bluuebunny/crossref_metadata_2025 huggingface dataset:
Solving the dilemma of transforming landslide hazard maps into effective policy and regulations
Authors: DeGraff J. V.
Published: January 2012

Abstract. As geoscientists, we often perceive the production of a map or model to adequately define landslide hazard for an area as the answer or end point for reducing risk to people and property. In reality, the risk to people and property remains pretty much the same as it did before the map existed. Real landslide risk reduction takes place when the activities and populations at risk are changed so the consequences of a landslide event results in lower losses. Commonly, this takes place by translating the information embodied in the landslide hazard map into some change in policy and regulation applying to the affected area. This is where the dilemma arises. Scientific information generally has qualifications, gradations, and conditions associated with it. Regulations are necessarily written in language that tries to avoid any need for interpretation. Effectively incorporating geologic information into regulations and ordinances requires continued involvement with their development and implementation. Unless geoscientists are willing to participate in that process, sustainable risk reduction is unlikely to occur.
Introducción
Authors: Arias César Correa , Marcelo Gonçalo , Nascimento Fernando
Published: January 2012

Es para nosotros un gusto presentar el tercer número de la revista Études Ricoeuriennes/Ricoeur Studies (ERRS) dedicado a la reflexión ética de Paul Ricœur.
Coronary Flow in Patients with Three-Vessel Disease: Simulated Hemodynamic Variables in relation to Angiographically Assessed Collaterality and History of Myocardial Infarction
Authors: Abouliatim Issam , Harmouche Majid , Drochon Agnès , Maasrani Mahmoud , Corbineau Hervé , Verhoye Jean-Philippe
Published: January 2012

We study patients with stenoses of the left main coronary artery (LMCA), left anterior descending artery (LAD), and left circumflex branch (LCx) and with chronic occlusion of the right coronary artery (RCA), undergoing off-pump coronary surgery. An analog electrical model is used to provide quantitative estimations of the distribution of flows and pressures across the coronary network (in the stenosed native arteries, the collateral branches, the capillary areas, and so forth). The present paper demonstrates that the clinical information collected for the 10 patients included in the study (Rentrop score, history of myocardial infarction, left ventricular ejection fraction (LVEF)) are well correlated with the predicted hydrodynamic data. Patients with a good collaterality (Rentrop score = 3) or patients without anterior myocardial infarction have (i) less severe stenoses on the LMCA, (ii) lower microvascular resistances, (iii) higher grafts flow rates when the revascularization is performed, (iv) higher collateral flow rates towards the territory of the occluded artery, (v) better perfusion of this area, and (vi) better total perfusion of the heart.
High Dose Infliximab in the Treatment of Refractory Uveitis: Does Dose Matter?
Authors: Sukumaran Sukesh , Marzan Katherine , Shaham Bracha , Reiff Andreas
Published: January 2012

Background. Infliximab (INF) has been shown to be beneficial in treating refractory uveitis, however, no data exist on optimal dosing and the efficacy of higher dosing. Objectives. To compare the efficacy of low-dose (LD) (<10 mg/kg), moderate-dose (MD) (≥10–15 mg/kg), and high-dose (HD) INF (≥15–20 mg/kg) in the treatment of uveitis. Methods. Retrospective chart review children with uveitis diagnosed at Childrens Hospital Los Angeles and Millers Children’s Hospital, CA, USA. Results. Of the 34 INF-treated children, 6 patients received LD, 19 received MD, and 9 received HD. Average disease duration prior to therapy was 10.6, 24.6, and 37.1 months each group, respectively. Topical steroids were discontinued after an average of 3 months, 9.5 months, and 10.2 months in the LD, MD, and HD groups, respectively. We found that 66% of patients receiving LD, 42% of MD, and 66% receiving HD INF failed therapy and required either dose escalation or alternate medication for disease control. Conclusions. INF is beneficial in the treatment of uveitis, and dose escalation up to 4 times above the approved dose is often necessary to achieve disease control in patients with uveitis. Doses < 10 mg/kg every 4 weeks may not be sufficient to control disease.
Strategies for collaboration agreements focusing on innovation
Authors: Cox Pamela
Published: January 2012

Collaborations focusing on innovation are often born with the conception of a technology, typically as a result of one sideâ€™s research effort. Collaborations for innovation can also be made through a deliberate process of identifying strategic synergies that should, with appropriate incentives, lead to jointly created technology in the selected area of interest. The predominant factors motivating the parties to collaborate will heavily influence the agreement structure selected to support the collaboration. If a specific technology was â€œbornâ€ prior to the collaboration, the parties will most likely memorialize their collaboration in an agreement specific to the joint development and commercialization for that technology. In contrast, when the parties are entering the collaboration to stimulate innovation, the agreement is often structured as a master agreement. Regardless of the agreement structure, there are two keys to a successful collaboration for innovation: (1) effective communication; and (2) balancing incentives.
Book Review: Constructing and Deconstructing Patents by Irah H. Donner
Authors: Orange David B.
Published: January 2012

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Digital health investment opportunities abound, but standouts deliver disruptive change
Authors: Burrill G. Steven
Published: January 2012

The convergence of ubiquitous smartphones, wireless Internet, and low-cost monitoring devices, is driving the emergence of a new world of digital health. At the same time, cost pressures on healthcare are creating demand for new ways to not just improve the way patients receive information and care and the way doctors provide it, but fundamentally change the way they interact with each other.Â The article discusses a venture capitalist's approach to investing in the sector.Â
Dissolution Profiles of Lanoxin Tablets in Media Supplemented with Soluble and Insoluble Forms of Fiber
Authors: Michael A. Sandoval  , Hugh D. Smyth  , Jason T. McConville
Published: January 2012

