bluuebunny/crossref_metadata_2025 huggingface dataset:
SZ‐685C, a marine anthraquinone, is a potent inducer of apoptosis with anticancer activity by suppression of the Akt/FOXO pathway
Authors: Xie Gui'e , Zhu Xun , Li Qing , Gu Minghui , He Zhenjian , Wu Jueheng , Li Jun , Lin Yongcheng , Li Mengfeng , She Zhigang , Yuan Jie
Published: January 2010

Background and purpose:  The aims of this study were to investigate the anti‐cancer activity of SZ‐685C, an anthracycline analogue isolated from marine‐derived mangrove endophytic fungi, and to explore the molecular mechanisms underlying such activity.

Experimental approach:  The effect of SZ‐685C on the viability of cancer cell lines was investigated using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. SZ‐685C‐induced apoptosis was assessed by Annexin V‐fluorescein isothiocyanate/propidium iodide staining, terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling assay and analysis of caspase activation. The effect of SZ‐685C on the Akt/FOXO pathway was studied using Western blotting analysis, and the in vivo anti‐tumour efficacy was examined in an MDA‐MB‐435 breast cancer xenograft model.

Key results:  SZ‐685C suppressed the proliferation of six cancer cell lines derived from human breast cancer, prostate cancer, glioma and hepatoma (IC50 values ranged from 3.0 to 9.6 µM) and the growth of breast cancer xenografts in mice. SZ‐685C had a direct apoptosis‐inducing effect through both the extrinsic and intrinsic apoptotic pathways, as shown by activation of caspase‐8 and 9 as well as effector caspase‐3 and poly (ADP‐ribose) polymerase. Phosphorylation of Akt and its downstream effectors, forkhead box protein O1 and forkhead box protein O3a, was down‐regulated in SZ‐685C‐treated cancer cells. Furthermore, the pro‐apoptotic protein Bim was up‐regulated by SZ‐685C treatment consistent with FOXO dephosphorylation.

Conclusions and implications:  SZ‐685C could induce apoptosis through the Akt/FOXO pathway, which consequently leads to the observed anti‐tumour effect both in vitro and in vivo. Our data suggest that SZ‐685C may be a potentially promising Akt inhibitor and anti‐cancer drug candidate.
Pharmacological stimulation and inhibition of insulin secretion in mouse islets lacking ATP‐sensitive K+channels
Authors: Szollosi A , Nenquin M , Henquin JC
Published: January 2010

Background and purpose: ATP‐sensitive potassium channels (KATPchannels) in beta cells are a major target for insulinotropic drugs. Here, we studied the effects of selected stimulatory and inhibitory pharmacological agents in islets lacking KATPchannels.

Experimental approach: We compared insulin secretion (IS) and cytosolic calcium ([Ca2+]c) changes in islets isolated from control mice and mice lacking sulphonylurea receptor1 (SUR1), and thus KATPchannels in their beta cells (Sur1KO).

Key results: While similarly increasing [Ca2+]cand IS in controls, agents binding to site A (tolbutamide) or site B (meglitinide) of SUR1 were ineffective inSur1KO islets. Of two non‐selective blockers of potassium channels, quinine was inactive, whereas tetraethylammonium was more active inSur1KO compared with control islets. Phentolamine, efaroxan and alinidine, three imidazolines binding to KIR6.2 (pore of KATPchannels), stimulated control islets, but only phentolamine retained weaker stimulatory effects on [Ca2+]cand IS inSur1KO islets. Neither KATPchannel opener (diazoxide, pinacidil) inhibitedSur1KO islets. Calcium channel blockers (nimodipine, verapamil) or diphenylhydantoin decreased [Ca2+]cand IS in both types of islets, verapamil and diphenylhydantoin being more efficient inSur1KO islets. Activation of α2‐adrenoceptors or dopamine receptors strongly inhibited IS while partially (clonidine > dopamine) lowering [Ca2+]c(control >Sur1KO islets).

Conclusions and implications: Those drugs retaining effects on IS in islets lacking KATPchannels, also affected [Ca2+]c, indicating actions on other ionic channels. The greater effects of some inhibitors inSur1KO than in control islets might be relevant to medical treatment of congenital hyperinsulinism caused by inactivating mutations of KATPchannels.
Thrombin activation of proteinase‐activated receptor 1 potentiates the myofilament Ca2+sensitivity and induces vasoconstriction in porcine pulmonary arteries
Authors: Maki Jun , Hirano Mayumi , Hoka Sumio , Kanaide Hideo , Hirano Katsuya
Published: January 2010

Background and purpose: Thrombus formation is commonly associated with pulmonary arterial hypertension (PAH). Thrombin may thus play an important role in the pathogenesis and pathophysiology of PAH. Hence, we investigated the contractile effects of thrombin and its mechanism in pulmonary artery.

Experimental approach: The cytosolic Ca2+concentrations ([Ca2+]i), 20 kDa myosin light chain (MLC20) phosphorylation and tension development were evaluated using the isolated porcine pulmonary artery.

