bluuebunny/crossref_metadata_2025 huggingface dataset:
Denosumab treatment for fibrous dysplasia
Authors: Boyce Alison M , Chong William H , Yao Jack , Gafni Rachel I , Kelly Marilyn H , Chamberlain Christine E , Bassim Carol , Cherman Natasha , Ellsworth Michelle , Kasa-Vubu Josephine Z , Farley Frances A , Molinolo Alfredo A , Bhattacharyya Nisan , Collins Michael T
Published: March 2012

Fibrous dysplasia (FD) is a skeletal disease caused by somatic activating mutations of the cyclic adenosine monophosphate (cAMP)-regulating protein, α-subunit of the Gs stimulatory protein (Gsα). These mutations lead to replacement of normal bone by proliferative osteogenic precursors, resulting in deformity, fracture, and pain. Medical treatment has been ineffective in altering the disease course. Receptor activator of NF-κB ligand (RANKL) is a cell-surface protein involved in many cellular processes, including osteoclastogenesis, and is reported to be overexpressed in FD-like bone cells. Denosumab is a humanized monoclonal antibody to RANKL approved for treatment of osteoporosis and prevention of skeletal-related events from bone metastases. We present the case of a 9-year-old boy with severe FD who was treated with denosumab for a rapidly expanding femoral lesion. Immunohistochemical staining on a pretreatment bone biopsy specimen revealed marked RANKL expression. He was started on monthly denosumab, with an initial starting dose of 1 mg/kg and planned 0.25 mg/kg dose escalations every 3 months. Over 7 months of treatment he showed marked reduction in pain, bone turnover markers (BTMs), and tumor growth rate. Denosumab did not appear to impair healing of a femoral fracture that occurred while on treatment. With initiation of treatment he developed hypophosphatemia and secondary hyperparathyroidism, necessitating supplementation with phosphorus, calcium, and calcitriol. BTMs showed rapid and sustained suppression. With discontinuation there was rapid and dramatic rebound of BTMs with cross-linked C-telopeptide (reflecting osteoclast activity) exceeding pretreatment levels, accompanied by severe hypercalcemia. In this child, denosumab lead to dramatic reduction of FD expansion and FD-related bone pain. Denosumab was associated with clinically significant disturbances of mineral metabolism both while on treatment and after discontinuation. Denosumab treatment of FD warrants further study to confirm efficacy and determine potential morbidity, as well as to determine the mechanism of RANKL in the pathogenesis of FD and related bone marrow stromal cell diseases. © 2012 American Society for Bone and Mineral Research.
miR-182 is a negative regulator of osteoblast proliferation, differentiation, and skeletogenesis through targeting FoxO1
Authors: Kim Kyoung Min , Park Su Jin , Jung Seung-Hyun , Kim Eun Jin , Jogeswar Gadi , Ajita Jami , Rhee Yumie , Kim Cheol-Hee , Lim Sung-Kil
Published: March 2012

Uncontrolled oxidative stress impairs bone formation and induces age-related bone loss in humans. The FoxO family is widely accepted to play an important role in protecting diverse cells from reactive oxygen species (ROS). Activation of FoxO1, the main FoxO in bone, stimulates proliferation and differentiation as well as inhibits apoptosis of osteoblast lineage cells. Despite the important role of FoxO1, little is known about how FoxO1 expression in bone is regulated. Meanwhile, several recent studies reported that microRNAs (miRNAs) could play a role in osteoblast differentiation and bone formation by targeting various transcriptional factors. Here, we identified one additional crucial miRNA, miR-182, which regulates osteoblastogenesis by repressing FoxO1 and thereby negatively affecting osteogenesis. Overexpression of miR-182 in osteoblast lineage cells increased cell apoptosis and inhibited osteoblast differentiation, whereas in vivo overexpression of miR-182 in zebrafish impaired bone formation. From in silico analysis and validation experiments, FoxO1 was identified as the target of miR-182, and restoration of FoxO1 expression in miR-182–overexpressing osteoblasts rescued them from the inhibitory effects of miR-182. These results indicate that miR-182 functions as a FoxO1 inhibitor to antagonize osteoblast proliferation and differentiation, with a subsequent negative effect on osteogenesis. To treat bone aging, an antisense approach targeting miR-182 could be of therapeutic value. © 2012 American Society for Bone and Mineral Research.
On Balanced Optimal Optical Orthogonal Codes
Authors: Zhao Hengming
Published: March 2012

Variable‐weight optical orthogonal codes (OOCs) were introduced by G.‐C. Yang for multimedia optical CDMA systems with multiple quality of service (QoS) requirement. In this paper, by using incomplete difference matrices and perfect relative difference families, a balanced ‐OOC is obtained for every positive integer .
Further Results on Large Sets of Resolvable Idempotent Latin Squares
Authors: Zhou Junling , Chang Yanxun
Published: March 2012

An idempotent Latin square of order v is called resolvable and denoted by RILS(v) if the off‐diagonal cells can be resolved into disjoint transversals. A large set of resolvable idempotent Latin squares of order v, briefly LRILS(v), is a collection of RILS(v)s pairwise agreeing on only the main diagonal. In this paper, it is established that there exists an LRILS(v) for any positive integer , except for , and except possibly for .
Use ofDesulfovibrioandEscherichia coliPd‐nanocatalysts in reduction of Cr(VI) and hydrogenolytic dehalogenation of polychlorinated biphenyls and used transformer oil
Authors: Macaskie Lynne E. , Humphries Andrea C. , Mikheenko Iryna P. , Baxter‐Plant Victoria S. , Deplanche Kevin , Redwood Mark D. , Bennett James A. , Wood Joe
Published: March 2012

BACKGROUND:Desulfovibriospp. biofabricate metallic nanoparticles (e.g. ‘Bio‐Pd’) which catalyse the reduction of Cr(VI) to Cr(III) and dehalogenate polychlorinated biphenyls (PCBs).Desulfovibriospp. are anaerobic and produce H2S, a potent catalyst poison, whereasEscherichia colican be pre‐grown aerobically to high density, has well defined molecular tools, and also makes catalytically‐active ‘Bio‐Pd’. The first aim was to compare ‘Bio‐Pd’ catalysts made byDesulfovibriospp. andE. coliusing suspended and immobilized catalysts. The second aim was to evaluate the potential for Bio‐Pd‐mediated dehalogenation of PCBs in used transformer oils, which preclude recovery and re‐use.