Lanoxin (digoxin) is available as 125 µg or 250 µg tablets for oral administration used to treat heart failure and arrhythmias. The objective of this study was to develop and investigate a comparativedissolutionstudy performed on lanoxin tablets in presence of insoluble or soluble forms of fiber. This study was performed to understand possible influence of fiber (psyillium husk, wheat dextrin, or powdered cellulose)on dissolutionof lanoxin in physiological relevant temperature and pH.Dissolutiontesting was performed using a USP dissolution testing apparatus II paddlerotating at 100 r/min, in 600 mL simulated gastric fluid (pH 1.2) which was maintained at (37 +/- 0.5 °C). A floating cellulose dialysis tube was used to collect sampling fractions. Quantification was performed using a developed and validated high performance liquid chromatographic (HPLC) method. Results indicate that the presence of psyillium husk in the dissolution medium hindered digoxin release. Statistical results reveal that the release profiles of digoxin in presence of wheat dextrin or powdered cellulose did not influence drug release.
Processing of Fine Particles of Soft Metals by Extreme Extrusion
Authors: Fedorov V. T. , Hahn H. , Ivanisenko Yu.
Published: January 2012

The processing of fine dispersed powder particles in the diameter range from 10 to 0.1 µm of soft metals, such as Sn and In, using extreme extrusion (EE) was achieved using a specially designed device. The effect of fine dispersion of bulk metals appears at extrusion rates and pressures, which are one to two orders of magnitude larger than in conventional extrusion. It is proposed that the main mechanism of the fine dispersion using EE is melting due to the high strain rate deformation and the subsequent spraying of the liquid.
The histone deacetylase inhibitor, romidepsin, suppresses cellular immune functions of cutaneous T‐cell lymphoma patients
Authors: Kelly‐Sell Michael J. , Kim Youn H. , Straus Suzanne , Benoit Bernice , Harrison Cameron , Sutherland Katherine , Armstrong Randall , Weng Wen‐Kai , Showe Louise C. , Wysocka Maria , Rook Alain H.
Published: January 2012

Romidepsin is the second histone deacetylase inhibitor (HDACi) approved for the treatment of advanced stages of cutaneous T‐cell lymphoma (CTCL). Recent in vitro data suggest that HDACis suppress immune function although these findings have not been confirmed in patients. Thus, we serially examined the cellular immune function of eight CTCL patients undergoing treatment with three cycles of romidepsin. We measured the patients' natural killer (NK) and dendritic cell (DC) function and performed an in vitro terminal deoxynucleotidyl transferase dUTP nick end labeling assay to measure cellular apoptosis. Patients' NK cell cytolytic activity decreased from baseline to the third cycle of treatment (P = 0.018) but stimulation with a toll‐like receptor (TLR) agonist increased this activity (P = 0.018). At baseline, a TLR agonist could both activate patients' DC (P = 0.043) and stimulate interleukin‐12 protein production (P = 0.043) but both were suppressed after the first cycle of romidepsin. Finally, we observed increased specificity for romidepsin‐induced CD4+ tumor cell apoptosis and dose‐dependent increases in cellular apoptosis of healthy cells in multiple lineages (P < 0.05). These findings raise concern that HDACis suppress immune function in CTCL patients and they support the concurrent use of multiple immune stimulatory agents to preserve the host immune response. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
Neuropsychological intra‐individual variability explains unique genetic variance of ADHD and shows suggestive linkage to chromosomes 12, 13, and 17
Authors: Frazier‐Wood Alexis C. , Bralten Janita , Arias‐Vasquez Alejandro , Luman Marjolein , Ooterlaan Jaap , Sergeant Joseph , Faraone Stephen V. , Buitelaar Jan , Franke Barbara , Kuntsi Jonna , Rommelse Nanda N. J.
Published: January 2012

Attention‐deficit/hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric disorder that is usually accompanied by neuropsychological impairments. The use of heritable, psychometrically robust traits that show association with the disorder of interest can increase the power of gene‐finding studies. Due to the robust association of intra‐individual variability with ADHD on a phenotypic and genetic level, intra‐individual variability is a prime candidate for such an attempt. We aimed to combine intra‐individual variability measures across tasks into one more heritable measure, to examine the relatedness to other cognitive factors, and to explore the genetic underpinnings through quantitative trait linkage analysis. Intra‐individual variability measures from seven tasks were available for 238 ADHD families (350 ADHD‐affected and 195 non‐affected children) and 147 control families (271 children). Intra‐individual variability measures from seven different tasks shared common variance and could be used to construct an aggregated measure. This aggregated measure was largely independent from other cognitive factors related to ADHD and showed suggestive linkage to chromosomes 12q24.3 (LOD = 2.93), 13q22.2 (LOD = 2.36), and 17p13.3 (LOD = 2.00). A common intra‐individual variability construct can be extracted from very diverse neuropsychological tasks; this construct taps into unique genetic aspects of ADHD and may relate to loci conferring risk for ADHD (12q24.3 and 17p13.3) and possibly autism (12q24.3). Given that joining of data across sites boosts the power for genetic analyses, our findings are promising in showing that intra‐individual variability measures are viable candidates for across site analyses where different tasks have been used. © 2012 Wiley Periodicals, Inc.
Responses to ethanol in C57BL/6 versus C57BL/6 × 129 hybrid mice
Authors: Lim Jana P. , Zou Mimi E. , Janak Patricia H. , Messing Robert O.
Published: January 2012