Key results: Thrombin induced a sustained contraction in endothelium‐denuded strips obtained from different sites of a pulmonary artery, ranging from the main pulmonary artery to the intrapulmonary artery. In the presence of endothelium, thrombin induced a transient relaxation. The contractile effect of thrombin was abolished by either a protease inhibitor or a proteinase‐activated receptor 1 (PAR1) antagonist, while it was mimicked by PAR1‐activating peptide (PAR1AP), but not PAR4AP. The thrombin‐induced contraction was associated with a small elevation of [Ca2+]iand an increase in MLC20 phosphorylation. Thrombin and PAR1AP induced a greater increase in tension for a given [Ca2+]ielevation than that obtained with high K+‐depolarization. They also induced a contraction at a fixed Ca2+concentration in α‐toxin‐permeabilized preparations.

Conclusions and implications: The present study revealed a unique property of the pulmonary artery. In contrast to normal arteries of the systemic circulation, thrombin induces a sustained contraction in the normal pulmonary artery, by activating PAR1and thereby increasing the sensitivity of the myofilament to Ca2+. This responsiveness of the pulmonary artery to thrombin may therefore contribute to the pathogenesis and pathophysiology of PAH.
Birds as Suppliers of Seed Dispersal in Temperate Ecosystems: Conservation Guidelines from Real‐World Landscapes
Authors: GARCIA DANIEL , ZAMORA REGINO , AMICO GUILLERMO C.
Published: February 2010

Abstract:  Seed dispersal by animals is considered a pivotal ecosystem function that drives plant‐community dynamics in natural habitats and vegetation recovery in human‐altered landscapes. Nevertheless, there is a lack of suitable ecological knowledge to develop basic conservation and management guidelines for this ecosystem service. Essential questions, such as how well the abundance of frugivorous animals predicts seeding function in different ecosystems and how anthropogenic landscape heterogeneity conditions the role of dispersers, remain poorly answered. In three temperate ecosystems, we studied seed dispersal by frugivorous birds in landscape mosaics shaped by human disturbance. By applying a standardized design across systems, we related the frequency of occurrence of bird‐dispersed seeds throughout the landscape to the abundance of birds, the habitat features, and the abundance of fleshy fruits. Abundance of frugivorous birds in itself predicted the occurrence of dispersed seeds throughout the landscape in all ecosystems studied. Even those landscape patches impoverished due to anthropogenic disturbance received some dispersed seeds when visited intensively by birds. Nonetheless, human‐caused landscape degradation largely affected seed‐deposition patterns by decreasing cover of woody vegetation or availability of fruit resources that attracted birds and promoted seed dispersal. The relative role of woody cover and fruit availability in seed dispersal by birds differed among ecosystems. Our results suggest that to manage seed dispersal for temperate ecosystem preservation or restoration one should consider abundance of frugivorous birds as a surrogate of landscape‐scale seed dispersal and an indicator of patch quality for the dispersal function; woody cover and fruit resource availability as key landscape features that drive seedfall patterns; and birds as mobile links that connect landscape patches of different degrees of degradation and habitat quality via seed deposition.
Triptan Exposure During Pregnancy and the Risk of Major Congenital Malformations and Adverse Pregnancy Outcomes: Results From The Norwegian Mother and Child Cohort Study
Authors: Nezvalová‐Henriksen Kateřina , Spigset Olav , Nordeng Hedvig
Published: January 2010

(Headache 2010;50:563‐575)

Objective.— To evaluate the safety of triptan therapy during pregnancy.

Background.— Information on the safety of triptan therapy during pregnancy is scarce and only available for sumatriptan, naratriptan, and rizatriptan. No associations with congenital malformations have been detected so far, but one study found a significant association between sumatriptan exposure during pregnancy and prematurity.

Methods.— The study population consisted of 69,929 pregnant women and their newborn children for whom data on drug exposure and pregnancy outcome were available. Information on triptan therapy and potential socio‐demographic and medical confounding factors was obtained from the Norwegian Mother and Child Cohort Study. Information on congenital malformations and other adverse pregnancy outcomes was obtained from the Norwegian Medical Birth Registry. The datasets were linked via the women's personal identification number. Pearson's χ2 tests and logistic regression analyses were used to identify associations between triptan therapy and pregnancy outcome.

Results.— No significant associations between triptan therapy during the first trimester and major congenital malformations (unadjusted OR: 1.0; 95% CI 0.8‐1.3, adjusted OR: 1.0; 95% CI 0.7‐1.2) or other adverse pregnancy outcomes were found. Triptan therapy during the second and/or third trimesters was significantly associated with atonic uterus (unadjusted OR: 1.5; 95% CI 1.1‐1.9, adjusted OR: 1.4; 95% CI 1.1‐1.8), and blood loss >500 mL during labor (unadjusted OR: 1.3; 95% CI 1.1‐1.5, adjusted OR: 1.3; 95% CI 1.1‐1.5).

Conclusions.— Triptan therapy during pregnancy was not associated with an overall increased risk of congenital malformations. It cannot, however, be excluded that a difference in the risk between triptan use and individual or rare congenital malformations may exist. A slight increase in the risk of atonic uterus and hemorrhage was associated with triptan use during the second and/or third trimesters. Although the present findings are reassuring, confirmation in independent studies is warranted.
Outpatient Home‐Based Continuous Intravenous Dihydroergotamine Therapy for Intractable Migraine
Authors: Charles James A. , Von Dohln Patricia
Published: January 2010

(Headache 2010;50:852‐860)

Background.— Established consecutive‐day inpatient intravenous dihydroergotamine protocols administered by bolus intravenous injection or continuous infusion injection in the hospital have demonstrated efficacy and safety in modifying the course of daily intractable headache. We conducted a study to determine efficacy, tolerability, and feasibility to treat patients with daily intractable headache with continuous intravenous dihydroergotamine in an outpatient home‐based setting.

