro‐4,7,8‐trihydroxynaphtho[2,3‐c]furan‐5(1H)‐one (1), and a new benzopyran, (2R*,4R*)‐3,4‐dihydro‐4‐methoxy‐2‐methyl‐2H‐1‐benzopyran‐5‐ol (2), together with four known related analogs, 3–6, were isolated from the culture of Nodulisporium sp. A4, an endophytic fungus from the stem of Aquilaria sinensis (Lour.) Gilg. The structures of the isolated compounds were determined by extensive analysis of their spectroscopic data as well as by comparison with literature reports. The isolated compounds 1–6 were evaluated for their cytotoxic activities against the NCI‐H460 and SF‐268 tumor cell lines.
Fluorescence Sensing and Selective Binding of a Novel 4,4′‐Sulfonyldianiline‐Bridged Bis(β‐cyclodextrin) for Bile Salts
Authors: Zhao Yan , Yang Yong Cun , Chi Shao Ming , Shi Hao , Zhao Yong , Zhu Hong You , Li Qi Lin , Wang Yu Fei
Published: May 2010

A novel 4,4′‐sulfonyldianiline‐bridged bis(β‐cyclodextrin (CD)) 2 was synthesized, and its complex stability constants (Ks) for the 1 : 1 inclusion complexation with bile salts, i.e., cholate (CA), deoxycholate (DCA), glycocholate (GCA), and taurocholate (TCA) have been determined in phosphate buffer (pH 7.2) at 25° by fluorescence spectroscopy. The result indicated that 2 can act as efficient fluorescent sensor and display remarkable fluorescence enhancement upon addition of optically inert bile salts. Structures of the inclusion complexes between bile salts and 2 were elucidated by 2D‐NMR experiments, indicating that the anionic tail group and the D ring of bile salts penetrate into one CD cavity of 2 from the wide opening deeply, while the phenyl moiety of the CD linker is partially self‐included in the other CD cavity to form a host–linker–guest binding mode. As compared with native β‐CD 1 upon complexation with bile salts, bis(β‐CD) 2 enhances the binding ability and molecular selectivity. Typically, 2 gives the highest Ks value of 26200 M−1 for the complexation with CA, which may be ascribed to the simultaneous contributions of hydrophobic, H‐bond, and electrostatic interactions. These phenomena are discussed from the viewpoints of multiple recognition and induce‐fit interactions between host and guest.
Three New Caged Prenylxanthones from Garcinia bracteata
Authors: Na Zhi , Hu Hua‐Bin , Fan Qing‐Fei
Published: May 2010

Three new caged prenylxanthones (xanthone=9H‐xanthen‐9‐one), named neobractatin (1), 3‐O‐methylneobractatin (2), and 3‐O‐methylbractatin (3), along with eight known compounds, were isolated from the twig of Garcinia bracteata. The structures of the new compounds were elucidated on the basis of 1D‐ and 2D‐NMR experiments, including HMBC, HSQC, 1H,1H‐COSY, and ROESY, as well as HR‐MS analysis.
Three New Homoisoflavanones from the Ophiopogon japonicusKer‐Gawler (Liliaceae)
Authors: Wang Yongyi , Xu Jinzhong , Zhang Lei , Qu Haibin
Published: May 2010

