bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomek-3000 and GenPlex SNP Genotyping in Forensic Genetics
Authors: Stangegaard Michael , Tomas Carmen , Hansen Anders J. , Frank-Hansen Rune , Børsting Claus , Morling Niels 
Published: September 2008

Single nucleotide polymorphism genotyping provides a supplement for conventional short tandem repeats-based kits currently used for human identification. GenPlex (Applied Biosystems (AB), Foster City, CA) is an SNP-genotyping kit based on a multiplex of 48 informative, autosomal SNPs from the SNP forID Consortium. Our objective was to setup, implement, and validate a small and affordable automated liquid-handling robot for forensic casework samples (buccal swaps on FTA-paper and Qiagen purified blood). The reaction scheme consisted of numerous steps and was cumbersome to perform consistently manually. Automation was accomplished with a Biomek-3000 (Beckmann Coulter) laboratory-automated workstation using five in-house-developed methods. All methods allowed the user to select the number of subsequent injections to the capillary electrophoresis instrument (ABI 3130 xl, AB) enabling processing of both partial and full plates. A total of 286 samples were analyzed in duplicates with the GenPlex reaction using the Biomek-3000. The results were compared with those obtained from the same samples using the SNaPshot(AB) single-base extension system. Full concordance of the results was obtained in all but one sample. The results demonstrate that the Biomek-3000 can perform a series of complex reactions leading to highly consistent forensic genetic SNP-typing results.
Automation of Sample Dispensing Using Pocket Tips for Evaluation of CYP2C9 Isoenzyme Reversible Inhibition in an Evolution Precision Pipetting Platform
Authors: Ramírez Manuel , Tudela Consuelo , Crespo Juan B. , Rubles Alicia , Jiménez Antonio , Tarazona Guillermo , Fernández Laura , Sánchez Pilar , Kroncke Doug , Tabanera Noemí , Pérez Joseé , Sánchez Manuel , Tormo José R. , Peláez Fernando 
Published: September 2008

Most of the medicinal chemistry compounds received from other Merck Research Laboratories (MRL) for evaluation in our in vitro counterscreenings are in pure DMSO solution. This solvent has shown to be a key interference factor in the radiometric evaluation of cytochrome P-450 (CYP) inhibition. To avoid this problem, we have been using a ternary solvent solution that keeps DMSO concentration to a minimum during the titration of the compounds.The equipment used at our laboratory to perform the dose—response titration of the compounds in the CYP assays is PerkinElmer Evolution Precision Pipetting Platform (EP3) robots with limited microliter capabilities using disposable tips. The need for a nanoliter dispensing technique that keeps the percentage of DMSO at levels that do not affect the assay, and the need to use pure DMSO solutions at high concentrations to avoid solubility issues of the compounds, moved us to design a new automated sample management process for all compounds that were requested to be tested in these assays.The PocketTips system (nAscent BioSciences Inc., Wellesley Hills, MA) seemed to be a good option for pipetting very low volumes without acquiring new expensive nanoliter liquid handling equipment. Apparent difficulties with implementation were the unavailability of PocketTips for the 96-tips head of the EP3 (PerkinElmer, Waltham, MA) and the need for testing several CYP isoenzymes (up to four) by using the same rack of tips to save run time and reduce costs.In this article, we discuss the entire process to introduce and validate a new dispensing process for sampling of compounds with multiple nanoliters dispensing at the assay level, indicating in detail how we implemented the use of recycled PocketTips in our PerkinElmer EP3 workstations.
Fully Automated Laboratory Robotic System for Automating Sample Preparation and Analysis to Reduce Cost and Time in Drug Development Process
Authors: Saitoh Satoshi , Yoshimori Takayuki 
Published: September 2008

