bluuebunny/crossref_metadata_2025 huggingface dataset:
Escalation: The Role of Problem Recognition and Cognitive Bias
Authors: Keil Mark , Depledge Gordon , Rai Arun
Published: August 2007

Escalation of commitment to a failing course of action is an enduring problem that remains central to the study of managerial behavior. Prior research suggests that escalation behavior results when decision makers choose to ignore negative feedback concerning the viability of a previously chosen course of action. Previous work has also suggested that certain cognitive biases might promote escalation behavior, but there has been little attempt to explore how biases other than framing affect escalation. In this article, we explore the extent to which decision makers actually perceive negative feedback as indicative of a problem and how this influences their decision to escalate. Although problem recognition and cognitive biases have been intensively studied individually, little is known about their effect on escalation behavior. In this research, we construct and test an escalation decision model that incorporates both problem recognition and two cognitive biases: selective perception and illusion of control. Our results revealed a significant inverse relationship between problem recognition and escalation. Furthermore, selective perception and illusion of control were found to significantly affect both problem recognition and escalation. The implications of these findings for research and practice are discussed. To improve problem recognition and reduce the incidence of escalation, practicing managers should implement modern project management practices that can help to identify and highlight potential problems while guarding against these two key cognitive biases that promote the behavior.
Internal Infrastructural Impacts on RFID Perceptions and Commitment: Knowledge, Operational Procedures, and Information‐Processing Standards
Authors: Bendoly Elliot , Citurs Alex , Konsynski Benn
Published: August 2007

For many firms, radio frequency identification (RFID) suggests not only a new alternative to existing tracking methods but also a means to a range of previously cost‐prohibitive internal control and supply chain coordination innovations. In any event, and even in light of possible external pressures to adopt, the full potential of RFID for an individual firm must ultimately be viewed in consideration with the infrastructural capabilities of that firm. Furthermore, because adoption decisions are fundamentally based on managerial perceptions, it is critical to consider how certain forms of infrastructure provide the necessary transparency into other infrastructural characteristics to augment such decisions. We use multisource survey data in this work to consider several elements that contribute to this infrastructure and subsequently to perceptions of RFID benefit and actual commitment to adoption. Results demonstrate that the complementary effects of these infrastructural capabilities significantly impact both perceptions of and commitments to RFID.
Embeddedness of Organizational Capabilities*
Authors: Grewal Rajdeep , Slotegraaf Rebecca J.
Published: August 2007

Managers must regularly make decisions on how to access and deploy their limited resources in order to build organizational capabilities for a sustainable competitive advantage. However, failure to recognize that organizational capabilities involve complex and intricately woven underlying processes may lead to an incomplete understanding of how capabilities affect competitive advantage. As a means of understanding this underlying complexity, we discuss how managerial decisions on resource acquisition and deployment influence capability embeddedness and argue that capability embeddedness has an incremental effect on firm performance beyond the effects from organizational resources and capabilities. To investigate these issues, we present a hierarchical composed error structure framework that relies on cross‐sectional data (and allows for generalizations to panel data). We demonstrate the framework in the context of retailing, where we show that the embeddedness of organizational capabilities influences retailer performance above and beyond the tangible and intangible resources and capabilities that a retailer possesses. Our results illustrate that understanding how resources and capabilities influence performance at different hierarchical levels within a firm can aid managers to make better decisions on how they can embed certain capabilities within the structural and social relationships within the firm. Moreover, understanding whether the underlying objectives of the capabilities that are being built and cultivated have convergent or divergent goals is critical, as it can influence the extent to which the embedded capabilities enhance firm performance.
Aberrant Crypt Foci and Semiparametric Modeling of Correlated Binary Data
Authors: Apanasovich Tatiyana V. , Ruppert David , Lupton Joanne R. , Popovic Natasa , Turner Nancy D. , Chapkin Robert S. , Carroll Raymond J.
Published: August 2007

Summary Motivated by the spatial modeling of aberrant crypt foci (ACF) in colon carcinogenesis, we consider binary data with probabilities modeled as the sum of a nonparametric mean plus a latent Gaussian spatial process that accounts for short‐range dependencies. The mean is modeled in a general way using regression splines. The mean function can be viewed as a fixed effect and is estimated with a penalty for regularization. With the latent process viewed as another random effect, the model becomes a generalized linear mixed model. In our motivating data set and other applications, the sample size is too large to easily accommodate maximum likelihood or restricted maximum likelihood estimation (REML), so pairwise likelihood, a special case of composite likelihood, is used instead. We develop an asymptotic theory for models that are sufficiently general to be used in a wide variety of applications, including, but not limited to, the problem that motivated this work. The splines have penalty parameters that must converge to zero asymptotically: we derive theory for this along with a data‐driven method for selecting the penalty parameter, a method that is shown in simulations to improve greatly upon standard devices, such as likelihood crossvalidation. Finally, we apply the methods to the data from our experiment ACF. We discover an unexpected location for peak formation of ACF.
Mortality Modeling of Early Detection Programs
Authors: Lee Sandra J. , Zelen Marvin
Published: August 2007