RESULTS:Catalysis via Bio‐PdD.desulfuricansand Bio‐PdE.coliwas compared at a mass loading of Pd:biomass of 1:3 via reduction of Cr(VI) in aqueous solution (immobilized catalyst) and hydrogenolytic release of Cl−from PCBs and used transformer oil (catalyst suspensions). In both cases Bio‐PdD.desulfuricansoutperformed Bio‐PdE.coliby ∼3.5‐fold, attributable to a ∼3.5‐fold difference in their Pd‐nanoparticle surface areas determined by magnetic measurements (Bio‐PdD.desulfuricans) and by chemisorption analysis (Bio‐PdE.coli). Small Pd particles were confirmed onD. desulfuricansand fewer, larger ones onE. colivia electron microscopy. Bio‐PdD.desulfuricans‐mediated chloride release from used transformer oil (5.6 ± 0.8 µg mL−1) was comparable with that observed using several PCB reference materials.

CONCLUSIONS:At a loading of 1:3 Pd:biomass Bio‐PdD.desulfuricansis 3.5‐fold more active than Bio‐PdE.coli, attributable to the relative catalyst surface areas reflected in the smaller nanoparticle sizes of the former. This study also shows the potential of Bio‐PdD.desulfuricansto remediate used transformer oil. Copyright © 2012 Society of Chemical Industry
Biological conversion of CO2 to CH4 using hydrogenotrophic methanogen in a fixed bed reactor
Authors: Lee Jun Chul , Kim Jae Hyung , Chang Won Seok , Pak Daewon
Published: March 2012

BACKGROUND: Biological conversion of CO2 to useful carbonic compounds such as methane is a potentially attractive technology for reducing its concentration in the atmosphere. One of the advantages of this technology over chemical conversion is that it requires much lower energy for reduction of CO2. In this article, biological conversion of CO2 to CH4 using hydrogenotrophic methanogens was examined in a fixed bed reactor inoculated with anaerobic mixed culture from the anaerobic digestor of a sewage treatment plant.

RESULTS: Methane formation commenced on the first day of operation of the fixed bed reactor. CO2 fed to the reactor was reduced with H2 by hydrogenotrophic methanogens. The feed ratio of CO2 to H2 is an important factor in determining the conversion rate of CO2. When the feed ratio is 4, methane is produced at the expected rate according to the chemical equation. The CO2 conversion rate was 100% when the gas retention time was 3.8 h in the fixed bed reactor.

CONCLUSIONS: The results show that the fixed bed reactor employing hydrogentrophic methanogens has the potential to be effective in converting CO2 to CH4 with a conversion rate of 100% at 3.8 h retention time. Copyright © 2012 Society of Chemical Industry
Caveolin‐1 and mitochondrial alterations in regenerating rat liver
Authors: Mastrodonato Maria , Portincasa Piero , Mentino Donatella , Rossi Roberta , Resta Leonardo , Ferri Domenico , Liquori Giuseppa Esterina
Published: March 2012

The liver has a remarkable ability to regenerate after partial hepatectomy (PH), although the factors governing such ability are still poorly understood. During the prereplicative phase of the regeneration, ultrastructural alterations of periportal hepatocytes were seen, including mitochondrial swelling, abnormal accumulation of lipids, and myelin figures which could lead to the formation of lipid droplets. As it has been hypothesized that caveolin‐1 is involved in lipidogenesis and in mitochondrial homeostasis, we aimed to study the subcellular distribution of caveolin‐1 in hepatocytes at an early stage following PH. Liver samples were processed for light and electron microscopy at 0 h, 24 h, and 96 h after PH. The expression and subcellular distribution of caveolin‐1 was assessed by immunohistochemical and immunocytochemical techniques. Following PH, at 24 h, membranes of altered mitochondria of periportal hepatocytes exhibited significant decrease of caveolin‐1 expression compared with control. Myelin figures showing high expression of caveolin‐1 were also seen. At 96 h, hepatocytes became ultrastructurally similar to the control liver, and the expression of caveolin‐1 on mitochondria showed a moderate increase compared with 24 h after PH. Decrease of expression of caveolin‐1 in the altered liver mitochondrial membranes at 24 h following PH, and the high expression of caveolin‐1 observed on myelin figures, suggests involvement of caveolin‐1 is in both mitochondrial homeostasis and lipidogenesis. Addressing the role played by caveolin‐1 during liver regeneration might disclose additional features of mitochondrial homeostasis and lipidogenesis during frequent metabolic liver diseases. Microsc. Res. Tech. 75:1026–1032, 2012. © 2012 Wiley Periodicals, Inc.
Saturation numbers for families of graph subdivisions
Authors: Ferrara Michael , Jacobson Michael , Milans Kevin G. , Tennenhouse Craig , Wenger Paul S.
Published: March 2012

