bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing Physical Activity of High Intensity to Reduce the Prevalence of Chronic Diseases and Improve Public Health
Authors: Rehn Tommy Aune , Winett Richard A , Wisløff Ulrik , Rognmo Øivind
Published: February 2013

High incidence and prevalence of chronic diseases, increasing obesity and inactivity as well as rising health expenditure represent a set of developments that cannot be considered sustainable, and will have dire long-term consequences given the increasing proportion of elderly people in our society. Based on a review of the experiences from previous large scale population-based prevention programs and the documented effects of increased physical activity and cardiorespiratory fitness on chronic diseases and its risk factors, we argue that increased physical activity, especially vigorous physical activity, is a major way to reduce the prevalence of chronic diseases and improve public health. We conclude that a coordinated population-based intervention program for improved health through increased physical activity in the entire population, with a special focus on high intensity exercise, urgently needs to be implemented nationally and internationally.
Letter to the Editor - The BRAF V600E Mutation is Not Present in All Cells of the Primary Melanoma and May Not Be Detected in All Metastatic Sites
Authors: Schneider Lars Alexander , Barth Thomas F.E. , Huber Margit Anna , Menzel Thomas , Scharffetter-Kochanek Karin , Thal Dietmar , Moller Peter , Marienfeld Ralf
Published: February 2013

The invention of targeted therapy for advanced stage melanoma has made it necessary to perform a mutation
analysis of each melanoma case in order to detect the BRAF V600E mutation required for the prescription of selective
BRAF inhibitors. In this new clinical context it is important to realize that the tumour seeds may come from different
tumour clones and thus not all carry the mutation. We present an illustrative case that shows this phenomenon and discuss
the consequences for clinical management in case of possible false negative mutation testing.
Peristaltic transport of a two-layered fluid in a catheterized tube
Authors: Medhavi Amit , Singh U.K.
Published: February 2013

The flow of a two-layered Newtonian fluid induced by peristaltic waves in a
catheterized tube has been investigated. The expressions for the flow
characteristics- the flow rate, the pressure drop and the friction forces at
the tube and catheter wall are derived. It is found that the pressure drop
increases with the flow rate but decreases with the increasing peripheral
layer thickness and a linear relationship between pressure and flow exists.
The pressure drop increases with the catheter size (radius) and assumes a
high asymptotic magnitude at the catheter size more that the fifty percent
of the tube size. The friction forces at the tube and catheter wall posses
characteristics similar to that of the pressure drop with respect to any
parameter. However, friction force at catheter wall assumes much smaller
magnitude than the corresponding value at the tube wall.
Subsistence System, Paleoecology, and 14C Chronology at Kanmer, a Harappan Site in Gujarat, India
Authors: Goyal Pankaj , Pokharia Anil K , Kharakwal Jeewan Singh , Joglekar Pramod , Rawat Y S , Osada Toshiki
Published: February 2013

This article presents the results of 4 excavation seasons in which botanical and animal remains were collected at the Harappan site of Kanmer in the Kachchh District of Gujarat, India. The findings revealed a subsistence economy consisting of food production with domesticated plants and animals, hunting, fishing, and wild plant gathering. Cultural relics and radiocarbon dating support our identification of different cultural periods at the site. This study provides new insights into the subsistence strategies during different phases of occupation and offers the potential for new subsistence models to be applied at nearby sites, particularly in this peripheral zone of the Indus civilization.
AMS Radiocarbon Dates from Prehispanic Fortifications in the Huaura Valley, Central Coast of Perú
Authors: Vega Margaret Brown , Craig Nathan M , Culleton Brendan J , Kennett Douglas J , Lindo Gerbert Asencios
Published: February 2013

In this paper, we report 11 AMS radiocarbon dates from 8 Prehispanic fortifications located in the Huaura Valley, central coast of Perú. Small fragments of organic material embedded in preserved mud mortar in architecture, and samples from construction layers exposed by looter's holes were used to date architectural features without undertaking extensive excavations. These dates contribute toward refining the chronology of fort building in the valley, and provide a test for assumptions about temporal change and architectural style. The results indicate that fortifications date to at least 3 periods. These data provide a starting point for exploring the occurrence of warfare through time on a regional scale.
Evaluating the Reliability of AMS Dates on Food Residue on Pottery from the Late Prehistoric Central Plains of North America
Authors: Roper Donna C
Published: February 2013

Age offsets of accelerator mass spectrometry (AMS) assays on food residue taken from pottery vessels are well-documented in Europe and Asia in cultural contexts were freshwater aquatic products are attested, but are less well studied in North America. The present study examines a series of residue dates from the late prehistoric Central Plains of North America, comparing them with context dates run on annual plant remains. At least 13 of 23 assays are either incongruent with ages on annual plant remains, inconsistent among themselves within a site, or not credible for their cultural context. The conclusion is that food residue from ceramics does not produce consistently accurate dates. Some possible factors that may serve to introduce old carbon to residue samples are discussed. It also is noted that one's conclusions about the reliability of residue may be conditioned by the precision of the age determinations and by the goals of a specific chronology-building effort.
Freshwater Radiocarbon Reservoir Effects at the Burial Ground of Minino, Northwest Russia
Authors: Wood R E , Higham T F G , Buzilhova A , Suvorov A , Heinemeier J , Olsen J
Published: February 2013

