bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of the Content of Modified Coal Tar Pitch Powder on the Strength of Carbon Bonded Alumina (Al2O3–C)
Authors: Soltysiak Stefan , Abendroth Martin , Kuna Meinhard , Dudczig Steffen
Published: October 2013

Among other ceramic materials carbon bonded alumina is used for the production of ceramic filters. The ceramic filters are utilized for the filtration of metal melts. A new generation of ceramic filters made of carbon bonded alumina has been developed. The aim of the study presented in this paper is the determination of mechanical parameters of the carbon bonded alumina. The investigations are carried out in order to evaluate the influence of the modified coal tar pitch powder (Cabores® P) content on the mechanical behavior. The parameters are determined by means of the Small Punch Test (SPT).
Long term outcome of Ph+ CML patients achieving complete cytogenetic remission with interferon based therapy moving from interferon to imatinib era
Authors: Malagola Michele , Breccia Massimo , Skert Cristina , Cancelli Valeria , Soverini Simona , Iacobucci Ilaria , Cattina Federica , Liberati Anna Maria , Tiribelli Mario , Annunziata Mario , Trabacchi Elena , De Vivo Antonio , Castagnetti Fausto , Martinelli Giovanni , Fogli Miriam , Stagno Fabio , Pica Gianmatteo , Iurlo Alessandra , Pregno Patrizia , Abruzzese Elisabetta , Pardini Simonetta , Bocchia Monica , Russo Sabina , Pierri Ivana , Lunghi Monia , Barulli Sara , Merante Serena , Mandelli Franco , Alimena Giuliana , Rosti Gianatonio , Baccarani Michele , Russo Domenico
Published: October 2013

Interferon α (IFNα) prolongs survival of CML patients achieving CCyR and potentially synergizes with TKIs. We report on the molecular status and long term outcome of 121 patients who were treated in Italy between 1986 and 2000 with IFNα based therapy and who obtained CCyR. After a median follow up of 16.5 years, 74 (61%) patients were switched to standard imatinib: 48 (65%) lost the CCyR on IFNα, and 36 (75%) are alive and in CCyR; 26 (35%) were switched to imatinib when they were still in CCyR on IFNα, and all 26 are alive and in CCyR. Forty‐seven patients (39%) were never switched to imatinib: 24 (51%) continued and 23 (49%) discontinued IFNα, respectively, and 39/47 (83%) are alive and in CCyR. At last follow‐up, the BCR‐ABL transcripts level was available in 96/101 living patients (95%) The BCR‐ABL:ABL ratio was between 0.1 and 0.01% (MR3.0) in 17%, and less than 0.01% (MR4.0) in 81% of patients. No patient was completely molecular negative (MR4.5 or MR5.0). The OS at 10 and 20 years is 92 and 84%, respectively. This study confirms that CCyR achieved with IFNα and maintained with or without imatinib or any other therapy significantly correlates with long term survival in CML patients who mostly have MR4.0. Complete molecular response (MR4.5 or MR5.0) seems to be unnecessary for such a long survival. This study further supports development of studies testing the clinical effect of the combinations of TKIs with IFNα. Am. J. Hematol. 89:119–124, 2014. © 2013 Wiley Periodicals, Inc.
Determination of rhynchophylline and hirsutine in rat plasma by UPLC‐MS/MS after oral administration of Uncaria rhynchophylla extract
Authors: Wu Yu‐Tse , Lin Lie‐Chwen , Tsai Tung‐Hu
Published: October 2013

An ultra‐performance liquid chromatography with tandem mass spectrometry (UPLC–MS/MS) method was developed and validated to concurrently determine rhynchophylline and hirsutine in rat plasma. The sample preparation of rat plasma was achieved by alkalization and liquid–liquid extraction. The mass transition of precursor ion → product ion pairs were monitored at m/z 385.2 → 160.0 for rhynchophylline, m/z 369.3 → 144.0 for hirsutine and m/z 414.0 → 220.0 for noscapine (internal standard). This method revealed linear relationships from 2.5 to 50 ng/mL (r2 > 0.997) for rhynchophylline and from 2.5 to 50 ng/mL (r2 > 0.998) for hirsutine. The limit of quantification values for rhynchophylline and hirsutine in rat plasma were both 2.5 ng/mL. Intra‐day and inter‐day precisions were within 10.6% and 12.5%, respectively, for rhynchophylline and hirsutine, and the accuracy (bias) was <10%. Liquid–liquid extraction of rat plasma samples resulted in insignificant matrix effect, and the extraction recoveries were >83.6% for rhynchophylline, 73.4% for hirsutine and 90.7% for the internal standard. This method was applied successfully to a pharmacokinetic study of rhynchophylline and hirsutine in rats after oral administration. Copyright © 2013 John Wiley & Sons, Ltd.
Ultra scale‐down device to predict dewatering levels of solids recovered in a continuous scroll decanter centrifuge
Authors: Lopes A. G. , Keshavarz‐Moore E.
Published: October 2013