Three new homoisoflavanones, 1–3, together with a known one, 4, were obtained from the AcOEt extract of the tuberous roots of Ophiopogon japonicus (Liliaceae). They were identified as (3R)‐2,3‐dihydro‐7‐hydroxy‐5‐methoxy‐3‐(4‐methoxybenzyl)‐6,8‐dimethyl‐4H‐chromen‐4‐one (1), (3R)‐3‐(1,3‐benzodioxol‐5‐ylmethyl)‐2,3‐dihydro‐7‐hydroxy‐5‐methoxy‐6,8‐dimethyl‐4H‐chromen‐4‐one (2), (3R)‐3‐(1,3‐benzodioxol‐5‐ylmethyl)‐2,3‐dihydro‐7‐hydroxy‐5‐methoxy‐6‐methyl‐4H‐chromen‐4‐one (3), and ophiopogonanone A (4). Their structures were determined on the basis of extensive NMR‐spectroscopic and mass‐spectrometric analyses. The three new compounds are rare homoisoflavanones which contain a MeO group at C(5). Compounds 1 and 2 showed weak cytotoxicity against the HepG2 (human hepatoma G2), KB (human oral epidermoid carcinoma), and MCF‐7 (human breast adenocarcinoma) cell lines in an MTT assay. Compound 3 exhibited weak cytotoxicity against HepG2 and MCF‐7, and moderate cytotoxicity against KB cell lines. Compound 4 showed moderate cytotoxicity against HepG2, KB, and MCF‐7 cell lines.
A New Coumarin and Carbazole Alkaloid from Clausena vestita D. D. Tao
Authors: Shi Xiao‐Jing , Ye Guan , Tang Wen‐Jie , Zhao Wei‐Min
Published: May 2010

Phytochemical investigation of the EtOH extract of Clausena vestita D. D. Tao led to the isolation of one new coumarin, clauslactone U (1), and one new carbazole alkaloid, clauszoline N (2), together with 28 known compounds. The structures of these compounds were established by using MS and 1D‐ and 2D‐NMR techniques, and by comparison with known analogues.
Perturbations of an Acetone‐Based Briggs–Rauscher System by α‐Tocopherol (Vitamin E)
Authors: Cervellati Rinaldo , Furrow Stanley D. , Greco Emanuela , Höner Kerstin , Venturi Maria Livia
Published: May 2010

The malonic acid (MA)‐based oscillating Briggs–Rauscher reaction (BR) in batch mode has been shown to be sensitive to various hydrophilic polyphenol antioxidants. Several of these have been shown to cause cessation of oscillations for a period of time before a restart occurs. The length of time before oscillations restart is related to the type of antioxidant and its concentration. Procedures have been devised to use this method as a tool for measuring antioxidant activity from pure compounds and from extracts of natural sources. The antioxidant activity has been related to the reaction of the antioxidants with HOO. radicals present in the oscillating system. Vitamin E (α‐tocopherol), a typical highly lipophilic antioxidant containing an phenolic OH group, is soluble in acetone that also is a suitable substrate for the BR reaction. Perturbations of a highly concentrated acetone‐based BR oscillator by acetonic solutions of vitamin E were studied. The inhibitory effects were found similar to those provoked by hydrophilic polyphenols in the MA‐based oscillator, but to obtain reasonable inhibition times, the concentration of vitamin E must be at the mM level instead μM. However, there is a region of concentrations where there is a nearly linear relation between concentration and inhibition time. A comparison with a hydrophilic diphenol (2,6‐dihydroxybenzoic acid) in the acetone‐based oscillator showed that the inhibitory reaction is much slower in this system than in the MA one. We were able to model the perturbations by vitamin E assuming its reaction with HOO. radicals by using the FCA mechanism previously reported with some little modifications.
Oligonucleotide Analogues with Integrated Bases and Backbones. Part 25
Authors: Bogliotti Nicolas , Vasella Andrea
Published: May 2010

The ability of A*[s]U dinucleosides to gel organic solvents and water is modulated by changing the nature of the substituents at OC(2′) and OC(3′), as evidenced by comparing the gelation of the dinucleosides 7–9 and the properties of the gels. A mere extension of the hydrophobic moiety, by replacing the isopropylidene groups of 2 by cyclohexylidene groups, as in 7, has a small effect, while changing the conformation of the ribose ring and reducing the size of the hydrophobic moiety, as in 8, has a strong effect on the scope of gelation, the minimum gelation concentration, as low as 0.07% for pentanol and decanol, and the properties of the gel. The fully deprotected dinucleoside 9 gels water at a minimal gelation concentration of 0.6%. A TEM of the corresponding xerogel shows the formation of fibers with a diameter of ca. 30 to 90 nm.
Regulation of circulating sclerostin levels by sex steroids in women and in men
Authors: Mödder Ulrike IL , Clowes Jackie A , Hoey Kelley , Peterson James M , McCready Louise , Oursler Merry Jo , Riggs B Lawrence , Khosla Sundeep
Published: May 2010