Although genetic background alters responses to ethanol, there has not yet been a methodical quantification of differences in ethanol‐related behaviors between inbred and hybrid mice commonly used in gene‐targeting studies. Here, we compared C57BL/6NTac × 129S6/SvEvTac F1 hybrid mice (B6129S6) with C57BL/6NTac inbred mice (B6NT), and C57BL/6J × 129X1/SvJ (B6129X1) and C57BL/6J × 129S4/SvJae F1 hybrids (B6129S4) with C57BL/6J mice (B6J), in five commonly used tests: continuous access two‐bottle choice drinking, intermittent limited‐access binge drinking, ethanol clearance, ethanol‐induced loss of the righting reflex, and conditioned place preference (CPP) for ethanol. We found that inbred B6J and B6NT mice showed greater ethanol preference and consumption than their respective hybrids when ethanol was continuously available. Within the intermittent limited‐access drinking procedure, though all lines showed similar intake over eight drinking sessions, the average of all sessions showed that B6NT mice drank significantly more ethanol than B6129S6 mice. In addition, B6J mice consumed more ethanol than B6129X1 mice, although they drank less than B6129S4 mice. No differences in ethanol LORR duration were observed between inbred and hybrid mice. Although ethanol clearance was similar among B6J mice and their respective hybrids, B6NT mice cleared ethanol more rapidly than B6129S6 mice. All lines developed CPP for ethanol. Our findings indicate that it may not be necessary to backcross hybrids to an inbred B6 background to study many ethanol‐related behaviors in gene‐targeted mice.
Bleach gel: A simple agarose gel for analyzing RNA quality
Authors: Aranda Patrick S. , LaJoie Dollie M. , Jorcyk Cheryl L.
Published: January 2012

RNA‐based applications requiring high‐quality, non‐degraded RNA are a foundational element of many research studies. As such, it is paramount that the integrity of experimental RNA is validated prior to cDNA synthesis or other downstream applications. In the absence of expensive equipment such as microfluidic electrophoretic devices, and as an alternative to the costly and time‐consuming standard formaldehyde gel, RNA quality can be quickly analyzed by adding small amounts of commercial bleach to TAE buffer‐based agarose gels prior to electrophoresis. In the presence of low concentrations of bleach, the secondary structure of RNA is denatured and potential contaminating RNases are destroyed. Because of this, the ‘bleach gel’ is a functional approach that addresses the need for an inexpensive and safe way to evaluate RNA integrity and will improve the ability of researchers to rapidly analyze RNA quality.
DIFFERENCES IN LENGTH OF STAY FOR HIP REPLACEMENT BETWEEN PUBLIC HOSPITALS, SPECIALISED TREATMENT CENTRES AND PRIVATE PROVIDERS: SELECTION OR EFFICIENCY?
Authors: Siciliani Luigi , Sivey Peter , Street Andrew
Published: January 2012

We investigate differences in patients’ length of stay between National Health Service (NHS) public hospitals, specialised public treatment centres and private treatment centres that provide elective (non‐emergency) hip replacement to publicly funded patients. We find that the specialised public treatment centres and private treatment centres have, on average, respectively 18% and 40% shorter length of stay compared with NHS public hospitals, even after controlling for differences in age, gender, number and type of diagnoses, deprivation and regional variation. Therefore, we interpret such differences as because of efficiency as opposed to selection of less complex patients. Quantile regression suggests that the proportional differences between different provider types are larger at the higher conditional quantiles of length of stay. Copyright © 2012 John Wiley & Sons, Ltd.
AN EVALUATION OF THE UK FOOD STANDARDS AGENCY'S SALT CAMPAIGN
Authors: Shankar Bhavani , Brambila‐Macias Jose , Traill Bruce , Mazzocchi Mario , Capacci Sara
Published: January 2012

Excessive salt intake is linked to cardiovascular disease and several other health problems around the world. The UK Food Standards Agency initiated a campaign at the end of 2004 to reduce salt intake in the population. There is disagreement over whether the campaign was effective in curbing salt intake or not. We provide fresh evidence on the impact of the campaign, by using data on spot urinary sodium readings and socio‐demographic variables from the Health Survey for England over 2003–2007 and combining it with food price information from the Expenditure and Food Survey. Aggregating the data into a pseudo‐panel, we estimate fixed effects models to examine the trend in salt intake over the period and to deduce the heterogeneous effects of the policy on the intake of socio‐demographic groups. Our results are consistent with a previous hypothesis that the campaign reduced salt intakes by approximately 10%. The impact is shown to be stronger among women than among men. Older cohorts of men show a larger response to the salt campaign compared to younger cohorts, while among women, younger cohorts respond more strongly than older cohorts. Copyright © 2012 John Wiley & Sons, Ltd.
Concentrations and annual fluxes of sediment‐associated chemical constituents from conterminous US coastal rivers using bed sediment data
Authors: Horowitz Arthur J. , Stephens Verlin C. , Elrick Kent A. , Smith James J.
Published: January 2012

Coastal rivers represent a significant pathway for the delivery of natural and anthropogenic sediment‐associated chemical constituents to the Atlantic, Pacific and Gulf of Mexico coasts of the conterminous USA. This study entails an accounting segment using published average annual suspended sediment fluxes with published sediment‐associated chemical constituent concentrations for (1) baseline, (2) land‐use distributions, (3) population density, and (4) worldwide means to estimate concentrations/annual fluxes for trace/major elements and total phosphorus, total organic and inorganic carbon, total nitrogen, and sulphur, for 131 coastal river basins. In addition, it entails a sampling and subsequent chemical analysis segment that provides a level of ‘ground truth’ for the calculated values, as well as generating baselines for sediment‐associated concentrations/fluxes against which future changes can be evaluated.