During centrifugation operation, the major challenge in the recovery of extracellular proteins is the removal of the maximum liquid entrapped within the spaces between the settled solids–dewatering level. The ability of the scroll decanter centrifuge (SDC) to process continuously large amounts of feed material with high concentration of solids without the need for resuspension of feeds, and also to achieve relatively high dewatering, could be of great benefit for future use in the biopharmaceutical industry. However, for reliable prediction of dewatering in such a centrifuge, tests using the same kind of equipment at pilot‐scale are required, which are time consuming and costly. To alleviate the need of pilot‐scale trials, a novel USD device, with reduced amounts of feed (2 mL) and to be used in the laboratory, was developed to predict the dewatering levels of a SDC. To verify USD device, dewatering levels achieved were plotted against equivalent compression (Gtcomp) and decanting (Gtdec) times, obtained from scroll rates and feed flow rates operated at pilot‐scale, respectively. The USD device was able to successfully match dewatering trends of the pilot‐scale as a function of both Gtcomp and Gtdec, particularly for high cell density feeds, hence accounting for all key variables that influenced dewatering in a SDC. In addition, it accurately mimicked the maximum dewatering performance of the pilot‐scale equipment. Therefore the USD device has the potential to be a useful tool at early stages of process development to gather performance data in the laboratory thus minimizing lengthy and costly runs with pilot‐scale SDC. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1494–1502, 2013
Bioavailability of valsartan oral dosage forms
Authors: Sunkara Gangadhar , Bende Girish , Mendonza Anisha E. , Solar‐Yohay Susan , Biswal Shibadas , Neelakantham Srikanth , Wagner Robert , Flarakos Jimmy , Zhang Yiming , Jarugula Venkateswar
Published: October 2013

The oral bioavailability of valsartan from extemporaneous suspension and solution formulations were evaluated relative to tablet formulation in two separate open‐label, randomized crossover studies in healthy adults. In both studies, the plasma concentrations of valsartan after oral administration were analyzed using validated liquid chromatography‐tandem mass spectrometry (LC–MS/MS) methods, and the corresponding pharmacokinetic parameters were estimated using noncompartmental analysis. The peak plasma concentration (Cmax) and area under the concentration time‐curves (AUC(0–∞)) of valsartan from the extemporaneous suspension were higher by 1.93‐ and 1.56‐fold, respectively, relative to the tablet formulation (P < .001). The Cmax and AUC(0–∞) of valsartan from the oral solution were higher by 2.21‐ and 1.74‐fold, respectively, relative to the tablet formulation (P < .001). These results indicate that both rate and extent of absorption of valsartan are higher in the two liquid dosage forms (extemporaneous suspension and solution formulations) relative to the solid oral dosage form (tablet formulation).
Monounsaturated fatty acids in serum triacylglycerols are associated with response to neoadjuvant chemotherapy in breast cancer patients
Authors: Hilvo Mika , Gade Stephan , Hyötyläinen Tuulia , Nekljudova Valentina , Seppänen‐Laakso Tuulikki , Sysi‐Aho Marko , Untch Michael , Huober Jens , von Minckwitz Gunter , Denkert Carsten , Orešič Matej , Loibl Sibylle
Published: October 2013

Changes in cellular lipid metabolism are a common feature in most solid tumors, which occur already in early stages of the tumor progression. However, it remains unclear if the tumor‐specific lipid changes can be detected at the level of systemic lipid metabolism. The objective of this study was to perform comprehensive analysis of lipids in breast cancer patient serum samples. Lipidomic profiling using an established analytical platform was performed in two cohorts of breast cancer patients receiving neoadjuvant chemotherapy. The analyses were performed for 142 patients before and after neoadjuvant chemotherapy, and the results before chemotherapy were validated in an independent cohort of 194 patients. The analyses revealed that in general the tumor characteristics are not reflected in the serum samples. However, there was an association of specific triacylglycerols (TGs) in patients' response to chemotherapy. These TGs containing mainly oleic acid (C18:1) were found in lower levels in those patients showing pathologic complete response before receiving chemotherapy. Some of these TGs were also associated with estrogen receptor status and overall or disease‐free survival of the patients. The results suggest that the altered serum levels of oleic acid in breast cancer patients are associated with their response to chemotherapy.
Initial breakdown pulses in intracloud lightning flashes and their relation to terrestrial gamma ray flashes
Authors: Marshall Thomas , Stolzenburg Maribeth , Karunarathne Sumedhe , Cummer Steve , Lu Gaopeng , Betz Hans‐Dieter , Briggs Michael , Connaughton Valerie , Xiong Shaolin
Published: October 2013

The initial breakdown stage of 10 intracloud lightning flashes that may have produced terrestrial gamma ray flashes (TGFs) is studied with wideband E‐change, multiband B‐change, and VHF lightning mapping data; these flashes fit published criteria known to be associated with TGFs. The (x, y, z, t) locations of fast initial breakdown pulses (IBPs) were determined with E‐change data using a time‐of‐arrival (TOA) technique. Each IBP includes one or more fast‐rising subpulses. Previous research has shown that a typical intracloud flash initiates just above the main negative cloud charge (MNCC), then an initial negative leader propagates upward in 1–20 ms to the bottom of the upper positive cloud charge (UPCC), thereby establishing a conducting path between the MNCC and UPCC. TOA locations indicate that IBPs are directly related to the initial negative leader. The IBPs primarily occur in short (<750 µs) bursts of two to five pulses, and each burst produces a slow, monotonic E‐change. Typically, one to three IBP bursts are needed to span the vertical gap from the MNCC to the UPCC, with successive bursts separated by 1–5 ms. In the B‐change data, each IBP burst has an associated ULF pulse and several LF pulses, and these are caused by the same physical events that produce the slow, monotonic E‐change and fast‐rising IBP subpulses, respectively. Based on similarities with known TGF‐associated signals, we speculate that a relativistic electron avalanche causes each LF pulse/IBP subpulse pair; thus, each pair has the potential to cause a TGF.
18F‐labeled folic acid derivatives for imaging of the folate receptor via positron emission tomography
Authors: Schieferstein Hanno , Ross Tobias L.
Published: October 2013