Sex steroids are important regulators of bone turnover, but the mechanisms of their effects on bone remain unclear. Sclerostin is an inhibitor of Wnt signaling, and circulating estrogen (E) levels are inversely associated with sclerostin levels in postmenopausal women. To directly test for sex steroid regulation of sclerostin levels, we examined effects of E treatment of postmenopausal women or selective withdrawal of E versus testosterone (T) in elderly men on circulating sclerostin levels. E treatment of postmenopausal women (n = 17) for 4 weeks led to a 27% decrease in serum sclerostin levels [versus +1% in controls (n = 18), p < .001]. Similarly, in 59 elderly men, we eliminated endogenous E and T production and studied them under conditions of physiologic T and E replacement, and then following withdrawal of T or E, we found that E, but not T, prevented increases in sclerostin levels following induction of sex steroid deficiency. In both sexes, changes in sclerostin levels correlated with changes in bone-resorption, but not bone-formation, markers (r = 0.62, p < .001, and r = 0.33, p = .009, for correlations with changes in serum C-terminal telopeptide of type 1 collagen in the women and men, respectively). Our studies thus establish that in humans, circulating sclerostin levels are reduced by E but not by T. Moreover, consistent with recent data indicating important effects of Wnts on osteoclastic cells, our findings suggest that in humans, changes in sclerostin production may contribute to effects of E on bone resorption. © 2011 American Society for Bone and Mineral Research.
Elevated serum lactate dehydrogenase isoenzymes and aspartate transaminase distinguish Albers-Schönberg disease (Chloride Channel 7 Deficiency Osteopetrosis) among the sclerosing bone disorders
Authors: Whyte Michael P , Kempa Lydia G , McAlister William H , Zhang Fan , Mumm Steven , Wenkert Deborah
Published: May 2010

Osteopetrosis (OPT) refers to the consequences of generalized failure of skeletal resorption during growth. Most cases are explained by loss-of-function mutation within the genes that encode either chloride channel 7 (CLCN7) or a vacuolar proton pump subunit (TCIRG1), each compromising acid secretion by osteoclasts. Patients suffer fractures and sometimes cranial nerve entrapment and insufficient medullary space for hematopoiesis. In 1996, we reported that a high serum level of the brain isoenzyme of creatine kinase (BB-CK), the CK of osteoclasts, characterizes OPT dueamong the sclerosing bone disorders (J Clin Endocrinol Metab. 1996;11:1438). Now, we show that elevation in serum of multiple lactate dehydrogenase (LDH) isoenzymes with aspartate transaminase (AST) distinguishes autosomal dominant OPT due to loss-of-function mutation in CLCN7 [Albers-Schönberg disease (A-SD)] among these conditions. Serum total LDH and AST levels as high as 3× and 2×, respectively, the upper limits of normal for age-appropriate controls, were persistent and essentially concordant in A-SD. Serum LDH was elevated in 7 of 9 children and in the 2 adults studied with A-SD. LDH isoenzyme quantitation showed excesses of LDH-2, -3, and -4. Neither total LDH nor AST increases were found in other forms of OPT, including bisphosphonate-induced OPT, or in 41 children and 6 adults representing 20 additional sclerosing bone disorders. Serum TRACP-5b and BB-CK also were markedly elevated in A-SD. Hence, high serum levels of several enzymes characterize A-SD. Elevated serum LDH isoenzymes and AST indicate a disturbance (of uncertain clinical significance) within multiple extraosseous tissues when there is CLCN7 deficiency. © 2010 American Society for Bone and Mineral Research.
Dysosteosclerosis presents as an “Osteoclast-Poor” form of osteopetrosis: Comprehensive investigation of a 3-year-old girl and literature review
Authors: Whyte Michael P , Wenkert Deborah , McAlister William H , Novack Deborah V , Nenninger Angie R , Zhang Xiafang , Huskey Margaret , Mumm Steven
Published: May 2010

