bluuebunny/crossref_metadata_2025 huggingface dataset:
Secreted APP regulates the function of full-length APP in neurite outgrowth through interaction with integrin beta1
Authors: Young-Pearse Tracy L , Chen Allen C , Chang Rui , Marquez Cesar , Selkoe Dennis J
Published: June 2008

Background

β-Amyloid precursor protein (APP) has been reported to play a role in the outgrowth of neurites from cultured neurons. Both cell-surface APP and its soluble, ectodomain cleavage product (APPs-α) have been implicated in regulating the length and branching of neurites in a variety of assays, but the mechanism by which APP performs this function is not understood.

Results

Here, we report that APP is required for proper neurite outgrowth in a cell autonomous manner, both in vitro and in vivo. Neurons that lack APP undergo elongation of their longest neurite. Deletion of APLP1 or APLP2, homologues of APP, likewise stimulates neurite lengthening. Intriguingly, wild-type neurons exposed to APPs-α, the principal cleavage product of APP, also undergo neurite elongation. However, APPs-α is unable to stimulate neurite elongation in the absence of cellular APP expression. The outgrowth-enhancing effects of both APPs-α and the deletion of APP are inhibited by blocking antibodies to Integrin β1 (Itgβ1). Moreover, full length APP interacts biochemically with Itgβ1, and APPs-α can interfere with this binding.

Conclusion

Our findings indicate that APPs-α regulates the function of APP in neurite outgrowth via the novel mechanism of competing with the binding of APP to Itgβ1.
The role of corticosteroids in severe community-acquired pneumonia: a systematic review
Authors: Salluh Jorge IF , Póvoa Pedro , Soares Márcio , Castro-Faria-Neto Hugo C , Bozza Fernando A , Bozza Patrícia T
Published: June 2008

Introduction

The purpose of this review was to evaluate the impact of corticosteroids on the outcomes of patients with severe community-acquired pneumonia (CAP).

Methods

We performed a systematic MEDLINE, Cochrane database, and CINAHL search (1966 to November 2007) to identify full-text publications that evaluated the use of corticosteroids in CAP.

Results

An initial literature search yielded 109 articles, and 105 studies were excluded after the first analysis. We found four studies eligible for analysis. On the basis of their results, the use of corticosteroids as adjunctive therapy in severe CAP should be categorized as a weak recommendation (two studies) and a strong recommendation (two studies) with either low- or moderate-quality evidence. However, no evidence of adverse outcomes or harm is present in the evaluated studies.

Conclusion

According to the GRADE system, available studies do not support the recommendation of corticosteroids as a standard of care for patients with severe CAP. Further randomized controlled trials with this aim should enroll a larger number of severely ill patients. However, in patients needing corticosteroids, it may be reasonable to conclude that corticosteroid administration is safe in patients with severe infections receiving antimicrobial therapy.
Association of HMGB1 polymorphisms with outcome in patients with systemic inflammatory response syndrome
Authors: Kornblit Brian , Munthe-Fog Lea , Madsen Hans O , Strøm Jens , Vindeløv Lars , Garred Peter
Published: June 2008

Introduction

High mobility group box 1 protein (HMGB1) is a pleiotropic cytokine, recently implicated in the pathophysiology of the systemic inflammatory response syndrome (SIRS) and sepsis. Data from experimental sepsis models show that administration of anti-HMGB1 antibodies significantly decreased mortality, even when administration was delayed for 24 hours, providing a window of opportunity for therapeutic intervention if transferred into a clinical setting. Whether genetic variation in the human HMGB1 gene is associated with disease susceptibility is unknown.

Methods

We sequenced the HMGB1 gene in 239 prospectively monitored patients with SIRS admitted to an intensive care unit and we measured the corresponding HMGB1 serum concentrations. Blood donors served as control individuals. Outcome parameters according to different HMGB1 genotypes were compared.

Results

Homozygosity and heterozygosity for a promoter variant (-1377delA) was associated with a decreased overall 4-year survival (15% versus 44%, hazard ratio = 1.80; P = 0.01) and with a decreased number of SIRS criteria. Carriage of an exon 4 variant (982C>T) was significantly associated with an increased number of SIRS criteria, a higher Simplified Acute Physiology Score II score, a lower PaO2/FiO2 ratio and lower serum HMGB1 levels (P = 0.01), and with a significantly higher probability of early death due to infection (P = 0.04). HMGB1 was undetectable in the control individuals.

