bluuebunny/crossref_metadata_2025 huggingface dataset:
The locative‐applicative in Eleme1
Authors: Bond Oliver
Published: March 2009

The Eleme locative‐applicative = is a non‐canonical applicative that demonstrates morphosyntactic properties commonly associated with clitics. It is employed in one of two functions: (i) to indicate an increase in the transitivity of a clause and (typically) to introduce an otherwise oblique function as a core argument of a base verb, or (ii) to indicate the presence of an atypical verbal complement. It is usually found in constructions containing a verb stem that expresses location, directed motion or transfer, but also functions as an obligatory component of the Eleme progressive construction. While locative and comitative expressions are common source‐constructions for progressives in Niger‐Congo languages, Eleme is apparently unique within the literature in that it includes an applicative with comitative function that must be enclitic to a verb of location to express progressive aspect.
Beyond the Courtroom Workgroup: Caseworkers as the New Satellite of Social Control
Authors: CASTELLANO URSULA
Published: March 2009

Many jurisdictions nationwide are faced with overcrowded jails, backlogged court dockets, and high rates of recidivism for mostly nonviolent offenders. To address these complex problems, law enforcement officials have institutionalized alternatives to incarceration programs, including work furloughs, electronic monitoring, and treatment courts. These recent trends in legal reform are designed to reduce and prevent criminal behavior by helping to reintegrate defendants back into their local communities. One aspect that has been largely unaddressed in prior research is that jail‐alternative programs are primarily staffed by caseworkers with outside nonprofit agencies. This important group of nonlegal actors plays a pivotal role in crafting decisions to divert low‐level offenders from the criminal justice system; few studies, however, explore the organizational contexts surrounding caseworkers' everyday decision‐making practices. In response, I draw upon ethnographic data to analyze the ways that pretrial release caseworkers in a California county evaluate defendants' entitlement to release on their own recognizance. The results of this study suggest that caseworkers exercise discretion beyond the traditional power structure of the courtroom workgroup. I conclude that caseworkers emerge as the new satellite of social control in contemporary courts.
Reconsidering Regulation and Governance Theory: A Learning Approach
Authors: WRIGHT JOHN S. F. , HEAD BRIAN
Published: March 2009

Theories and frameworks for regulation of particular industries or types of behavior have grown in richness in recent years. This article identifies three perspectives within contemporary regulatory theory: “normative,”“descriptive,” and “poststructuralist” perspectives. We ask whether contemporary models of regulatory governance arrangements adequately capture and explain the characteristics and operation of existing regulatory spaces. We outline three key models linked to these perspectives (responsive regulation, smart regulation, and nodal governance) and discuss their relevance with specific reference to one complex case study, the gambling industry in a federal polity, Australia, where the regulatory arrangements are quite diverse. We argue that regulatory theory needs to remain flexible if it is to inform an understanding of concrete regulatory challenges, thereby assisting analysts and practitioners to assess current and potential approaches for improved regulatory governance arrangements. Accordingly, we build a case for considering a learning perspective on regulation and governance theory linked to pragmatism.
Expectation of empowerment as a determinant of citizen participation in waste management planning1,2
Authors: MAEDA HIROE , HIROSE YUKIO
Published: March 2009

Abstract: The study investigated the determinants of citizen participation in the development of a waste management plan. It was hypothesized that people would decide whether or not to participate in the planning based on the expectation of empowerment to be gained by their participation, not on the general evaluation of citizen participation. Four hundred and twenty‐four volunteers responded to a self‐report mailed survey conducted in August 2001 in Nisshin City. Nisshin City was selected as a city where the municipal government was starting to develop a basic plan for waste reduction and recycling. Major findings from the survey were: (a) the direct social benefits (i.e., making a better plan by citizen participation) were the main determinant of the general evaluation of citizen participation; and (b) expectation of personal empowerment (i.e., sense of self‐efficacy and solidarity) was the main determinant of behavioral intention to citizen participation.
Effect of inhibitors of mitogen‐activated protein kinase kinase on α1B‐adrenoceptor phosphorylation
Authors: Alcántara‐Hernández R. , Adolfo García‐Sáinz J.
Published: March 2009

1 Mitogen‐activated protein kinases mediate hormone/neurotransmitter action on proliferation and differentiation and participate in receptor regulation. The effect of inhibitors of mitogen‐activated kinase kinase (MEK) on α1B‐adrenoceptor phosphorylation state and function was studied using different cell lines. It was observed that at nanomolar concentrations the MEK inhibitors, PD98059 (2′‐amino‐3′‐methoxyflavone) and UO126 [1,4‐(diamino‐2,3‐dicyano/1,4‐bis‐(2‐aminophenylthio)‐butadiene], increased α1B‐adrenoceptor phosphorylation and diminished the functional response of this receptor to noradrenaline. These agents did not alter the action of lysophosphatidic acid.

2 Staurosporine (IC50 ≈ 0.8 nm) (a general protein kinase inhibitor) and bis‐indolyl‐maleimide I (IC50 ≈ 200 nm) (a selective protein kinase C inhibitor) inhibited PD98059‐induced α1B‐adrenoceptor phosphorylation. In contrast, neither wortmannin (phosphoinositide 3‐kinase inhibitor) nor genistein (protein tyrosine kinase inhibitor) had any effect. The data suggest the possibility that MEK might exert control on the activity of the enzymes that regulate receptor phosphorylation, such as G‐protein‐coupled receptor kinases, protein kinase C or serine/threonine protein phosphatases.