We have developed a fully automated laboratory robotic system (FA-LAS) capable of conducting most of routine experiments. Main objectives for developing this novel robotic system are to streamline the analytical tasks by automating sample preparations and analytical procedures, and to ensure the safety of analysts by assigning risk-involving procedures, such as handling of highly active substances. FA-LAS integrates numbers of unique functional devices and is highly competent for analyses of various research and development products. Comparative evaluations of FA-LAS with conventional manual preparation for drug substances and pharmaceutical products' real quantitative high performance liquid chromatography (HPLC) tests fulfilled this study's targeted criteria, which are 100 ± 5% for accuracy and coefficient of variation (%CV) ≤ 3% for repeatability for both HPLC analyses of drug substances and pharmaceutical products. In addition, several advantages over conventional manual methods were confirmed, such as reducing “working hour” for analysts, eliminating “working-hour” restriction, and decreasing drastically lag time for each prepared sample toward HPLC analysis. FA-LAS's unique features will work as a bridge between the sample management system and automatic documentation system, and it will reduce drastically in human resources, budgets, and time frame for development of pharmaceutical products.
Haem and folate transport by proton-coupled folate transporter/haem carrier protein 1 (SLC46A1)
Authors: Laftah Abas H. , Latunde-Dada Gladys O. , Fakih Sarah , Hider Robert C. , Simpson Robert J. , McKie Andrew T. 
Published: September 2008

Haem carrier protein 1 (HCP1) was originally identified and characterised as a mammalian haem transporter. However, recent evidence has shown that it is also a proton-coupled folate transporter (PCFT) and mutations in the gene cause hereditary folate deficiency in humans. We therefore investigated haem and folate transport characteristics of PCFT/HCP1 bothin vivoandin vitroin CD-1 mice and in the presence or absence of a blocking antibody for PCFT/HCP1, and also in cultured cells (which express PCFT/HCP1 endogenously) to elucidate the specificity and selectivity of PCFT/HCP1. Thein vivostudy showed that the addition of folic acid inhibited59Fe-labelled haem transport in hypoxic mice but had no effect in normal mice. Usingin vitromethods, the results showed increased [3H]folate uptake into everted duodenum from hypoxic mice but uptake was reduced by the addition of haem or PCFT/HCP1 antibodies to the medium. Caco-2 cells transiently transfected with small interfering RNA (siRNA) PCFT/HCP1 duplex oligos resulted in a 69 % reduction in PCFT/HCP1 mRNA when compared with the control siRNA. Both haem and folate uptake were significantly (P < 0·05) reduced in cells transfected with PCFT/HCP1 siRNA; however, the magnitude of reduction with folic acid uptake was greater (48 %) than that of haem (22·5 %). Overall the data support PCFT/HCP1 as a primary folate transporter with a lower affinity for haem. PCFT/HCP1 could therefore play a physiological role in Fe nutrition and the data highlight the potential for the interaction of folate and haem at the level of intestinal absorption.
Maternal undernutrition programmes atherosclerosis in the ApoE*3-Leiden mouse
Authors: Yates Zoe , Tarling Elizabeth J. , Langley-Evans Simon C. , Salter Andrew M. 
Published: September 2008

Poor quality of nutrition during fetal development is associated with adverse health outcomes in adult life. Epidemiological studies suggest that markers of fetal undernutrition are predictive of risk of the metabolic syndrome and CHD. Here we show that feeding a low-protein diet during pregnancy programmed the development of atherosclerosis in ApoE*3-Leiden mice. ApoE*3-Leiden mice carry a mutation of human ApoE*3 rendering them prone to atherosclerosis when fed a diet rich in cholesterol. It was noted that fetal exposure to protein restriction led to a greater degree of dyslipidaemia in mice when fed an atherogenic diet, with low-protein-exposed ApoE*3 mice having elevated total plasma cholesterol (34 % higher;P < 0·001) and TAG (39 % higher;P < 0·001) relative to offspring exposed to a control dietin utero. The low-protein group developed more severe atherosclerotic lesions within the aortic arch (2·61-fold greater lesion area;P < 0·001). Analysis of a targeted gene array suggested a potential role for members of the LDL receptor superfamily, along with similar programmed suppression of the mRNA expression of hepatic sterol regulatory element-binding protein-1c. This indicates that disordered lipid metabolism may play a role in the fetal programming of atherosclerosis in this model. Whereas earlier studies have shown early programming of cardiovascular risk factors, these results demonstrate for the first time that the interaction of prenatal undernutrition with a postnatal atherogenic diet increases the extent of atherosclerotic disease.
Late Neoproterozoic amphibolite-facies metamorphism of a pre-Caledonian basement block in southwest Wedel Jarlsberg Land, Spitsbergen: new evidence from U–Th–Pb dating of monazite
Authors: MAJKA JAROSLAW , MAZUR STANISLAW , MANECKI MACIEJ , CZERNY JERZY , HOLM DANIEL K. 
Published: September 2008