Conclusion

The present article is the first report of clinical implications of variation in the human HMGB1 gene. Two polymorphisms were determined as significant risk factors associated with early and late mortality, which may provide insight into the molecular background of SIRS and sepsis, suggesting a possible role for HMGB1 genetics in future prognostic evaluation.
Genetic analysis of the human infective trypanosome Trypanosoma brucei gambiense: chromosomal segregation, crossing over, and the construction of a genetic map
Authors: Cooper Anneli , Tait Andy , Sweeney Lindsay , Tweedie Alison , Morrison Liam , Turner C Michael R , MacLeod Annette
Published: June 2008

Background

Trypanosoma brucei is the causative agent of human sleeping sickness and animal trypanosomiasis in sub-Saharan Africa, and it has been subdivided into three subspecies: Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, which cause sleeping sickness in humans, and the nonhuman infective Trypanosoma brucei brucei. T. b. gambiense is the most clinically relevant subspecies, being responsible for more than 90% of all trypanosomal disease in humans. The genome sequence is now available, and a Mendelian genetic system has been demonstrated in T. brucei, facilitating genetic analysis in this diploid protozoan parasite. As an essential step toward identifying loci that determine important traits in the human-infective subspecies, we report the construction of a high-resolution genetic map of the STIB 386 strain of T. b. gambiense.

Results

The genetic map was determined using 119 microsatellite markers assigned to the 11 megabase chromosomes. The total genetic map length of the linkage groups was 733.1 cM, covering a physical distance of 17.9 megabases with an average map unit size of 24 kilobases/cM. Forty-seven markers in this map were also used in a genetic map of the nonhuman infective T. b. brucei subspecies, permitting comparison of the two maps and showing that synteny is conserved between the two subspecies.

Conclusion

The genetic linkage map presented here is the first available for the human-infective trypanosome T. b. gambiense. In combination with the genome sequence, this opens up the possibility of using genetic analysis to identify the loci responsible for T. b. gambiense specific traits such as human infectivity as well as comparative studies of parasite field populations.
Estimating quality factor and mean grain size of sediments from high-resolution marine seismic data
Authors: Pinson Luke J. W. , Henstock Timothy J. , Dix Justin K. , Bull Jonathan M.
Published: June 2008

Seismic quality factor has the potential to characterize sediment properties but seldom is used by the industry for offshore site investigations because of practical difficulties with reflection seismology (e.g., restricted bandwidth) and because of uncertainties in rock-physics models. A spectral-ratio analysis of high-resolution marine seismic data can determine a quality factor to within a 95% confidence of [Formula: see text] within the uppermost [Formula: see text] of unconsolidated marine sediments. Our spectral-ratio technique does not require assumptions on how attenuation scales with frequency. Emphasis is placed on interpretation of spectral signatures before applying an iteratively reweighted robust least-squares regression to subdue the effects of noise and local heterogeneities when determining the quality factor of a sediment package. We combined data from boomer and chirp sources toexamine attenuation over four octaves of frequency [Formula: see text] and to demonstrate that expanding the frequency range improves the precision and accuracy of quality-factor fits. We obtain frequency-independent quality factors with 95% confidence intervals of 135 [Formula: see text] and 107 [Formula: see text] for silty clays with mean grain sizes of 7.7 and [Formula: see text], respectively, and 63 [Formula: see text] for a modern sand deposit with mean grain size [Formula: see text], from the Solent (U. K.). Sediments with higher quality factors require more independent observations to achieve a desirable 95% confidence. We required only 45 traces over sands and 1250 traces over the lowest attenuating silty clays. By constructing an empirical model of quality factor against mean grain size from published sediment studies, the mean grain sizes of our Solent sediments can be located, and we find that quality factor can be used to distinguish between coarse grain-dominated and clay-dominated sediments.
Bisphosphonate-Related Osteonecrosis of the Jaws: A Case-Control Study of Risk Factors in Breast Cancer Patients
Authors: Kyrgidis Athanassios , Vahtsevanos Konstantinos , Koloutsos Georgios , Andreadis Charalampos , Boukovinas Ioannis , Teleioudis Zisis , Patrikidou Anna , Triaridis Stefanos
Published: June 2008

Purpose

Osteonecrosis of the jaws (ONJ) was initially described in 2001 in patients receiving intravenous bisphosphonate (BP) treatment. The objective of the present study was to determine whether routine dental procedures can be considered as possible risk factors for the development of ONJ in breast cancer patients receiving BP.