If ancient carbon is incorporated into lakes and rivers, it can be transferred along the foodchain where it can cause radiocarbon dates to appear erroneously old. This effect is known as the 14C freshwater reservoir effect (FRE), and causes particular problems when dating human remains. Several studies have attempted to use carbon and/or nitrogen stable isotopes to predict the size of the FRE, with mixed success. We have examined whether the FRE at the Mesolithic-Neolithic burial ground of Minino, northwest Russia, is correlated with these stable isotope systems. To assess the size of the FRE, 9 pairs of human bone and burial goods were dated, such as spears and pendants made of herbivore bone. In addition, further human and faunal bones were analyzed for carbon and nitrogen stable isotopes. Although these stable isotopes suggest that freshwater resources dominated the protein intake of those buried at Minino, no relationship between stable isotopes and the FRE was found. Instead, we found that the FRE was relatively consistent at 490 ± 80 14C yr. With caution, this can be subtracted from burials at Minino to provide a low-resolution chronology for the burial ground. We demonstrate that it is not possible to assume that a relationship exists between stable isotopes and 14C, and each population thought to be affected by a FRE must be examined individually.
The Patterns of Neolithization in the North Eurasian Forest Zone: A Comment on Hartz et al. (2012)
Authors: Kuzmin Yaroslav V
Published: February 2013

Recently, an article was published in this journal (Hartz et al. 2012), presenting new data on the age of early ceramics in eastern Europe (in particular, the central Russian Plain) and discussing the issues related to the appearance of pottery (i.e. Neolithization) in this region, with wider implications of the results for northern Eurasia. I was one of the reviewers of this paper, which is acknowledged by the authors. However, despite my numerous remarks and comments, many of them were not taken into account. As a result, the work by Hartz et al. (2012) suffers from several flaws; here I point them out and briefly discuss the issue of the Neolithization of Eurasia.
Comments on the Use of Ezee-Filters™ and Ultrafilters at Orau
Authors: Brock Fiona , Higham Tom , Ramsey Christopher Bronk
Published: February 2013

We report variations in age of recent batches of ultrafilter humectant, and also clarify the pore size of Ezee-filters™ used at the Oxford Radiocarbon Accelerator Unit (ORAU).
New HPLC method for in vitro dissolution study of antihypertensive mixture amlodipine and perindopril using an experimental design
Authors: Gumieniczek Anna , Mączka Paulina , Inglot Tadeusz , Pietraś Rafał , Lewkut Elżbieta , Perczak Kinga
Published: February 2013

A new HPLC method was developed for the determination of amlodipine and perindopril in their binary mixture as a part of a routine control of combined formulations. For the first time an HPLC method was used for an in vitro dissolution study of tablets containing the above drugs. The presented method was validated to meet official requirements and this validation included specificity, stability, linearity, precision and accuracy. Chromatography was carried out using a LiChrospher RP-18 column, a mixture containing acetonitrile and phosphate buffer of pH 3.0 (50:50, v/v) as mobile phase and UV detection at 225 nm. The dissolution test was performed using 900 mL of phosphate buffer at pH 5.5 containing 1% cetylpyridini chloride (CPC) at 37°C and 75 rpm, using the paddle method. Robustness procedure was done according to the plan defined by the Plackett-Burman design. The effects of acetonitrile content, pH of the buffer and flow rate of the mobile phase, column temperature, pH and CPC content in the dissolution medium as well as rotation speed of the paddle were considered. After that, both graphical and statistical methods were used for identification of significant and non-significant effects.
Sensitive and fast determination of papaverine by adsorptive stripping voltammetry on renewable mercury film electrode
Authors: Piech Robert , Paczosa-Bator Beata
Published: February 2013

The renewable mercury film electrode, applied for the determination of papaverine traces using differential pulse adsorptive stripping voltammetry (DP AdSV) is presented. The calibration graph obtained for papaverine is linear from 1.25 nM (0.42 µg L−1) to 95 nM (32.2 µg L−1) for a preconcentration time of 60 s, with correlation coefficient of 0.998. For the renewable mercury electrode (Hg(Ag)FE) with a surface area of 9.1 mm2 the detection limit for a preconcentration time of 60 s is 0.7 nM (0.24 µg L−1). The repeatability of the method at a concentration level of the analyte as low as 17 µg L−1, expressed as RSD is 3.3% (n=5). The proposed method was successfully applied and validated by studying the recovery of papaverine from drugs, urine and synthetic solution.
Investigation of SOFC material properties for plant-level modeling
Authors: Kupecki Jakub , Milewski Jarosław , Jewulski Janusz
Published: February 2013

This article describes results of a recent study of SOFC (Solid Oxide Fuel Cell) material properties using a numerical tool. The created model was validated against experimental data collected for two different solid oxide fuel cells. With focus on ionic and electronic conductivities, temperature influence was investigated. Results are presented, compared with available data, and discussed. Model of a micro-CHP (Combined Heat and Power) unit based on a SOFC stack was used for evaluation of system performance with different cells. On-site generated bio-syngas was considered as a fuel fed for the unit. The overall system efficiency was analyzed using an Aspen HYSYS modeling environment. Properties of two generic electrolyte materials were implemented in the models for evaluation of a co-generative unit operation. Electrical and overall efficiencies of systems based on those cells were compared and differences were observed. Micro-scale power units with fuel cells are a promising technology for highly efficient distributed cogeneration. As it was concluded, selection of a proper cell is crucial to assure high system efficiency.
Kinetics and mechanism of solid state imidapril hydrochloride degradation and its degradation impurities identification
Authors: Regulska Katarzyna , Stanisz Beata
Published: February 2013