For a family of graphs, a graph G is ‐saturated if G contains no member of as a subgraph, but for any edge in , contains some member of as a subgraph. The minimum number of edges in an ‐saturated graph of order n is denoted . A subdivision of a graph H, or an H‐subdivision, is a graph G obtained from H by replacing the edges of H with internally disjoint paths of arbitrary length. We let denote the family of H‐subdivisions, including H itself. In this paper, we study when H is one of or , obtaining several exact results and bounds. In particular, we determine exactly for and show for n sufficiently large that there exists a constant such that . For we show that will suffice, and that this can be improved slightly depending on the value of . We also give an upper bound on for all t and show that . This provides an interesting contrast to a 1937 result of Wagner (Math Ann, 114 (1937), 570–590), who showed that edge‐maximal graphs without a K5‐minor have at least edges.
Strict perpendicular orientation of neural crest‐derived neurons in vitro is dependent on an extracellular gradient of voltage
Authors: Pan Linjie , Borgens Richard Ben
Published: March 2012

We report extraordinary perpendicular orientations of neurons dependent on the presence of an external direct current (DC) voltage gradient. We chose chick dorsal root and postganglionic sympathetic neurons to evaluate. These were cultured in observation chambers in which the cells were separated from electrode products or substrate effects and maintained at 35°C. Both types of neurons showed a rapid restructuring of their anatomy. Typically, neurites that were not perpendicular to the voltage gradient were quickly resorbed into the cell body within a few minutes. Over 3–6 hr, significant new neurite growth occurred and was patterned perpendicular to the DC electrical field (Ef). This preferred asymmetry was dependent on the Ef, as was the initial retrograde degeneration of fibers. At 400–500 mV/mm, over 90% of the cells in culture assumed this orientation. Removal of the DC Ef led to a loss of the preferred orientation, with further random growth within the chambers. This is the first report of such responses in dorsal root ganglion neurons. We also used sympathetic neurons as a meaningful comparison to analyze whether there were any qualitative or quantitative differences between these two cell types of neural crest origin. We discuss the means by which these orientations were achieved. © 2012 Wiley Periodicals, Inc.
A2 noradrenergic nerve cell metabolic transducer and nutrient transporter adaptation to hypoglycemia: Impact of estrogen
Authors: Koshy Cherian Ajeesh , Briski Karen P.
Published: March 2012

CNS neurons exhibit sustained activation by recurring hypoglycemia in the presence of estrogen. We investigated the impact of estradiol on fuel uptake and detection of energy imbalance by hindbrain A2 metabolosensory neurons during acute vs. chronic hypoglycemia. A2 neurons were laser dissected from estradiol benzoate (EB)‐ and oil (O)‐implanted ovariectomized rats after single or serial injection of neutral protamine Hagedorn (NPH) insulin for single‐cell qPCR or high‐sensitivity Western blotting. Acute NPH increased A2 GLUT3 mRNA but not protein in EB, but decreased both profiles in O rats. Single insulin dosing did not alter monocarboxylate transporter‐2 (MCT2) mRNAs in EB or O, but increased MCT2 protein in EB. Preceding hypoglycemia augmented baseline transporter mRNA and protein in O, but decreased GLUT4 and increased MCT2 proteins in EB. Chronic NPH increased A2 MCT2 and GLUT3 proteins in EB, but elevated GLUT4 protein in O. A2 phospho‐AMPK (pAMPK) protein was progressively diminished by acute and chronic hypoglycemia in EB, but elevated in O after serial NPH. Dopamine‐β‐hydroxylase (DβH) transcripts were decreased in EB during acute and chronic hypoglycemia, but unaltered by serial NPH dosing in O. These results suggest that estrogen enhances A2 lactate utilization during acute hypoglycemia, thereby lessening AMPK activation relative to euglycemic controls. Cellular adaptation to chronic hypoglycemia may involve estrogen‐dependent augmentation of lactate and GLUT3‐mediated glucose uptake and hormone‐independent increases in GLUT4 expression, coincident with diminished pAMPK‐mediated signaling of energy deficiency. The data also imply that increased lactate and glucose uptake during recurring hypoglycemia may be required for sustained DβH transcriptional reactivity to this metabolic stress. © 2012 Wiley Periodicals, Inc.
Therapeutic effects of tetramethylpyrazine nitrone in rat ischemic stroke models
Authors: Sun Yewei , Yu Pei , Zhang Gaoxiao , Wang Liang , Zhong Haijing , Zhai Ziyuan , Wang Linda , Wang Yuqiang
Published: March 2012

Free radical‐mediated neuronal cell damage is an important pathological process in ischemic stroke. We have previously reported a novel dual‐functional agent, 2‐[[(1,1‐dimethylethyl)oxidoimino]‐methyl]‐3,5,6‐trimethylpyrazine (TBN), a derivative of tetramethylpyrazine armed with anitrone moiety. In this report, we further evaluate TBN'stherapeutic parameters in a rat middle cerebral artery occlusion (MCAO) model. Its abilities to cross the blood–brain barrier, scavenge free radicals, and inhibitCa2+ influx were also investigated. TBN showed significant activity in both the transient MCAO (t‐MCAO) and permanent MCAO (p‐MCAO) stroke models in the rat. The therapeutic time window is 8 hr in the t‐MCAO model. TBN readily crossed the blood–brain barrier and in vitro had strong activity in neutralizing ·OH, O−
2·, and ONOO− and significantly decreased intracellular Ca2+concentration. TBN is a promising new treatment forischemic stroke, with multiple mechanisms of action. It blocks Ca2+ overload and neutralizes ·OH, O−2·, and ONOO−. © 2012 Wiley Periodicals, Inc.
Comparison of nutritional quality between conventional and organic dairy products: a meta‐analysis
Authors: Palupi Eny , Jayanegara Anuraga , Ploeger Angelika , Kahl Johannes
Published: March 2012