Summary Consider a group of subjects who are offered an opportunity to receive a sequence of periodic special examinations for the purpose of diagnosing a chronic disease earlier relative to usual care. The mortality for the early detection group is to be compared with a group receiving usual care. Benefit is reflected in a potential reduction in mortality. This article develops a general probability model that can be used to predict cumulative mortality for each of these groups. The elements of the model assume (i) a four‐state progressive disease model in which a subject may be in a disease‐free state (or a disease state that cannot be detected), preclinical disease state (capable of being diagnosed by a special exam), clinical state (diagnosis by usual care), and a death state; (ii) age‐dependent transitions into the states; (iii) age‐dependent examination sensitivity; (iv) age‐dependent sojourn time in each state; and (v) the distribution of disease stages on diagnosis conditional on modality of detection. The model may be used to (i) compare mortality rates for different screening schedules; (ii) explore potential benefit of subpopulations; and (iii) compare relative reductions in disease‐specific mortality due to advances and dissemination of both treatment and early detection screening programs.
Preliminary Investigations into Tris(2,2′‐bipyridyl) Ruthenium (III) as a Chemiluminescent Reagent for the Detection of 3,6‐Diacetylmorphine (Heroin) on Surfaces
Authors: Agg Kent M. , Barnett Neil W. , Lewis Simon W. , Pearson James R.
Published: August 2007

Abstract:  The use of tris(2,2′‐bipyridyl) ruthenium (III) as a chemiluminescent spray reagent spot‐test for heroin is discussed. Two forms of the reagent are investigated an aqueous and an anhydrous where both were found to give vastly different results. The aqueous reagent giving slow, low intensity chemiluminescence whilst the anhydrous reagent gave a fast, bright response in the presence of 3,6‐diacetylmorphine. The anhydrous reagent is less sensitive the slow, intensity response is characteristic of only two opiates tested 3,6‐diacetylmorphine and 3‐monoacetylmorphine.
The Characteristics of Head Wounds Inflicted by “Humane Killer” (Captive‐Bolt Gun)—A 15‐Year Study*
Authors: Simic Milan , Draskovic Dragan , Stojiljkovic Goran , Vukovic Radenko , Budimlija Zoran M.
Published: August 2007

The “humane killer” or captive‐bolt gun, is the tool/weapon widely used in meat industry and private farmer households for slaughtering animal stock. Out of 17,250 autopsies performed at the Institute of Forensic Medicine in Novi Sad during the 15‐year period (1991–2005), 29 cases of suicides and two homicides were committed by captive‐bolt pistols. Wounds inflicted by captive‐bolt guns have specific morphological features, distinctive from wounds made by other kinds of hand firearms. Selected features of the captive‐bolt wounds (punched round entrance and a double pattern of smoke soiling) depend on distance and angle of instrument at the time of firing. Autopsy findings were compared with an experimental model consisting of 20 domestic pigs. Obtained results confirmed that the appearance of the entrance hole and soot deposits, along with differences in shape, location, extent, and density of soot blackening, could be useful in identification of weapon, direction of discharge, shooting distance, and angle of the muzzle to the frontal and sagittal planes of the head at the moment of fire.
Stalking and Huntington’s Disease: A Neurobiological Link?
Authors: Soliman Sherif , Haque Shuja , George Edwin
Published: August 2007

Abstract:  This case report describes a patient with Huntington’s Disease (HD) who allegedly stalked her therapist. The patient developed recurrent thoughts about her therapist as well as amorous feelings towards her therapist. She engaged in stalking behavior including unwelcome gifts, multiple telephone calls to the therapist’s office and home, and making threats towards the therapist. The patient continued to contact the therapist after the therapist filed a Personal Protection Order. The patient was successfully treated with risperidone and fluvoxamine. Through a focused review of the relevant literature, the authors explore the potential relationship between the patient’s obsessional thoughts, amorous feelings towards her therapist, the basal ganglia dysfunction, and the stalking behavior. The authors posit a hypothesis of stalking as a novel early manifestation of HD in this patient. To the best of the authors’ knowledge, this is the first reported case of stalking occurring with potentially causal organic lesions.
HPLC–DAD Determination of Mepivacaine in Cerebrospinal Fluid from a Fatal Case
Authors: Nieddu Maria , Boatto Gianpiero , Serra Domenico , Soro Aldo , Lorenzoni Salvatore , Lubinu Francesco
Published: August 2007

Abstract:  A fatal case involving mepivacaine‐induced epidural anesthesia is described. The pathological findings were typical of cardiac shock from ischemic origin. Cerebrospinal fluid (CSF) was obtained several hours after death and mepivacaine was identified by gas chromatography‐mass spectrometry (GC‐MS). Its concentration was determined by high performance liquid chromatography with diode array detection (HPLC–DAD). Extraction from CSF was performed by deproteinization with acetonitrile. The mepivacaine concentration in the sample was 264 μg/mL. Concentrations of mepivacaine in CSF following epidural anesthesia are not reported in literature to our knowledge. This is the first reported case of death in which the mepivacaine concentration in CSF has been determined.
Independence Day Explosion on Lovers Key*
Authors: Harding Brett A. , Wolf Barbara C.
Published: August 2007

The display of fireworks is a popular holiday celebration in the United States. Because injuries due to recreational fireworks‐related explosions among private consumers are relatively common, the sale of fireworks is regulated by the federal government and is also limited by state and local laws. In contrast, because fireworks display companies are under tight safety regulations, explosions in the professional pyrotechnics industry are uncommon occurrences, and the literature contains rare reports of injuries and fatalities resulting from such explosions. We report the 2003 Fourth of July commercial fireworks explosion on Lovers Key in southwest Florida that resulted in five fatalities. Events occurring during the investigation of the scene of this explosion illustrate the unique considerations and hazards for medicolegal death investigators, law enforcement and other investigative agencies. Additionally, this case demonstrates unusual aspects of the postmortem examinations performed on victims of fireworks‐related incidents.
The Analysis of Tire Rubber Traces Collected After Braking Incidents Using Pyrolysis‐Gas Chromatography/Mass Spectrometry
Authors: Sarkissian Garry
Published: August 2007