Methods.— A total of 31 patients fulfilling ICHD‐II criteria for chronic daily headache, 25 with chronic migraine and 6 with medication overuse headache, were treated with outpatient home‐based continuous intravenous dihydroergotamine for 3 days. Patients were pretreated with 10 mg intravenous metoclopramide prior to the first day of infusion and administered 3 mg dihydroergotamine given continuously at a rate of 42 mL/hour on day 1 and 2, and administered 1.5 mg on day 3 at the rate of 21 mL/hour. The primary end point was a change in pain intensity, as measured by an 11‐point numeric pain intensity scale at the end of 3 days. The secondary end point was reduction in headache frequency at long‐term follow‐up.

Results.— Patients reported an average of 63.4% reduction in the intensity of migraine pain by the end of the 3‐day infusion. Side effects were minimal and no serious adverse effects occurred. Approximately one‐third of patients became completely headache‐free after day 3, and 1 patient had no improvement. Long‐term follow‐up data indicated an average 86% reduction in headache frequency and almost every patient converted from chronic daily headache to episodic migraine except for 1 patient. Patients with medication overuse headache were no longer consuming the daily offending medication.

Conclusions.— Efficacy and safety of our outpatient home‐based intravenous dihydroergotamine program compared favorably to that of established inpatient intravenous pulse injection and continuous infusion protocols for the treatment of intractable migraine. The use of outpatient continuous intravenous dihydroergotamine is an effective and well‐tolerated therapy for intractable migraine but without the added cost and inconvenience of hospitalization.
Liberation theology and the voice of the indigenous other in Guatemala
Authors: ROHLOFF PETER
Published: January 2010

The legacy of the liberation theology in Guatemala is complex. Although it mobilized progressive Catholic forces at times, it has not overcome reactionary and conservative church elements. Most importantly, it has not proven entirely capable of rising above elitism, nor has it moved beyond paternalism toward Maya culture.
The Roman Catholic Church: committed to the poor in Guatemala
Authors: JACOBSON R. DANIEL , HOLDEN WILLIAM N.
Published: January 2010

The coexistence of conservative and liberation perspectives within the Roman Catholic Church still causes disagreements. However, since Vatican II, the Catholic Church in Guatemala has established a commitment to act as a church of the poor. There is tension between Guatemala's elite and the Church, which has led to the murders of Church members and the issuance of death threats to others. Although the growth of evangelical movements has caused the Church to lose influence, the Church remains committed to the poor, which places it in sharp contradistinction to neoliberalism.
Historical limits: narrowing possibilities in ‘Ontario's most historic town’
Authors: STERN PAMELA , HALL PETER V.
Published: January 2010

Place branding in heritage tourism development is presented as a strategy that opens up new possibilities for attracting investors and visitors by distilling, capturing and shaping what is distinctive about a place. This representational fix is an efficient marketing device in the sense that it represents places through widely intelligible symbols. Branding is also a limiting activity that locks places in time and class relations. While place branding has always had this dual effect, we argue that it has particularly insidious and limiting consequences for local development under current conditions of roll‐out neoliberalism. Beginning in the 1960s, several prominent residents and outsiders initiated efforts to transform the Town of Cobalt, Ontario, into a mining heritage tourism destination. In 2001, the town entered and won a contest to be named Ontario's Most Historic Town. The following year it persuaded Parks Canada to designate it as a national historic site. These two events provided renewed external validation for the efforts to brand Cobalt as a heritage site and began a new cycle of mining heritage tourism development. However, instead of breaking the dependency relationships that characterize resource regions, the current round of place branding has acted to circumscribe the range of possible economic development options.
Reconfiguring freedom: Muslim piety and the limits of secular law and public discourse in France
Authors: FERNANDO MAYANTHI L.
Published: January 2010

Through an analysis of the practice of veiling, I first examine how pious Muslim French women reconcile the dominant secular oppositions between personal autonomy and religious authority, and between the “true” self and religious norms, as they constitute themselves as religious subjects. I then turn to the 2004 law banning headscarves in public schools, and to the attendant public debates, exploring how this Muslim French religiosity was rendered incommensurable in secular law and unintelligible in public discourse. In so doing, I bring into focus both the underlying assumptions and exigencies of French secularity as well as some of its aporias.
The time of the interval: Historicity, modernity, and epoch in rural France
Authors: HODGES MATT
Published: January 2010

With recognition that historical consciousness, or “historicity,” is culturally mediated comes acknowledgment that periodization of history into epochs is as much a product of cultural practice as a reflection of historical “fact.” In this article, I examine popular “modernist” invocations of epoch in rural France—those positing traditional pasts against fluid presents with uncertain futures—which scholars frequently subordinate to analyses of collective memory and identity politics. Submitting this “response” to French modernity to temporal analysis reveals an additional critique in this periodization, one that valorizes enduring social time over processual temporalities, with implications for the temporal frameworks and ideology of anthropologists.
Being neurologically human today: Life and science and adult cerebral plasticity (an ethical analysis)
Authors: REES TOBIAS
Published: January 2010