3 Coimmunoprecipitation studies showed a constant association of total extracellular signal‐regulated kinase 2 (ERK2) with α1B‐adrenoceptors. Association of phospho‐ERK 1/2 to α1B‐adrenoceptors increased not only in response to agonist but also in response to agents that increase α1B‐adrenoceptor and ERK1/2 phosphorylation [such as endothelin‐1, phorbol 12‐myristate‐13‐acetate (PMA) and epidermal growth factor (EGF)]; not surprisingly, PD98059 decreased this effect.

4 Our data show that blockade of MEK activity results in increased α1B‐adrenoceptor phosphorylation, diminished adrenoceptor function and perturbation of receptor–ERK1/2 interaction.
Cytochrome P450 metabolites of arachidonic acid play a role in the enhanced cardiac dysfunction in diabetic rats following ischaemic reperfusion injury
Authors: Yousif M. H. M. , Benter I. F. , Roman R. J.
Published: March 2009

1 This study examined the contribution of cytochrome P450 metabolites of arachidonic acid in mediating ischaemia/reperfusion (I/R)‐induced cardiac dysfunction in normal and diabetic rats.

2 We first compared the metabolism of arachidonic acid in microsomes prepared from the hearts of control rats and rats treated with streptozotocin (55 mg kg−1) to induce diabetes. The production of dihydroxyeicosatrienoic acids and epoxyeicosatrienoic acids (EETs) were similar in microsomes prepared from the hearts of control and diabetic rats, but the production of 20‐hydroxyeicosatetraenoic acid (20‐HETE) was two‐fold higher in diabetic hearts than in control animals.

3 We then compared the change in left ventricular pressure (Pmax), left ventricular end‐diastolic pressure, coronary flow and coronary vascular resistance in isolated perfused hearts obtained from control and diabetic animals after 40 min of global ischaemia (I) followed by 30 min of reperfusion (R). The decline in cardiac function was three‐ to five‐fold greater in the hearts obtained from diabetic vs. control animals.

4 Pretreatment of the hearts with N‐hydroxy‐N′‐(4‐butyl‐2‐methyl‐phenyl)‐formamidine (HET0016, 1 μm), a selective inhibitor of the synthesis of 20‐HETE, for 30 min before I/R resulted in significant improvement in the recovery of cardiac function in the hearts obtained from diabetic but not in control rats. Perfusion with an inhibitor of soluble epoxide hydrolase, 1‐cyclohexyl‐3‐dodecyl urea (CDU), before I/R improved the recovery of cardiac function in hearts obtained from both control and diabetic animals. Perfusion with both HET0016 and CDU resulted in significantly better recovery of cardiac function of diabetic hearts following I/R than that seen using either drug alone. Pretreatment of the hearts with glibenclamide (1 μm), an inhibitor of ATP‐sensitive potassium channels, attenuated the cardioprotective effects of both CDU and HET0016.

5 This is the first study to suggest that acute blockade of the formation of 20‐HETE and/or reduced inactivation of EETs could be an important strategy to reduce cardiac dysfunction following I/R events in diabetes.
Characteristics of Important Stopover Locations for Migrating Birds: Remote Sensing with Radar in the Great Lakes Basin
Authors: BONTER DAVID N. , GAUTHREAUX JR SIDNEY A. , DONOVAN THERESE M.
Published: March 2009

Abstract: A preliminary stage in developing comprehensive conservation plans involves identifying areas used by the organisms of interest. The areas used by migratory land birds during temporal breaks in migration (stopover periods) have received relatively little research and conservation attention. Methodologies for identifying stopover sites across large geographic areas have been, until recently, unavailable. Advances in weather‐radar technology now allow for evaluation of bird migration patterns at large spatial scales. We analyzed radar data (WSR‐88D) recorded during spring migration in 2000 and 2001 at 6 sites in the Great Lakes basin (U.S.A.). Our goal was to link areas of high migrant activity with the land‐cover types and landscape contexts corresponding to those areas. To characterize the landscapes surrounding stopover locations, we integrated radar and land‐cover data within a geographic information system. We compared landscape metrics within 5 km of areas that consistently hosted large numbers of migrants with landscapes surrounding randomly selected areas that were used by relatively few birds during migration. Concentration areas were characterized by 1.2 times more forest cover and 9.3 times more water cover than areas with little migrant activity. We detected a strong negative relationship between activity of migratory birds and agricultural land uses. Examination of individual migration events confirmed the importance of fragments of forested habitat in highly altered landscapes and highlighted large concentrations of birds departing from near‐shore terrestrial areas in the Great Lakes basin. We conclude that conservation efforts can be more effectively targeted through intensive analysis of radar imagery.
Ethanol‐Induced Extracellular Signal Regulated Kinase: Role of Dopamine D1 Receptors
Authors: Ibba Federico , Vinci Stefania , Spiga Saturnino , Peana Alessandra T. , Assaretti Anna R. , Spina Liliana , Longoni Rosanna , Acquas Elio
Published: March 2009

Background:  Addictive drugs activate extracellular signal regulated kinase (ERK) in brain regions critically involved in their affective and motivational properties. The aim of this study was to demonstrate the ethanol‐induced activation of ERK in the nucleus accumbens (Acb) and in the extended amygdala [bed nucleus of the stria terminalis lateralis (BSTL) and central nucleus of the amygdala (CeA)] and to highlight the role of dopamine (DA) D1 receptors in these effects.