As a contribution to the debate on the comparison of nutritional quality between conventional versus organic products, the present study would like to provide new results on this issue specifically on dairy products by integrating the last 3 years' studies using a meta‐analysis approach with Hedges' d effect size method. The current meta‐analysis shows that organic dairy products contain significantly higher protein, ALA, total omega‐3 fatty acid, cis‐9,trans‐11 conjugated linoleic acid, trans‐11 vaccenic acid, eicosapentanoic acid, and docosapentanoic acid than those of conventional types, with cumulative effect size ( ± 95% confidence interval) of 0.56 ± 0.24, 1.74 ± 0.16, 0.84 ± 0.14, 0.68 ± 0.13, 0.51 ± 0.16, 0.42 ± 0.23, and 0.71 ± 0.3, respectively. It is also observed that organic dairy products have significantly (P < 0.001) higher omega‐3 to ‐6 ratio (0.42 vs. 0.23) and Δ9‐desaturase index (0.28 vs. 0.27) than the conventional types. The current regulation on organic farming indeed drives organic farms to production of organic dairy products with different nutritional qualities from conventional ones. The differences in feeding regime between conventional and organic dairy production is suspected as the reason behind this evidence. Further identical meta‐analysis may be best applicable for summarizing a comparison between conventional and organic foodstuffs for other aspects and food categories. Copyright © 2012 Society of Chemical Industry
Antimicrobial activity of saponin‐rich fraction from Camellia oleifera cake and its effect on cell viability of mouse macrophage RAW 264.7
Authors: Hu Jie‐Lun , Nie Shao‐Ping , Huang Dan‐Fei , Li Chang , Xie Ming‐Yong , Wan Yin
Published: March 2012

BACKGROUND: As a by‐product of oil production, several million tons of Camellia oleifera cake is discarded every year in China. The aim of this study was to evaluate the antimicrobial activity of a saponin‐rich fraction isolated from C. oleifera cake and investigate its effect on the cell viability of RAW 264.7, a macrophage‐like cell line present in almost all mouse tissues.

RESULTS: The saponin‐rich fraction was isolated from C. oleifera cake in several steps and had a saponin content of 95.42 ± 0.10% (w/w). It showed significant inhibitory activity against the bacteria Staphylococcus aureus, Escherichia coli and Bacillus subtilis and the fungi Mucor racemosus, Aspergillus oryzae, Rhizopus stolonifer, Saccharomyces cerevisiae and Penicillium glaucum, with minimum inhibitory concentrations of 31.3, 31.3, 62.5, 250, 250, 250, 31.3 and 125 µg ml−1 respectively. In addition, mouse macrophage RAW 264.7 pretreated with the saponin‐rich fraction (80–200 µg mL−1) exhibited a significant loss of cell viability in a dose‐dependent manner.

CONCLUSION: These results may be useful for the future application of saponins from C. oleifera cake. However, the potential use of the saponin‐rich fraction as an antimicrobial agent should be decided according to the target micro‐organisms in order to avoid causing harm in humans. Copyright © 2012 Society of Chemical Industry
Effect of location in the canopy on the colour development of three apple cultivars during growth
Authors: Unuk Tatjana , Tijskens LMM (Pol) , Germšek Blaž , Zadravec Peter , Vogrin Andrej , Hribar Janez , Simčič Marjan , Tojnko Stanislav
Published: March 2012

BACKGROUND: Homogeneity in appearance is one of the quality aspects asked for in the supply chain. Decreasing the biological variation in batches of harvested apples (cultivars Braeburn, Fuji and Gala) becomes increasingly important. Skin colour is one of the aspects that determine both optimal harvest and stage of development. Skin colour is affected by location in the canopy. The rules of development of biological variation are now established and will be used on skin colour data.

RESULTS: The Minolta colour aspects a*, b* and L* measured before commercial harvest change in a sigmoidal fashion and can be analysed including the biological variation, with a logistic model in indexed nonlinear regression, obtaining explained parts of above 90%. The mechanism of colour change is not affected by state of development or location in the canopy. The location in the canopy affects the intensity of both red and green colouring compounds. The variation in colouration is not affected by the location in the canopy.

CONCLUSION: The red‐coloured apple cultivar (Gala) depends more on the location in the canopy than the less‐coloured cultivars (Fuji and Braeburn). The colour development in Fuji apples is considerably slower, with a much larger variation in stage of development. The location in the canopy affects all aspects of biological variation (biological shift factor and asymptotic starting level of colouration) for all three colour aspects L*, a* and b*, but only the mean value, not the standard deviation. The biological shift factors per colour aspects are linearly related. Once induced, variation remains constant during development. Copyright © 2012 Society of Chemical Industry
Thermally Cross‐Linkable Poly(p‐xylylene)s for Advanced Low‐Dielectric Applications
Authors: Mulpuri Syamkumar V. , Shin Boo‐Gyo , Bognitzki Michael , Greiner Andreas , Yoon Do Y.
Published: March 2012

A novel series of poly(p‐xylylene) homopolymer and copolymers containing thermally cross‐linkable cyclohexenyl moiety are prepared via base‐catalyzed Gilch route to yield high‐molecular‐weight polymers. The resulting polymers are highly soluble in a wide range of organic solvents and could be solution cast into flexible and transparent films. The polymers are thermally stable up to 350 °C and the glass transition temperature (Tg) is in the range of 136 − 250 °C. They undergo thermal cross‐linking via the cyclohexenyl moiety. The cross‐linked polymer exhibits a high Tg of 294 °C, a low coefficient of thermal expansion (CTE) of 45 ppm K−1. A low dielectric constant of 2.5 and a very low dielectric loss tan δ of 0.0004 at 1 GHz are obtained, which are superior to conventional interconnect polymers.
Synthesis and Characterization of a 2,4,6‐Tri(2‐thienyl)pyridine‐Based Conjugated Polymer for OFET Applications
Authors: Cao Kangli , Sun Xiangnan , Zhang Qing , Liu Yunqi
Published: March 2012