Automobile tire marks can routinely be found at the scenes of crime, particularly hit‐and‐run accidents and are left on road surfaces because of sudden braking or the wheels spinning. The tire marks are left due to the friction between the tire rubber and the solid road surface, and do not always demonstrate the tire tread pattern. However, the tire mark will contain traces of the tire. In this study, Pyrolysis Gas Chromatography/Mass Spectrometry was used to analyze 12 tires from different manufacturer’s and their traces collected after braking incidents. Tire marks were left on a conglomerate road surface with sudden braking. The samples were pyrolysed without removal of contaminant in a micro‐furnace type pyrolyser. Quantitative and qualitative analysis were performed on all the samples. All 12 samples were distinguished from each other. Each of the tire traces were identified as coming from there original source.
Studies of the Chronological Course of Wisdom Tooth Eruption in a Black African Population
Authors: Olze Andreas , Van Niekerk Piet , Schulz Ronald , Schmeling Andreas
Published: August 2007

The importance of forensic age estimation in living subjects has grown over the last few years. In dental age estimation, tooth eruption is a parameter of developmental morphology that can be analyzed by either clinical examination or by evaluation of dental X‐rays. In the present study, we determined the stage of wisdom tooth eruption in 410 male and 106 female Black South African subjects of known age (12–26 years) based on radiological evidence from 516 conventional orthopantomograms. Four eruption stages were determined (no emergence, alveolar emergence, gingival emergence, complete emergence). Statistical scores were determined for the individual stages separately for both sexes. The data presented here can be utilized for forensic estimation of the minimum and most probable ages of investigated persons.
The Detection of Multiply Charged Dyes Using Matrix‐Assisted Laser Desorption/Ionization Mass Spectrometry for the Forensic Examination of Pen Ink Dyes Directly from Paper
Authors: Dunn Jamie D. , Allison John
Published: August 2007

Abstract:  Laser desorption mass spectrometry (LDMS) is emerging as a technique for questioned document examination. Its use is limited to detecting ink dyes that are neutral or singly charged. Several inks contain dyes that are multiply charged and LDMS cannot be employed for their identification. We have successfully detected >20 polyionic dyes that can be used in the manufacture of inks using matrix‐assisted laser desorption/ionization (MALDI) MS, directly from paper, with the matrix, 2‐(4‐hydroxyphenylazo)benzoic acid (HABA), and the additive, diammonium hydrogen citrate (DAHC). For example, Acid Violet 49, a charged dye containing one positively‐charged site and two negatively charged sulfonate groups, cannot be detected by LDMS, but forms intact, singly charged ions in the MALDI MS experiment. The method described is also useful for identifying multiply charged dye mixtures that are used in modern pen inks.
A Comparison of Email Versus Letter Threat Contacts toward Members of the United States Congress*
Authors: Schoeneman‐Morris Katherine A. , Scalora Mario J. , Chang Grace H. , Zimmerman William J. , Garner Yancey
Published: August 2007

To better understand inappropriate correspondence sent to public officials, 301 letter cases and 99 email cases were randomly selected from the United States Capitol Police investigative case files and compared. Results indicate that letter writers were significantly more likely than emailers to exhibit indicators of serious mental illness (SMI), engage in target dispersion, use multiple methods of contact, and make a problematic approach toward their target. Emailers were significantly more likely than letter writers to focus on government concerns, use obscene language, and display disorganization in their writing. Also, letter writers tended to be significantly older, have more criminal history, and write longer communications. A multivariate model found that disorganization, SMI symptoms, problematic physical approach, and target dispersion significantly differentiated between the correspondence groups. The group differences illuminated by this study reveal that letter writers are engaging in behavior that is higher risk for problematic approach than are emailers.
Bioterrorism: Processing Contaminated Evidence, the Effects of Formaldehyde Gas on the Recovery of Latent Fingermarks*
Authors: Hoile Rebecca , Walsh Simon J. , Roux Claude
Published: August 2007

Abstract:  In the present age of heightened emphasis on counter terrorism, law enforcement and forensic science are constantly evolving and adapting to the motivations and capabilities of terrorist groups and individuals. The use of biological agents on a population, such as anthrax spores, presents unique challenges to the forensic investigator, and the processing of contaminated evidence. In this research, a number of porous and nonporous items were contaminated with viable anthrax spores and marked with latent fingermarks. The test samples were then subjected to a standard formulation of formaldehyde gas. Latent fingermarks were then recovered postdecontamination using a range of methods. Standard fumigation, while effective at destroying viable spores, contributed to the degradation of amino acids leading to loss of ridge detail. A new protocol for formaldehyde gas decontamination was developed which allows for the destruction of viable spores and the successful recovery of latent marks, all within a rapid response time of less than 1 h.
Measurement of health‐related quality of life with glaucoma: validation of the Glau‐QoL© 36‐item questionnaire
Authors: Béchetoille Alain , Arnould Benoit , Bron Alain , Baudouin Christophe , Renard Jean‐Paul , Sellem Eric , Brouquet Yves , Denis Philippe , Nordmann Jean‐Philippe , Rigeade Marie‐Claude , Bassols Ana , Benmedjahed Khadra , Guillemin Isabelle , Rouland Jean‐François
Published: August 2007

Purpose:  To validate a glaucoma‐specific health‐related quality of life (HRQoL) questionnaire: the Glau‐QoL©.