Methods:  Ethanol (0.5, 1, and 2 g/kg) was administered by gavage and ERK phosphorylation was determined in the nucleus Acb (shell and core), BSTL, and CeA by immunohistochemistry. The DA D1 receptor antagonist, SCH 39166 (SCH) (50 μg/kg), was administered 10 minutes before ethanol (1 g/kg).

Results:  Quantitative microscopic examination showed that ethanol, dose‐dependently increased phospho‐ERK immunoreactivity (optical and neuronal densities) in the shell and core of nucleus Acb, BSTL, and CeA. Pretreatment with SCH fully prevented the increases elicited by ethanol (1 g/kg) in all brain regions studied.

Conclusions:  The results of this study indicate that ethanol, similar to other addictive drugs, activates ERK in nucleus Acb and extended amygdala via a DA D1 receptor‐mediated mechanism. Overall, these results suggest that the D1 receptors/ERK pathway may play a critical role in the motivational properties of ethanol.
Green Niche Market Development
Authors: Andrews Clinton , DeVault David
Published: March 2009

This article introduces a multiagent simulation framework for investigating the emergence of niche markets for environmentally innovative products. It clarifies how consumer preferences, business strategy, and government policy interact during market development. The framework allows investigation of the effects of uncertainty and agents’ corresponding coping strategies. We describe the model, illustrate how it works when applied to the case of hybrid cars, and analyze results spanning several policy cases and a range of scenarios that make different assumptions about the heterogeneity of agents. Heterogeneity within each agent class strongly influences aggregate outcomes. Innovative firms can create green products in response to or in anticipation of government regulation, but true green niche markets do not emerge unless there are also green consumers. Niche markets do not go mainstream unless scale economies drive costs down to parity with conventional products. Preferred environmental innovation policies change with heterogeneity assumptions.
Power, Trust, and Risk:
Authors: Grimen Harald
Published: March 2009

In modern discussions among health professionals there is a strange lack of discussions of power. This is most notably true for the discussions about proper physician–patient relations and the discussions about trust. This article explores some of the consequences of this absence. It is argued that the absence of the issue of power hampers a serious and open moral discussion of important institutional forms in the health care system. It is also argued that some of the proposals for how to organize physician–patient interaction are rather unrealistic, mainly because the issue of power is neglected. Finally, the article develops some ideas about how power ought to be approached in modern health care.
Relationship Between Engineering Properties, Mineralogy, and Microstructure in Cement‐Based Hydroceramic Materials Cured at 200°–350°C
Authors: Kyritsis Konstantinos , Hall Christopher , Bentz Dale P. , Meller Nicola , Wilson Moira A.
Published: March 2009

Cement‐based materials used to seal geothermal or deep oil wells are exposed to severe conditions. Optimizing engineering properties such as strength and permeability is therefore very important. We have synthesized hydroceramic materials for such applications based on the CaO−Al2O3−SiO2−H2O (CASH) system and cured them over a range of temperatures (200°–350°C). Depending on initial composition and curing temperature, hydroceramics of complex and diverse mineralogy and microstructure are formed. The minerals found include portlandite, jaffeite, xonotlite, gyrolite, 11 Å tobermorite, truscottite, hydrogarnet, and calcium aluminum silicate hydrate. These cement‐based hydroceramic materials develop complicated pore structures, which strongly affect bulk properties. We report the compressive strength and permeability of these materials and show how these bulk engineering properties are related to microstructure. The compressive strength was found to be in the range 2–52 MPa and the intrinsic permeability in the range 0.5 × 10−17 to 3300 × 10−17 m2. Scanning electron microscopy (SEM) was used for imaging the hydroceramic microstructures. Further, we have computed the intrinsic permeability from 2‐D SEM images by using the Stokes equation solver, Permsolver, applied to reconstructed 3‐D images and the results are shown to be in good agreement with experimentally determined values.
Synthesis, Phase Characterization, and Properties of Chemical Solution‐Deposited Nickel Manganite Thermistor Thin Films
Authors: Schulze Heidi , Li Jing , Dickey Elizabeth C. , Trolier‐McKinstry Susan
Published: March 2009

Nickel manganite spinel thin films prepared by chemical solution deposition exhibit negative temperature coefficient of resistance (TCR) values between −3.3 and −4.5%/K. In contrast to bulk thermistors, dense films could be prepared completely within the spinel phase field. Thus, decomposition into the NiO phase and a Mn‐rich spinel, which is problematic in bulk ceramics, is minimized in thin films. For films prepared outside of the single‐phase field, phase separation cannot always be detected using X‐ray diffraction. In such cases, transmission electron microscopy is useful in identifying decomposition. It is found that the lattice parameters for films with compositions ranging between Mn/(Mn+Ni)=0.14 and 0.77 are smaller than the values reported for nickel manganite spinels, suggesting cation deficiency. Single‐phase spinel films are compared with single‐phase bixbyite films synthesized between 630° and 930°C. The bixbyite phase exhibits lower TCR and lower resistivity (TCR=−3.1 to −3.3%/K and resistivity values=400–1600 Ω·cm) compared with spinel (TCR=−3.6 to −4.1%/K and resistivity values=3500–21 000 Ω·cm). Composite films (achieved by controlling the pyrolysis to create a low local pO2 during annealing) show intermediate values (TCR=−3.0 to −3.8%/K and resistivity values=470–6600 Ω·cm).
Detection of Undiagnosed Diabetes and Prediabetic States in High‐risk Emergency Department Patients
Authors: Charfen Michelle A. , Ipp Eli , Kaji Amy H. , Saleh Tawny , Qazi Mohammed F. , Lewis Roger J.
Published: March 2009

Background:  Diabetes is often not diagnosed until complications appear, and one‐third of those with diabetes may be undiagnosed. Prediabetes and diabetes are conditions in which early detection would be appropriate, because the duration of hyperglycemia is a predictor of adverse outcomes, and there are effective interventions to prevent disease progression and to reduce complications.