2,4,6‐Tri(2‐thienyl)pyridine is used to synthesize the new conjugated polymer PBDTTPy for OFET applications. The concept of introducing electron‐deficient pyridine repeating units and meta‐linked structures into a conjugated polymer to reduce its HOMO energy level and thereby increase its ambient stability is tested. The absorption spectrum of the polymer thin film displays a large bathochromic shift compared with its solution absorption spectrum. The polymer PBDTTPy shows a typical amorphous structure in the solid state. The first OFET device based on a conjugated polymer with meta‐linked trithienylpyridine units is reported. PBDTTPy exhibits p‐type transport under ambient conditions in a bottom‐gate, top‐contact OFET device with a mobility of 2.4 × 10−4 cm2 V−1 s−1.
Red‐Emitting Dendritic Iridium(III) Complexes for Solution Processable Phosphorescent Organic Light‐Emitting Diodes
Authors: Qin Tianshi , Ding Junqiao , Baumgarten Martin , Wang Lixiang , Müllen Klaus
Published: March 2012

Functionalization of a red phosphorescent iridium(III) complex core surrounded by rigid polyphenylene dendrons with a hole‐transporting triphenylamine surface allows to prevent the intermolecular aggregation‐induced emission quenching, improves charge recombination, and therefore enhances photo‐ and electroluminescence efficiencies of dendrimer in solid state. These multifunctional shape‐persistent dendrimers provide a new pathway to design highly efficient solution processable materials for phosphorescent organic light‐emitting diodes (PhOLEDs).
A Fully Substituted 3‐Silolene Functions as Promising Building Block for Hyperbranched Poly(Silylenevinylene)
Authors: Zhao Zujin , Guo Yanju , Jiang Tao , Chang Zhengfeng , Lam Jacky W. Y. , Xu Liwen , Qiu Huayu , Tang Ben Zhong
Published: March 2012

A 3‐silolene derivative, 2,2,5,5‐tetrakis(dimethylsilyl)‐1,1‐dimethyl‐3,4‐diphenyl‐3‐silolene (TDMSHS), is first synthesized and characterized by X‐ray diffraction crystallography and spectroscopic methods. Hydrosilylation polymerization of TDMSHS with 1,1‐dimethyl‐2,5‐bis(4‐ethynylphenyl)‐3,4‐diphenylsilole in the presence of Karstedt's catalyst generates a stereoregular silole‐containing hyperbranched poly(silylenevinylene) (hb‐SPSV) with a high molecular weight ($\overline{M}_{\rm w}$ = 146 000, $\overline{M}_{\rm w}$/$\overline{M}_{\rm n}$ = 1.5) in high yield (≈95%). hb‐SPSV exhibits excellent thermal stability and strong fluorescence, and the emission of its aggregates in aqueous mixture can be quenched efficiently by picric acid with large quenching constants KSV up to 414400 M−1.
Fragment Informatics and Computational Fragment‐Based Drug Design: An Overview and Update
Authors: Sheng Chunquan , Zhang Wannian
Published: March 2012

Fragment‐based drug design (FBDD) is a promising approach for the discovery and optimization of lead compounds. Despite its successes, FBDD also faces some internal limitations and challenges. FBDD requires a high quality of target protein and good solubility of fragments. Biophysical techniques for fragment screening necessitate expensive detection equipment and the strategies for evolving fragment hits to leads remain to be improved. Regardless, FBDD is necessary for investigating larger chemical space and can be applied to challenging biological targets. In this scenario, cheminformatics and computational chemistry can be used as alternative approaches that can significantly improve the efficiency and success rate of lead discovery and optimization. Cheminformatics and computational tools assist FBDD in a very flexible manner. Computational FBDD can be used independently or in parallel with experimental FBDD for efficiently generating and optimizing leads. Computational FBDD can also be integrated into each step of experimental FBDD and help to play a synergistic role by maximizing its performance. This review will provide critical analysis of the complementarity between computational and experimental FBDD and highlight recent advances in new algorithms and successful examples of their applications. In particular, fragment‐based cheminformatics tools, high‐throughput fragment docking, and fragment‐based de novo drug design will provide the focus of this review. We will also discuss the advantages and limitations of different methods and the trends in new developments that should inspire future research.
Minimizing the total weighted delivery time in container transportation scheduling
Authors: Lee Kangbok , Choi Byung‐Cheon , Leung Joseph Y‐T. , Pinedo Michael L. , Briskorn Dirk
Published: March 2012

We consider the problem of transporting containers from one port to another using a fleet of ships. Each ship has a capacity constraint that limits the total number of containers it can carry; each ship calls on a specific set of ports that is referred to as its route and each ship follows a fixed route with a fixed departure time at each port. Each container has a release date, that is, the date when it becomes available for shipping at its origination port; it cannot be loaded onto a ship before its release date. Also, each container has an importance factor referred to as its weight. The delivery time of a container is defined as the time when the container is delivered by a ship at its destination port. We consider the problem of minimizing the total weighted delivery times over all containers. We consider three scenarios with regard to the routes of the ships, namely, (i) identical routes, (ii) nested routes, and (iii) arbitrary routes. We determine the computational complexity of the problems and provide heuristics with their worst‐case analyses. © 2012 Wiley Periodicals, Inc. Naval Research Logistics, 2012
ARF suppresses hepatic vascular neoplasia in a carcinogen‐exposed murine model
Authors: Busch Stephanie E , Gurley Kay E , Moser Russell D , Kemp Christopher J
Published: March 2012