Currently, between 260 and 270 Mt of suspended sediment are discharged annually from the conterminous USA; about 69% is discharged from Gulf rivers (n = 36), about 24% from Pacific rivers (n = 42), and about 7% from Atlantic rivers (n = 54). Elevated sediment‐associated chemical concentrations relative to baseline levels occur in the reverse order of sediment discharges: Atlantic rivers (49%) > Pacific rivers (40%) > Gulf rivers (23%). Elevated trace element concentrations (e.g. Cu, Hg, Pb, Zn) frequently occur in association with present/former industrial areas and/or urban centres, particularly along the northeast Atlantic coast. Elevated carbon and nutrient concentrations occur along both the Atlantic and Gulf coasts but are dominated by rivers in the urban northeast and by southeastern and Gulf coast (Florida) ‘blackwater’ streams. Elevated Ca, Mg, K, and Na distributions tend to reflect local petrology, whereas elevated Ti, S, Fe, and Al concentrations are ubiquitous, possibly because they have substantial natural as well as anthropogenic sources. Almost all the elevated sediment‐associated chemical concentrations found in conterminous US coastal rivers are lower than worldwide averages. Copyright © 2012 John Wiley & Sons, Ltd.
Using chlorofluorocarbons (CFCs) and tritium to improve conceptual model of groundwater flow in the South Coast Aquifers of Laizhou Bay, China
Authors: Han D. M. , Song X. F. , Currell Matthew J. , Tsujimura Maki
Published: January 2012

The southern coastal plain of Laizhou Bay, which is the area most seriously affected by salt water intrusion in north China, is a large alluvial depression, which represents one of the most important hydrogeological units in the coastal region of northern China. Chlorofluorocarbons (CFCs, including CFC‐11, CFC‐12 and CFC‐113) and tritium were used together for dating groundwater up to 50 years old in the study area. There are two cones of depression, caused by intensive over‐exploitation of fresh groundwater in the south and brine water in the north. The assigned CFC apparent ages for shallow groundwater range from 8 a to >50 a. A binary mixing model based on CFC‐113 and CFC‐12 concentrations in groundwater was used to estimate fractions of young and pre‐modern water in shallow aquifers and to identify groundwater mixing processes during saltwater intrusion. Discordance between concentrations of different CFC compounds indicate that shallow groundwater around the Changyi cone of depression is vulnerable to contamination. Pumping activities, CFC contamination, mixing and/or a large unsaturated zone thickness (e.g. >20 m) may be reasons for some groundwater containing CFCs without tritium. Saline intrusion mainly occurs because of large head gradients between fresh groundwater in the south and saline water bodies in the north, forming a wedge of saline water below/within fresh aquifer layers. Both CFC and tritium dates indicate that the majority of the saline water is from >50 a, with little or no modern seawater component. Based on the distribution of CFC apparent ages, tritium contents plus chemical and physical data, a conceptual model of groundwater flow along the investigated Changyi‐Xiaying transect has been developed to describe the hydrogeological processes. Three regimes are identified from south to north: (i) fresh groundwater zone, with a mixing fraction of 0.80–0.65 ‘young’ water calculated with the CFC binary mixing model (groundwater ages <34 a) and 1.9–7.8TU of tritium; (ii) mixing zone characterized by a mixing fraction of 0.05–0.65 young groundwater (ages of 23–44 a), accompanied by local vertical recharge and upward leakage of older groundwater; and (iii) salt water zone, mostly comprising waters with ages beyond the dating range of both CFCs and tritium. Some shallow groundwater in the north of the Changyi groundwater depression belongs to the >50a water group (iii), indicating slow velocity of groundwater circulation and possible drawing in of saline or deep groundwater that is tracer‐free. Copyright © 2012 John Wiley & Sons, Ltd.
Hydrogeological investigation of karst system properties by common use of diverse methods: a case study of Lička Jesenica springs in Dinaric karst of Croatia
Authors: Terzić Josip , Stroj Andrej , Frangen Tihomir
Published: January 2012

Lička Jesenica is a sinking river situated in the Dinaric karst environment of the Lika region of Croatia. The two main karst springs, Veliko Vrelo and Malo Vrelo, provide the majority of Lička Jesenica's water. Because of the quality and abundance of the water they contain, these springs are strategically important to the public water supply. Previous knowledge regarding the springs` karst system has been negligible. Therefore, a bulk hydrogeological research program was conducted with the purposes of establishing protection zones and assessing the springs' water‐supply potential. The research work comprised the following methods: hydrogeological mapping, setting up of monitoring stations for evaluating discharge and water quality, time series analyses (hydrograph–chemograph), hydrochemical analyses, and geophysical surveys. The main results and conclusions of the research include the following: (i) confirmation that both springs drain a common aquifer; (ii) determination of the highly vulnerable nature of the karst systems; (iii) identification of the Veliko Vrelo Spring's more direct connection to the aquifer‐drainage system in comparison to the Malo Vrelo; (iv) estimation of the positions and depths of the springs` main feeding conduits; (v) confirmation of the extent of the geologically presumed catchment area; and (vi) finally, establishment of sanitary protection zones. Copyright © 2012 John Wiley & Sons, Ltd.
Childhood leukemia around French nuclear power plants—The geocap study, 2002–2007
Authors: Sermage‐Faure Claire , Laurier Dominique , Goujon‐Bellec Stéphanie , Chartier Michel , Guyot‐Goubin Aurélie , Rudant Jérémie , Hémon Denis , Clavel Jacqueline
Published: January 2012