Objectives:  The objectives were to determine the prevalence of diabetes mellitus and prediabetes in emergency department (ED) patients with an elevated random glucose or risk factors for diabetes but without previously diagnosed diabetes and to identify which at‐risk ED patients should be considered for referral for confirmatory diagnostic testing.

Methods:  This two‐part study was composed of a prospective 2‐year cohort study, and a 1‐week cross‐sectional survey substudy, set in an urban ED in Los Angeles County, California. A convenience sample was enrolled of 528 ED patients without previously diagnosed diabetes with either 1) a random serum glucose ≥ 140 mg/dL regardless of the time of last food intake or a random serum glucose ≥ 126 mg/dL if more than 2 hours since last food intake or 2) at least two predefined diabetes risk factors. Measurements included presence of diabetes risk factors, ED glucose, cortisol, insulin and glycosylated hemoglobin (HbA1c), and 2‐hour oral glucose tolerance test results, administered at 6‐week follow‐up.

Results:  Glycemic status was confirmed at follow‐up in 256 (48%) of the 528 patients. Twenty‐seven (11%) were found to have diabetes, 141 (55%) had prediabetes, and 88 (34%) had normal results. Age, ED glucose, HbA1c, cortisol, and random serum glucose ≥ 140 mg/dL were associated with both diabetes and prediabetes on univariate analysis. A random serum glucose ≥ 126 mg/dL after 2 hours of fasting was associated with diabetes but not prediabetes; ED cortisol, insulin, age ≥ 45 years, race, and calculated body mass index (BMI) were associated with prediabetes but not diabetes. In multivariable models, among factors measurable in the ED, the only independent predictor of diabetes was ED glucose, while ED glucose, age ≥ 45 years, and symptoms of polyuria and polydipsia were independent predictors of prediabetes. All at‐risk subjects with a random ED blood glucose > 155 mg/dL had either prediabetes or diabetes on follow‐up testing.

Conclusions:  A substantial fraction of this urban ED study population was at risk for undiagnosed diabetes and prediabetes, and among the at‐risk patients referred for follow‐up, the majority demonstrated diabetes or prediabetes. Notably, all patients with two risk factors and a random serum glucose > 155 mg/dL were later diagnosed with prediabetes or diabetes. Consideration should be given to referring ED patients with risk factors and a random glucose > 155 mg/dL for follow‐up testing.
The Recovery of Latent Fingermarks from Evidence Exposed to Ionizing Radiation*
Authors: Colella Michael , Parkinson Andrew , Evans Tegan , Lennard Chris , Roux Claude
Published: March 2009

Abstract:  Continual reports of illicit trafficking incidents involving radioactive materials have prompted authorities to consider the likelihood of forensic evidence being exposed to radiation. In this study, we investigated the ability to recover latent fingermark evidence from a variety of substrates that were exposed to ionizing radiation. Fingermarks deposited on common surfaces, including aluminum, glass, office paper, and plastic, were exposed to doses ranging from 1 to 1000 kGy, in an effort to simulate realistic situations where evidence is exposed to significant doses of radiation from sources used in a criminal act. The fingermarks were processed using routine fingermark detection techniques. With the exception of glass and aluminum substrates, radiolysis had a considerable effect on the quality of the developed fingermarks. The damage to ridge characteristics can, in part, be attributed to chemical interactions between the substrate and the components of the fingermark secretions that react with the detection reagents.
Differential cytokine activity and morphology during wound healing in the neonatal and adult rat skin
Authors: Wagner W. , Wehrmann M.
Published: March 2009

Wound‐healing mechanisms change during transition from prenatal to postnatal stage. Cytokines are known to play a key role in this process. The current study investigated the differential cytokine activity and healing morphology during healing of incisional skin wounds in rats of the ages neonatal (p0), 3 days old (p3) and adult, after six different healing times (2 hrs to 30 days). All seven tested cytokines (Transforming Growth Factor (TGF) α, TGFβ1, −β2 and −β3, IGF 1, Platelet Derived Growth Factor A (PDGF A), basic Fibroblast Growth Factor (bFGF) exhibited higher expression in the adult wounds than at the ages p0 and p3. Expression typically peaked between 12 hrs and 3 days post‐wounding, and was not detectable any more at days 10 and 30. The neonate specimen showed more rapid re‐epithelialization, far less inflammation and scarring, and larger restitution of original tissue architecture than their adult counterparts, resembling a prenatal healing pattern. The results may encourage the use of neonatal rat skin as a wound‐healing model for further studies, instead of the more complicated prenatal animal models. Secondly, the data may recommend inhibition of PDGF A, basic FGF or TGF‐β1 as therapeutic targets in efforts to optimize wound healing in the adult organism.
Effect of mitogen‐activated protein kinases on chemokine synthesis induced by substance P in mouse pancreatic acinar cells
Authors: Ramnath Raina Devi , Sun Jia , Adhikari Sharmila , Bhatia Madhav
Published: March 2009