Hepatic haemangiosarcoma is a deadly malignancy whose aetiology remains poorly understood. Inactivation of the CDKN2A locus, which houses the ARF and p16INK4a tumour suppressor genes, is a common event in haemangiosarcoma patients, but the precise role of ARF in vascular tumourigenesis is unknown. To determine the extent to which ARF suppresses vascular neoplasia, we examined the incidence of hepatic vascular lesions in Arf‐deficient mice exposed to the carcinogen urethane [intraperitoneal (i.p.), 1 mg/g]. Loss of Arf resulted in elevated morbidity and increased the incidence of both haemangiomas and incipient haemangiosarcomas. Suppression of vascular lesion development by ARF was heavily dependent on both Arf gene‐dosage and the genetic strain of the mouse. Trp53‐deficient mice also developed hepatic vascular lesions after exposure to urethane, suggesting that ARF signals through a p53‐dependent pathway to inhibit the development of hepatic haemangiosarcoma. Our findings provide strong evidence that inactivation of Arf is a causative event in vascular neoplasia and suggest that the ARF pathway may be a novel molecular target for therapeutic intervention in haemangiosarcoma patients. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
MR imaging of the fetal musculoskeletal system
Authors: Nemec Stefan Franz , Nemec Ursula , Brugger Peter C. , Bettelheim Dieter , Rotmensch Siegfried , Graham John M. , Rimoin David L. , Prayer Daniela
Published: March 2012

Magnetic resonance imaging (MRI) appears to be increasingly used, in addition to standard ultrasonography for the diagnosis of abnormalities in utero. Previous studies have recently drawn attention to the technical refinement of MRI to visualize the fetal bones and muscles. Beyond commonly used T2‐weighted MRI, echoplanar, thick‐slab T2‐weighted and dynamic sequences, and three‐dimensional MRI techniques, are about to provide new imaging insights into the normal and the pathological musculoskeletal system of the fetus. This review emphasizes the potential significance of MRI in the visualization of the fetal musculoskeletal system. © 2012 John Wiley & Sons, Ltd.
Intracranial translucency at 11–13 weeks of gestation: prospective evaluation and reproducibility of measurements
Authors: Adiego Begoña , Illescas Tamara , Martinez‐Ten Pilar , Bermejo Carmina , Perez‐Pedregosa Javier , Wong Amy E. , Sepulveda Waldo
Published: March 2012

Objective

This paper aimed to determine the feasibility of identification and measurement reproducibility of intracranial translucency (IT) in our population.

Methods

This is a prospective study in which five accredited operators attempted to identify and measure the IT during first‐trimester sonographic screening for aneuploidy in 990 fetuses. The presence or absence of spina bifida was determined at the time of the second‐trimester scan or after birth. Measurement reproducibility was assessed through intraclass correlation coefficient (ICC) on a subgroup of 150 fetuses.

Results

Identification and measurement of the IT were possible in 961 (97%) cases. The mean IT anteroposterior diameter was 1.8 mm (SD ± 0.37; range 0.8–3.1), and the size increased linearly with advancing gestation (IT = 0.74 + 0.02 × crown–rump length; r2 = 0.15, p < 0.0001). The only fetus with spina bifida in this series presented with absent IT. Intra‐observer and inter‐observer ICCs were 0.79 and 0.75, respectively (95% confidence intervals 0.72–0.84 and 0.67–0.81, respectively; both p < 0.001).

Conclusions

The IT increases linearly with increasing crown–rump length and seems to be of value in the first‐trimester detection of spina bifida. It is easy to identify and measure and shows excellent intra‐observer and inter‐observer reproducibility measurements. © 2012 John Wiley & Sons, Ltd.
Development of reference equations for spirometry in japanese children aged 6–18 years
Authors: Takase Masato , Sakata Hiroshi , Shikada Masahiro , Tatara Katsuyoshi , Fukushima Takayoshi , Miyakawa Tomoo
Published: March 2012

Background

Spirometry is the most widely used pulmonary function test and the measured values of spirometric parameters need to be evaluated using reference values predicted for the corresponding race, sex, age, and height. However, none of the existing reference equations for Japanese children covers the entire age range of 6–18 years. The Japanese Society of Pediatric Pulmonology had organized a working group in 2006, in order to develop a new set of national standard reference equations for commonly used spirometric parameters that are applicable through the age range of 6–18 years.

Methods

Quality assured spirometric data were collected through 2006–2008, from 14 institutions in Japan. We applied multiple regression analysis, using age in years (A), square of age (A2), height in meters (H), square of height (H2), and the product of age and height (AH) as explanatory variables to predict forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF), forced expiratory flow between 25% and 75% of the FVC (FEF25–75%), instantaneous forced expiratory flow when 50% (FEF50%) or 75% (FEF75%) of the FVC have been expired.

Results

Finally, 1,296 tests (674 boys, 622 girls) formed the reference data set. Distributions of the percent predicted values did not differ by ages, confirming excellent fit of the prediction equations throughout the entire age range from 6 to 18 years. Cut‐off values (around 5 percentile points) for the parameters were also determined.