The folate receptor (FR) is already known as a proven target in diagnostics and therapy of cancer. Furthermore, the FR is involved in inflammatory and autoimmune diseases. The major advantage as a valuable target is its strongly limited expression in healthy tissues. Over the past two decades, several folic acid‐based radiopharmaceuticals addressing the FR have been developed, and some of them show great potential for applications in clinical routine. However, most of these radiofolates were developed for single photon emission computed tomography imaging, and only a few can be used for positron emission tomography (PET) imaging. The development of suitable 18F‐labeled derivatives for PET imaging of the FR has aroused great interest and recent studies revealed very promising candidates for further development and translation into human applications. In this review, we focus on the development of 18F‐labeled folic acid derivatives for PET imaging of the FR and discuss various radiochemical strategies and approaches towards 18F‐folates. Besides radiochemistry and 18F‐labeling, we briefly look into the crucial pharmacological parameters and the preclinical in vivo performance of those 18F‐folates. Copyright © 2013 John Wiley & Sons, Ltd.
Oral vaccination with a liposome‐encapsulated influenza DNA vaccine protects mice against respiratory challenge infection
Authors: Liu Jing , Wu Jianqi , Wang Bing , Zeng Sheng , Qi Feifei , Lu Changlong , Kimura Yoshinobu , Liu Beixing
Published: October 2013

It is well accepted that vaccination by oral administration has many advantages over injected parenteral immunization. The present study focuses on whether oral vaccination with a DNA vaccine could induce protective immunity against respiratory challenge infection. The M1 gene of influenza A virus was used to construct DNA vaccine using pcDNA 3.1(+) plasmid, a eukaryotic expression vector. The cationic liposomes were used to deliver the constructed DNA vaccine. In vitro and in vivo expression of M1 gene was observed in the cell line and in the intestine of orally vaccinated C57BL/6 mice, respectively. It became clear that this type of oral DNA vaccination was capable of inducing both humoral and cellular immune responses, together with an augmentation of IFN‐γ production. In addition, oral vaccination with liposome‐encapsulated DNA vaccine could protect the mice against respiratory challenge infection. These results suggest that gastrointestinal tract, a constituent member of the common mucosal immune system, is a potent candidate applicable as a DNA vaccine route against virus respiratory diseases. J. Med. Virol. 86:886–894, 2014. © 2013 Wiley Periodicals, Inc.
A stochastic inventory routing problem for infectious medical waste collection
Authors: Nolz Pamela C. , Absi Nabil , Feillet Dominique
Published: October 2013

Abstract–

We consider the problem of designing a logistic system to organize adequate collection of infectious medical waste. Waste materials are produced by patients in self‐treatment, stored at pharmacies and picked up by local authorities for disposal. The problem is formulated as a collector‐managed inventory routing problem, encompassing stochastic aspects, which are common in such problems. Social objectives, specifically the satisfaction of pharmacists and local authorities, as well as the minimization of public health risks, are considered for the real‐world‐motivated inventory routing problem. To optimize the planning process for a predefined time horizon, we take advantage of radio frequency identification technology, which allows an improvement of the planning process for pharmacists as well as local authorities. We develop two solution approaches to optimize the determination of visit dates and corresponding vehicle routes. We design a sampling method and an approach based on an adaptive large neighborhood search algorithm to treat the stochastic problem. The suggested approaches are tested on real‐world data from the region of Provence‐Alpes‐Côte d'Azur, in France. To evaluate the performance of the proposed solution methods, the results for different waste collection scenarios are analyzed and compared. © 2013 Wiley Periodicals, Inc. NETWORKS, Vol. 63(1), 82–95 2014
Negative electron affinity of diamond and its application to high voltage vacuum power switches
Authors: Takeuchi D. , Koizumi S. , Makino T. , Kato H. , Ogura M. , Ohashi H. , Okushi H. , Yamasaki S.
Published: October 2013

This paper reviews the electron emission properties of hydrogen terminated diamond surfaces with a negative electron affinity (NEA), and presents the recent development of 10 kV vacuum switches based on diamond PIN junction electron emitters that utilize such NEA surfaces. The background to this topic, including the electron emission mechanism through NEA, the electronic states of diamond with free excitons, and free carrier injection from a heavily doped layer with hopping conduction into a high purity intrinsic layer with band conduction, is also discussed. Our 10 kV vacuum power switch featuring an NEA diamond PIN junction electron emitter exhibited a breakthrough power transmission efficiency of 73% at 9.8 kV. This result validates the principle of such vacuum power switches, which have the potential to operate at 100 kV with an efficiency beyond 99.9%.
Investigation of NV centers in nano‐ and ultrananocrystalline diamond pillars
Authors: Petkov E. , Rendler T. , Petkov C. , Schnabel F. , Reithmaier J. P. , Wrachtrup J. , Popov C. , Kulisch W.
Published: October 2013