A detailed stability testing of solid state imidapril hydrochloride (IMD) was performed and its degradation products were identified. The analysis was conducted according to ICH guidelines Q1A(R2). Pure IMD samples were exposed to stress conditions of elevated temperature and relative humidity (T = 363 K, RH = 76.4%) in order to accelerate degradation. The regular loss of IMD content with time, and the formation of two degradation impurities were observed. The appropriate reaction rate constants k (for IMD degradation and for the formation of product I and II) were calculated using Prout-Tompkins equation. The obtained degradation products were separated and identified by means of LC-MS technique. Based on the obtained m/z values, the masses and the structures of the formed degradation impurities were established. Also IMD degradation scheme was constructed. It was demonstrated that under the applied analytical conditions, IMD degradation follows an autocatalytic reaction model with the rate constant k = (4.764 ± 0.34)×10 −6 s −1 and with the parallel formation of two degradation products: imidaprilat and the diketopiperazine derivative. The obtained experimental results are in agreement with IMD degradation pathways proposed theoretically.
Voltammetric methods of reboxetine analysis and the mechanism of its electrode reactions
Authors: Altunöz-Erdoğan Deniz , Erk Nevin , Kılıç Esma
Published: February 2013

Reboxetine (RBX) electrochemical redox behavior at hanging mercury drop (HMDE) and glassy carbon electrodes (GCE) was studied in various pH Britton-Robinson universal buffers using cyclic voltammetry and square-wave voltammetry. RBX was reduced at the HMDE and oxidized at the GCE with reversible adsorption controlled and irreversible diffusion controlled processes respectively. The anodic peak is due to the amine and the cathodic peak may correspond to oxygen protonation. An oxidation reaction mechanism is proposed. The linear relation between peak currents and RBX concentration allowed simple, sensitive, precise and inexpensive voltammetric procedures to be developed. The limit of detection was 0.04 µM RBX. The procedures were successfully applied to human urine and RBX tablet assay. Therapeutic RBX concentrations in human serum were not detected due to strong drug-protein binding. Using bovine serum albumin, the methods were used to investigate the effect of serum protein binding on RBX determination.
Triple Negative Breast Cancer-An Overview and Review of Literature
Authors: Gupta Amit , Jain Jyotika , Kumar Ajay , Kumar Sunil , Wadhwa Neelam
Published: February 2013

Triple-negative breast cancer refers to a specific subtype of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) or Her2/neu. About 12-17 % of ca breast  have triple negative ca breast This subtype of breast cancer is clinically characterized as more aggressive and less responsive to standard treatment and associated with overall poorer prognosis. Chemotherapy is the choice of systemic therapy for triple-negative tumors. They are more susceptible to non-receptor mediated therapies than other tumors. A number of new strategies are currently being tested in clinical trials.DOI: http://dx.doi.org/10.3126/ajms.v3i2.5384 Asian Journal of Medical Sciences 3(2012) 16-20
Time Series Comparison of Models of Auto and Motorcycle Ownership and Mode Choice in a Changing Transportation Environment
Authors: Yagi Sadayuki , Nobel Deo , Kawaguchi Hirohisa
Published: February 2013

This paper presents the results of models of household auto and motorcycle ownership and mode choice that were respectively developed on the basis of two large-scale travel surveys conducted nearly a decade apart. In the Jakarta, Indonesia, metropolitan area, unprecedented changes in the transportation environment, including growth in vehicle ownership and resultant changes in mode shares, occurred during this time. A time series comparison of the models was made, the implications of the major changes that occurred in Jakarta are discussed. Interpretation of the effects of different variables (including basic travel, household, and individual characteristics) in the models estimated for 2002 and 2010 led to insights relative to the changes in the transportation environment and an increase in the complexity of travel behavior. As long as the context of the society does not change, both models should remain unchanged with fixed parameters over a period of time. However, the models indicate quite different parameters with different degrees of significance. Transferability of disaggregate choice models may not always apply in developing urban areas such as Jakarta, even though the model structure remains the same. Such implications may also be worth studying for other urban areas, although similarities may be restricted to regions that share modal and cultural norms.
Characteristics of Mixed Traffic on Urban Arterials with Significant Volumes of Motorized Two-Wheelers
Authors: Asaithambi Gowri , Kanagaraj Venkatesan , Srinivasan Karthik K. , Sivanandan R.
Published: February 2013