Conclusions

We recommend the use of this new set of prediction equations together with suggested cut‐off values, for assessment of spirometry in Japanese children and adolescents. Pediatr Pulmonol. 2013; 48:35–44. © 2012 Wiley Periodicals, Inc.
Severe central sleep apnea in a child with leukemia on chronic methadone therapy
Authors: Amos Louella B. , D'Andrea Lynn A.
Published: March 2012

We describe a child with acute myeloid leukemia (AML) who developed severe central sleep apnea (CSA) on methadone therapy for chronic pain management. His chemotherapy‐related cerebral atrophy and renal insufficiency with impaired methadone clearance may have also contributed to the severity of his sleep‐disordered breathing. Maintenance methadone treatment is not a common pediatric practice; therefore, the adverse effects of methadone therapy, including CSA, are rarely reported in children. Pediatr Pulmonol. 2013; 48:85–87. © 2012 Wiley Periodicals, Inc.
Pulmonary function and airway responsiveness in young competitive swimmers
Authors: Silvestri Michela , Crimi Emanuele , Oliva Simona , Senarega Daniela , Tosca Maria Angela , Rossi Giovanni A. , Brusasco Vito
Published: March 2012

Rationale

Strong physical activities are often associated with large lung volumes and relatively reduced flow, which may represent a physiological variant but also an obstructive abnormality. Competitive swimmers have also spirometric values even larger than other athletes, although they are at increased risk for asthma or airway hyperresponsiveness.

Aim

We aimed to investigate whether lung volumes increase with duration of swimming training and are related to an obstructive abnormality associated with airway hyperresponsiveness and asthma‐like symptoms.

Methods

Forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), airway responsiveness, and skin prick test were measured in 34 children/adolescents (age: 7–19 yrs old) trained for competitive swimming. Their “lifetime” exposure, i.e., the hours spent in pool was very strongly correlated with their age at the time of study. The effect of swimming activity was therefore estimated from the relationships between lung function data and age.

Results

FVC Z‐score was positively correlated with age, indicating that absolute values increased more than expected with normal growth, but FEV1/FVC was negatively correlated with age. Although the majority of subjects had allergic sensitization to aeroallergens and about one half had asthma‐like symptoms and/or airway hyperresponsiveness, these conditions did not alter the relationships between lung function and age.

Conclusion

Intense swimming activity may cause a greater than normal lung growth, irrespective of the presence of allergic sensitization or airway hyperresponsiveness. The associated reduction of FEV1/FVC may represent a physiological variant rather than a true obstructive abnormality. Pediatr Pulmonol. 2013; 48:74–80. © 2012 Wiley Periodicals, Inc.
Flexible bronchoscopy in managing a child with pulmonary hydatid disease
Authors: Burgess Christopher , Masters I. Brent , Francis Paul , Grimwood Keith , Chang Anne B.
Published: March 2012

Few articles have described the airway management of parenchymal lung hydatid cysts complicated by endobronchial or airway involvement, and none have described the use of flexible bronchoscopy (FB) therapeutically in children. We present a child with a ruptured pulmonary hydatid cyst who underwent repeated FB for removal of cystic material from an obstructed right upper lobe segmental bronchus. This child did not require thoracic surgery and made a full clinical recovery, demonstrating that in selected cases FB may offer curative treatment. Pediatr Pulmonol. 2012. 47:1140–1142. © 2012 Wiley Periodicals, Inc.
Effects of buprofezin and diflubenzuron on various developmental stages of Asian citrus psyllid, Diaphorina citri
Authors: Tiwari Siddharth , Clayson Paul J , Kuhns Emily H , Stelinski Lukasz L
Published: March 2012

BACKGROUND: Diaphorina citri populations in Florida are developing resistance to commonly used neurotoxic insecticides. Alternatives to neurotoxins, such as insect growth regulators, are needed to control this season‐long subtropical pest to prevent or delay development of insecticide resistance. In the present investigation, two insect growth regulators (IGRs), buprofezin and diflubenzuron, were evaluated against various developmental stages of D. citri.

RESULTS: The 0–1‐day‐old D. citri eggs were more susceptible to buprofezin and diflubenzuron than the 3–4‐day‐old eggs. Adult emergence was completely suppressed by treating first‐ or third‐instar nymphs with buprofezin or diflubenzuron at 30–240 or 23–184 µg mL−1 rates respectively. Treatment of fifth‐instar nymphs with diflubenzuron at a rate of 184 µg mL−1 and with buprofezin at 30–240 µg mL−1 rates resulted in approximately 20 and 15–80% reductions in adult emergence respectively. The mean number of eggs per plant was reduced at 5 days after topical treatment with diflubenzuron. Mean egg hatch per plant was reduced at 5 and 6–15 days after topical treatments with buprofezin and diflubenzuron respectively.

CONCLUSION: Buprofezin and diflubenzuron effectively suppressed D. citri adult emergence. D. citri were more susceptible as early (first–third‐instar) than late (fifth‐instar) nymphs. Both IGRs inhibited egg production and egg hatch. Reduction in the number of subsequent offspring suggests reduced vertical transmission of Candidatus Liberibacter asiaticus, the pathogen thought to cause citrus greening disease. The present results indicate that both IGRs tested here should be effective tools for rotation in insecticide‐based D. citri management programs. Copyright © 2012 Society of Chemical Industry
Mosquito adulticidal activity of a biosurfactant produced by Bacillus subtilis subsp. subtilis
Authors: Geetha Irudayaraj , Paily Kummankottil P , Manonmani Arulsamy M
Published: March 2012

BACKGROUND: A biosurfactant, surfactin, produced by a strain of Bacillus subtilis subsp. subtilis (VCRC B471), was effective in killing mosquito larval and pupal stages. As it was lethal to the non‐feeding pupal stage, it was presumed that it could kill the adult mosquitoes also. In this study, the adulticidal effect of the biosurfactant was assessed in the laboratory against a malaria vector, Anopheles stephensi.