Diamond nanopillars with diameters of 1 μm down to 50 nm have been fabricated from two types of diamond thin films, namely nanocrystalline diamond (NCD) and ultrananocrystalline diamond (UNCD) using electron beam lithography (EBL) and reactive ion etching (RIE) in an inductively coupled oxygen plasma (ICP). Aim of the study was to investigate the suitability of these pillars to incorporate nitrogen‐vacancy (NV) color centers for applications in quantum information technology (QIT). The first part of the investigation is devoted to a characterization of the pillars, their shape, size, and properties. The second part of this investigation concerns the optical properties of NCD and UNCD nanopillars and the incorporation of NV centers within them. Among others, fluorescence mapping and photoluminescence measurements have been employed for this purpose. It turned out that NCD pillars are quite promising for the applications in QIT envisioned. At the present time, the opposite is the case for UNCD pillars. The reasons for these differences will be discussed on the basis of the differences of the two materials NCD and UNCD.
Synthesis of silicon nanopowder from silane gas by RF thermal plasma
Authors: So Keun‐Soo , Lee Hyunjun , Kim Tae‐Hee , Choi Sooseok , Park Dong‐Wha
Published: October 2013

Silicon nanopowder that can be applied as a selective emitter in solar cells was prepared from the decomposition of silane (SiH4) gas by a radio‐frequency (RF) thermal plasma. The RF thermal plasma offers a high‐temperature and contamination‐free environment to produce pure silicon material from SiH4. A steep temperature gradient in the thermal plasma enables the rapid quenching of decomposed material to synthesize nanosized particles. In this experiment, the input power of RF thermal plasma was controlled from 8 to 12 kW. The raw material of SiH4 gas was injected into an argon thermal plasma plume with argon carrier gas. Argon was also used as quenching gas to suppress the growth of silicon nanoparticles. In addition to the input power, the flow rates of carrier and quenching gases were employed as operating variables. The flow rates of carrier and quenching gases were controlled from 15 to 45 L min−1 and from 50 to 250 L min−1, respectively. Polycrystalline spherical silicon nanoparticles that were less than 100 nm in diameter were observed by transmission electron microscopy, Brunauer–Emmett–Teller (BET) surface area measurement, X‐ray diffractometry, and Raman spectrometry. Among the operating variables, the flow rate of carrier gas showed the most significant effect on the size of the nanopowder. The smallest mean particle size of 36 nm was obtained from the highest carrier gas flow rate of 45 L min−1, because the growth of nanopowder was limited by the enhanced axial velocity and quenching rate of in‐flight silicon nanopowder.
CVD precursors for transition metal oxide nanostructures: molecular properties, surface behavior and temperature effects
Authors: Tabacchi Gloria , Fois Ettore , Barreca Davide , Gasparotto Alberto
Published: October 2013

Integrated analyses on a series of β‐diketonate‐diamine transition metal complexes (M = Fe, Co, Cu, Zn) highlight the metal center influence on molecular physico‐chemical properties and provide understanding of the favorable behavior of these compounds as precursors in the chemical vapor deposition (CVD) growth of metal/metal oxide nanomaterials. The Zn complex, which shows the most symmetric coordination environment in the gas phase, is activated in contact with the heated CVD growth surface model. First‐principles simulations evidenced surface‐induced rolling motion of the Zn precursor in the 363–750 K range, suggesting the relevance of vibrationally excited molecular rolling as activation pathway in high temperature surface chemistry.

Molecular properties (left) and hot‐surface behavior (right) of the Zn(hfa)2TMEDA CVD precursor.
Mechanical and electrical properties of the epoxy composites with graphite nanoplatelets and carbon nanotubes
Authors: Vovchenko Ludmila , Lazarenko Oleksandra , Matzui Ludmila , Perets Yulia , Zhuravkov Alexander , Fedorets Volodymyr , Normand Francois Le
Published: October 2013

The influence of various types of fillers – graphite nanoplatelets (GNPs), multi‐walled carbon nanotubes (CNTs) and additional boron nitride (BN) – on the mechanical properties of epoxy resins (ED20 and SEDM2) has been investigated. The content of carbon nanofiller in such composite materials (CMs) varies from 3 to 10 wt.%, while the content of BN was 27 wt.%. The mechanical properties were investigated by the uniaxial compression of cylindrical specimens of CMs. It was found that the values of elastic and plastic deformation, elastic modulus and compression strength depend on the type of epoxy resin, content of carbon filler and availability of BN in CM. Namely, the insertion of carbon fillers into the polymer matrix increases the plastic deformation of CMs, and the addition of BN increases the elastic properties of CMs. It was also shown that the compression of CM specimens leads to a significant decrease of the electrical resistance which is explained by the decrease of the contact resistance between carbon filler particles in conductive chains.
Magnetic force microscopy study of shape engineered FEBID iron nanostructures
Authors: Gavagnin Marco , Wanzenboeck Heinz D. , Belic Domagoj , Shawrav Mostafa M. , Persson Anders , Gunnarsson Klas , Svedlindh Peter , Bertagnolli Emmerich
Published: October 2013