Patients and Methods

Twenty breast cancer patients who developed ONJ receiving BP treatment were included in group A, whereas group B consisted of 40 matched controls (breast cancer patients who did not progress to ONJ receiving BP treatment). Routine dental care, smoking habits, history of tooth extraction, use of dentures, and root canal therapy were recorded.

Results

Our results indicate that history of tooth extraction during zoledronic acid treatment (adjusted odds ratio [OR] = 16.4; 95% CI, 3.4 to 79.6) and the use of dentures (adjusted OR = 4.9; 95% CI, 1.2 to 20.1) increase the risk of developing ONJ.

Conclusion

The outcome of the present study suggests early referral by oncologists for dental evaluation for every patient to be treated with BP. These results raise the current American Society of Clinical Oncology Level of Evidence linking certain dental procedures with ONJ from V to III. Further studies are needed to assess other possible risk factors and also to highlight the etiopathogenesis mechanism of ONJ.
Phase II Randomized Trial of Two Nonoperative Regimens of Induction Chemotherapy Followed by Chemoradiation in Patients With Localized Carcinoma of the Esophagus: RTOG 0113
Authors: Ajani Jaffer A. , Winter Kathryn , Komaki Ritsuko , Kelsen David P. , Minsky Bruce D. , Liao Zhongxing , Bradley Jeffrey , Fromm Mitchel , Hornback David , Willett Christopher G.
Published: June 2008

Purpose

Two nonoperative approaches (one without fluorouracil) using induction chemotherapy and then definitive chemoradiotherapy developed at two centers were compared in patients with localized esophageal cancer (LEC). The primary end point was to assess whether any approach would achieve a ≥ 77.5% 1-year survival rate, surpassing the historical 66% rate from the Radiation Therapy Oncology Group (RTOG) protocol 9405.

Patients and Methods

In a multi-institutional cooperative group setting, patients with LEC who had unresectable cancer, were unwilling to undergo surgery, or were medically unfit for surgery were randomly assigned to receive either induction with fluorouracil, cisplatin, and paclitaxel and then fluorouracil plus paclitaxel with 50.4 Gy of radiation (arm A) or induction with paclitaxel plus cisplatin and then the same chemotherapy with 50.4 Gy of radiation (arm B). Safety and survival rates were assessed.

Results

A total of 84 patients were randomly assigned (arm A, n = 41; arm B, n = 43), and 72 were assessable (arm A, n = 37; arm B, n = 35). The median survival time was 28.7 months for patients in arm A and 14.9 months for patients in arm B (18.8 months for patients in RTOG 9405). The 1-year survival rate of 75.7% in arm A was close to, but did not meet or surpass, the 77.5% goal. The 2-year survival rate was 56% for arm A and 37% for arm B. Grade 3 (arm A = 54%, arm B = 43%) and grade 4 toxicities (arm A = 27%, arm B = 40%) were frequent. Treatment-related death occurred in 3% of patients in arm A and 6% of patients in arm B.

Conclusion

Both arms of RTOG 0113 were associated with high morbidity, and the study did not meet its 1-year survival end point.
The Economic Consequences of Legal Origins
Authors: Porta Rafael La , Lopez-de-Silanes Florencio , Shleifer Andrei
Published: June 2008

In the last decade, economists have produced a considerable body of research suggesting that the historical origin of a country's laws is highly correlated with a broad range of its legal rules and regulations, as well as with economic outcomes. We summarize this evidence and attempt a unified interpretation. We also address several objections to the empirical claim that legal origins matter. Finally, we assess the implications of this research for economic reform.
Transfers in Cash and In-Kind: Theory Meets the Data
Authors: Currie Janet , Gahvari Firouz
Published: June 2008