Throughout the 20th century, scientists believed that the adult human brain is fully developed, organized in fixed and immutable function‐specific neural circuits. Since the discovery of the profound plasticity of the human brain in the late 1990s, this belief has been thoroughly undermined. In this article, combining ethnographic and historical research, I develop an “ethical analysis” to show that (and in what concrete sense) the emergence of adult cerebral plasticity was a major mutation of the neurologically human—a metamorphosis of the confines within which neuroscience requires all those who live under the spell of the brain to think and live the human.
Akt mediates 17β‐estradiol and/or estrogen receptor‐α inhibition of LPS‐induced tumor necresis factor‐α expression and myocardial cell apoptosis by suppressing the JNK1/2‐NFκB pathway
Authors: Liu Chung‐Jung , Lo Jeng‐Fan , Kuo Chia‐Hua , Chu Chun‐Hsien , Chen Li‐Ming , Tsai Fuu‐Jen , Tsai Chang‐Hai , Tzang Bor‐Show , Kuo Wei‐Wen , Huang Chih‐Yang
Published: January 2010

Evidence shows that women have lower tumour necrosis factor‐α (TNF‐α) levels and lower incidences of heart dysfunction and sepsis‐related morbidity and mortality. To identify the cardioprotective effects and precise cellular/molecular mechanisms behind estrogen and estrogen receptors (ERs), we investigated the effects of 17β‐estradiol (E2) and estrogen receptor α (ERα) on LPS‐induced apoptosis by analyzing the activation of survival and death signalling pathways in doxycycline (Dox)‐inducible Tet‐On/ERα H9c2 myocardial cells and ERα‐transfected primary cardiomyocytes overexpressing ERα. We found that LPS challenge activated JNK1/2, and then induced IκB degradation, NFκB activation, TNF‐α up‐regulation and subsequent myocardial apoptotic responses. In addition, treatments involving E2, membrane‐impermeable BSA‐E2 and/or Dox, which induces ERα overexpression, significantly inhibited LPS‐induced apoptosis by suppressing LPS‐up‐regulated JNK1/2 activity, IκB degradation, NFκB activation and pro‐apoptotic proteins (e.g. TNF‐α, active caspases‐8, t‐Bid, Bax, released cytochrome c, active caspase‐9, active caspase‐3) in myocardial cells. However, the cardioprotective properties of E2, BSA‐E2 and ERα overexpression to inhibit LPS‐induced apoptosis and promote cell survival were attenuated by applying LY294002 (PI3K inhibitor) and PI3K siRNA. These findings suggest that E2, BSA‐E2 and ERα expression exert their cardioprotective effects by inhibiting JNK1/2‐mediated LPS‐induced TNF‐α expression and cardiomyocyte apoptosis through activation of Akt.
Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases
Authors: Haan Claude , Behrmann Iris , Haan Serge
Published: January 2010

Introduction

Structure/function: the potential interest of the Jak domains as drug targets

The growing family of ATP‐competitive nanomolar Jak inhibitors

Analogue‐sensitive kinases and possible applications to Jaks

Structure‐based interpretation of the Jak mutations

Perspectives

Gain‐of‐function mutations in the genes encoding Janus kinases have been discovered in various haematologic diseases. Jaks are composed of a FERM domain, an SH2 domain, a pseudokinase domain and a kinase domain, and a complex interplay of the Jak domains is involved in regulation of catalytic activity and association to cytokine receptors. Most activating mutations are found in the pseudokinase domain. Here we present recently discovered mutations in the context of our structural models of the respective domains. We describe two structural hotspots in the pseudokinase domain of Jak2 that seem to be associated either to myeloproliferation or to lymphoblastic leukaemia, pointing at the involvement of distinct signalling complexes in these disease settings. The different domains of Jaks are discussed as potential drug targets. We present currently available inhibitors targeting Jaks and indicate structural differences in the kinase domains of the different Jaks that may be exploited in the development of specific inhibitors. Moreover, we discuss recent chemical genetic approaches which can be applied to Jaks to better understand the role of these kinases in their biological settings and as drug targets.
Melatonin suppresses cyclosporine A‐induced autophagy in rat pituitary GH3 cells
Authors: Yoo Yeong‐Min , Jeung Eui‐Bae
Published: January 2010