Methods:  Patients with ocular hypertension (OHT) or glaucoma took part in a cross‐sectional psychometric validation study (n = 573) and a separate reproducibility study (n = 244). Patients answered the 36‐item Glau‐QoL©, designed from in‐depth patient interviews.

Results:  The clinical validity of the Glau‐QoL© was excellent and clearly demonstrated that as disease severity and visual field impairment increased, HRQoL scores for the Psychological Wellbeing, Self‐image, Daily Life, Driving, Anxiety and Burden of Treatment domains were negatively affected. Increased age and lower visual acuity were also associated with lower HRQoL scores, although to a lesser extent than the previously mentioned criteria. Worsening of HRQoL domains correlated with the clinical stage of glaucoma: Anxiety and Burden of Treatment scores dropped noticeably when patients were first diagnosed and started treatment, followed by a decrease in scores for Driving, Daily Life, Psychological Wellbeing, and Self‐image as clinical conditions worsened. Psychometric validation showed acceptable convergent and discriminant validity of the Glau‐QoL©, and good reproducibility, with intraclass correlation coefficients (ICC) and concordance correlation coefficients (CCC) ≥ 0.69. Internal consistency reliability was high (Cronbach's α coefficients > 0.70) for the Daily Life, Psychological Wellbeing, Burden of Treatment and Driving domains; acceptable (coefficients of 0.65 and 0.68, respectively) for the Self‐image and Anxiety domains; and weak (coefficient = 0.58) for the Confidence in Health Care domain.

Conclusions:  The Glau‐QoL© questionnaire is a valid and specific HRQoL instrument that demonstrates excellent correlations with disease progression in patients with glaucoma and/or OHT.
Visual recovery after vitrectomy for macular hole using 25‐gauge instruments
Authors: Shinoda Hajime , Shinoda Kei , Satofuka Shingo , Imamura Yutaka , Ozawa Yoko , Ishida Susumu , Inoue Makoto
Published: August 2007

Purpose:  To determine whether vitrectomy with 25‐gauge instruments contributes to better postoperative visual recovery after macular hole (MH) surgery.

Methods:  The medical records for 46 consecutive eyes operated for MH by a single surgeon were retrospectively examined. Vitrectomy had been performed with a 25‐gauge instrument in 23 eyes (25‐G group) and with a 20‐gauge instrument in 23 eyes (20‐G group). Postoperative visual acuity (VA) in logMAR (logarithm of the minimum angle of resolution) units after 1 week and 1, 3, 6, 9 and 12 months, operating time, and volume of intraocular irrigating fluid were compared between the two groups.

Results:  Mean preoperative logMAR VA was 0.72 in the 25‐G group and 0.68 in the 20‐G group (p = 0.282, unpaired t‐test). One week after surgery, VA was significantly better in the 25‐G group (0.40 ± 0.34) than in the 20‐G group (0.58 ± 0.30) (p = 0.020). This significant difference was maintained until 9 months after surgery, but was no longer evident at 12 months (p = 0.182). Operating time was significantly shorter in the 25‐G group (56 ± 16 mins) than in the 20‐G group (85 ± 28 mins) (p = 0.003, unpaired t‐test). The volume of intraocular irrigating fluid was significantly less in the 25‐G group (244 ± 72 ml) than in the 20‐G group (416 ± 113 ml) (p < 0.0001).

Conclusions:  The use of 25‐gauge vitrectomy instruments leads to better postoperative visual recovery following surgery for MH during the first 9 months, probably as a result of shorter surgical time and a lower volume of intraocular irrigating fluid.
Morphometry of human terminal and vellus hair follicles
Authors: Vogt Annika , Hadam Sabrina , Heiderhoff Marc , Audring Heike , Lademann Juergen , Sterry Wolfram , Blume‐Peytavi Ulrike
Published: August 2007

Abstract:  Previous studies suggest that drug delivery systems based on particles can be used to deposit active compounds in hair follicles and to target hair follicle‐associated cell populations. The development of application protocols is complicated by the fact that there is no information available on the size and the position of key target structures in the different hair follicle types and their intra‐ and interindividual variation. Therefore, we performed morphometric measurements on histological sections of human terminal (THF) and vellus hair follicles (VHF) from the scalp and the retroauricular region. With 3864 ± 605 μm and 580 ± 84 μm in THF compared to 646 ± 140 μm and 225 ± 34 μm in VHF, the total length and the length of the infundibulum differed significantly as determined by paired t‐test (P < 0.0001). The same level of significance was observed for the position and the length of the bulge region. The thickness of the epithelial lining was lowest in VHF (45 ± 14 μm at 100 μm from skin surface) compared to 65 ± 20 μm at 150 μm in THF, while the thickness of the interfollicular epidermis ranged between 64 ± 12 μm and 99 ± 18 μm in VHF‐bearing skin and 72 ± 16 μm and 136 ± 37 μm in THF‐bearing skin. In addition, the diameter of the hair follicle opening was determined at 50 μm intervals from the skin surface. Our data suggest that hair follicle types in defined body regions represent rather homogenous groups and that particle‐based drug delivery may be a feasible approach, also in larger numbers of individuals. We provide precise information on the size and the position of key target structures in VHF and THF.
A dual concept of nevogenesis:Theoretical considerations based on dermoscopic features of melanocytic nevi
Authors: Zalaudek Iris , Hofmann‐Wellenhof Rainer , Kittler Harald , Argenziano Giuseppe , Ferrara Gerardo , Petrillo Luca , Kerl Helmut , Soyer H. Peter
Published: August 2007