The capability to control matter down to the nanoscale level in combination with the novel magnetic properties of nanomaterials have attracted increasing attention in the last few decades due to their applications in magnetic sensing, hard disc data storage and logic devices. Therefore, many efforts have been devoted to the implementation of both nanofabrication methods as well as characterization of magnetic nanoelements. In this study, Fe‐based nanostructures have been synthesized on Si(100) by focused electron beam induced deposition (FEBID) utilizing iron pentacarbonyl as precursor. The so obtained nanostructures exhibit a remarkably high iron content (Fe > 80 at.%), expected to give rise to a ferromagnetic behaviour. For that reason, magnetic force microscopy (MFM) analyses were performed on the obtained FEBID Fe nanostructures. Moreover, object oriented micromagnetic framework (OOMMF) magnetic simulations have been executed to study the influence of the geometry on the magnetic properties of iron single‐domain nanowires.

FEBID is a mask‐less nanofabrication method based on the injection of precursor gas molecules in proximity of the deposition area where their decomposition is locally induced by a focused electron beam.
On the nature and temperature dependence of the fundamental band gap of In2O3
Authors: Irmscher K. , Naumann M. , Pietsch M. , Galazka Z. , Uecker R. , Schulz T. , Schewski R. , Albrecht M. , Fornari R.
Published: October 2013

The onset of optical absorption in In2O3 at about 2.7 eV is investigated by transmission spectroscopy of single crystals grown from the melt. This absorption is not defect related but is due to the fundamental band gap of In2O3. The corresponding spectral dependence of the absorption coefficient is determined up to α = 2500 cm−1 at a photon energy hν = 3.05 eV at room temperature without indication of saturation. A detailed analysis of the hν dependence of α including low‐temperature absorption data shows that the absorption process can be well approximated by indirect allowed transitions. It is suggested that the fundamental band gap of In2O3 is of indirect nature. The temperature dependence of the fundamental band gap is measured over a wide range from 9 to 1273 K and can be well fitted by a single‐oscillator model. Compared to other semiconductors the reduction of the gap with increasing temperature is exceptionally strong in In2O3.
Identification of a vitamin D3-specific hydroxylase genes through actinomycetes genome mining
Authors: Ban Jun-Gyu , Kim Hyun-Bum , Lee Mi-Jin , Anbu Periasamy , Kim Eung-Soo
Published: October 2013

We previously completed whole-genome sequencing of a rare actinomycete named Sebekia benihana, and identified the complete S. benihana cytochrome P450 complement (CYPome), including 21 cytochrome P450 hydroxylase (CYP), seven ferredoxin (FD), and four ferredoxin reductase (FDR) genes. Through targeted CYPome disruption, a total of 32 S. benihana CYPome mutants were obtained. Subsequently, a novel cyclosporine A region-specific hydroxylase was successfully determined to be encoded by a CYP-sb21 gene by screening the S. benihana CYPome mutants. Here, we report that S. benihana is also able to mediate vitamin D3 (VD3) hydroxylation. Among the 32 S. benihana CYPome mutants tested, only a single S. benihana CYP mutant, ΔCYP-sb3a, failed to show regio-specific hydroxylation of VD3 to 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3. Moreover, the VD3 hydroxylation activity in the ΔCYP-sb3a mutant was restored by CYP-sb3a gene complementation. Since all S. benihana FD and FDR disruption mutants maintained VD3 hydroxylation activity, we conclude that CYP-sb3a, a member of the bacterial CYP107 family, is the only essential component of the in vivo regio-specific VD3 hydroxylation process in S. benihana. Expression of the CYP-sb3a gene exhibited VD3 hydroxylation in the VD3 non-hydroxylating Streptomyces coelicolor, implying that the regio-specific hydroxylation of VD3 is carried out by a specific P450 hydroxylase in S. benihana.
Galsulfase (Naglazyme®) therapy in infants with mucopolysaccharidosis VI
Authors: Harmatz Paul R. , Garcia Paula , Guffon Nathalie , Randolph Linda M. , Shediac Renée , Braunlin Elizabeth , Lachman Ralph S. , Decker Celeste
Published: October 2013

Objective

To evaluate the efficacy and safety of two dose levels of galsulfase (Naglazyme®) in infants with MPS VI.

Study design

This was a phase 4, multicenter, multinational, open‐label, two‐dose level study. Subjects were randomized 1:1 to receive weekly infusions of 1.0 or 2.0 mg/kg of galsulfase for a minimum of 52 weeks. Progression of skeletal dysplasia was determined by monitoring physical appearance, radiographic changes, and growth. Urinary glycosaminoglycan (GAG) levels, gross and fine motor function, cardiac function, vision, hearing, and health resource utilization were evaluated. Safety assessments were performed.