Abstract:  Cyclosporine A (CsA) is a powerful immunosuppressive drug with side effects including the induction of chronic nephrotoxicity including endoplasmic reticulum (ER) stress in tubular cells. Recently, it was reported that autophagy is induced by ER stress and serves to alleviate the associated deleterious effects. In the current study, CsA treatment (0–100 μm) decreased cell survival of rat pituitary GH3 cells in a dose‐dependent manner. At concentrations ranging from 1.0 to 10 μm, CsA induced a dose‐dependent increase in the expression of microtubule‐associated protein 1 light chain 3 (LC3)‐I and LC3‐II. Cells treated with 2.5 μm CsA exhibited cytoplasmic vacuolation, indicating that CsA induces autophagy in rat pituitary GH3 cells. In the presence of 1.0–10 μm CsA, the expression of catalase decreased while that of the ER stress markers, ER luminal binding protein (BiP) and inositol‐requiring enzyme 1 alpha (IRE1α), increased as compared those levels in untreated cells. These results suggested that CsA‐induced autophagy is dependent on ER stress. To determine whether melatonin would protect cells against CsA‐induced autophagy, we treated rat pituitary GH3 cells with melatonin in the presence of CsA. Melatonin treatment (100 and 200 μm) suppressed autophagy induced by 2.5 and 5 μm CsA. Furthermore, co‐treatment with 100 μm melatonin inhibited LC3‐II expression, and increased catalase and phosphorylated p‐ERK levels in the presence of 2.5 and 5 μm CsA. BiP and IRE1α expression in melatonin‐co‐treated cells was superior to that in cells treated with 2.5 and 5 μm CsA alone. Thus, melatonin suppresses CsA‐mediated autophagy in rat pituitary GH3 cells.
Comparison of regional lower limb glucose metabolism in older adults during walking
Authors: Shimada H. , Kimura Y. , Lord S. R. , Oda K. , Ishii K. , Suzuki T. , Ishiwata K.
Published: February 2010

Glucose metabolism in lower limb muscles during walking has an important role in gait efficiency and endurance. The purpose of this study was to identify differences in muscle activity during walking between healthy young and older adults using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). Ten healthy young men (24 ± 2 years) and 10 healthy older men (76 ± 2 years) participated in this study. An FDG PET assessment of each subject was conducted after 50 min of treadmill walking. The images of glucose metabolism in 18 regions of interest were estimated from the standardized uptake value (SUV). The older adults showed a significantly higher FDG uptake in the semitendinosus, biceps femoris, iliacus, gluteus minimus, gluteus medius, and gluteus maximus muscles than the young adults: FDG uptake ratios of SUV in the old to SUV in the young were 3.02, 3.19, 1.66, 1.64, 3.68, and 3.05, respectively. During walking, the FDG uptake in older adults was higher in hamstrings and deep layer hip muscles than that in young adults. These results suggest that intervention to facilitate efficient muscle activity during walking should be practiced to improve gait endurance in older adults with impaired walking patterns.
Effect of ultrasound‐guided, peritendinous injections of adalimumab and anakinra in chronic Achilles tendinopathy: a pilot study
Authors: Fredberg U. , Ostgaard R.
Published: February 2010

A new review suggested that an inflammatory process may be related to the development of tendinopathy and that the inflammation may also play a role in chronic tendinopathy. Hitherto, peritendinous injections of glucocorticosteroids have been used to reduce the inflammation. In an attempt to reduce the possible side effects and the high frequency of relapse of symptoms after local treatments with glucocorticosteroids, new anti‐inflammatory treatments were tested. Ultrasound‐guided, peritendinous injections of adalimumab (tumor necrosis factor ‐α blocker) and anakinra (interleukin‐1 receptor antagonist) were evaluated with regard to reducing pain, tendon thickness, and the blood flow in chronic Achilles tendinopathy. We found in this small pilot study that peritendinous injections of adalimumab had a significant effect on pain sensation at rest in chronic Achilles tendinopathy. Adalimumab had no effect on tendon thickness and contrary to all expectation, the tendon thickness in the anakinra‐treated patients increased significantly after 12 weeks. Adalimumab showed a significant tendency to reduce the blood flow in the tendon over 12 weeks, whereas anakinra had no effect on the blood flow.
A Hybrid Finite‐Difference and Analytic Element Groundwater Model
Authors: Haitjema H.M. , Feinstein D.T. , Hunt R.J. , Gusyev M.A.
Published: January 2010

Regional finite‐difference models tend to have large cell sizes, often on the order of 1–2 km on a side. Although the regional flow patterns in deeper formations may be adequately represented by such a model, the intricate surface water and groundwater interactions in the shallower layers are not. Several stream reaches and nearby wells may occur in a single cell, precluding any meaningful modeling of the surface water and groundwater interactions between the individual features. We propose to replace the upper MODFLOW layer or layers, in which the surface water and groundwater interactions occur, by an analytic element model (GFLOW) that does not employ a model grid; instead, it represents wells and surface waters directly by the use of point‐sinks and line‐sinks. For many practical cases it suffices to provide GFLOW with the vertical leakage rates calculated in the original coarse MODFLOW model in order to obtain a good representation of surface water and groundwater interactions. However, when the combined transmissivities in the deeper (MODFLOW) layers dominate, the accuracy of the GFLOW solution diminishes. For those cases, an iterative coupling procedure, whereby the leakages between the GFLOW and MODFLOW model are updated, appreciably improves the overall solution, albeit at considerable computational cost. The coupled GFLOW–MODFLOW model is applicable to relatively large areas, in many cases to the entire model domain, thus forming an attractive alternative to local grid refinement or inset models.
A triad of evidence for care of women with genital piercings
Authors: Young Cathy , Armstrong Myrna L. , Roberts Alden E. , Mello Inola , Angel Elayne
Published: January 2010

Purpose: To add three further dimensions of evidence for the care of women with genital piercings (GPs).