Dysosteosclerosis (DSS), an extremely rare dense bone disease, features short stature and fractures and sometimes optic atrophy, cranial nerve palsy, developmental delay, and failure of tooth eruption in infancy or early childhood consistent with osteopetrosis (OPT). Bone histology during childhood shows unresorbed primary spongiosa from deficient osteoclast action. Additionally, there is remarkable progressive flattening of all vertebrae and, by adolescence, paradoxical metaphyseal osteopenia with thin cortical bone. Reports of consanguinity indicate autosomal recessive inheritance, yet more affected males than females suggest X-linked recessive inheritance. We investigated a nonconsanguineous girl with DSS. Osteosclerosis was discovered at age 7 months. Our studies, spanning ages 11 to 44 months, showed weight at approximately 50th percentile, and length diminishing from approximately 30th percentile to –2.3 SD. Head circumference was +4 SD. The patient had frontal bossing, blue sclera, normal teeth, genu valgum, and unremarkable joints. Radiographs showed orbital and facial sclerosis, basilar thickening, bone-in-bone appearance of the pelvis, sclerotic long bone ends, and fractures of ribs and extremities. Progressive metaphyseal widening occurred as vertebrae changed from ovoid to flattened and became beaked anteriorly. A hemogram was normal. Consistent with OPT, serum parathyroid hormone (PTH) concentrations reflected dietary calcium levels. Serum bone alkaline phosphatase, osteocalcin, and TRACP-5b were subnormal. The iliac crest contained excessive primary spongiosa and no osteoclasts. No mutations were identified in the splice sites or exons for the genes encoding chloride channel 7, T-cell immune regulator 1, OPT-associated transmembrane protein 1, and monocyte colony-stimulating factor (M-CSF) and its receptor C-FMS, ANKH, OPG, RANK, and RANKL. Genomic copy-number microarray was unrevealing. Hence, DSS is a distinctive OPT of unknown etiology featuring osteoclast deficiency during early childhood. How osteopenia follows is an enigma of human skeletal pathobiology. © 2010 American Society for Bone and Mineral Research.
Mutations of SQSTM1 are associated with severity and clinical outcome in paget disease of bone
Authors: Visconti Micaela Rios , Langston Anne L , Alonso Nerea , Goodman Kirsteen , Selby Peter L , Fraser William D , Ralston Stuart H
Published: May 2010

Paget disease of bone (PDB) is a common disorder characterized by increased bone turnover at one of more sites throughout the skeleton. Genetic factors play an important role in the pathogenesis of PDB, and the most important predisposing gene is SQSTM1, which is mutated in about 10% of patients. Here we investigated the relationship between SQSTM1 mutation status, disease severity, and clinical outcome in 737 patients who took part in a randomized study of two different management strategies for the disease. Mutations of SQSTM1 were detected in 80 of 737 (10.9%) patients. Mutation carriers had an earlier age at diagnosis (59.4 ±11.5 versus 65.0 ± 10.4 years, p < .0001) and a greater number of affected bones (3.2 ± 1.2 versus 2.1 ± 1.2, p < .001) and more commonly required orthopedic surgery (26.2% versus 16.1%, p = .024) and bisphosphonate therapy (86.3% versus 75.2%, p = .01) than those without mutations. Quality of life, as assessed by the short-form-36 (SF36) physical summary score, was significantly reduced in carriers (34.0 ± 11.3 versus 37.1 ± 11.4, p = .036). During the study, fractures were more common in carriers (12.5% versus 5.3%, p = .011), although most of these occurred in unaffected bone. This study demonstrates that SQSTM1 mutations are strongly associated with disease severity and complications of PDB. Genetic testing for SQSTM1 mutations may be of value in identifying individuals at risk of developing severe disease, but further studies will be required to determine if a program of genetic testing and early intervention in these individuals would be cost-effective or be of benefit in preventing these complications. © 2010 American Society for Bone and Mineral Research.
Adverse interaction of low-calcium diet and low 25(OH)D levels on lumbar spine mineralization in late-pubertal girls
Authors: Esterle Laure , Nguyen Minh , Walrant-Debray Odile , Sabatier Jean-Pierre , Garabedian Michèle
Published: May 2010