Results

Four infants (aged 3.3–12.7 months) participated in the study. Galsulfase was well tolerated at 1.0 and 2.0 mg/kg/week dose levels with no drug‐related serious adverse events. Two subjects experienced a total of four possible treatment‐related adverse events which were all considered mild. Length and weight remained within age‐expected norms. Skeletal abnormalities continued to progress in all subjects. High baseline urinary GAG levels (mean: 870 μg/mg creatinine) decreased by approximately 70 %; these reduced levels were maintained (mean: 220 μg/mg creatinine at week 52) despite the development of anti‐galsulfase antibodies. Hearing, cardiac function, hepatosplenomegaly, and facial dysmorphism stabilized or improved, but corneal clouding progressed. There was no clear difference in safety or efficacy between the two doses.

Conclusions

Galsulfase at two dose levels was safe and well tolerated in infants. Normal growth was maintained but skeletal abnormalities continued to progress. Urinary GAG levels decreased with treatment. Early initiation of galsulfase may prevent or slow progression of some disease manifestations.
Selective Ethanolysis of Fish Oil Catalyzed by Immobilized Lipases
Authors: Moreno‐Pérez Sonia , Guisan Jose M. , Fernandez‐Lorente Gloria
Published: October 2013

Selective ethanolysis of fish oil was catalyzed by immobilized lipases and their derivatives in organic media. Lipases from Candida antarctica B (CALB), Thermomyces lanuginosa (TLL) and Rhizomucor miehei (RML) were studied. The three lipases were immobilized by anion exchange and hydrophobic adsorption. The discrimination between the ethyl ester of eicosapentaenoic acid (EE‐EPA) and the ethyl ester of docosahexaenoic acid (EE‐DHA) depends on the lipase, the immobilization support, the physico‐chemical modifications of the immobilized lipase derivatives and on the solvents used. TLL and RML were much more selective than CALB. EE‐EPA is released 20‐fold faster than EE‐DHA when ethanolysis was catalyzed, in cyclohexane, by TLL hydrophobically adsorbed on Sepabeads C18. The selectivity and stability of the different derivatives in these polar organic solvents were further improved after physico‐chemical modification. The best results for activity‐selectivity‐stability were obtained in cyclohexane for TLL adsorbed on Sepabeads C18 and further modified via solid‐phase physical modification with a polyethylenimine polymer. In this case, the initial selectivity was higher than 20, and a 80 % of EPA was released as ethyl ester after 3 h at 25 °C. At this conversion, mixtures of ethyl esters highly enriched in the ethyl ester of EPA with less than 5 % of the EE‐DHA were obtained. TLL derivatives remained fully active after incubation for 24 h in anhydrous solvents.
Model-based scaling of the streamwise energy density in high-Reynolds-number turbulent channels
Authors: Moarref Rashad , Sharma Ati S. , Tropp Joel A. , McKeon Beverley J.
Published: October 2013

We study the Reynolds-number scaling and the geometric self-similarity of a gain-based, low-rank approximation to turbulent channel flows, determined by the resolvent formulation of McKeon & Sharma (J. Fluid Mech., vol. 658, 2010, pp. 336–382), in order to obtain a description of the streamwise turbulence intensity from direct consideration of the Navier–Stokes equations. Under this formulation, the velocity field is decomposed into propagating waves (with single streamwise and spanwise wavelengths and wave speed) whose wall-normal shapes are determined from the principal singular function of the corresponding resolvent operator. Using the accepted scalings of the mean velocity in wall-bounded turbulent flows, we establish that the resolvent operator admits three classes of wave parameters that induce universal behaviour with Reynolds number in the low-rank model, and which are consistent with scalings proposed throughout the wall turbulence literature. In addition, it is shown that a necessary condition for geometrically self-similar resolvent modes is the presence of a logarithmic turbulent mean velocity. Under the practical assumption that the mean velocity consists of a logarithmic region, we identify the scalings that constitute hierarchies of self-similar modes that are parameterized by the critical wall-normal location where the speed of the mode equals the local turbulent mean velocity. For the rank-1 model subject to broadband forcing, the integrated streamwise energy density takes a universal form which is consistent with the dominant near-wall turbulent motions. When the shape of the forcing is optimized to enforce matching with results from direct numerical simulations at low turbulent Reynolds numbers, further similarity appears. Representation of these weight functions using similarity laws enables prediction of the Reynolds number and wall-normal variations of the streamwise energy intensity at high Reynolds numbers (${Re}_{\tau } \approx 1{0}^{3} {\unicode{x2013}} 1{0}^{10} $). Results from this low-rank model of the Navier–Stokes equations compare favourably with experimental results in the literature.
The Relationship Between School Connectedness and Mental Health During the Transition to Secondary School: A Path Analysis
Authors: Lester Leanne , Waters Stacey , Cross Donna
Published: October 2013