Substance P, acting via its neurokinin 1 receptor (NK1 R), plays an important role in mediating a variety of inflammatory processes. Its interaction with chemokines is known to play a crucial role in the pathogenesis of acute pancreatitis. In pancreatic acinar cells, substance P stimulates the release of NFκB‐driven chemokines. However, the signal transduction pathways by which substance P‐NK1 R interaction induces chemokine production are still unclear. To that end, we went on to examine the participation of mitogen‐activated protein kinases (MAPKs) in substance P‐induced synthesis of pro‐inflammatory chemokines, monocyte chemoanractant protein‐1 (MCP‐I), macrophage inflammatory protein‐lα (MIP‐lα) and macrophage inflammatory protein‐2 (MIP‐2), in pancreatic acini. In this study, we observed a time‐dependent activation of ERK1/2, c‐Jun N‐terminal kinase (JNK), NFκB and activator protein‐1 (AP‐1) when pancreatic acini were stimulated with substance P. Moreover, substance P‐induced ERK 1/2, JNK, NFκB and AP‐1 activation as well as chemokine synthesis were blocked by pre‐treatment with either extracellular signal‐regulated protein kinase kinase 1 (MEK1) inhibitor or JNK inhibitor. In addition, substance P‐induced activation of ERK 112, JNK, NFκB and AP‐1‐driven chemokine production were attenuated by CP96345, a selective NK1 R antagonist, in pancreatic acinar cells. Taken together, these results suggest that substance P‐NK1 R induced chemokine production depends on the activation of MAPKs‐mediated NFκB and AP‐1 signalling pathways in mouse pancreatic acini.
Neurons produce FGF2 and VEGF and secrete them at least in part by shedding extracellular vesicles
Authors: Schiera Gabriella , Proia Patrizia , Alberti Chiara , Mineo Marco , Savettieri Giovanni , Di Liegro Italia
Published: March 2009

We previously found that neurons are able to affect the ability of brain capillary endothelial cells to form in vitro a monolayer with properties resembling the blood‐brain barrier. We then looked, by immunofluorescence and western analysis, for factors, produced by neurons, with the potential to influence growth and differentiation of endothelial cells. In the present paper, we report that neurons produce both vascular endothelial growth factor and fibroblast growth factor 2, two well‐known angiogenic factors. More interestingly, we gained evidence that both factors are released by neurons, at least in part, by shedding of extracellular vesicles, that contain β1 integrin, a membrane protein already known to be part of extracellular vesicles released by tumour cells. Shedding of extracellular vesicles by neurons was also confirmed by scanner electron microscopy.
Cell biology and clinical promise of G‐CSF: immunomodulation and neuroprotection
Authors: Xiao Bao‐Guo , Lu Chuan‐Zhen , Link Hans
Published: March 2009

Introduction

The immunomodulation of G‐CSF in adaptive immunity

The neuroprotection of G‐CSF in cerebral ischemia and neurodegeneration

G‐CSF‐Bridge between immunomodulation and neuroprotection

Weighing G‐CSF in immunomodulation and neuroprotection

Conclusion and perspectives

In the light of the enthusiasm to use of recombinant human granulocyte colony‐stimulating factor (G‐CSF) for immunomodulation and neuroprotection, it should be remembered that the current knowledge is based on a century of laborious research. G‐CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis. Although the precise mechanisms of G‐CSF are not known, there is growing evidence supporting the notion that G‐CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration. Here, we describe the immunomodulation and the neuroprotection that can be achieved with G‐CSF, and summarize possible mechanisms of G‐CSF as a potential therapeutic agent in autoimmune diseases and neurological disorders. Our understanding of these novel sites of action of G‐CSF has opened therapeutic avenues for the treatment of autoimmune diseases and neurological disorders, and has translated the beneficial effects of G‐CSF from basic experiments to clinical patients.
New biomedical devices with selective peptide recognition properties. Part 1: Characterization and cytotoxicity of molecularly imprinted polymers
Authors: Rechichi A. , Cristallini C. , Vitale U. , Ciardelli G. , Barbani N. , Vozzi G. , Giusti P.
Published: March 2009

Molecular imprinting is a technique for the synthesis of polymers capable to bind target molecules selectively. The imprinting of large proteins, such as cell adhesion proteins or cell receptors, opens the way to important and innovative biomedical applications. However, such molecules can incur into important conformational changes during the preparation of the imprinted polymer impairing the specificity of the recognition cavities. The “epitope approach” can overcome this limit by adopting, as template, a short peptide sequence representative of an accessible fragment of a larger protein. The resulting imprinted polymer can recognize both the template and the whole molecule thanks to the specific cavities for the epitope. In this work two molecularly imprinted polymer formulations (a macroporous monolith and nanospheres) were obtained using the protected peptide Z‐Thr‐Ala‐Ala‐OMe, as template, and Z‐Thr‐Ile‐Leu‐OMe, as analogue for the selectivity evaluation, methacrylic acid, as functional monomer, and trimethylolpropane trimethacrylate and pentaerythritol triacrylate (PETRA), as cross‐linkers. Polymers were synthesized by precipitation polymerization and characterized by standard techniques. Polymerization and rebinding solutions were analyzed by high performance liquid chromatography. The highly cross‐linked polymers retained about 70% of the total template amount, against (20% for the less cross‐linked ones). The extracted template amount and the rebinding capacity decreased with the cross‐linking degree, while the selectivity showed the opposite behaviour. The PETRA cross‐linked polymers showed the best recognition (MIP 2−, α= 1.71) and selectivity (MIP 2+, α′= 5.58) capabilities. The cytotoxicity tests showed normal adhesion and proliferation of fibroblasts cultured in the medium that was put in contact with the imprinted polymers.
Electron microscope tomography: further demonstration of nanocontacts between caveolae and smooth muscle sarcoplasmic reticulum
Authors: Gherghiceanu Mihaela , Popescu L.M.
Published: March 2009