AbstractSouthwest Spitsbergen, Wedel Jarlsberg Land, consists of two Proterozoic crustal blocks with differing metamorphic histories. Both blocks experienced Caledonian greenschist-facies metamorphism, but only the southern block records an earlier pervasive M1 amphibolite-facies metamorphism and strong deformational fabric. In situ EMPA total-Pb monazite geochronology from both matrix and porphyroblast inclusion results indicate that the older M1 metamorphism occurred at 643 ± 9 Ma, consistent with published cooling ages of c. 620 Ma (hornblende) and 580 Ma (mica) obtained from these same rocks. This region thus contains a lithostratigraphic profile and metamorphic history which are unique within the Svalbard Archipelago. Documentation of a pervasive late Neoproterozoic Barrovian metamorphism is difficult to reconcile with a quiescent non-tectonic regime typically inferred for this region, based on the occurrence of rift-drift sequences on the Baltic and Laurentian passive margins. Instead, our new metamorphic age implies an exotic origin of the pre-Devonian basement exposed in SW Spitsbergen and supports models of terrane assembly postulated for the Svalbard Archipelago.
Seven ‘deadly’ assumptions: unravelling the implications of HIV/AIDS among grandmothers in South Africa and beyond
Authors: CHAZAN MAY 
Published: September 2008

ABSTRACTOver the past few years, the pivotal roles older women play in responding to the unprecedented HIV/AIDS epidemic in southern Africa has received increasing recognition by academics, governments, funding agencies, non-governmental organisations, and citizens around the world. Yet, discourses surrounding AIDS and ‘grandmotherhood’ are laden with a number of ungrounded assumptions that have important implications for researchers, advocates and decision-makers. Drawing on ethnographic and survey data predominantly from South Africa, this paper challenges seven such assumptions. The paper illustrates how certain prevailing ‘wisdoms’ about grandmothers and AIDS in southern Africa are not entirely accurate and may mask many women's struggles and vulnerabilities, perpetuate stereotypes and misguide well-meaning policies. It also suggests that the societal impacts of AIDS in the region are, at present, not as dramatic as often portrayed, largely because the strength and resilience of many older women have cushioned some of the negative consequences. The paper thus calls for more nuanced and forward-looking analyses and interventions – ones that recognise grandmothers as central to the society's thin safety net and that grapple with older women's complex and diverse vulnerabilities.
Financial strain, negative social interaction, and self-rated health: evidence from two United States nationwide longitudinal surveys
Authors: KRAUSE NEAL , NEWSOM JASON T. , ROOK KAREN S. 
Published: September 2008

ABSTRACTThree hypotheses concerning negative social interaction in later life were evaluated in this study. First, it was predicted that greater personal economic difficulty is associated with more frequent negative social interaction with social network members in general. Secondly, it was proposed that more frequent negative social interaction exacerbates the undesirable effect of personal financial strain on change in self-rated health during late life. Thirdly, an effort was made to see if some types of negative social interaction, but not others, accentuate the undesirable effects of personal economic problems on self-rated health. Data from two nationwide longitudinal surveys that were conducted in the United States revealed that greater personal financial difficulty is associated with more interpersonal conflict. The findings further indicate that the undesirable effects of personal economic difficulty on change in self-rated health are more pronounced at progressively higher levels of negative social interaction. Finally, the data suggest that one form of negative social interaction (not getting help when it is expected) is more likely to intensify the unwanted effects of personal financial strain on self-rated health than other types of negative social interaction.
An on-line task modification method for singularity avoidance of robot manipulators
Authors: Qiu Changwu , Cao Qixin , Miao Shouhong 
Published: September 2008

SUMMARYIn this paper, we present an on-line task modification method (OTMM) to realize singularity avoidance for nonredundant and redundant manipulators at the velocity level. The method introduces a correction vector, constructed from the task velocity and the singular vector corresponding to the minimum singular value, into the task velocity. The performance is simply affected by the choice of the lower limit of the minimum singular value and a scalar adjusting function, which is monotone with respect to the minimum singular value. The method makes unnecessary avoiding the singularity point by off-line path planning for nonredundant or redundant manipulators, and the effort to check whether the singularity is escapable for redundant manipulators. The simulation results show the effectiveness of the OTMM for on-line singularity avoidance in manipulator motion control.
Game theoretic applications to environmental and natural resource problems
Authors: SUMAILA USSIF RASHID , DINAR ARIEL , ALBIAC JOSE 
Published: September 2008