Mixed traffic in the cities of many developing countries is characterized by a lack of lane discipline, varying compositions of constituent vehicle types, and significant intraclass variability in static and dynamic characteristics. However, the influence of these factors on traffic flow parameters is not well understood. This study addressed the influence of lane discipline, intraclass variability, and composition on traffic flow characteristics under heterogeneous traffic conditions in Chennai, India. A microscopic traffic simulation model was calibrated and validated with field data from a four-lane divided urban arterial road in Chennai. The preliminary analysis indicated that factors such as composition, intraclass variability, and lane discipline had a statistically significant effect on stream speed. Speed–flow and speed–density relationships were developed on the basis of simulation results. These results showed a clear influence of lack of lane discipline, variability, and composition on stream speed. The influence varied depending on volume level and type of subject vehicle. The effect of composition on capacity was quantified. When two-wheelers had a predominant share, they enjoyed better performance in the absence of lane discipline. However, when cars and heavy vehicles had a significant presence, the impact of the lack of lane discipline was much smaller. The simulation model was applied to evaluate a range of traffic control measures based on vehicle type and lane. The results showed the promise of some measures based on vehicle class, namely, the exclusion of autorickshaws or autorickshaws and heavy vehicles. The findings have interesting implications for efficiency, user experience, and equity in mixed traffic.
Developing Bicycle Equivalents for Mopeds in Shanghai, China
Authors: Chen Xiaohong , Han Hui , Lin Bin
Published: February 2013

The bicycle equivalent (BE) of the moped is a key nonmotorized traffic flow parameter when bicycles and mopeds share the same lanes. However, this parameter should not be considered a constant, because it may be affected by factors such as the mixed proportion of the nonmotorized traffic flow. This study estimated the effects of traffic flow characteristics and road design parameters on the BE. Basic traffic flow parameters (i.e., flow, density, and speed) were extracted from video data collected at three observation sites in Shanghai, China. A concept method was used to calculate the BE of mopeds in terms of their time–space resource occupancy on traffic facilities. The free-flow speed characteristics of bicycles and mopeds were investigated, and relationships between speeds and densities in the mixed traffic flow were analyzed. The BEs were estimated for a range of characteristics related to traffic condition or road design (i.e., moped percentage, traffic flow density, width of nonmotorized traffic lanes, and nonmotorized traffic lane grades). The effects of these characteristics on the BE and the variation trends of the BE were observed, and reasons for these trends are discussed. The study findings provide valuable support for the measurement of nonmotorized traffic mixed with mopeds and bicycles in different traffic and road design conditions and could support future studies for capacity and level of service of dedicated nonmotorized lanes.
Comparative Study of Impacts of Red Light Cameras in China
Authors: Sun Jian , Dong Sheng , Bing Xue , Ni Ying
Published: February 2013

Red light violation (RLV) is a major cause of accidents at signalized intersections. To discourage RLV, several authorities have installed red light cameras (RLCs) at signalized intersections in China. Field observations of critical driver and vehicle parameters were used to extensively investigate RLC effects at two similar intersections, with and without RLC, in Shanghai, China. Related parameters included vehicle speed, driving behaviors during phase transition, RLV, probability of rear-end collision, and driving smoothness. It was concluded that (a) the speed of vehicles passing the RLC intersection was higher; (b) RLCs could simultaneously increase unusual decision behaviors and expand the Type II dilemma zone; (c) RLCs significantly decreased the possibility of RLV and right-angle collision; (d) RLCs had a negative effect on the probability of rear-end collisions, especially for vehicles close to the stop line (however, for those that were not, RLC made rear-end collision more likely); and (e) RLCs would result in a deterioration of driving smoothness because of diverse driving habits.
Sustainable Urban Transport Policy in India
Authors: Mani Akshay , Pai Madhav , Aggarwal Rishi
Published: February 2013

Autorickshaws are ubiquitous in Indian cities. They play an important role in urban mobility by serving as an intermediate public transport mode and providing taxi-like services. Despite their role in urban transport, autorickshaws have received limited policy attention at the national level, which has resulted in problems with quality of service and in environmental and safety issues. Given the critical need to promote sustainable transport in a rapidly urbanizing India, this paper presents key policy focus areas for the autorickshaw sector. These policy areas are based on a structured assessment of the importance of autorickshaws in cities, their role in sustainable transport, the sustainability challenges facing the sector and opportunities to address them, and gaps in the current policy framework. Available literature, government and industry websites, and surveys of stakeholders (regulatory authorities and autorickshaw drivers) were used in this research. The key findings include the following: autorickshaw services play an important role in sustainable transport strategies for managing private motorization and encouraging the use of sustainable modes (public transport); however, as an unorganized sector, autorickshaw services face environmental and safety challenges caused by engine and vehicle design issues that need to be addressed to ensure the role of autorickshaws in sustainable transport. A policy vision is presented to promote organizational reforms and develop sustainable solutions for fuel and engine and vehicle design, and recommendations are provided on the next steps for the central government in taking the policy vision forward.
Evaluation of Accident-Induced Indirect Costs for Measuring Penalties on Violations of Laws
Authors: Yin Shengchao , Chen Xiqun , Li Meng , Shi Qixin , Li Zhiheng
Published: February 2013

Traffic accidents cause significant economic losses, which include not only direct costs, such as damage to vehicles and road facilities, but also indirect costs, such as traffic delays for other travelers. For severe accidents involving violations of laws, the direct economic loss is trivial compared with the indirect economic loss resulting from long hours of congestion and large numbers of affected travelers. Drivers who violate transportation laws should be subject to legal liabilities for both direct and indirect economic losses. To calculate the penalties for violating laws related to traffic accidents, it is important to establish a standard for evaluating the indirect costs of accidents. A general framework for estimating accident-induced indirect costs is proposed. As a key component of the estimation procedures, the delay estimation can be conducted by reconstructing the spatial–temporal traffic flow evolutions on the basis of intelligent transportation system sensors or archived data, or both. The proposed evaluation methodology, which measures on-site arrival–departure cumulative flows and speeds, was compared with the spatial–temporal traffic state evolution approach. As a case study, the proposed approach was applied to two severe traffic accidents that occurred on the G6 Highway (Beijing–Tibet Highway). The promising results verify the feasibility and accuracy of the proposed procedures. The analytic study results also support drafting the related national standard in China.
Linear Electro Optic Effect for High Repetition Rate Carrier Envelope Phase Control of Ultra Short Laser Pulses
Authors: Gobert Olivier , Rovera Daniele , Mennerat Gabriel , Comte Michel
Published: February 2013