No consensus has been reached on the serum 25-hydroxyvitamin D [25(OH)D] levels required to ensure optimal bone health around menarche. We searched for a possible interaction of 25(OH)D levels and calcium intake on lumbar spine mineralization and on biologic features of bone metabolism in healthy late-pubertal girls. Lumbar spine parameters (ie, area, mineral content, and density) and calcium intake were evaluated in 211 healthy white adolescent girls at pubertal stages IV–V (11 to 16.9 years), together with biologic markers of calcium and bone metabolism and with International External Quality Assessment Scheme for Vitamin D Metabolite (DEQAS)–validated serum 25(OH)D levels. A high prevalence of 25(OH)D levels ≤ 30 nmol/L (41%), ≤40 nmol/L (61%), and ≤50 nmol/L (70%) was found during winter–spring. Parathyroid hormone (PTH) levels were inversely associated with 25(OH)D levels (p = .0021). In contrast, lumbar spine mineral content and density were not associated with 25(OH)D, excepted when calcium intake was below 600 mg/day (p = .0081). Girls with such low calcium intake and 25(OH)D levels of 40 nmol/L or less (9% of the cohort) had a 0.4 to 0.7 SD lower mean areal bone mineral density Z-score than girls with higher calcium intake and/or higher 25(OH)D status. The adverse association between lumbar spine mineralization and combined calcium deficiency–low 25(OH)D levels remained significant in the 91 girls who could be followed over 4 years after their initial evaluation. We conclude that low 25(OH)D levels (≤40 nmol/L) are observed frequently during winter–spring in late-pubertal European girls, which may exacerbate the negative impact of calcium deficiency on lumbar spine mineralization. © 2010 American Society for Bone and Mineral Research.
Sclerostin antibody treatment enhances metaphyseal bone healing in rats
Authors: Agholme Fredrik , Li Xiaodong , Isaksson Hanna , Ke Hua Zhu , Aspenberg Per
Published: May 2010

Sclerostin is the product of the SOST gene. Loss-of-function mutations in the SOST gene result in a high-bone-mass phenotype, demonstrating that sclerostin is a negative regulator of bone mass. Primarily expressed by osteocytes in bone, sclerostin is reported to bind the LRP5/6 receptor, thereby antagonizing canonical Wnt signaling and negatively regulating bone formation. We therefore investigated whether systemic administration of a sclerostin-neutralizing antibody would increase the regeneration of traumatized metaphyseal bone in rats. Young male rats had a screw inserted in the proximal tibia and were divided into six groups given 25 mg/kg of sclerostin antibody or control twice a week subcutaneously for 2 or 4 weeks. In four groups, the screws were tested for pull-out strength. At the time of euthanasia, a similar screw also was inserted in the contralateral tibia and pull-out tested immediately. Sclerostin antibody significantly increased the pull-out force by almost 50% compared with controls after 2 and 4 weeks. Also, the screws inserted at the time of euthanasia showed increased pull-out force. Micro–computed tomography (µCT) of the remaining two groups showed that the antibody led to a 30% increase in bone volume fraction in a region surrounding the screw. There also was a general increase in trabecular thickness in cancellous bone. Thus, as measured by the amount of bone and its mechanical resistance, the sclerostin antibody increased bone formation during metaphyseal repair but also in untraumatized bone. © 2010 American Society for Bone and Mineral Research.
Identification of a gene module associated with BMD through the integration of network analysis and genome-wide association data
Authors: Farber Charles R
Published: May 2010