The dermoscopic features of melanocytic nevi in children are clearly different from those in adults. While nevi in children show almost exclusively globular patterns, those in adults usually exhibit reticular patterns. These remarkable differences could be explained by a dual concept of nevogenesis, based on current clinico‐epidemiologic, dermoscopic, histopathologic and genetic data.
Winter compensatory growth under field conditions partly offsets low energy reserves before winter in a damselfly
Authors: De Block Marjan , A. McPeek Mark , Stoks Robby
Published: August 2007

Despite the survival value of high energy reserves during winter, animals often face energy deficits when entering winter. Compensatory growth in energy reserves during the winter period to buffer such deficits may increase winter survival and alleviate the need for costly compensatory mechanisms before or after winter when predation risk is much higher. However, such compensatory responses in energy reserves during winter have not been demonstrated under field conditions. We explored if Lestes eurinus damselfly larvae can compensate for suboptimal energy reserves during winter at 4°C when their ponds are covered with ice. In a field enclosure experiment, we demonstrated compensatory growth in terms of body mass and energy reserves in larvae whose energy status was previously manipulated in the laboratory. These results were supported by patterns in body mass and energy reserves over winter in two natural unmanipulated populations. Winter survival was high overall and not affected by compensatory growth. We hypothesize that the observed compensatory growth in energy reserves during winter may shape life history decisions in autumn and spring, and may make resource availability during winter as or more important than energy reserves before winter.
Differences in sympathetic neuroeffector transmission to rat mesenteric arteries and veins as probed byin vitrocontinuous amperometry and video imaging
Authors: Park Jinwoo , Galligan James J. , Fink Gregory D. , Swain Greg M.
Published: August 2007

As arteries are resistance blood vessels while veins perform a capacitance function, it might be expected that sympathetic neural control of arteries and veins would differ. The function of sympathetic nerves supplying mesenteric arteries (MA) and veins (MV) in rats was investigated usingin vitrocontinuous amperometry with a carbon fibre microelectrode and video imaging. We simultaneously measured noradrenaline (NA) overflow at the blood vessel adventitial surface and vasoconstriction evoked by electrical stimulation of perivascular sympathetic nerves. Sympathetic nerve arrangement was studied using glyoxylic acid‐induced fluorescence of NA. We found that: (i) there were significant differences between MA and MV in the arrangement of sympathetic nerves; (ii) frequency–response curves for NA overflow and vasoconstriction for MV were left‐shifted compared to MA; (iii) the P2X receptor antagonist, pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS, 10 μm), reduced constrictions in MA but not in MV while the α1‐adrenergic receptor antagonist, prazosin (0.1 μm), blocked constrictions in MV but not in MA; (iv) NA overflow for MA was enhanced by the α2‐adrenergic receptor antagonist, yohimbine (1.0 μm), and attenuated by the α2‐adrenergic receptor agonist, UK 14,304 (1.0 μm), while yohimbine and UK 14,304 had little effect in MV; (v) cocaine (10 μm) produced larger increases in NA overflow in MA than in MV; (vi) UK 14,304 constricted MV but not MA while yohimbine reduced constrictions in MV but not MA. We conclude that there are fundamental differences in sympathetic neuroeffector mechanisms in MA and MV, which are likely to contribute to their different haemodynamic functions.
Cue‐evoked encoding of movement planning and execution in the rat nucleus accumbens
Authors: Taha Sharif A. , Nicola Saleem M. , Fields Howard L.
Published: August 2007

The nucleus accumbens is involved in the modulation of motivated behaviour by reward‐associated sensory information. However, little is known about the specific nature of the nucleus accumbens' contribution to generating movement. We investigated motor encoding by nucleus accumbens neurons in rats performing a delayed response task that allowed us to dissociate the effects of sensory and motor events on firing. In a subset of neurons, firing in the delay period preceding movement was highly selective; this selectivity was tightly correlated with the direction of the subsequent movement, but not with the sensory properties of the instructive cue. Direction selectivity in this population of neurons developed over the course of the delay period, with the strongest selectivity apparent just prior to movement onset. Selectivity was also apparent in nucleus accumbens neurons during movement, such that firing showed a tight correlation with movement direction, but not the instructive cue presented nor the spatial destination of the movement. These results are consistent with the hypothesis that a subpopulation of nucleus accumbens neurons contributes to the selection and execution of specific motivated behaviours.
IP3‐dependent nuclear Ca2+ signalling in the mammalian heart
Authors: Zima Aleksey V. , Bare Dan J. , Mignery Gregory A. , Blatter Lothar A.
Published: August 2007