We review theoretical explanations for in-kind transfers in light of the limited empirical evidence. After reviewing the traditional paternalistic arguments, we consider explanations based on imperfect information and self-targeting. We then discuss the large literature on in-kind programs as a way of improving the efficiency of the tax system and a range of other possible explanations, including the “Samaritan's Dilemma,” pecuniary effects, credit constraints, asymmetric information amongst agents, and political economy considerations. Our reading of the evidence suggests that paternalism and interdependent preferences are leading overall explanations for the existence of in-kind transfer programs but that some of the other arguments may apply to specific cases. Political economy considerations must also be part of the story.
Is the U.S. Labor Market Really that Exceptional? A Review of Richard Freeman's America Works: The Exceptional U.S. Labor Market
Authors: Nickell Stephen
Published: June 2008

America Works is a splendid book and Richard Freeman is to be congratulated on producing a work that sets out what is right and what is wrong with the U.S. labor market while being a joy to read. While I am generally sympathetic to both the analysis and the conclusions, there are a number of points of disagreement that I highlight in this review. In particular, I would add to his policy recommendations by taking a gamble and enacting a law that entitled all employees in the United States to four weeks paid holiday per year in addition to public holidays. This may transform summertime in the United States.
The Enigma of India's Arrival: A Review of Arvind Virmani's Propelling India: From Socialist Stagnation to Global Power
Authors: Basu Kaushik
Published: June 2008

India's high growth over the last fifteen years has inspired several recent books and papers to examine the growth's source and sustainability—the two-volume study by Arvind Virmani being a case in point. This paper evaluates these recent works. It is argued that the cause of the take-off does not fit into any easy ideological category as suggested by Virmani. The current high growth has been achieved in several steps, with distinct factors of propulsion behind each step. There is reason to expect the growth to be sustainable, although destabilizing political tensions will arise from the increasing inequality. The paper also evaluates how India's growth relates to the global economy.
A Review of David Colander's The Making of an Economist, Redux
Authors: Hamermesh Daniel S
Published: June 2008

David Colander's update/reworking of his 1987 volume draws conclusions about graduate study in economics from interviews with students in selected leading U.S. programs. Although not formally statistical, the interviews support the conclusion that most of the core of graduate instruction (except macro) is handled very well. Colander's concern about the lack of attention to training teachers is well founded. His conclusion that fewer idiots savants are being trained than in the 1980s is overly optimistic, and his worry about stresses that graduate students express is misplaced.
Email, ethics and data collection in social work research: some reflections from a research project
Authors: Parker Jonathan
Published: June 2008

This article explores some of the issues arising from data collection and contact methods employed in a research project exploring the links between practice learning and the recruitment and retention of social work staff in local authorities in England. The project employed email and attachment questionnaire and interview methods for data collection. Questions relating to consent, reminders and tracking of participants, as well as data quality and management were brought centre stage. This article explores some of the ethical and practice issues arising from this new approach and suggests some ways forward.
State of the art in impact assessment of policy-oriented international agricultural research
Authors: Raitzer David A. , Ryan James G.
Published: June 2008

Policy-oriented research (POR) represents an increasing share of the Consultative Group on International Agricultural Research’s (CGIAR’s) portfolio. A literature inventory finds 24 studies of the diffusion, influence or impact of this research, of which only three assess impact. There are many influences behind policy formulation, through which research insights permeate, if influential. Hence, attribution and counterfactual difficulties have led many assessments to focus only on analysis of the processes of creating policy influence, rather than also assessing impacts from resulting policy changes. To satisfy CGIAR investor expectations for documented impacts, approaches are proposed for ‘demand-led’ and ‘supply-led’ POR case studies.
Situating children in international development policy: challenges involved in successful evidence-informed policy influencing
Authors: Jones Nicola , Villar Eliana
Published: June 2008

This article presents a framework for analysing the impacts of evidence-informed policy entrepreneurship, and applies it to a longitudinal policy research project on childhood poverty in the developing world. Drawing on insights from Keck and Sikkink’s (1998) work on transnational advocacy, the discussion highlights five key dimensions of possible policy impact: framing debates and policy agenda formulation; securing discursive commitments from key policy actors; bringing about procedural changes; policy reform; and behavioural change. The analysis pays particular attention to the interplay of culture, politics and values in the uptake of research evidence in the policy process, and the challenges of cross-institutional partnership approaches to knowledge translation initiatives.
Will the lessons be learned? Reflections on local authority evaluations and the use of research evidence
Authors: Clark Jill , Hall Elaine
Published: June 2008