The aim of this work is to study the risk of childhood acute leukemia (AL) around French nuclear power plants (NPPs). The nationwide Geocap case–control study included the 2,753 cases diagnosed in mainland France over 2002–2007 and 30,000 contemporaneous population controls. The last addresses were geocoded and located around the 19 NPPs. The study used distance to NPPs and a dose‐based geographic zoning (DBGZ), based on the estimated dose to bone marrow related to NPP gaseous discharges. An odds ratio (OR) of 1.9 [1.0–3.3], based on 14 cases, was evidenced for children living within 5 km of NPPs compared to those living 20 km or further away, and a very similar association was observed in the concomitant incidence study (standardized incidence ratio (SIR) = 1.9 [1.0–3.2]). These results were similar for all the 5‐year‐age groups. They persisted after stratification for several contextual characteristics of the municipalities of residence. Conversely, using the DBGZ resulted in OR and SIR close to one in all of the dose categories. There was no increase in AL incidence over 1990–2001 and over the entire 1990–2007 period. The results suggest a possible excess risk of AL in the close vicinity of French NPPs in 2002–2007. The absence of any association with the DBGZ may indicate that the association is not explained by NPP gaseous discharges. Overall, the findings call for investigation for potential risk factors related to the vicinity of NPP and collaborative analysis of multisite studies conducted in various countries.
Association of lung adenocarcinoma clinical stage with gene expression pattern in noninvolved lung tissue
Authors: Frullanti Elisa , Colombo Francesca , Falvella Felicia S. , Galvan Antonella , Noci Sara , De Cecco Loris , Incarbone Matteo , Alloisio Marco , Santambrogio Luigi , Nosotti Mario , Tosi Davide , Pastorino Ugo , Dragani Tommaso A.
Published: January 2012

Associations between clinical outcome of cancer patients and the gene expression signature in primary tumors at time of diagnosis have been reported. To test whether gene expression patterns in noninvolved lung tissue might correlate with clinical stage in lung adenocarcinoma (ADCA) patients, we compared the transcriptome of noninvolved lung samples from 60 ADCA smoker patients of clinical stage I versus 60 patients with stage >I. Quantitative PCR of 10 genes with the most significant differential expression confirmed the statistical association with clinical stage in eight genes, six of which were downregulated in high‐stage patients. Five of these six genes were also downregulated in lung ADCA tissue as compared to noninvolved tissue. Studies in vitro indicated that four of the genes (SLC14A1, SMAD6, TMEM100 and TXNIP) inhibited colony formation of lung cancer cell lines transfected to overexpress the genes, suggesting their potential tumor‐suppressor activity. Our findings suggest that individual variations in the transcriptional profile of noninvolved lung tissue may reflect the lung ADCA patient's predisposition to tumor aggressiveness.
Influence of bone affinity on the skeletal distribution of fluorescently labeled bisphosphonates in vivo
Authors: Roelofs Anke J , Stewart Charlotte A , Sun Shuting , Błażewska Katarzyna M , Kashemirov Boris A , McKenna Charles E , Russell R Graham G , Rogers Michael J , Lundy Mark W , Ebetino Frank H , Coxon Fraser P
Published: January 2012

Bisphosphonates are widely used antiresorptive drugs that bind to calcium. It has become evident that these drugs have differing affinities for bone mineral; however, it is unclear whether such differences affect their distribution on mineral surfaces. In this study, fluorescent conjugates of risedronate, and its lower-affinity analogues deoxy-risedronate and 3-PEHPC, were used to compare the localization of compounds with differing mineral affinities in vivo. Binding to dentine in vitro confirmed differences in mineral binding between compounds, which was influenced predominantly by the characteristics of the parent compound but also by the choice of fluorescent tag. In growing rats, all compounds preferentially bound to forming endocortical as opposed to resorbing periosteal surfaces in cortical bone, 1 day after administration. At resorbing surfaces, lower-affinity compounds showed preferential binding to resorption lacunae, whereas the highest-affinity compound showed more uniform labeling. At forming surfaces, penetration into the mineralizing osteoid was found to inversely correlate with mineral affinity. These differences in distribution at resorbing and forming surfaces were not observed at quiescent surfaces. Lower-affinity compounds also showed a relatively higher degree of labeling of osteocyte lacunar walls and labeled lacunae deeper within cortical bone, indicating increased penetration of the osteocyte canalicular network. Similar differences in mineralizing surface and osteocyte network penetration between high- and low-affinity compounds were evident 7 days after administration, with fluorescent conjugates at forming surfaces buried under a new layer of bone. Fluorescent compounds were incorporated into these areas of newly formed bone, indicating that “recycling” had occurred, albeit at very low levels. Taken together, these findings indicate that the bone mineral affinity of bisphosphonates is likely to influence their distribution within the skeleton. © 2012 American Society for Bone and Mineral Research.
Activation of PKR/eIF2α signaling cascade is associated with dihydrotestosterone‐induced cell cycle arrest and apoptosis in human liver cells
Authors: Dai Rongyang , Yan Dongmei , Li Juan , Chen Shaokun , Liu Youping , Chen Run , Duan Chunyan , Wei Mei , Li Hong , He Tao
Published: January 2012