During the transition from primary to secondary school, students typically experience a new social environment, moving from primary school with small intact classes throughout the day with one main teacher, to a larger secondary school with teachers, classrooms and often classmates changing throughout the day. During this time, students report a reduced sense of connectedness, which has been associated with symptoms of depression and anxiety. This study investigated the temporal association between feeling connected to school and mental health prior to and over the transition period. Data were obtained from 3,459 students in a longitudinal study of adolescents’ knowledge, attitudes and experiences of bullying victimisation and perpetration during the transition from primary school to secondary school. Students completed a questionnaire at four time points from Grade 7 to the end of Grade 9. Path analysis was used to model relationships between school connectedness, depression and anxiety. The findings suggest reciprocal relationships between connectedness and mental health where increased connectedness to school is associated with decreased depression and anxiety; conversely, increased depression and anxiety is associated with decreased connectedness to school. The significant reciprocal associations found in the cross-lag models in the first two years of secondary school indicate the need to intervene during the transition period to improve students’ social and mental health outcomes.
The Force of Face-to-Face Diplomacy: Mirror Neurons and the Problem of Intentions
Authors: Holmes Marcus
Published: October 2013

Face-to-face diplomacy has long been the lynchpin of international politics, yet it has largely been dismissed as irrelevant in theories of cooperation and conflict—as “cheap talk” because leaders have incentives to dissemble. However, diplomats and leaders have argued for years that there is often no substitute for personally meeting a counterpart to hash out an agreement. This article argues that face-to-face diplomacy provides a signaling mechanism that increases the likelihood of cooperation. Face-to-face meetings allow individuals to transmit information and empathize with each other, thereby reducing uncertainty, even when they have strong incentives to distrust the other. The human brain has discrete architecture and processes devoted to parsing others' intentions via cues in face-to-face interaction. These processes enable actors to directly access the intentions of others with a higher degree of certainty than economic and game-theoretic models of bargaining predict.
The Demise of Peace Treaties in Interstate War
Authors: Fazal Tanisha M.
Published: October 2013

The conclusion of peace treaties following war was a norm of international politics for millennia. Since approximately 1950, however, the rate at which interstate wars have ended with a formal peace treaty has declined dramatically. I argue that the costs of concluding peace treaties have risen with the development of the modern canon of the law of war. Using an original data set, I find that states today prefer to avoid admitting to a state of war and risk placing their leaders and soldiers at risk of punishment for any violations of the law of war.
Thinking Ahead: Government Time Horizons and the Legalization of International Investment Agreements
Authors: Blake Daniel J.
Published: October 2013

International institutions help governments make credible commitments to other state and nonstate actors by raising the costs of commitment violation. However, in doing so these institutions generate sovereignty costs for national governments by constraining the autonomy they have to develop and implement policy. Governments respond to this trade-off between the credibility of commitments and policy autonomy differently depending on their time horizons and this shapes their preferences over the design of credibility-enhancing institutions. Governments with long time horizons expect to govern in the future, anticipate that conditions may shift over time, and therefore seek institutional designs that will afford them greater freedom to modify policies in response to changing economic and political conditions. Governments with shorter time horizons, on the other hand, do not anticipate being in power long into the future and therefore are less concerned about maintaining greater room to manipulate policy. I develop this argument in the context of bilateral investment treaties (BITs), focusing in particular on the legalization of obligation in national treatment commitments. I test the argument using an original data set of the design of national treatment obligations in a random sample of 342 BITs. I find that net importers of FDI with longer time horizons are more likely to build in greater policy autonomy in their BITs by scaling back the legalization of their national treatment obligations and that this relationship is robust to controlling for selection into investment treaties.
Using Field Experiments in International Relations: A Randomized Study of Anonymous Incorporation1
Authors: Findley Michael G. , Nielson Daniel L. , Sharman J.C.
Published: October 2013

Efforts to fight international money laundering, corruption, and terrorist financing depend crucially on the prohibition barring the formation of anonymous shell companies. To study the effectiveness of this prohibition, we perform the first international relations (IR) field experiment on a global scale. With university institutional review board (IRB) clearance, we posed as consultants requesting confidential incorporation from 1,264 firms in 182 countries. Testing arguments drawn from IR theory, we probe the treatment effects of specifying (1) the international standards (managerialism), (2) penalties for noncompliance with these standards (rationalism), (3) the desire to follow norms through complying with international standards (constructivism), and (4) status as a U.S. customer. We find that firms prompted about possible legal penalties for violating standards (rationalism) were significantly less likely to respond to inquiries and less likely to comply with international law compared to the placebo condition. Some evidence also suggests that the constructivist condition caused significantly greater rates of noncompliance. The U.S. origin condition and the managerial condition had no significant effects on compliance rates. These results present anomalies for leading theories and underscore the importance of determining causal effects in IR research.
Economic Actors' Lobbying Influence on the Prospects for War and Peace
Authors: Brooks Stephen G.
Published: October 2013

Political scientists and economists have long been interested in the role of special interests in the policymaking process. In the past few years, a series of important new books have argued forcefully that the lobbying activities of economic actors have an important influence on the prospects for war and peace. All of these analyses claim that whether economic actors enhance or decrease the likelihood of conflict ultimately depends on the domestic political balance between economic actors who have a strong vested interest in pushing for peace versus those that do not. I advance two contrary arguments. At least among the advanced states, I posit there are no longer any economic actors who will be favorable toward war and who will lobby the government with this preference. All of the identified mechanisms that previously contributed to such lobbying in these states have been swept away with the end of colonialism and the rise of economic globalization. In particular, I show that the current structure of the global economy now makes it feasible for foreign direct investment to serve as an effective substitute for conquest in a way that was not possible in previous eras. My second argument concerns those economic actors in advanced states with a preference for peace. I posit that it has become unnecessary for them to directly lobby the government to avoid war on economic grounds because economic globalization—the accumulation of decisions by economic actors throughout the globe—now has sufficiently clear economic incentives for leaders.
Administration of antibiotics to ewes at the beginning of the dry-period
Authors: Petridis Ioannis G , Fthenakis George C
Published: October 2013