This paper is devoted to analyzing the principle and applications of the linear electro-optic (EO) effect for the control of the carrier-envelope-phase (CEP). We introduce and detail here an original method, which relies on the use of an EO dispersive prism pair in a compressor-like configuration. We show that, by choosing an adequate geometry, it is possible to shift the CEP without changing the group delay (isochronous carrier-envelope-phase shifter) or change the induced group delay without varying the CEP. According to our calculations, when applying an electric field around 400 V/cm to the rubidium titanyle phosphate (RTP) prisms in a double pass configuration (2 × 40 mm total length), one obtains a CEP shift of π rad at 800 nm without inducing a group delay. In contrast, this CEP shift is obtained for an electric field around 1.4 kV/cm in a RTP rectangular slab of the same total length and, in this case, the group delay is of the order of a few fs.
Heavy Metal Pollution of Lakes along the Mid-Lower Reaches of the Yangtze River in China: Intensity, Sources and Spatial Patterns
Authors: Zeng Haiao , Wu Jinglu
Published: February 2013

Lakes in the middle and lower reaches of the Yangtze River form a shallow lake group unique in the World that is becoming increasingly polluted by heavy metals. Previous studies have largely focused on individual lakes, with limited exploration of the regional pattern of heavy metal pollution of the lake group in this area. This paper explores the sources, intensity and spatial patterns of heavy metal pollution of lake sediments. A total of 45 sample lakes were selected and the concentrations of key metal elements in the sediments of each lake were measured. The cluster analysis (CA), principal component analysis (PCA) and Geo-accumulation index (Ig) analysis permitted analysis of the source and pollution intensity of the target lakes. Results suggested a notable spatial variation amongst the sample lakes. Lakes in the upper part of the lower reach of the Yangtze River surrounded by typical urban landscapes were strongly or extremely polluted, with high concentrations of Pb, Zn, Cu and Cd in their sediments. This was attributed to large amount of untreated industrial discharges and municipal sewage produced within the lake catchments. In contrast, the heavy-metal pollution of lakes in the Taihu Delta area was notably lower due to industrial restructuring and implementation of effective environmental protection measures. Lakes along the middle reach of Yangtze River surrounded by agricultural areas were unpolluted to moderately polluted by heavy metals overall. Our results suggested that lakes in the central part of China require immediate attention and efforts should be made to implement management plans to prevent further degradation of water quality in these lakes.
Regulation of Translation Initiation under Biotic and Abiotic Stresses
Authors: Echevarría-Zomeño Sira , Yángüez Emilio , Fernández-Bautista Nuria , Castro-Sanz Ana , Ferrando Alejandro , Castellano M.
Published: February 2013

Plants have developed versatile strategies to deal with the great variety of challenging conditions they are exposed to. Among them, the regulation of translation is a common target to finely modulate gene expression both under biotic and abiotic stress situations. Upon environmental challenges, translation is regulated to reduce the consumption of energy and to selectively synthesize proteins involved in the proper establishment of the tolerance response. In the case of viral infections, the situation is more complex, as viruses have evolved unconventional mechanisms to regulate translation in order to ensure the production of the viral encoded proteins using the plant machinery. Although the final purpose is different, in some cases, both plants and viruses share common mechanisms to modulate translation. In others, the mechanisms leading to the control of translation are viral- or stress-specific. In this paper, we review the different mechanisms involved in the regulation of translation initiation under virus infection and under environmental stress in plants. In addition, we describe the main features within the viral RNAs and the cellular mRNAs that promote their selective translation in plants undergoing biotic and abiotic stress situations.
Marine Drugs Best Paper Award 2013
Authors: Han Ophelia
Published: February 2013

To recognize the most outstanding papers in the area of research, development and production of drugs from the sea, including marine natural product chemistry, that have been published in Marine Drugs, we would like to start an annual “Best Paper Award”. [...]
Eleganolone, a Diterpene from the French Marine Alga Bifurcaria bifurcata Inhibits Growth of the Human Pathogens Trypanosoma brucei and Plasmodium falciparum
Authors: Gallé Jean-Baptiste , Attioua Barthélémy , Kaiser Marcel , Rusig Anne-Marie , Lobstein Annelise , Vonthron-Sénécheau Catherine
Published: February 2013