ABSTRACTGame theory has been useful as an analytical framework for assessing environmental and resource regulations and policies. The papers in this volume provide the latest methodological and applied works in game theory to a wide range of natural and environmental resource problems such as fishing, grazing, pollution, climate change, water allocation, and stochastic production processes. The findings in the papers suggest that game theory is an effective tool for the analysis of the efficient use of shared natural resources; it can be used to identify stable agreements between parties to a resource conflict, and show how non-cooperation over global public goods/bads has a high social cost tag.
Initial experience of 3-tesla apparent diffusion coefficient values in characterizing squamous cell carcinomas of the head and neck
Authors: Srinivasan A. , Dvorak R. , Rohrer S. , Mukherji S.K. 
Published: September 2008

Background: With the increased clinical use of 3-Tesla (3T) magnets, it becomes important to identify the potential applications of advanced magnetic resonance (MR) imaging techniques such as diffusion-weighted imaging in head and neck pathologies. Purpose: To establish the 3T apparent diffusion coefficient (ADC) values for normal neck structures, and to examine the utility of ADC values in distinguishing head and neck squamous cell carcinomas (HNSCC) from normal neck anatomy. Material and Methods: 3T diffusion-weighted imaging was performed on 10 normal volunteers and 10 patients with known HNSCC. In the volunteers, mean ADC was calculated in the parotid gland, submandibular gland, base of the tongue, pterygoid muscle, masseter muscle, paraspinal muscles, true vocal cord, thyroid gland, thyroid cartilage, cricoid cartilage, and lymph nodes. The mean tumor ADC value was calculated from the 10 patients with HNSCC and compared with the normal ADC values from various neck structures. Results: The mean ADC value measured in the HNSCC was 1.101 (±0.214)×10−3mm2/s. This was significantly lower than ADC values of paraspinal muscles, pterygoid muscle, masseter muscle, thyroid gland, and base of the tongue ( P=0.0006, 0.0002, 0.0001, 0.001, and 0.002, respectively). The tumor ADC values were not significantly different from ADC values of parotid and submandibular glands ( P=0.057 and 0.14, respectively). Conclusion: 3T ADC values show potential for distinguishing HNSCC from normal extracranial head and neck structures.
The regulatory framework for marine dredging indicators and their operational efficiency within the UK: a possible model for other nations?
Authors: Bayer Elizabeth , Barnes Richard A. , Rees Hubert L. 
Published: September 2008

Abstract
Bayer, E., Barnes, R. A., and Rees, H. L. 2008. The regulatory framework for marine dredging indicators and their operational efficiency within the UK: a possible model for other nations? – ICES Journal of Marine Science, 65: 1402–1406. The use of indicators within marine policy and legislation is a developing phenomenon worldwide. As governments begin to take a more holistic approach to marine management, it is inevitable that economic and social goals will increasingly become enshrined in environmental regulations. Consequently, it is imperative to reach an understanding as to how scientific, economic, and social goals are interconnected, and how they influence indicator development. Arguably, a more integrated framework is needed to provide policy-makers and legislators with a coherent approach to applying marine indicators within the context of sustainable development. We examine a variety of indicators used in support of the environmental management of the UK marine aggregate-extraction industry and discuss the current UK regulatory framework in relation to the requirements of two EC directives. Additionally, we explore the depth to which interfacing occurs between various policy goals (i.e. scientific, social, economic, and legal). The study highlights the importance of good communication between the various government agencies and disciplines to better achieve sustainable-development objectives. If effective interfacing can be achieved, with scientific aims properly embedded within policy and legislative agendas, then the UK could provide a useful regulatory model for other Member States.
NAI2 Is an Endoplasmic Reticulum Body Component That Enables ER Body Formation in Arabidopsis thaliana
Authors: Yamada Kenji , Nagano Atsushi J. , Nishina Momoko , Hara-Nishimura Ikuko , Nishimura Mikio 
Published: September 2008