Data sources: Following a literature review, a cross‐sectional study replicated previous work, using a web‐based survey. This triad of evidence provides (a) descriptive quantitative data (N = 240) about women with GPs, (b) qualitative data about women with GPs, as well as (c) clinical observations from 60 healthcare providers (HCPs) who have cared for women with GPs.

Conclusions: Three important findings about women with GPs were validated: (a) GPs were deliberate actions, sought for personal and sexual expression; (b) women with GPs treat piercings as a normal, meaningful part of their lives which produce sexual enhancement and expression; and (c) they continue to seek information about GP care from nonhealth providers. New data indicate that they have experienced depression (47%), abuse (physical 18%; emotional, 27%; sexual, 14%), and forced sexual activity (35%) in their lives. Several unsubstantiated assumptions about women with GPs are challenged with these data.

Implications for practice: GPs should not delay important health care. Health‐protective, as well as health promotion, behaviors are important to reduce risks. Nurse practitioners (NPs) can become effective and resourceful advocates in three specific areas of care: (a) responsiveness to women with GPs, (b) collaborative decision making for the removal of jewelry, and (c) promotion of applicable patient education.
Release of Naturally Derived Antimicrobial Agents from LDPE Films
Authors: Cran Marlene J. , Rupika L.A.S. , Sonneveld Kees , Miltz Joseph , Bigger Stephen W.
Published: January 2010

ABSTRACT:  The migration of the naturally derived antimicrobial (AM) agents, linalool, carvacrol, and thymol, from low‐density polyethylene (LDPE) films containing ethylene vinyl acetate (EVA) copolymer into the food simulants, isooctane and various ethanol/water mixtures, was studied with a view towards examining the applicability of a first‐order kinetic approach as well as a diffusion model approach for describing these systems. The results suggest that the proposed models adequately describe the release of AM agents. The combination of kinetic and diffusion analyses can provide additional information about the release process using the same data set. The analyses suggest that the release of linalool from LDPE/EVA depends on the EVA content in the formulation and that an optimum level of EVA is required to minimize the rate of release. A modification of the existing “idealized diffusion” model is proposed that enables the model to be applied to systems that demonstrate a departure from linearity when subjected to conventional analysis. The applicability of the idealized diffusion model was compared with the “simulant‐limited” model and the results suggest that the former model is appropriate for describing most real systems when the simulant (or foodstuff) is favored in the partitioning of the AM agent between the film and the simulant.
Hydroxyl Radical and Ferryl‐Generating Systems Promote Gel Network Formation of Myofibrillar Protein
Authors: Xiong Youling L. , Blanchard Suzanne P. , Ooizumi Tooru , Ma Yuanyuan
Published: January 2010

ABSTRACT:  The objective of the study was to examine how oxidatively induced protein cross‐linking would influence the gelation properties of myofibrillar protein (MP) under meat processing conditions. MP suspensions in 0.6 M NaCl at pH 6 were treated with an iron‐catalyzed oxidizing system (IOS: 10 μM FeCl3, 0.1 mM ascorbic acid, 0.05 to 5 mM H2O2) or a H2O2‐activated metmyoglobin oxidizing system (MOS: 0.01 to 0.1 mM metmyoglobin/H2O2) that produced hydroxyl radical and ferryl species, respectively. Both oxidizing systems promoted MP thermal gelation, which was evidenced by rapid protein–protein interaction and the enhancement in storage modulus (elasticity) of the gel network as revealed by dynamic rheological testing in the 20 to 74 °C temperature range. This gelation‐enhancing effect was attributed to the shift of myosin aggregation in the early stage of heating from predominantly head–head association (nonoxidized control samples) to prevalently tail–tail cross‐linking through disulfide bonds. However, both hardness and water‐holding capacity of chilled gels tended to decline when MP was exposed to ≥1 mM H2O2 in IOS and to all concentrations of metmyoglobin in MOS. Microscopic examination confirmed a more porous structure in oxidized gels when compared with nonoxidized protein gels. The results demonstrated that mild oxidation altered the mode of myosin aggregation in favor of an elastic gel network formation, but it did not improve or had a negative effect on water‐binding properties of MP gels.

Practical Application: Mild oxidation promotes protein network formation and enhances gelation of myofibrillar protein under normal salt and pH conditions used in meat processing. This oxidative effect, which involves disulfide linkages, is somewhat similar to that in bakery product processing where oxidants are used to improve dough performance through gluten protein interaction.
An Overview of the Victims’ Rights Movement: Historical, Legislative, and Research Developments†
Authors: Mastrocinque Jeanna M.
Published: February 2010

The Victims' Rights Movement has made considerable accomplishments since the 1960s, when an increasing crime rate, coupled with the underreporting of crime, inspired concerns regarding crime victims. In subsequent decades the Victims' Rights Movement evolved and gained considerable momentum. This paper examines the historical development of the Victims' Rights Movement, including the movement's focus on specific types of victimization and crimes. State and Federal responses to the movement are also presented, with attention to constitutional developments and debates. Finally, current issues are presented and future research is suggested.
Do male and female black‐backed woodpeckers respond differently to gaps in habitat?
Authors: Pierson Jennifer C. , Allendorf Fred W. , Saab Victoria , Drapeau Pierre , Schwartz Michael K.
Published: January 2010