In cardiac myocytes the type‐2 inositol 1,4,5‐trisphosphate receptor (IP3R2) is the predominant isoform expressed. The IP3R2 channel is localized to the SR and to the nuclear envelope. We studied IP3‐dependent nuclear Ca2+ signals ([Ca2+]Nuc) in permeabilized atrial myocytes and in isolated cardiac nuclei. In permeabilized myocytes IP3 (20 μm) and the more potent IP3R agonist adenophostin (5 μm) caused an elevation of [Ca2+]Nuc. An IP3‐dependent increase of [Ca2+]Nuc was still observed after pretreatment with tetracaine to block Ca2+ release from ryanodine receptors (RyRs), and the effect of IP3 was partially reversed or prevented by the IP3R blockers heparin and 2‐APB. Isolated nuclei were superfused with an internal solution containing the Ca2+ indicator fluo‐4 dextran. Exposure to IP3 (10 μm) and adenophostin (0.5 μm) increased [Ca2+]Nuc by 25 and 27%, respectively. [Ca2+]Nuc increased to higher levels than [Ca2+]Cyt immediately adjacent to the outer membrane of the nuclear envelope, suggesting that a significant portion of nuclear IP3 receptors are facing the nucleoplasm. When nuclei were pretreated with heparin or 2‐APB, IP3 failed to increase [Ca2+]Nuc. Isolated nuclei were also loaded with the membrane‐permeant low‐affinity Ca2+ probe fluo‐5N AM which compartmentalized into the nuclear envelope. Exposure to IP3 and adenophostin resulted in a decrease of the fluo‐5N signal that could be prevented by heparin. Stimulation of IP3R caused depletion of the nuclear Ca2+ stores by approximately 60% relative to the maximum depletion produced by the ionophores ionomycin and A23187. The fluo‐5N fluorescence decrease was particularly pronounced in the nuclear periphery, suggesting that the nuclear envelope may represent the predominant nuclear Ca2+ store. The data indicate that IP3 can elicit Ca2+ release from cardiac nuclei resulting in localized nuclear Ca2+ signals.
Neuron type‐specific effects of brain‐derived neurotrophic factor in rat superficial dorsal horn and their relevance to ‘central sensitization’
Authors: Lu Van B. , Ballanyi Klaus , Colmers William F. , Smith Peter A.
Published: August 2007

Chronic constriction injury (CCI) of the rat sciatic nerve increases the excitability of the spinal dorsal horn. This ‘central sensitization’ leads to pain behaviours analogous to human neuropathic pain. We have established that CCI increases excitatory synaptic drive to putative excitatory, ‘delay’ firing neurons in the substantia gelatinosa but attenuates that to putative inhibitory, ‘tonic’ firing neurons. Here, we use a defined‐medium organotypic culture (DMOTC) system to investigate the long‐term actions of brain‐derived neurotrophic factor (BDNF) as a possible instigator of these changes. The age of the cultures and their 5–6 day exposure to BDNF paralleled the protocol used for CCI in vivo. Effects of BDNF (200 ng ml−1) in DMOTC were reminiscent of those seen with CCI in vivo. These included decreased synaptic drive to ‘tonic’ neurons and increased synaptic drive to ‘delay’ neurons with only small effects on their membrane excitability. Actions of BDNF on ‘delay’ neurons were exclusively presynaptic and involved increased mEPSC frequency and amplitude without changes in the function of postsynaptic AMPA receptors. By contrast, BDNF exerted both pre‐ and postsynaptic actions on ‘tonic’ cells; mEPSC frequency and amplitude were decreased and the decay time constant reduced by 35%. These selective and differential actions of BDNF on excitatory and inhibitory neurons contributed to a global increase in dorsal horn network excitability as assessed by the amplitude of depolarization‐induced increases in intracellular Ca2+. Such changes and their underlying cellular mechanisms are likely to contribute to CCI‐induced ‘central sensitization’ and hence to the onset of neuropathic pain.
Neurosteroid migration to intracellular compartments reduces steroid concentration in the membrane and diminishes GABA‐A receptor potentiation
Authors: Li Ping , Shu Hong‐Jin , Wang Cunde , Mennerick Steven , Zorumski Charles F. , Covey Douglas F. , Steinbach Joe Henry , Akk Gustav
Published: August 2007

Neurosteroids are potent modulators of GABA‐A receptors. We have examined the time course of development of potentiation of α1β2γ2L GABA‐A receptors during coapplication of GABA and an endogenous neurosteroid (3α,5α)‐3‐hydroxypregnan‐20‐one (3α5αP). The simultaneous application of 3α5αP with 5 μm GABA resulted in a biphasic rising phase of current with time constants of 50–60 ms for the rapid phase and 0.3–3 s for the slow phase. The properties of the rapid phase were similar at all steroid concentrations but the time constant of the slower phase became successively shorter as the steroid concentration was increased. Potentiation developed very rapidly (τ= 130 ms) when cells were preincubated with 300 nm 3α5αP before application of GABA + 3α5αP, and in outside‐out patch recordings, suggesting that steroid diffusion to intracellular compartments competes with receptor potentiation by depleting the cell membrane of steroid. Very low steroid concentrations (3–5 nm) potentiated GABA responses but the effects took minutes to develop. Intracellular accumulation of a fluorescent steroid analogue followed a similar time course, suggesting that slow potentiation results from slow accumulation within plasma membrane rather than indirect effects, such as activation of second messenger systems. In cell‐attached single‐channel recordings, where 3α5αP is normally applied through the pipette solution, addition of steroid to the bath solution dramatically shifted the steroid potentiation concentration–effect curve to lower steroid concentrations. We propose that bath‐supplied steroid compensates for the diffusion of pipette‐supplied steroid out of the patch to the rest of the cell membrane and/or intracellular compartments. The findings suggest that previous studies overestimate the minimum concentration of steroid capable of potentiating GABA actions at GABA‐A receptors. The results have implications for the physiological role of endogenous neurosteroids.
Cardiac metabolic adaptations in response to chronic hypoxia
Authors: Essop M. Faadiel
Published: August 2007