The objective of the present paper is to review the significance of administration of antibiotics at the end of a lactation period/beginning of the dry-period in ewes. During the stage of active involution, there is an increased risk of new mastitis cases and recrudescence of subclinical infections that had occurred during the previous lactation period. The main pathogens involved in the so-called ‘dry-period mastitis’ are coagulase-negative staphylococci. The principle of antibiotic administration at the end of a lactation period involves the intramammary infusion of a preparation to both mammary glands of ewes in the flock. Although a variety of products is licensed for administration in ewes, preferably the product for administration should be selected on the results of susceptibility testing of bacteria to be isolated from samples from ewes in the flock. In many clinical studies from around the world, performed in dairy- or mutton-production flocks, administration of antimicrobial agents at the end of a lactation period has been found beneficial in curing intramammary infections present at cessation of a lactation period, as well as in minimising the risk for intramammary infections during the dry-period. In dairy flocks, there are also benefits from increase in milk yield and decrease flock bulk milk mean somatic cell counts during the subsequent lactation period. Antibiotic administration at drying-off may be performed to all animals in a flock (‘complete’) or only to those considered to be infected (‘selective’). In all cases, after administration of the antibiotic, definite and complete cessation of the lactation period is essential for success of the procedure. Moreover, maintenance of the prescribed withdrawal periods is essential to safeguard public health. The procedure should always be applied as part of a strategic udder health management plan in a flock; implementation improves the welfare of animals and affords significant financial benefits to the farmer. A mastitis prevention scheme during lactation will minimise the incidence of the disease; effective treatment of cases of the disease during lactation will decrease the bacterial populations in the flock and limit risk of infection of other animals. Administration of antibiotics at the end of a lactation period will complement the above procedures and will contribute to improved mammary health for the forthcoming lactation period.
A review of vitamin D status and CVD
Authors: Cashman Kevin D.
Published: October 2013

Beyond the well-accepted effects on the skeleton, low vitamin D status has been linked to increased risk of several non-skeletal disease, including CVD. If low serum 25-hydroxyvitamin D (25(OH)D) concentration is causally linked to risk of CVD then this is important not only because low vitamin D status is quite common particularly in winter in countries above 40°N, but also of key relevance is the fact that such low vitamin D status can be improved by food-based strategies. The overarching aim of the present paper is to review the current evidence-base to support a link between low vitamin D status and CVD risk. The review initially briefly overviews how mechanistically vitamin D may play a role in CVD and then reviews the current available evidence-base to support a link between low vitamin D status and CVD risk, with particular emphasis on data from the randomised control trials, cohort studies and recent meta-analysis data as well as to the conclusions of a number of authoritative agencies/bodies. Finally, the review summarises current serum 25(OH)D concentrations within a select number of adult populations in the context of different definitions of vitamin D status proposed recently, and then briefly highlights food-based strategies for increasing vitamin D intake and status. In conclusion, at present the data for a causal link between low vitamin D status and CVD are mixed and ambiguous; however, should causality be affirmed by ongoing and future studies, there are food-based strategies for enhanced vitamin D status in the population which could ultimately lower risk of CVD.
Ageing and apoE change DHA homeostasis: relevance to age-related cognitive decline
Authors: Hennebelle Marie , Plourde Mélanie , Chouinard-Watkins Raphaël , Castellano Christian-Alexandre , Barberger-Gateau Pascale , Cunnane Stephen C.
Published: October 2013

Epidemiological studies fairly convincingly suggest that higher intakes of fatty fish andn-3 fatty acids are associated with reduced risk of Alzheimer's disease (AD). DHA in plasma is normally positively associated with DHA intake. However, despite being associated with lower fish and DHA intake, unexpectedly, plasma (or brain) DHA is frequently not lower in AD. This review will highlight some metabolic and physiological factors such as ageing andapoEpolymorphism that influence DHA homeostasis. Compared with young adults, blood DHA is often slightly but significantly higher in older adults without any age-related cognitive decline. Higher plasma DHA in older adults could be a sign that their fish or DHA intake is higher. However, our supplementation and carbon-13 tracer studies also show that DHA metabolism, e.g. transit through the plasma, apparent retroconversion and β-oxidation, is altered in healthy older compared with healthy young adults.ApoE4increases the risk of AD, possibly in part because it too changes DHA homeostasis. Therefore, independent of differences in fish intake, changing DHA homeostasis may tend to obscure the relationship between DHA intake and plasma DHA which, in turn, may contribute to making older adults more susceptible to cognitive decline despite older adults having similar or sometimes higher plasma DHA than in younger adults. In conclusion, recent development of new tools such as isotopically labelled DHA to study DHA metabolism in human subjects highlights some promising avenues to evaluate how and why DHA metabolism changes during ageing and AD.