Androgen receptor (AR) signaling plays an important role in the development and progression of several liver diseases, including hepatocellular carcinoma (HCC) and non‐alcoholic fatty liver disease (NAFLD). Dihydrotestosterone (DHT) is the active metabolite of the major circulating androgen, testosterone. In this study, we investigated the effect of DHT on human liver cells. We found that DHT not only induces cell cycle arrest but also initiates apoptosis in androgen‐sensitive liver cells, such as SMMC‐7721 and L02. Importantly, DHT/AR induces the activation of RNA‐dependent protein kinase (PKR)/eukaryotic initiation factor‐2 alpha (eIF2α) cascades in androgen‐sensitive liver cells. PKR/eIF2α activation‐induced growth arrest and DNA damage‐inducible gene 153 (GADD153) and heat shock protein 27 (Hsp27) expression contribute to cell cycle arrest in response to DHT. It is notable that DHT administration results in androgen‐sensitive liver cells apoptosis, at least in part, through PKR/eIF2α/GADD153 cascades. These results suggest that the androgen/AR pathway plays a pivotal role in liver cell growth and apoptosis regulating, whose deregulation might be involved in the pathogenesis of liver diseases. J. Cell. Biochem. 113: 1800–1808, 2012. © 2012 Wiley Periodicals, Inc.
Ab initio calculation of structure and transport properties of He…X (X = Zn, Cd, Hg) van der Waals complexes
Authors: Sládek Vladimír , Lukeš Vladimír , Ilčin Michal , Biskupič Stanislav
Published: January 2012

The ground state ab initio CCSD(T) potential curves using various basis sets (aug‐cc‐pVXZ‐PP (X = D, T, Q, 5)) is obtained for the dimers of helium with IIb group metals. The effect of the position of the (mid) bond‐functions on the interaction energy is discussed. A Symmetry Adapted Perturbation Theory decomposition of the interaction energy is provided and the trends in the dimer stabilizing and destabilizing contributions are depicted. The spline fitted potential curves are applied together with rigorous statistical formulae in order to obtain the transport coefficients (viscosity coefficients, diffusion coefficients) and the second virial coefficient both for pure constituents and mixtures. The obtained theoretical results are compared with available experimental data. Molecular dynamics is used to obtain reliable values of the diffusion coefficients for all the systems under study. © 2012 Wiley Periodicals, Inc.
Mechanisms of the cascade synthesis of substituted 4‐amino‐1,2,4‐triazol‐3‐one from huisgen zwitterion and aldehyde hydrazone: A DFT study
Authors: Zhang Wenjing , Zhu Yanyan , Wei Donghui , Tang Mingsheng
Published: January 2012

The detailed reaction mechanisms of the title reaction are shed light on by using the density functional theory (DFT). The calculated results have demonstrated that the whole reaction takes place via four processes (processes (I–IV)), among which, three possible reaction mechanisms are proposed for process (II) (channels 1–3) and two for process (IV) (channels 4–5). According to our calculated results, channel 3 and channel 5 are verified to be most energetically favorable. As interpreted in the text, in process (II), the proton transfer should be performed prior to the nucleophilic attack, and the AA‐Type transfer strategy is more likely to occur. The global reactivity index (GRI) and frontier molecular orbital (FMO) analyses of the aldehyde hydrazone have further supported the AA‐Type mechanism. In process (IV), however, the titled product has been demonstrated to be formed by the synergetic elimination of two protons via a six‐membered ring transition state. Taking an integrated view, the highest energy barrier for the whole reaction along the most favorable pathway is 32.19 kcal/mol, which is consistent with the mild thermal experimental conditions. More interestingly, the qualified mechanisms in this work have given a perfect explanation to the optimal reactants molar ratio of highest yields (R1/R2/R3= 2/1/1) employed in the experiment. © 2012 Wiley Periodicals, Inc.
Application of colloidal gas aphrons for pollution remediation
Authors: Hashim Mohd. Ali , Mukhopadhyay Soumyadeep , Gupta Bhaskar Sen , Sahu Jaya Narayan
Published: January 2012

Colloidal gas aphrons (CGAs), first described by Felix Sebba in his book Foams and Biliquid Foams—Aphrons in 1987, consist of a system of spherical microbubbles with diameters mostly above 25 µm and classified as kugelschaums (ball foam). They possess some colloidal properties and can be pumped at uniform rate through pipes and channels, much like liquids. Also, they have high stability due to very small size and thick surfactant shells. Research work published over the past two decades indicate effective applications of CGAs for clarification of particles and microorganisms, protein separation, gas and nutrient transfer and pollutant separation from water and soil matrices. In this review paper, the techniques for generating CGAs and their application to pollution abatement are discussed. Some mineral separation processes by CGA flotation have also been reviewed because of their relevance to contaminant removal processes. The CGAs were found to function on the principles of bubble entrained floc flotation, electrostatic and ionic interaction, diffusion of entrapped gas and hydrophobicity of the pollutant particles. Two tables have also been provided to present a comparative overview of the generation technologies and the effectiveness of pollution remediation techniques. Copyright © 2012 Society of Chemical Industry
Sewage sludge toxicity in edaphic organism: Analysis of midgut responses in the diplopodRhinocricus padbergi
Authors: Bozzatto Vlamir , Fontanetti Carmem Silvia
Published: January 2012