A spatial relationship between caveolae and sarcoplasmic reticulum (SR) in smooth muscle cells (SMC) was previously reported in computer‐assisted three‐dimensional reconstruction from transmission electron microscope serial sections. The knowledge of the three‐dimensional organization of the cortical space of SMC is essential to understand caveolae function at the cellular level. Cellular tomography using transmission electron microscopy tomography (EMT) is the only available technology to reliably chart the inside of a cell and is therefore an essential technology in the study of organellar nanospatial relationships. Using EMT we further demonstrate here that caveolae and peripheral SR in visceral SMC build constantly spatial units, presumably responsible for a vectorial control of free Ca2+ cytoplasmic concentrations in definite nanospaces.
Prevalence of dental fear and phobia relative to other fear and phobia subtypes
Authors: Oosterink Floor M. D. , De Jongh Ad , Hoogstraten Johan
Published: March 2009

The purpose of the present study was to estimate the point prevalence of dental fear and dental phobia relative to 10 other common fears and Diagnostic and Statistical Manual of Mental Disorders (DSM)‐IV‐TR subtypes of specific phobia. Data were also analysed to examine differences with regard to severity, presence of distressing recollections of fear‐related events, gender, and prevalence across age. Data were obtained by means of a survey of 1,959 Dutch adults, 18–93 yr of age. Phobias were assessed based on DSM‐IV‐TR criteria, whereas severity of present fears was assessed using visual analogue scales. The prevalence of dental fear was 24.3%, which is lower than for fear of snakes (34.8%), heights (30.8%), and physical injuries (27.2%). Among phobias, dental phobia was the most common (3.7%), followed by height phobia (3.1%) and spider phobia (2.7%). Fear of dental treatment was associated with female gender, rated as more severe than any other fear, and was most strongly associated with intrusive re‐experiencing (49.4%). The findings suggest that dental fear is a remarkably severe and stable condition with a long duration. The high prevalence of dental phobia in the Netherlands is intriguing and warrants investigation in other countries.
Cynical hostility as a determinant of poor oral health status in an adult population
Authors: Suominen‐Taipale A. L. , Mettovaara H.‐L. , Uutela A. , Härkänen T. , Vehkalahti M. M. , Knuuttila M. L. E.
Published: March 2009

Our aim in this study was to determine whether there is an association between cynical hostility and clinically determined poor oral health, and whether this association is confounded by socioeconomic position and mediated by health behavior. The sample consisted of 4,207 dentate Finns, 30–64 yr of age. Oral health was measured in terms of numbers of missing teeth, of decayed teeth, and of teeth with periodontal pockets (≥ 4 mm). Cynical hostility was measured using the cynical distrust self‐administered questionnaire. The subjects with the highest level of cynical hostility had fewer teeth, and a greater number of decayed teeth as well as teeth with deepened periodontal pockets compared to subjects with the lowest level of cynical hostility. The associations between cynical hostility and number of missing and decayed teeth were clearly confounded by level of education. Poor oral health behavior was shown to be a possible mediator between cynical hostility and number of decayed teeth, but not of missing teeth or teeth with deepened periodontal pockets. General health‐related behavior did not serve as a possible mediator in any of the associations. In conclusion, cynical hostility can be considered as a risk marker for poor oral health. Interventions aimed to improve oral health should focus on psychosocial factors and on less‐educated subjects.
Transforming growth factor‐β1 expression is up‐regulated in maturation‐stage enamel organ and may induce ameloblast apoptosis
Authors: Tsuchiya Masahiro , Sharma Ramaswamy , Tye Coralee E. , Sugiyama Toshihiro , Bartlett John D.
Published: March 2009

Transforming growth factor‐β1 (TGF‐β1) regulates a variety of cellular responses that are dependent on the developmental stage and on the origins of the cell or the tissue. In mature tissues, and especially in tissues of epithelial origin, TGF‐β1 is generally considered to be a growth inhibitor that may also promote apoptosis. The ameloblast cells of the enamel organ epithelium are adjacent to and responsible for the developing enamel layer on unerupted teeth. Once the enamel layer reaches its full thickness, the tall columnar secretory‐stage ameloblasts shorten, and a portion of these maturation‐stage ameloblasts become apoptotic. Here we investigate whether TGF‐β1 plays a role in apoptosis of the maturation‐stage ameloblasts. We demonstrate in vitro that ameloblast lineage cells are highly susceptible to TGF‐β1‐mediated growth arrest and are prone to TGF‐β1‐mediated cell death/apoptosis. We also demonstrate in vivo that TGF‐β1 is expressed in the maturation‐stage enamel organ at significantly higher levels than in the earlier secretory‐stage enamel organ. This increased expression of TGF‐β1 correlates with an increase in expression of the enamel organ immediate‐early stress‐response gene and with a decrease in the anti‐apoptotic Bcl2 : Bax expression ratio. We conclude that TGF‐β1 may play an important role in ameloblast apoptosis during the maturation stage of enamel development.
Simulation of the Vapor Intrusion Process for Nonhomogeneous Soils Using a Three‐Dimensional Numerical Model
Authors: Bozkurt Ozgur , Pennell Kelly G. , Suuberg Eric M.
Published: March 2009