We used population‐ and individual‐based genetic approaches to assess barriers to movement in black‐backed woodpeckers (Picoides arcticus), a fire‐specialist that mainly occupies the boreal forest in North America. We tested if male and female woodpeckers exhibited the same movement patterns using both spatially implicit and explicit genetic analyses to define population structure and movement patterns of both sexes among populations. Three genetic groups were identified, a large, genetically continuous population that spans from the Rocky Mountains to Quebec, a small isolated population in South Dakota and a separate population in the western portion of their distribution (Oregon). Patterns of genetic diversity suggest extensive gene flow mediated by both males and females within the continuous boreal forest. However, male‐mediated gene flow is the main form of connectivity between the continuously distributed group and the smaller populations of South Dakota and Oregon that are separated by large areas of unforested habitat, which apparently serves as a barrier to movement of female woodpeckers.
Efficacy and safety of tafluprost 0.0015% versus latanoprost 0.005% eye drops in open‐angle glaucoma and ocular hypertension: 24‐month results of a randomized, double‐masked phase III study
Authors: Uusitalo Hannu , Pillunat Lutz E , Ropo Auli ,   on behalf of the Phase III Study Investigators
Published: January 2010

Purpose:  The objective of the study was to compare the long‐term efficacy and safety of tafluprost 0.0015% with latanoprost 0.005% eye drops in patients with open‐angle glaucoma or ocular hypertension.

Methods:  This double‐masked, active‐controlled, parallel‐group, multinational, multicentre, phase III study was conducted at 49 centres in 8 countries. Eligible patients were assigned to treatment administered once daily at 20:00 hrs for up to 24 months. Change from baseline intraocular pressure (IOP) was the primary efficacy variable. Adverse events were recorded and ocular safety was evaluated. Both tafluprost and latanoprost were preserved with benzalkonium chloride.

Results:  From 533 patients randomized, 402 patients completed 24 months of therapy. Both treatments had a substantial IOP‐lowering effect which persisted throughout the study (−7.1 mmHg for tafluprost and −7.7 mmHg for latanoprost at 24 months). Although the IOP‐lowering effect during the study was slightly larger with latanoprost, this difference was clinically small and the noninferiority of tafluprost to latanoprost over all diurnal IOP measurements was shown with anova and almost reached with ancova (upper limits of the 95% confidence intervals 1.38 and 1.52 for the overall period, respectively). The noninferiority limit was 1.5 mmHg.

Conclusions:  Tafluprost is a new effective and well‐tolerated treatment for glaucoma and ocular hypertension.
The Leonard Award Address Presented 1996 July 25, Berlin, Germany: The elemental composition of stony cosmic spherules
Authors: BROWNLEE D. E. , BATES B. , SCHRAMM L.
Published: February 2010

Abstract— Five hundred stony cosmic spherules collected from deep‐sea sediments, polar ice, and the stratosphere have been analyzed for major and some minor element composition. Typical spherules are products of atmospheric melting of millimeter sized and smaller meteoroids. The samples are small and modified by atmospheric entry, but they are an important source of information on the composition of asteroids. The spherules in this study were all analyzed in an identical manner, and they provide a sampling of the solar system's asteroids that is both different and less biased than provided by studies of conventional meteorites. Volatile elements such as Na and S are depleted due to atmospheric heating, while siderophiles are depleted by less understood causes. The refractory nonsiderophile elements appear not to have been significantly disturbed during atmospheric melting and provide important clues on the elemental composition of millimeter sized meteoroids colliding with the Earth. Typical spherules have CM‐like composition that is distinctively different than ordinary chondrites and most other meteorite types. We assume that C‐type asteroids are the primary origin of spherules with this composition. Type S asteroids should also be an important source of the spherules, and the analysis data provide constraints on their composition. A minor fraction of the spherules are melt products of precursor particles that did not have chondritic elemental compositions. The most common of these are particles that are dominated by olivine. The observed compositions of spherules are inconsistent with the possibility that an appreciable fraction of the spherules are simply chondrules remelted during atmospheric entry.
Fall, recovery and description of the Coleman chondrite
Authors: OSBORN WAYNE , MATTY DAVID , VELBEL MICHAEL , BROWN PETER , WACKER JOHN
Published: February 2010

Abstract— A 0.5 kg stony meteorite associated with a bright bolide seen over southeastern Michigan on 1994 October 20 has been recovered. The circumstances of the fall and recovery of this chondrite, named Coleman, are presented. The most likely trajectory from the observations of the event implies preatmospheric orbital parameters typical of meteorites. Gamma‐ray spectrometry of the cosmogenic radionuclides showed that the recovered mass was an interior fragment of a larger body and revealed abnormally high 22Na and 26Al activity. Electron microprobe analysis yielded compositions of Fa24.1 and Fs20.3, which are consistent with an L‐chondrite classification. Petrographically, the presence of chondrules, the observed mineralogy and the degree of chondrule‐matrix integration suggests assignment to petrologic type 6.
Petrogenetic models for magmatism on the eucrite parent body: Evidence from orthopyroxene in diogenites
Authors: SHEARER C. K. , FOWLER G. W. , PAPIKE J. J.
Published: February 2010

Abstract—Diogenites are recognized as a major constituent of the howardite, eucrite and diogenite (HED) meteorite group. Recently, several papers (Mittlefehldt, 1994; Fowleret al, 1994, 1995) have identified trace‐element systematics in diogenites that appeared to mimic simple magmatic processes that involved large degrees of crystallization (up to 95% orthopyroxene) of basalt with extremely high normative hypersthene. Such a crystallization scenario linking all the diogenites is highly unlikely. The purpose of this study is to explore other possible models relating the diogenites.