Diplopods are agile saprophagous invertebrates with the ability to colonize several soil layers. They feed on waste and decaying organic matter, making the soil in which they are present better aerated and mineral‐enriched. Because of their habits, diplopods have been suggested to be used in studies to analyze possible toxic effects of impacted soils in edafic fauna. In that respect, this study aimed at checking the feasibility of using morphological analysis from millipede's midgut as a biomarker for soils exposed to sewage sludge from sewage treatment plants. Histological and histochemical techniques, applied to the speciesRhinocricus padbergi's midgut, were used. Two sewage sludge samples were used; they were collected in two small towns in the countryside of São Paulo State. Both cities are part of the Piracicaba–Capivari–Jundiaí basin (PCJ‐1 and PCJ‐3). For 7 and 15‐day periods, the animals were exposed to 10% concentrations and crude sludge for the PCJ‐1sample and to 1, 10, and 50% concentrations and sludge for the PCJ‐3 sample. The material exposed to the PCJ‐1 sample showed an increase in the presence of cytoplasmic granules in both concentrations in all periods and a slight increase in the rate of epithelial renewal. The material of PCJ‐3 sample presented the same alterations observed in PCJ‐1 sample in higher frequence and over that high quantity of neutral polysaccharides in the hepatic cells layer. We can conclude that with the increase of sewage sludge concentrations tested, there is an increase in morphophysiologicals alterations frequencies found in the diplopods' midgut. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.
CCL19 (ELC) improves TH1‐polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model
Authors: Nguyen‐Hoai Tam , Baldenhofer Gerd , Ahmed Mona Sayed , Pham‐Duc Minh , Gries Margarete , Lipp Martin , Dörken Bernd , Pezzutto Antonio , Westermann Jörg
Published: January 2012

Background

DNA vaccination is an attractive approach for tumor vaccination because plasmid DNA (pDNA) can be used as a ‘general vaccine’ across major histocompatibility complex barriers. Coexpression of immunomodulatory molecules can help to amplify the immunogenicity of DNA vaccines. CCL19 (ELC) is a CC chemokine with immunoregulatory properties, binding to the chemokine receptor CCR7 that is expressed on dendritic cells (DCs) and T cells. In vivo, CCL19 is a key regulator for the interactions between DCs and T cells in regional lymph nodes.

Methods

pDNA encoding Her2/neu and CCL19 was used as an intramuscular vaccine. Vaccination was performed in BALB/c mice, which were subsequently challenged with syngeneic Her2/neu+ tumor cells. Groups of mice were immunized with pDNA(Her2/neu) plus pDNA(CCL19), pDNA(Her2/neu) plus pDNA(CCL19) plus pDNA(GM‐CSF), pDNA(Her2/neu) plus pDNA(GM‐CSF), pDNA(Her2/neu), pDNA(CCL19), pDNA(GM‐CSF) or mock vector. Tumor protection by the vaccine and immune responses were monitored.

Results

Coadministration of pDNA(Her2/neu) and pDNA(CCL19) led to substantial improvement of tumor protection by the vaccine and induced a TH1‐polarized, Her2/neu‐specific immune response. Forty‐seven days after the tumor challenge, 58% of the mice coinjected with pDNA(Her2/neu) and pDNA(CCL19) remained tumor‐free compared to 22% after vaccination with pDNA(Her2/neu) alone. Additional administration of pDNA(GM‐CSF) led to further improvement of tumor protection and an amplification of Her2/neu‐specific immune responses.

Conclusions

CCL19 is able to induce a TH‐1 polarization of the anti‐Her2/neu immune response, which can be further amplified by granulocyte macrophage‐colony‐stimulating factor (GM‐CSF). Clinical use of a pDNA(Her2/neu‐CCL19 ± GM‐CSF) vaccine might be promising in Her2/neu + breast cancer in the clinical situation of minimal residual disease. Copyright © 2012 John Wiley & Sons, Ltd.
Effect of age and gender on cell proliferation and cell surface characterization of synovial fat pad derived mesenchymal stem cells
Authors: Fossett Emma , Khan Wasim S. , Longo Umile Giuseppe , Smitham Peter J.
Published: January 2012

Cell based therapies are being investigated for biological repair of a variety of disorders. Previous work has shown that mesenchymal stem cells (MSCs) from older patients have reduced proliferation rates. As age is associated with greater musculoskeletal morbidity, e.g., osteoarthritis, an optimal MSC expansion strategy is required for older patients. In this in vitro study we investigate how age and gender affect MSC proliferation rate and cell surface characterization, as well as identify a relationship between seeding density and proliferation that could be applied to therapeutic MSC uses. Synovial fat pad derived MSCs were isolated and expanded from 14 patients undergoing total knee replacements. The cells were seeded at densities between 50 and 10,000 cells/cm2 and cell proliferation studies, flow cytometry, and cell surface staining were performed. Females were found to have consistently higher cell proliferation and cell surface marker expression. The cell surface marker CD105 had a constant expression irrespective of age. A statistically significant inverse relationship was found between seeding densities and cell proliferation rates. This study has shown that patient characteristics do effect cell proliferation rate and cell surface characterization, but as seeding density has a significant relationship with proliferation rate, it can be altered, possibly along with other cell culturing strategies, to compensate for the effects of patient factors on MSCs. We have also shown that gender affects cell proliferation and cell surface characterization, something most previous studies may have failed to identify as they group male and female patients together. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1013–1018, 2012
Structural and ultrastructural changes of full‐cycle cultured Pacific bluefin tuna (Thunnus orientalis) muscle slices during chilled storage
Authors: Roy Bimol Chandra , Ando Masashi , Itoh Tomohiro , Tsukamasa Yasuyuki
Published: January 2012