RESULTS: The biosurfactant surfactin, separated from the culture supernatant of the production strain, showed mosquito adulticidal activity when tested as ultralow‐volume (ULV) spray in a Peet‐Grady chamber. Knockdown activity and mortality were found to increase with increasing surfactin dosage. Knockdown dosage (KD) and lethal dosage (LD) were calculated by statistical analysis. The KD50 and KD90 dosages were 10.73 and 26.39 mg m−3 respectively. The LD50 and LD90 dosages were 16.13 and 39.21 mg m−3. The average droplet size of B. subtilis surfactin was 17.5 ± 1.07 µm.

CONCLUSION: The present study indicates that the biosurfactant surfactin, produced by B. subtilis subsp. subtilis (VCRC B471), is a potential bioadulticide for ULV spray against malaria‐transmitting Anopheles stephensi mosquitoes. This is the first report of a mosquito adulticide from a microbial source. Copyright © 2012 Society of Chemical Industry
Native chemical ligation in dimethylformamide can be performed chemoselectively without racemization
Authors: Dittmann Marc , Sadek Muheeb , Seidel Ralf , Engelhard Martin
Published: March 2012

Native chemical ligation of unprotected peptides in organic solvents has been previously reported as a fast, efficient, and suitable method for coupling of hydrophobic peptides. However, it has not been determined whether the reaction can be carried out without possible side reactions or racemization. Here, we present a study on the chemoselectivity of this method by model reactions designed to test the reactivity of Arg and Lys side chains as well as that of α‐amino groups. A possible racemization of the C‐terminal amino acid of the N‐terminal peptide was also investigated. The results show that ligation in organic solvents can be conducted chemoselectively without side reactions with other nucleophilic groups. Furthermore, no racemization of the C‐terminal amino acid was observed if both educts were added simultaneously. Thus, native chemical ligation can be performed either in aqueous buffer systems or in organic solvents paving the way for the synthesis of larger hydrophobic peptides and/or membrane proteins. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.
Doping in mixed films of differently substituted phthalocyanines measured in‐situ during film growth
Authors: Cornelius Lena , Beu Max , Keil Christopher , Schlettwein Derck
Published: March 2012

Mixed films of unsubstituted phthalocyaninato copper (H16PcCu) and its perfluorinated derivative (F16PcCu) were prepared by co‐evaporation in different molecular mixtures. The films were analyzed in‐situ by conduction measurements. High admixtures of H16PcCu in F16PcCu films disturbed the charge transport. Optical transmission spectroscopy consequently showed the disturbance of the F16PcCu solid state structure for increased admixtures of H16PcCu. The spectral signatures of both the βbilayer‐structure and the β‐structure of F16PcCu decreased. Low admixtures of H16PcCu increased the conductivity, indicating a successful dopant interaction at widely preserved crystallinity of F16PcCu. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantum mechanical study on plasmon resonances in small ring clusters
Authors: Yin Hai‐Feng , Zhang Hong
Published: March 2012

The collectivity of the electronic motion in small sodium clusters with ring structure is studied by time‐dependent density functional theory. The formation and development of collective resonances in the absorption spectra were obtained as a function of the ring radius. In small ring clusters, besides the lower‐energy mode and the higher‐energy mode, there is another plasmon resonance mode, that is, the reverse two‐dipole mode. For the reverse two‐dipole mode, the formations of these two dipoles are due to the external field inducement and the shielding effect, although the resonant excitation is mainly due to the coupling effect of the electrons of these two dipoles. © 2012 Wiley Periodicals, Inc.
Density functional theory and multicomponent wave functions
Authors: Karwowski Jacek
Published: March 2012

Some consequences of using multicomponent wave functions are analyzed. In particular, paradoxical properties of a density functional derived from Dirac and Lévy‐Leblond equations are discussed. The application of a recently formulated N‐electron “relativistic Schrödinger theory,” based on a 4N‐component wave function, to the construction of a Lorentz and gauge covariant density functional theory is suggested. © 2012 Wiley Periodicals, Inc.
Approximate analytical versus numerical solutions of Schrödinger equation under molecular Hua potential
Authors: Hassanabadi H. , Yazarloo B. H. , Zarrinkamar S. , Solaimani M.
Published: March 2012

We solve the D‐dimensional Schrödinger equation under the Hua potential by using a Pekeris‐type approximation and the supersymmetry quantum mechanics. The reliability of the spectrum is checked via a comparison with the finite difference method. This interaction resembles Eckart, Morse, and Manning–Rosen potentials. Some useful quantities are reported via the Hellmann–Feynman Theorem. © 2012 Wiley Periodicals, Inc.
Electronic structure and coordination chemistry of phenanthridine ligand in first‐row transition metal complexes: A DFT study
Authors: Benmachiche Akila , Zendaoui Saber‐Mustapha , Bouaoud Salah‐Eddine , Zouchoune Bachir
Published: March 2012

The geometric parameters, electronic structures, and haptotropic migration of a series of hypothetical compounds of general formula CpM(C13H9N) and (CO)3M(C13H9N) (M = fist row transition metal, Cp = C5H5, and C13H9N = phenanthridine ligand) are investigated by means of the density functional theory. The phenanthridine ligand can bind to the metal through η1 to η6 coordination mode, in agreement with the electron count and the nature of the metal, showing its capability to adapt itself to the electronic demand of the metal as well as to the polycyclic aromatic hydrocarbons. In the investigated species, the most favored closed‐shell count is 18‐electron except for the Ti and V models which are deficient open‐shell 16‐electron configuration. This study has shown the difference in coordination ability of this heteropolycyclic ligand: the coordination of the central C5N ring is less favored than the terminal C6 rings, in agreement with the π‐electron density localization. Most of the investigated complexes are expected to exhibit a rich fluxional behavior. This flexibility favors the possibility for the existence of several isomers as well as their interconversion through haptotropic shifts. © 2012 Wiley Periodicals, Inc.