Organic extracts of 20 species of French seaweed have been screened against Trypanosoma brucei rhodesiense trypomastigotes, the parasite responsible for sleeping sickness. These extracts have previously shown potent antiprotozoal activities in vitro against Plasmodium falciparum and Leishmania donovani. The selectivity of the extracts was also evaluated by testing cytotoxicity on a mammalian L6 cell line. The ethyl acetate extract of the brown seaweed, Bifurcaria bifurcata, showed strong trypanocidal activity with a mild selectivity index (IC50 = 0.53 µg/mL; selectivity index (SI) = 11.6). Bio-guided fractionation led to the isolation of eleganolone, the main diterpenoid isolated from this species. Eleganolone contributes only mildly to the trypanocidal activity of the ethyl acetate extract (IC50 = 45.0 µM, SI = 4.0). However, a selective activity against P. falciparum erythrocytic stages in vitro has been highlighted (IC50 = 7.9 µM, SI = 21.6).
Thalassospiramide G, a New γ-Amino-Acid-Bearing Peptide from the Marine Bacterium Thalassospira sp.
Authors: Um Soohyun , Pyee Yuna , Kim Eun-Hee , Lee Sang , Shin Jongheon , Oh Dong-Chan
Published: February 2013

In the chemical investigation of marine unicellular bacteria, a new peptide, thalassospiramide G (1), along with thalassospiramides A and D (2–3), was discovered from a large culture of Thalassospira sp. The structure of thalassospiramide G, bearing γ-amino acids, such as 4-amino-5-hydroxy-penta-2-enoic acid (AHPEA), 4-amino-3,5-dihydroxy-pentanoic acid (ADPA), and unique 2-amino-1-(1H-indol-3-yl) ethanone (AIEN), was determined via extensive spectroscopic analysis. The absolute configuration of thalassospiramide D (3), including 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA), was rigorously determined by 1H–1H coupling constant analysis and chemical derivatization. Thalassospiramides A and D (2–3) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW 264.7 cells, with IC50 values of 16.4 and 4.8 μM, respectively.
Neglschisandrins E–F: Two New Lignans and Related Cytotoxic Lignans from Schisandra neglecta
Authors: Chen Min , Xu Xiumei , Xu Bing , Yang Panpan , Liao Zhihua , Morris-Natschke Susan , Lee Kuo-Hsiung , Chen Daofeng
Published: February 2013

Phytochemical investigation of an ethanolic extract of stems of Schisandra neglecta led to the isolation and identification of two new dibenzocyclooctadiene lignans, designated neglschisandrins E (1) and F (2), and thirteen known lignans. All structures and stereochemistries were determined by spectroscopic methods, including 2D-NMR techniques. The isolates were evaluated for in vitro cytotoxic activity. Among them, compounds 2–6 exhibited moderate to weak cytotoxicity against the human colorectal carcinoma HCT-8 cell line with EC50 values of 7.33~19.8 μg/mL. In addition, compounds 2–4 also exhibited marginal cytotoxicity against the human lung carcinoma A549 cell line with EC50 values of 11.8~15.0 μg/mL.
Artificial and Natural Sialic Acid Precursors Influence the Angiogenic Capacity of Human Umbilical Vein Endothelial Cells
Authors: Bayer Nils , Schubert Uwe , Sentürk Zehra , Rudloff Silvia , Frank Sandra , Hausmann Heike , Geyer Hildegard , Geyer Rudolf , Preissner Klaus , Galuska Sebastian
Published: February 2013

N-acetylneuraminic acid (Neu5Ac) represents the most common terminal carbohydrate residue in many mammalian glycoconjugates and is directly involved in a number of different physiological as well as pathological cellular processes. Endogenous sialic acids derive from the biosynthetic precursor molecule N-acetyl-D-mannosamine (ManNAc). Interestingly, N-acyl-analogues of D-mannosamine (ManN) can also be incorporated and converted into corresponding artificial sialic acids by eukaryotic cells. Within this study, we optimized a protocol for the chemical synthesis of various peracetylated ManN derivatives resulting in yields of approximately 100%. Correct molecular structures of the obtained products ManNAc, N-propanoyl-ManN (ManNProp) and N-butyl-ManN (ManNBut) were verified by GC-, ESI-MS- and NMR-analyses. By applying these substances to human umbilical vein endothelial cells (HUVECs), we could show that each derivative was metabolized to the corresponding N-acylneuraminic acid variant and subsequently incorporated into nascent glycoproteins. To investigate whether natural and/or artificial sialic acid precursors are able to modulate the angiogenic capacity of HUVECs, a spheroid assay was performed. By this means, an increase in total capillary length has been observed when cells incorporated N-butylneuraminic acid (Neu5But) into their glycoconjugates. In contrast, the natural precursor ManNAc inhibited the growth of capillaries. Thus, sialic acid precursors may represent useful agents to modulate blood vessel formation.
Hirtinone, a Novel Cycloartane-Type Triterpene and Other Compounds from Trichilia hirta L. (Meliaceae)
Authors: Vieira Ivo , De Aquino Azevedo Otoniel , De Souza Jucimar , Braz-Filho Raimundo , Dos Santos Gonçalves Milena , De Araújo Marcelo
Published: February 2013

One novel triterpene cycloartane-type, named hirtinone (1), six protolimonoids – nilocitin (2), dihydronilocitin B (3), melianone epimers (4) and (5), piscidinol A (6) and melianone lactone (7), one tertranortriterpenoid, hirtin (8), and one sesquiterpene, spathulenol (9), were identified in the fruits of Trichilia hirta. The structures were established by 1D and 2D NMR (1H and 13C-NMR, DEPTQ, 1H-1H-COSY, 1H-1H-NOESY, HSQC and HMBC), high resolution mass spectroscopy (HR-ESI-MS) and infrared (IR) spectral data.
Electron and hydrogen self-exchange of free radicals of sterically hindered tertiary aliphatic amines investigated by photo-CIDNP
Authors: Goez Martin , Frisch Isabell , Sartorius Ingo
Published: February 2013