Since a constant supply of oxygen is essential to sustain life, organisms have evolved multiple defence mechanisms to ensure maintenance of the delicate balance between oxygen supply and demand. However, this homeostatic balance is perturbed in response to a severe impairment of oxygen supply, thereby activating maladaptive signalling cascades that result in cardiac damage. Past research efforts have largely focused on determining the pathophysiological effects of severe lack of oxygen. By contrast, and as reviewed here, exposure to moderate chronic hypoxia may induce cardioprotective properties. The hypothesis put forward is that chronic hypoxia triggers regulatory pathways that mediate long‐term cardiac metabolic remodelling, particularly at the transcriptional level. The novel proposal is that exposure to chronic hypoxia triggers (a) oxygen‐sensitive transcriptional modulators that induce a switch to increased carbohydrate metabolism (fetal gene programme) and (b) enhanced mitochondrial respiratory capacity to sustain and increase efficiency of mitochondrial energy production. These compensatory protective mechanisms preserve contractile function despite hypoxia.
Widespread Lateral Gene Transfer from Intracellular Bacteria to Multicellular Eukaryotes
Authors: Hotopp Julie C. Dunning , Clark Michael E. , Oliveira Deodoro C. S. G. , Foster Jeremy M. , Fischer Peter , Torres Mónica C. Muñoz , Giebel Jonathan D. , Kumar Nikhil , Ishmael Nadeeza , Wang Shiliang , Ingram Jessica , Nene Rahul V. , Shepard Jessica , Tomkins Jeffrey , Richards Stephen , Spiro David J. , Ghedin Elodie , Slatko Barton E. , Tettelin Hervé , Werren John H.
Published: August 2007

Although common among bacteria, lateral gene transfer—the movement of genes between distantly related organisms—is thought to occur only rarely between bacteria and multicellular eukaryotes. However, the presence of endosymbionts, such as
Wolbachia pipientis
, within some eukaryotic germlines may facilitate bacterial gene transfers to eukaryotic host genomes. We therefore examined host genomes for evidence of gene transfer events from
Wolbachia
bacteria to their hosts. We found and confirmed transfers into the genomes of four insect and four nematode species that range from nearly the entire
Wolbachia
genome (>1 megabase) to short (<500 base pairs) insertions. Potential
Wolbachia
-to-host transfers were also detected computationally in three additional sequenced insect genomes. We also show that some of these inserted
Wolbachia
genes are transcribed within eukaryotic cells lacking endosymbionts. Therefore, heritable lateral gene transfer occurs into eukaryotic hosts from their prokaryote symbionts, potentially providing a mechanism for acquisition of new genes and functions.
Target Protectors Reveal Dampening and Balancing of Nodal Agonist and Antagonist by miR-430
Authors: Choi Wen-Yee , Giraldez Antonio J. , Schier Alexander F.
Published: August 2007

MicroRNAs (miRNAs) repress hundreds of target messenger RNAs (mRNAs), but the physiological roles of specific miRNA-mRNA interactions remain largely elusive. We report that zebrafish microRNA-430 (miR-430) dampens and balances the expression of the transforming growth factor–β (TGF-β) Nodal agonist
squint
and the TGF-β Nodal antagonist
lefty
. To disrupt the interaction of specific miRNA-mRNA pairs, we developed target protector morpholinos complementary to miRNA binding sites in target mRNAs. Protection of
squint
or
lefty
mRNAs from miR-430 resulted in enhanced or reduced Nodal signaling, respectively. Simultaneous protection of
squint
and
lefty
or absence of miR-430 caused an imbalance and reduction in Nodal signaling. These findings establish an approach to analyze the in vivo roles of specific miRNA-mRNA pairs and reveal a requirement for miRNAs in dampening and balancing agonist/antagonist pairs.
Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination
Authors: Lee Min Gyu , Villa Raffaella , Trojer Patrick , Norman Jessica , Yan Kai-Ping , Reinberg Danny , Di Croce Luciano , Shiekhattar Ramin
Published: August 2007

Methylation of histone H3 lysine 27 (H3K27) is a posttranslational modification that is highly correlated with genomic silencing. Here we show that human UTX, a member of the Jumonji C family of proteins, is a di- and trimethyl H3K27 demethylase. UTX occupies the promoters of
HOX
gene clusters and regulates their transcriptional output by modulating the recruitment of polycomb repressive complex 1 and the monoubiquitination of histone H2A. Moreover, UTX associates with mixed-lineage leukemia (MLL) 2/3 complexes, and during retinoic acid signaling events, the recruitment of the UTX complex to
HOX
genes results in H3K27 demethylation and a concomitant methylation of H3K4. Our results suggest a concerted mechanism for transcriptional activation in which cycles of H3K4 methylation by MLL2/3 are linked with the demethylation of H3K27 through UTX.
Dysprosium(III) Ion-Selective Electrochemical Sensor Based on 6-Hydrazino-1,5-diphenyl-6,7-dihydropyrazolo[3,4-d]pyrimidine-4(5H)-imine
Authors: Zamani Hassan Ali , Ganjali Mohammad Reza , Seifi Nasim
Published: August 2007