This paper presents model simulation results of vapor intrusion into structures built atop sites contaminated with volatile or semivolatile chemicals of concern. A three‐dimensional finite element model was used to investigate the importance of factors that could influence vapor intrusion when the site is characterized by nonhomogeneous soils. Model simulations were performed to examine how soil layers of differing properties alter soil‐gas concentration profiles and vapor intrusion rates into structures. The results illustrate difference in soil‐gas concentration profiles and vapor intrusion rates between homogeneous and layered soils. The findings support the need for site conceptual models to adequately represent a site’s geology when conducting site characterizations, interpreting field data, and assessing the risk of vapor intrusion at a given site. For instance, in layered geologies, a lower permeability and diffusivity soil layer between the source and building often limits vapor intrusion rates, even if a higher permeability layer near the foundation permits increased soil‐gas flow rates into the building. In addition, the presence of water‐saturated clay layers can considerably influence soil‐gas concentration profiles. Therefore, interpreting field data without accounting for clay layers in the site conceptual model could result in inaccurate risk calculations. Important considerations for developing more accurate conceptual site models are discussed in light of the findings.
Macro‐ and Micro‐Purge Soil‐Gas Sampling Methods for the Collection of Contaminant Vapors
Authors: Schumacher Brian A. , Zimmerman John H. , Sibert Christopher R. , Varner Katrina E. , Riddick Lee A.
Published: March 2009

Purging influence on soil‐gas concentrations for volatile organic compounds (VOCs), as affected by sampling tube inner diameter and sampling depth (i.e., system volume) for temporary probes in fine‐grained soils, was evaluated at three different field sites. A macro‐purge sampling system consisted of a standard, hollow, 3.2‐cm outer diameter (OD) drive probe with a retractable sampling point attached to an appropriate length of 0.48‐cm inner diameter (ID) Teflon® tubing. The macro‐purge sampling system had a purge system volume of 24.5 mL at a 1‐m depth. In contrast, the micro‐purge sampling systems were slightly different between the field sites and consisted of a 1.27‐cm OD drive rod with a 0.10‐cm ID stainless steel tube or a 3.2‐cm OD drive rod with a 0.0254‐cm inner diameter stainless steel tubing resulting in purge system volumes of 1.2 and 7.05 mL at 1‐m depths, respectively. At each site and location within the site, with a few exceptions, the same contaminants were identified in the same relative order of abundances indicating the sampling of the same general soil atmosphere. However, marked differences in VOC concentrations were identified between the sampling systems, with micro‐purge samples having up to 27 times greater concentrations than their corresponding macro‐purge samples. The higher concentrations are the result of a minimal disturbance of the ambient soil atmosphere during purging. The minimal soil‐gas atmospheric disturbance of the micro‐purge sampling system allowed for the collection of a sample that is more representative of the soil atmosphere surrounding the sampling point. That is, a sample that does not contain an atmosphere that has migrated from distance through the geologic material or from the surface in response to the vacuum induced during purging soil‐gas concentrations. It is thus recommended that when soil‐gas sampling is conducted using temporary probes in fine‐grained soils, the sampling system use the smallest practical ID soil‐gas tubing and minimize purge volume to obtain the soil‐gas sample with minimal risk of leakage so that proper decisions, based on more representative soil‐gas concentrations, about the site can be made.
The perceived and actual diagnostic utility of veterinary cytological samples
Authors: Skeldon N. , Dewhurst E.
Published: March 2009

Objectives: To establish the proportion of cytology samples sent to a commercial veterinary laboratory that yields diagnostically useful information in the context of current use and perceptions of cytology.

Methods: Nine hundred and forty‐five cytology submissions were retrospectively collected and categorised according to diagnostic utility. A survey into the use and perceptions of cytology was distributed at the British Small Animal Veterinary Association Congress 2008.

Results: A specific diagnosis was reached in 23·1 per cent of samples and a cytological diagnosis in 35·3 per cent. 22·4 per cent of samples yielded some useful information, but 19·2 per cent were unacceptable. Seventy‐four participants in the survey took an average of 3·9 cytological samples per week, of which they examined 27·0 per cent in‐house only, 21·6 per cent in‐house before sending to an external laboratory and 51·4 per cent were sent externally without prior examination. “To obtain a definitive diagnosis” was the principal reason cited for performing cytology.

Clinical Significance: Results suggest that cytology is underused and may be applied in an inappropriate context in the UK. It is hoped that illustrating the diagnostic outcome of samples received by a commercial laboratory will encourage increased, appropriate use of cytology.
Sex‐Specific Impact of Aldosterone Receptor Antagonism on Ventricular Remodeling and Gene Expression after Myocardial Infarction
Authors: Kanashiro‐Takeuchi Rosemeire M. , Heidecker Bettina , Lamirault Guillaume , Dharamsi Jennifer W. , Hare Joshua M.
Published: March 2009