The photoreactions of diazabicyclo[2,2,2]octane (DABCO) and triisopropylamine (TIPA) with the sensitizers anthraquinone (AQ) and xanthone (XA) or benzophenone (BP) were investigated by time-resolved photo-CIDNP (photochemically induced dynamic nuclear polarization) experiments. By varying the radical-pair concentration, it was ensured that these measurements respond only to self-exchange reactions of the free amine-derived radicals (radical cations DH•+ or α-amino alkyl radicals D•) with the parent amine DH; the acid–base equilibrium between DH•+ and D• also plays no role. Although the sensitizer does not at all participate in the observed processes, it has a pronounced influence on the CIDNP kinetics because the reaction occurs through successive radical pairs. With AQ, the polarizations stem from the initially formed radical-ion pairs, and escaping DH•+ then undergoes electron self-exchange with DH. In the reaction sensitized with XA (or BP), the polarizations arise in a secondary pair of neutral radicals that is rapidly produced by in-cage proton transfer, and the CIDNP kinetics are due to hydrogen self-exchange between escaping D• and DH. For TIPA, the activation parameters of both self-exchange reactions were determined. Outer-sphere reorganization energies obtained with the Marcus theory gave very good agreement between experimental and calculated values of ∆G‡298.
Malaria Inhibits Surface Expression of Complement Receptor 1 in Monocytes/Macrophages, Causing Decreased Immune Complex Internalization
Authors: Fernandez-Arias Cristina , Lopez Jean Pierre , Hernandez-Perez Jean Nikolae , Bautista-Ojeda Maria Dolores , Branch OraLee , Rodriguez Ana
Published: February 2013

Complement receptor 1 (CR1) expressed on the surface of phagocytic cells binds complement-bound immune complexes (IC), playing an important role in the clearance of circulating IC. This receptor is critical to prevent accumulation of IC, which can contribute to inflammatory pathology. Accumulation of circulating IC is frequently observed during malaria, although the factors contributing to this accumulation are not clearly understood. We have observed that the surface expression of CR1 on monocytes/macrophages and B cells is strongly reduced in mice infected with Plasmodium yoelii, a rodent malaria model. Monocytes/macrophages from these infected mice present a specific inhibition of complement-mediated internalization of IC caused by the decreased CR1 expression. Accordingly, mice show accumulation of circulating IC and deposition of IC in the kidneys that inversely correlate with the decrease in CR1 surface expression. Our results indicate that malaria induces a significant decrease on surface CR1 expression in the monocyte/macrophage population that results in deficient internalization of IC by monocytes/macrophages. To determine whether this phenomenon is found in human malaria patients, we have analyzed 92 patients infected with either P. falciparum (22 patients) or P. vivax (70 patients) , the most prevalent human malaria parasites. The levels of surface CR1 on peripheral monocytes/macrophages and B cells of these patients show a significant decrease compared with uninfected control individuals in the same area. We propose that this decrease in CR1 plays an essential role in impaired IC clearance during malaria.
A Nonallergenic Birch Pollen Allergy Vaccine Consisting of Hepatitis PreS–Fused Bet v 1 Peptides Focuses Blocking IgG toward IgE Epitopes and Shifts Immune Responses to a Tolerogenic and Th1 Phenotype
Authors: Marth Katharina , Breyer Isabella , Focke-Tejkl Margarete , Blatt Katharina , Shamji Mohamed H. , Layhadi Janice , Gieras Anna , Swoboda Ines , Zafred Domen , Keller Walter , Valent Peter , Durham Stephen R. , Valenta Rudolf
Published: February 2013

Allergen-specific immunotherapy is the only allergen-specific and disease-modifying treatment for allergy. The construction and characterization of a vaccine for birch pollen allergy is reported. Two nonallergenic peptides, PA and PB, derived from the IgE-reactive areas of the major birch pollen allergen Bet v 1 were fused to the hepatitis B surface protein, PreS, in four recombinant fusion proteins containing different numbers and combinations of the peptides. Fusion proteins expressed in Escherichia coli and purified to homogeneity showed a lack of IgE reactivity and allergenic activity when tested with sera and basophils from patients allergic to birch pollen. Compared to Bet v 1 allergen, peptides PA and PB showed reduced T cell activation in PBMCs from allergic patients, whereas PreS fusion proteins induced less IL-5 and more IL-10 and IFN-γ. Immunization of rabbits with the fusion proteins, in particular with a PreS fusion protein 2PAPB-PreS, containing two copies of each peptide, induced high levels of IgG Abs against the major IgE-reactive site on Bet v 1 and related allergens. These IgG Abs inhibited allergic patients’ IgE binding to Bet v 1 better than did IgG induced by immunization with complete Bet v 1. Furthermore, 2PAPB-PreS–induced IgG inhibited Bet v 1–induced basophil activation in allergic patients and CD23-facilitated allergen presentation. Our study exemplifies novel beneficial features for a PreS carrier–based peptide vaccine for birch pollen, which, in addition to the established reduction in allergenic activity, include the enhanced focusing of blocking Ab responses toward IgE epitopes, immunomodulatory activity, and reduction of CD23-facilitated allergen presentation.
IL-1 Receptor Regulates microRNA-135b Expression in a Negative Feedback Mechanism during Cigarette Smoke–Induced Inflammation
Authors: Halappanavar Sabina , Nikota Jake , Wu Dongmei , Williams Andrew , Yauk Carole L. , Stampfli Martin
Published: February 2013