A Dy(III) ion-selective electrode based on 6-hydrazino-1,5-diphenyl-6,7-dihydropyrazolo[3,4-d]pyrimidine-4(5H)-imine (HDDPI) as an excellent sensing material was developed. The sensor exhibits a Nernstian behavior (a slope of 19.6 ± 0.3 mV per decade) over a wide concentration range (from 1.0 × 10-1 to 8.0 × 10-7 M Dy) with a detection limit of 4.2 × 10-7 M. The sensor response is independent of pH of the solution in the pH range 3.5-8.3. The sensor possesses the advantages of short conditioning time, fast response time (<10 s) and in particular, good selectivity and sensitivity to the dysprosium ion in the presence of a variety of cations, including alkali, alkaline earth, transition and heavy metal ions. The sensor also showed a great enhancement in selectivity coefficients for dysprosium ions, in comparison with the formerly mentioned dysprosium sensors. The electrode can be used for at least 10 weeks without any considerable divergence in the potentials. The proposed electrode was successfully used as an indicator electrode in potentiometric titration of Dy(III) ions with EDTA. The membrane sensor was also used in the determination of concentration of F- ions in some mouth washing solutions and in the Dy3+ recovery from solution.
Analysis of Nicotine in Antismoking Pharmaceutical Products by Differential Pulse Polarography and Voltammetry
Authors: Hannisdal Atle , Mikkelsen Øyvind , Schrøder Knut H.
Published: August 2007

A fast and simple differential pulse polarographic method was developed for analysis of nicotine in various pharmaceutical formulations (chewing gum, tablets (drops) and patches). This method requires a simple liquid-liquid extraction procedure for chewing gum and patches, or a direct dilution in supporting electrolyte for tablets before polarographic analysis. The polarographic analysis was done in a Britton-Robinson buffer (pH 6.2) as supporting electrolyte. The multimode electrode from Metrohm was used as working electrode (dropping mercury electrode). This method was applied to the determination of the nicotine content in chewing gum, tablets and patches by using the standard addition method. The results are in good agreement with the content declared by the manufacturer. The method is fast, simple and reliable, and it is a complementary method to the chromatographic method being used today for quantitative analysis of nicotine in pharmaceutical formulations. The limit of quantification is assumed to be far below 0.1 mg/l in the polarographic vessel. The method uses simple dilution and/or extraction procedures for sample preparation before polarographic analysis. It is also shown that it is possible to use a glassy carbon electrode with a mercury film (MTFE electrode) for the determination of nicotine in antismoking pharmaceutical products.
Peripheral blood culture contamination in adults and venepuncture technique: prospective cohort study
Authors: Qamruddin A , Khanna N , Orr D
Published: August 2007

Aims:

To test the hypothesis that compliance with a hospital protocol on peripheral blood culture (PBC) collection in adults is associated with a reduction in PBC contamination, and to investigate likely contributing factors for contamination.

Methods:

A prospective cohort study was conducted, utilising data collection by participant questionnaire completion, and utilising bacteriology laboratory results on PBCs. Participants were all healthcare workers involved in obtaining PBCs from adults.

Results:

1460 PBCs with questionnaires were received. Contamination among the 1460 PBCs as a whole was 8.8%. 766 of the questionnaires were sufficiently complete to allow analysis of blood culture contamination in relation to protocol compliance. Among these, protocol compliance was 30% and contamination was 8.0%. When the protocol was complied with, 2.6% of PBCs were contaminated, but when the protocol was not followed, contamination was significantly higher at 10.3% (OR 4.35, 95% CI 1.84 to 12.54). Univariate analysis on all 1460 PBCs suggested that the site for blood collection, and disinfection of the venepuncture site were important factors in PBC contamination: when no venepuncture site disinfection was performed, contamination was significantly higher than when alcohol was used (5.1% versus 15.8%, OR 3.46, 95% CI 2.01 to 5.97); when a PBC collection site other than a fresh peripheral vein was used, contamination was significantly higher (7.3% versus 12.0%, OR 1.75, 95% CI 1.03 to 2.96).

Conclusions:

Compliance with a hospital protocol on PBC collection technique in adults significantly reduces blood culture contamination.
Geology of the shear-hosted Brookbank gold prospect in the Beardmore–Geraldton belt, Wabigoon subprovince, Ontario
Authors: DeWolfe Jerry C , Lafrance Bruno , Stott Greg M
Published: August 2007

The Beardmore–Geraldton belt consists of steeply dipping, intercalated panels of metavolcanic and metasedimentary rocks along the southern margin of the granite–greenstone Wabigoon subprovince in the Archean Superior Province, Ontario. It is an important past-producing gold belt that includes classic epigenetic iron-formation-hosted deposits near Geraldton and turbidite-hosted deposits, north of Beardmore. The Brookbank gold prospect belongs to a third group of related gold deposits that formed along dextral shear zones localized at contacts between panels of metasedimentary and metavolcanic rocks. The Brookbank prospect occurs along a steeply dipping shear zone at the contact between footwall polymictic conglomerate and hanging-wall calc-alkaline arc basalt. Early during shearing the basalt acted as a structural and chemical trap that localized brittle deformation, veining, and gold deposition, ankerite–sericite–chlorite–epidote–pyrite alteration, and the replacement of metamorphic magnetite and ilmenite by gold-bearing pyrite. This produced a low grade (≤5 g/t Au) ankerite-rich alteration zone that extends up to 20 m into the hanging-wall basalt. Later during shearing, gold was deposited within higher grade (≤20 g/t Au) quartz–orthoclase–pyrite alteration zones superimposed on the wider ankerite-rich alteration zone. Auriferous quartz–carbonate veins oriented clockwise and counter-clockwise to the shear zone walls are folded and boudinaged, respectively, consistent with dextral slip along the shear zone. A key finding of the study is that different groups of gold deposits in the belt, including epigenetic iron formation gold deposits near Geraldton, formed during post-2690 Ma regional dextral transpression across the belt.