Bone mineral density (BMD) is influenced by a complex network of gene interactions; therefore, elucidating the relationships between genes and how those genes, in turn, influence BMD is critical for developing a comprehensive understanding of osteoporosis. To investigate the role of transcriptional networks in the regulation of BMD, we performed a weighted gene coexpression network analysis (WGCNA) using microarray expression data on monocytes from young individuals with low or high BMD. WGCNA groups genes into modules based on patterns of gene coexpression. and our analysis identified 11 gene modules. We observed that the overall expression of one module (referred to as module 9) was significantly higher in the low-BMD group (p = .03). Module 9 was highly enriched for genes belonging to the immune system–related gene ontology (GO) category “response to virus” (p = 7.6 × 10−11). Using publically available genome-wide association study data, we independently validated the importance of module 9 by demonstrating that highly connected module 9 hubs were more likely, relative to less highly connected genes, to be genetically associated with BMD. This study highlights the advantages of systems-level analyses to uncover coexpression modules associated with bone mass and suggests that particular monocyte expression patterns may mediate differences in BMD. © 2010 American Society for Bone and Mineral Research.
Inhibition of TGF-β signaling by 1D11 antibody treatment increases bone mass and quality in vivo
Authors: Edwards James R , Nyman Jeffry S , Lwin Seint T , Moore Megan M , Esparza Javier , O'Quinn Elizabeth C , Hart Andrew J , Biswas Swati , Patil Chetan A , Lonning Scott , Mahadevan-Jansen Anita , Mundy Gregory R
Published: May 2010

Transforming growth factor β (TGF-β) is an abundant bone matrix protein that influences osteoblast and osteoclast interactions to control bone remodeling. As such, TGF-β represents an obvious pharmacologic target with the potential to regulate both bone formation and resorption to improve bone volume and strength. To investigate the skeletal effect of TGF-β inhibition in vivo, we used an antibody (1D11) specifically directed at all three isoforms of TGF-β. Normal mice were treated with 1D11 or control antibody (4 weeks), and cortical and trabecular bone was assessed by micro–computed tomographic (µCT) scanning. Bone volume and cellular distribution were determined by histomorphometric analysis of vertebrae and long bones. Also, whole-bone strength was assessed biomechanically by three-point bend testing, and tissue-level modulus and composition were analyzed by nanoindentation and Raman microspectroscopy, respectively. TGF-β blockade by 1D11 increased bone mineral density (BMD), trabecular thickness, and bone volume by up to 54%, accompanied by elevated osteoblast numbers and decreased osteoclasts. Biomechanical properties of bone also were enhanced significantly by 1D11 treatment, with increased bending strength and tissue-level modulus. In addition, Raman microspectroscopy demonstrated that 1D11-mediated TGF-β inhibition in the bone environment led to an 11% increase in the mineral-to-collagen ratio of trabecular bone. Together these studies demonstrate that neutralizing TGF-β with 1D11 increases osteoblast numbers while simultaneously decreasing active osteoclasts in the marrow, resulting in a profound increase in bone volume and quality, similar to that seen in parathyroid hormone (PTH)–treated rodent studies. © 2010 American Society for Bone and Mineral Research.
Time‐dependent quantum study of H(2S) + FO(2Π) → OH(2Π) + F(2P) reaction on the 13A′ and 13A″ states
Authors: Gogtas Fahrettin , Tutuk Rukiye , Kurban Mustafa
Published: May 2010

The dynamics of the H(2S) + FO(2Π) → OH(2Π) + F(2P) reaction on the adiabatic potential energy surface of the 13A′ and 13A″ states is investigated. The initial state selected reaction probabilities for total angular momentum J = 0 have been calculated by using the quantum mechanical real wave packet method. The integral cross sections and initial state selected reaction rate constants have been obtained from the corresponding J = 0 reaction probabilities by means of the simple J‐Shifting technique. The initial state‐selected reaction probabilities and reaction cross section do not manifest any sharp oscillations and the initial state selected reaction rate constants are sensitive to the temperature. © 2010 Wiley Periodicals, Inc. J Comput Chem 2010