Although microRNA-135b (miR-135b) is known to be associated with cancer, with recent work showing that it is massively induced in the pulmonary tissues of mice challenged with nanoparticles suggests a critical role for this microRNA in mediating inflammatory response. In this study, we investigated the expression and function of miR-135b in mice exposed to cigarette smoke or nontypeable Haemophilus influenzae (NTHi). Exposure to both cigarette smoke and NTHi elicited robust lung inflammation, but increased miR-135b expression was observed only in the lungs of cigarette smoke–exposed mice. Using IL-1R 1 knockout mice, we show that miR-135b expression is IL-1R1 dependent. A series of in vitro experiments confirmed the role of IL-1R1 in regulating miR-135b expression. In vitro activation of the IL-1R1 pathway in mouse embryonic fibroblast (NIH3T3) and lung epithelial (FE1) cells resulted in increased miR-135b, which was blocked by IL-1R1 antagonists or small interfering RNA–mediated silencing of IL-1R1 expression. Overexpression of mature miR-135b in NIH3T3 cells (pEGP-mmu-mir-135b) resulted in the suppression of endogenous levels of IL-1R1 expression. pEGP-mmu-miR-135b cells transiently transfected with luciferase reporter vector containing the 3′UTR of mouse IL-1R1 showed reduced luciferase activity. Finally, we demonstrate that miR-135b targets IL-1–stimulated activation of Caspase-1, the IL-1R1 downstream activator of IL-1β leading to suppressed synthesis of the active form of IL-1β protein. These results suggest that miR-135b expression during cigarette smoke–induced inflammation is regulated by IL-1R1 in a regulatory feedback mechanism to resolve inflammation.
Disparate Roles for STAT5 in Primary and Secondary CTL Responses
Authors: Mitchell Diana M. , Williams Matthew A.
Published: February 2013

IL-2 signals during the primary response to infection are essential in shaping CD8+ T cell fate decisions. How CD8+ T cells integrate IL-2 signals in the development of functional memory is not well understood. Because IL-2 induces potent activation of the STAT5 transcription factor, we tested the role of STAT5 in CD8+ memory T cell differentiation and function using a model system in which STAT5 activity is inducibly abrogated upon CD8+ T cell activation. We report that STAT5 activity is broadly important for the expansion and effector function of all effector CTL subsets. After pathogen clearance, STAT5 was required for the survival of effector phenotype memory CTLs during the contraction phase. However, despite its role in supporting full primary CD8+ T cell expansion, and unlike IL-2, STAT5 activity is not required for the development of memory CD8+ T cells capable of robust secondary expansion upon rechallenge. Our findings highlight differential requirements for survival signals between primary and secondary effector CTL, and demonstrate that IL-2–dependent programming of memory CD8+ T cells capable of secondary expansion and secondary effector differentiation is largely STAT5 independent.
Agenesis of Dorsal Pancreas with Eventration of Diaphragm and Intrapancreatic Pseudocyst: A Rare Entity
Authors: Chaudhary Poras , Arora Moninder P.
Published: February 2013

A case of acute pancreatitis in a 43-year-old male patient, which was eventually diagnosed as agenesis of dorsal pancreas with eventration of left hemidiaphragm and intrapancreatic pseudocyst is being reported.
Comparative Study of Different Treatment Options of Grade III and IV Diabetic Foot Ulcers to Reduce the Incidence of Amputations
Authors: Chaudhary Poras , Khandelwal Sachin , Poddar Dev Datta , Saxena Neeraj , Singh Rana , Biswal Upendra C.
Published: February 2013

This study aims to compare the efficacy of antiseptic dressings, hyperbaric oxygen therapy, and recombinant human platelet derived growth factor (rhPDGF) for two reasons: i) to reduce the incidence of lower limb amputations in diabetic foot ulcer; ii) to limit the duration of stay in the hospital. A prospective randomized trial was conducted on 60 patients with stage III and IV diabetic foot ulcers (International Association of Enterostomal Therapy classification) and patients were divided randomly in three different therapy groups - antiseptics, hyperbaric oxygen therapy, recombinant platelet derived growth factor, with 20 patients in each group. Patients were managed initially on inpatient and then on outpatient basis till the ulcer healed completely. Results among three groups were compared using unpaired T test and the level of significance was set at P<0.05 using ANOVA. This study compares the efficacy of hyperbaric oxygen therapy, antiseptic dressings, and rhPDGF in grade III and IV diabetic foot ulcers. P value (0.0348) was significant for complete wound contraction while p value healing time (0.6534) and ulcer size (0.0593) in the groups was not significant. PDGF is safe, effective and easy to apply. Results are comparable with hyperbaric oxygen (HBO) therapy and cost of treatment is lower than other therapies. Diabetic foot ulcer management requires multidisciplinary and aggressive approach. PDGF should be recommended for all grade III and IV diabetic foot ulcer at least 8 weeks old. HBO is equally good an option but has limitations and side effects.