Background: This study examined the structural and ultrastructural changes of dorsal and ventral muscle tissues of full‐cycle cultured Pacific bluefin tuna (PBT), Thunnus orientalis Temminck & Schlegel 1844, cut into slices simulating sashimi and placed in chilled storage for varying periods. Structural and ultrastructural changes were determined in order to understand the physical texture by breaking strength measurement.

Results: Progressive deterioration of myofibril structure was observed during chilled storage (4 °C) of PBT muscle slices over 5 days post mortem. Muscle degradation included detachment between myofibres, detachment of the plasmalemma, disruption of mitochondria, loss of Z‐line density and alignment, cementation of myofibrils, loss of the hexagonal arrangement of thick versus thin myofilaments and migration of subsarcolemmal nuclei to intermyofibrillar spaces.

Conclusion: Loss of myofibre‐myofibre adhesion, detachment of the plasmalemma and disruption of other components did not lower the breaking strength of PBT muscle. This provides evidence that the muscle breaking strength of PBT is not only associated with the detachment of myofibres or detachment of the plasmalemma. Other factors that produce cement‐like substances, such as cementation of the myofibrillar components and degradation of the sarcoplasmic reticulum, may also increase breaking strength. Copyright © 2011 Society of Chemical Industry
Turban pin aspiration: New fashion, new syndrome
Authors: Ilan Ophir , Eliashar Ron , Hirshoren Nir , Hamdan Kasem , Gross Menachem
Published: January 2012

Objectives/Hypothesis:

Turban pin aspiration syndrome is a new clinical entity afflicting young Islamic girls wearing a turban.The goal of this study was to present our experience in diagnosis and treatment of this new entity, define its clinical and epidemiologic features, and shed a new light on the role of fashion in the increased incidence.

Study Design:

A retrospective study in a tertiary university hospital.

Methods:

Review of clinical parameters and epidemiologic features of 26 patients diagnosed with turban pin aspiration syndrome admitted to the Hadassah‐Hebrew University Hospitals in Jerusalem from 1990 to 2010.

Results:

All patients were Muslim females with an average age of 16 years. In all cases, the history was positive for accidental aspiration. Most of the pins were located in the trachea (42%). In 20 cases, the pins were extracted by rigid bronchoscopy without major complications. Fluoroscopy‐assisted rigid bronchoscopy was used successfully in three cases. In one case, the object was self‐ejected by coughing before the bronchoscopy, and two patients were referred to the chest unit for thoracotomy.

Conclusions:

Clinicians should be aware of this distinct form of foreign body aspiration, its method of diagnosis, and extraction techniques. A cultural investigation showed a difference in the turban‐fastening technique of young girls as compared with their mothers. Removal by rigid bronchoscopy is a safe method with a high success rate and should be considered as the preferred extraction method of choice. Laryngoscope, 2012
New evidence on innovation and market structure
Authors: Jadlow Joseph M.
Published: January 2012

Arrow and Demsetz have disagreed on theoretical grounds as to whether the incentive to invent is likely to be greater in a competitive industry or a monopoly one. Past empirical studies of the relationship between the rate of innovation and market structure have suggested that innovation occurs at a faster rate within a competitive market structure. This paper employs more detailed data and a larger sample of markets than have most previous studies of this relationship. Using a sales‐weighted measure of innovation, the paper finds a positive and statistically significant relationship between the overall rate of innovation In individual markets and the level of seller concentration. This implies that public policy which reduces concentration may, through its impact on incentives, have the side effect of reducing the rate of innovation in the markets involved.
Workers' co‐operatives in Denmark
Authors: George Donald A. R.
Published: January 2012

The paper describes the growth and organization of workers' production co‐operatives in Denmark. Various theoretical propositions concerning workers' co‐operatives are tested empirically. All these propositions entail comparisons between co‐operatives and conventional firms in the same industry and are concerned with firms' lifespans, scale elasticities, factor intensities and productivity. In the light of empirical findings the paper briefly discusses the applicability to workers' co‐operatives of the theory of labour‐managed firms.
Strategic groupings as competitive benchmarks for formulating future competitive strategy: A modelling approach
Authors: Kumar K. Ravi , Thomas Howard , Fiegenbaum Avi
Published: January 2012

Previous studies on strategic groups have examined issues such as the identification of strategic groups, the relationship between strategic groups structure and industry performance, and the movement of strategic groups over time. In contrast to previous studies, this paper uses the analytical concepts of game theory to explore the question of what strategic groups will exist in the future. These benchmark (future) strategic groups represent long‐run strategic positions available within an industry and thus reference points for firms in developing sustainable competitive strategies. The benchmark strategic groups are discussed and comments are offered to illustrate how firms can use the benchmark information to redirect their strategic positions in order to survive and remain competitive in the long run.