Abstract
Plants develop various endoplasmic reticulum (ER)–derived structures, each of which has specific functions. The ER body found in Arabidopsis thaliana is a spindle-shaped structure that specifically accumulates high levels of PYK10/BGLU23, a β-glucosidase that bears an ER-retention signal. The molecular mechanisms underlying the formation of the ER body remain obscure. We isolated an ER body–deficient mutant in Arabidopsis seedlings that we termed nai2. The NAI2 gene (At3g15950) encodes a member of a unique protein family that is only found in the Brassicaceae. NAI2 localizes to the ER body, and a reduction in NAI2 gene expression elongates ER bodies and reduces their numbers. NAI2 deficiency does not affect PYK10 mRNA levels but reduces the level of PYK10 protein, which becomes uniformly diffused throughout the ER. NAI1, a transcription factor responsible for ER body formation, regulates NAI2 gene expression. These observations indicate that NAI2 is a key factor that enables ER body formation and the accumulation of PYK10 in ER bodies of Arabidopsis. Interestingly, ER body–like structures are also restricted to the Brassicales, including the Brassicaceae. NAI2 homologs may have evolved specifically in Brassicales for the purpose of producing ER body–like structures.
Three flavonoids targeting the β‐hydroxyacyl‐acyl carrier protein dehydratase from Helicobacter pylori: Crystal structure characterization with enzymatic inhibition assay
Authors: Zhang Liang , Kong Yunhua , Wu Dalei , Zhang Haitao , Wu Jian , Chen Jing , Ding Jianping , Hu Lihong , Jiang Hualiang , Shen Xu 
Published: September 2008

AbstractFlavonoids are the major functional components of many herbal and insect preparations and demonstrate varied pharmacological functions including antibacterial activity. Here by enzymatic assay and crystal structure analysis, we studied the inhibition of three flavonoids (quercetin, apigenin, and (S)‐sakuranetin) against the β‐hydroxyacyl‐acyl carrier protein dehydratase from Helicobacter pylori (HpFabZ). These three flavonoids are all competitive inhibitors against HpFabZ by either binding to the entrance of substrate tunnel B (binding model A) or plugging into the tunnel C near the catalytic residues (binding model B) mainly by hydrophobic interaction and hydrogen‐bond pattern. Surrounded by hydrophobic residues of HpFabZ at both positions of models A and B, the methoxy group at C‐7 of (S)‐sakuranetin seems to play an important role for the inhibitor's binding to HpFabZ, partly responsible for the higher inhibitory activity of (S)‐sakuranetin than those of quercetin and apigenin against HpFabZ (IC50 in μM: (S)‐sakuranetin, 2.0 ± 0.1; quercetin: 39.3 ± 2.7; apigenin, 11.0 ± 2.5). Our work is expected to supply useful information for understanding the potential antibacterial mechanism of flavonoids.
Structural and biochemical studies of TREX1 inhibition by metals. Identification of a new active histidine conserved in DEDDh exonucleases
Authors: Brucet Marina , Querol‐Audí Jordi , Bertlik Kamila , Lloberas Jorge , Fita Ignacio , Celada Antonio 
Published: September 2008

AbstractTREX1 is the major exonuclease in mammalian cells, exhibiting the highest level of activity with a 3′→5′ activity. This exonuclease is responsible in humans for Aicardi‐Goutières syndrome and for an autosomal dominant retinal vasculopathy with cerebral leukodystrophy. In addition, this enzyme is associated with systemic lupus erythematosus. TREX1 belongs to the exonuclease DEDDh family, whose members display low levels of sequence identity, while possessing a common fold and active site organization. For these exonucleases, a catalytic mechanism has been proposed that involves two divalent metal ions bound to the DEDD motif. Here we studied the interaction of TREX1 with the monovalent cations lithium and sodium. We demonstrate that these metals inhibit the exonucleolytic activity of TREX1, as measured by the classical gel method, as well as by a new technique developed for monitoring the real‐time exonuclease reaction. The X‐ray structures of the enzyme in complex with these two cations and with a nucleotide, a product of the exonuclease reaction, were determined at 2.1 Å and 2.3 Å, respectively. A comparison with the structures of the active complexes (in the presence of magnesium or manganese) explains that the inhibition mechanism is caused by the noncatalytic metals competing with distinct affinities for the two metal‐binding sites and inducing subtle rearrangements in active centers. Our analysis also reveals that a histidine residue (His124), highly conserved in the DEDDh family, is involved in the activity of TREX1, as confirmed by mutational studies. Our results shed further light on the mechanism of activity of the DEDEh family of exonucleases.