Computational major‐element melting models of a variety of different potential bulk compositions for the eucrite parent body (EPB) mantle indicate that these compositions show a similar sequence in residuum mineral assemblage with increasing degrees of partial melting. Numerous bulk compositions would produce melts with Mg# appropriate for diogenitic parent magmas at low to moderate degrees of partial melting (15% to 30%). These calculations also show that melts with similar Mg# and variable incompatible element concentrations may be produced during small to moderate degrees of EPB mantle melting.

The trace‐element characteristic of the orthopyroxene in diogenites does not support a model for large amounts of fractional crystallization of a single “hypersthene normative” basaltic magma following either small‐scale or large‐scale EPB mantle melting. Small degrees of fractional crystallization of a series of distinct basaltic magmas are much more likely. Only two melting models that we considered hold any promise for producing different batches of “diogenitic magmas.” The first model involves the fractional melting of a homogeneous source that produces parental magmas to diogenites with an extensive range of incompatible elements and limited variations in Mg#. There are several requirements for this model to work. The first requirement of this model is that the Dorthopyroxene/meltmust change during melting or crystallization to compress the range of incompatible elements in the calculated diogenitic magmas. The second prerequisite is that either some of the calculated diogenitic magmas are parental to eucrites or the Mg# in diogenitic magmas are influenced by slight changes in oxygen fugacity during partial melting. The second model involves batch melting of a source that reflects accretional heterogeneities capable of generating diogenitic magmas with the calculated Mg# and incompatible element contents. Both of these models require small to moderate degrees of partial melting that may limit the efficiency of core separation.
The metamorphic history of eucrites and eucrite‐related meteorites and the case for late metamorphism
Authors: SEARS DEREK W. G. , SYMES STEVEN J. K. , BATCHELOR J. DAVID , AKRIDGE D. GLEN , BENOIT PAUL H.
Published: February 2010

Abstract— We report induced thermoluminescence (TL) data for separates from three howardite, eucrite and diogenite (HED) meteorites and the Vaca Muerta mesosiderite. The results of thermal modeling of the surface of their parent body are also described. The TL sensitivities for matrix samples from the LEW 85300, 302 and 303 paired eucrites and the Bholghati howardite are lower than the TL sensitivities for the clasts, which is consistent with regolith working of the matrix in fairly mature regoliths. Within an isochemical series of HED meteorites, TL sensitivity reflects metamorphic intensity, but clast‐to‐clast variations in the TL sensitivities of the Vaca Muerta mesosiderite and clasts in the EET 87509, 513 and 531 paired howardite primarily reflect differences in mineralogy and petrology. Thermoluminescence peak temperatures indicate that all the components from the LEW 85300, 302 and 303 paired eucrites experienced a reheating event involving temperatures >800 °C, which is thought to have been due to impact heating, and therefore that the event was concurrent with or postdated brecciation. The Vaca Muerta clasts are essentially unmetamorphosed, but the induced TL data indicate that the remaining howardite, eucrite, dioenite and mesosiderite (HEDM) meteorites experienced metamorphism to a variety of intensities but involving temperatures <800 °C. Laboratory heating experiments show that temperatures >800 °C cause a change in TL peak temperature. Feldspars from a variety of terrestrial and extraterrestrial sources show this behavior, and x‐ray diffraction and kinetic studies suggest that it is indirectly related to Al, Si disordering.

Cooling rates are not consistent with autometamorphism following the initial igneous event or with heating by subsequent eruptions of lava onto the surface of the HED parent body. Instead, our thermal models suggest that the metamorphism occurred within a regolith ejecta blanket of up to a few kilometers thick, with different levels of metamorphism corresponding to different thicknesses of blanket, between essentially 0 and ∼2 km, rather than different burial depths in a regolith of uniform thickness. We argue that metamorphism occurred 3.9 Ga ago and was associated with the resetting of the Ar‐Ar system for the HED meteorites.
The density and porosity of meteorites from the Vatican collection
Authors: CONSOLMAGNO S.J. G. J. , BRITT D. T.
Published: February 2010

Abstract— We have developed a nondestructive technique to measure the densities and porosities of large (50 g to several kilogram) meteorite samples and have begun a systematic measurement program starting with meteorites from the Vatican Observatory collection. Our technique utilizes a modified Archimedean method (40 μm glass spheres substituting for the fluid) to determine bulk density, and an unusually large He pycnometer to determine grain density. From these, the porosity is calculated. We report here our first results for 89 samples (nearly doubling the published database on porosities of meteorite hand samples), including porosities of 35 different meteorites. These include several types not previously reported: eight iron meteorites, six stony‐iron meteorites, an enstatite chondrite, the CI carbonaceous chondrite Orgueil, and the shergottite‐nakhlatite‐chassignite (SNC) meteorite Nakhla.