Aldosterone receptor antagonism reduces mortality and improves post‐myocardial infarction (Ml) remodeling. Because aldosterone and estrogen signaling pathways interact, we hypothesized that aldosterone blockade is sex‐specific. Therefore, we investigated the mpact of eplerenone on left ventricular (LV) remodeling and gene expression of male infarcted rats versus female infarcted rats. Ml and Sham animals were randomized to receive eplerenone (100 mg/kg/day) or placebo 3 days post‐surgery for 4 weeks and assessed by echocardiography. In the Ml placebo group, left ventricular end‐diastolic dimension (LVEDD) increased from 7.3 ± 0.4 mm to 10.2 ± 1.0 mm (p < 0.05) and ejection fraction (EF) decreased from 82.3 + 4% to 45.5 + 11% (p < 0.05) in both sexes (p= NS between groups). Eplerenone attenuated LVEDD enlargement more effectively in females (8.8 ± 0.2 mm, p < 0.05 vs. placebo) than in males (9.7 ± 0.2 mm, p= NS vs. placebo) and improved EF in females (56.7 ± 3%, p < 0.05 vs. placebo) but not in males (50.6 + 3%, p= NS vs. placebo). Transcriptomic analysis using Rat_230–2.0 microarrays (Affymetrix) revealed that in females 19% of downregu‐lated genes and 44% of upregulated genes post‐MI were restored to normal by eplerenone. In contrast, eplerenone only restored 4% of overexpressed genes in males. Together, these data suggest that aldosterone blockade reduces Ml‐induced cardiac remodeling and phenotypic alterations of gene expression preferentially in females than in males. The use of transcriptomic signatures to detect greater benefit of eplerenone in females has potential implications for personalized medicine.
Unexpected Hepatotoxicity of Rifampin and Saquinavir/Ritonavir in Healthy Male Volunteers
Authors: Schmitt Christophe , Riek Myriam , Winters Katie , Schutz Malte , Grange Susan
Published: March 2009

Objectives.  Rifampin is a potent inducer of the cytochrome P450 3A4 isoenzyme (CYP3A4) that metabolizes most protease inhibitor (PI) antiretrovirals. This study was designed to evaluate the steady‐state pharmacokinetics and tolerability of the coadministration of the PIs saquinavir and ritonavir (a CYP3A4 inhibitor used as a pharmacoenhancer of other PIs) and rifampin when coadministered in healthy HIV‐negative volunteers.

Methods.  In an open‐label, randomized, one sequence, two‐period crossover study involving 28 healthy HIV‐negative volunteers, arm 1 was randomized to receive saquinavir/ritonavir 1000/100 mg twice daily while arm 2 received rifampin 600 mg once daily for 14 days. Both arms were then to receive concomitant saquinavir/ritonavir and rifampin for 2 additional weeks. Vital signs, electrocardiography, laboratory analyses, and blood levels of total saquinavir, ritonavir, rifampin, and desacetyl‐rifampin, the primary metabolite of rifampin, were measured.

Results.  In arm 1, 10/14 (71%) and, in arm 2, 11/14 (79%) participants completed the first study phase; eight participants in arm 1 and nine in arm 2 went on to receive both saquinavir/ritonavir and rifampin. Following substantial elevations (≥ grade 2) in hepatic transaminases in participants receiving the coadministered agents, the study was discontinued prematurely. Two participants in arm 1 displayed moderate elevations after five and four doses of rifampin, respectively. In arm 2, all participants experienced severe elevations within 4 days of initiating saquinavir/ritonavir. Clinical symptoms (e.g., nausea, vomiting, abdominal pain, and headache) were more common and severe in arm 2. Clinical symptoms abated and transaminases normalized following drug discontinuation. Limited pharmacokinetic data suggest a possible relationship between transaminase elevation and elevated rifampin and desacetyl‐rifampin concentrations.

Conclusions.  Although not confirmed in HIV‐infected patients, the data indicate that rifampin should not be coadministered with saquinavir/ritonavir.
Vilazodone: A 5‐HT1AReceptor Agonist/Serotonin Transporter Inhibitor for the Treatment of Affective Disorders
Authors: Dawson Lee A. , Watson Jeannette M.
Published: March 2009

Vilazodone(EMD 68843; 5‐{4‐[4‐(5‐cyano‐3‐indolyl)‐butyl]‐1‐piperazinyl}‐benzofuran‐2‐carboxamide hydrochloride) is a combined serotonin specific reuptake inhibitor (SSRI) and 5‐HT1Areceptor partial agonist currently under clinical evaluation for the treatment of major depression. This molecule was designed based on the premise that negative feedback circuitry, mediated via 5‐HT1receptors, limits the acute SSRI‐induced enhancements in serotonergic neurotransmission. If the hypothesis is correct, combination of SSRI with 5‐HT1Apartial agonism should temporally enhance the neuroplastic adaptation and subsequently hasten therapeutic efficacy compared to current treatments. Preclinicalin vitroevaluation has confirmed vilazodone's primary pharmacological profile both in clonal and native systems, that is, serotonin reuptake blockade and 5‐HT1Apartial agonism. However,in vivoand in contrast to combination of 8‐OH‐DPAT and paroxetine, vilazodone selectively enhanced serotonergic output in the prefrontal cortex of rats. Behavioral evaluations, in the ultrasonic vocalization model of anxiety in rats, demonstrated anxiolytic efficacy. In the forced swim test (a putative model of depression), vilazodone also showed efficacy but at a single dose only. In man, vilazodone abolished REM sleep and demonstrated clinical antidepressant efficacy equivalent to an SSRI. Ongoing clinical evaluations will hopefully reveal whether the founding hypothesis was valid and if vilazodone will produce a more rapid onset of antidepressant efficacy.
Nomenclatural notes to Flora Nordica Vol. 6 (Thymelaeaceae–Apiaceae)
Authors: Jonsell Bengt , Ericsson Stefan , Fröberg Lars , Rostański Krzysztof , Snogerup Sven , Widén Björn
Published: March 2009

The following names in Flora Nordica Vol. 6 are subject to nomenclatural action: Helianthemum oelandicum var. canescens (typified), Epilobium hornemannii (typified), Oenothera nuda (validated), Myriophyllum spicatum (emendation of typification), Viola rupestris subsp. relicta (typified), Hippophaë rhamnoides (typified), Angelica archangelica subsp. littoralis (typified). – Flora Nordica Note no. 35.