Sure Start programmes are complex, community-based initiatives – forerunners of the Children’s Centres Initiative – that have been evaluated nationally and locally. Using an in-depth, retrospective case study of an evaluation of one local programme, the authors raise key issues pertinent to both practice and evaluation in the field, highlighting conflicts and dilemmas both within evaluation generally and, specifically, relating to the evaluation of this programme. We illustrate the difficulties placed on local evaluators by the lack of clear structures within which to work, and provide useful lessons as we move forward into the development and evaluations of new services for children and families.
Improving the quality of integrated policy analysis: impact assessment for sustainable development in the European Commission
Authors: Franz Jennifer S. , Kirkpatrick Colin
Published: June 2008

While a broad consensus has emerged around the need for a balanced approach to impact assessment, there is continuing debate on the appropriate methodology and tools. The purpose of this article is to evaluate the case for using economic valuation techniques in order to integrate the different dimensions of sustainable development and provide an improved methodology for assessing the sustainable development impacts of policy interventions. We explore this issue in the context of the approach used in the European Commission for assessing the potential contribution of the Commission’s policy interventions to Europe’s sustainable development strategy.
An effect size index for comparing two independent alpha coefficients
Authors: Liu Hsin‐Yun , Weng Li‐Jen
Published: June 2008

Since Cronbach proposed the α coefficient in 1951, researchers have contributed to the derivation of its sampling distribution and the testing of related statistical hypotheses. Yet, there has been no research on effect size index relevant to coefficient α to our knowledge. Considering the importance of effect size in understanding quantitative research findings, we therefore developed an effect size index Δ for the comparison of two independent αs with equal test length based on the asymptotic distribution of under the assumptions of normality and compound symmetry. Simulations indicated that the index was applicable when the sample size was at least 100. The robustness of the derived index when the required assumptions were violated was also explored. It is suggested that the index should be applicable in most cases of unequal test lengths and could be extended to non‐normally distributed component scores. Moreover, a small simulation was conducted to explore the behaviour of Δ with correlated errors, a frequently studied situation violating the assumption of compound symmetry. The proposed index was found to be robust unless a large number of highly correlated errors were present in the data.
Responding mindfully to unpleasant thoughts and images: Reliability and validity of the Southampton mindfulness questionnaire (SMQ)
Authors: Chadwick Paul , Hember Martin , Symes Janette , Peters Emmanuelle , Kuipers Elizabeth , Dagnan Dave
Published: June 2008

Objective

To assess the reliability and validity of the Southampton mindfulness questionnaire (SMQ), a 16‐item measure of mindful awareness of distressing thoughts and images.

Methods

A total of 256 people participated, comprising a non‐clinical community sample of 134 (83 meditators and 51 non‐meditators) and a clinical sample of 122 people with a current distressing psychosis. To assess concurrent validity, non‐clinical participants and half clinical participants (total 197 participants) completed the mindful attention awareness scale (MAAS). Predicted links were assessed with affect, and 59 patients completed a validated measure to assess link between mindfulness and intensity of ‘delusional’ experience.

Results

The scale has a single factor structure, was internally reliable, significantly correlated with the MAAS, showed expected associations with affect, and distinguished among meditators, non‐meditators and people with psychosis.

Conclusions

The data support use of the SMQ in clinical practice and research to assess mindful responding to distressing thoughts and images.
Exploring the relationship between children's knowledge of text message abbreviations and school literacy outcomes
Authors: Plester Beverly , Wood Clare , Joshi Puja
Published: June 2008

This paper presents a study of 88 British 10–12‐year‐old children's knowledge of text message (SMS) abbreviations (‘textisms’) and how it relates to their school literacy attainment. As a measure of textism knowledge, the children were asked to compose text messages they might write if they were in each of a set of scenarios. Their text messages were coded for types of text abbreviations (textisms) used, and the ratio of textisms to total words was calculated to indicate density of textism use. The children also completed a short questionnaire about their mobile phone use. The ratio of textisms to total words used was positively associated with word reading, vocabulary, and phonological awareness measures. Moreover, the children's textism use predicted word reading ability after controlling for individual differences in age, short‐term memory, vocabulary, phonological awareness and how long they had owned a mobile phone. The nature of the contribution that textism knowledge makes to children's word reading attainment is discussed in terms of the notion of increased exposure to print, and Crystal's (2006a) notion of ludic language use.
The moment of truth: Conceptualizing managerial work‐life policy allowance decisions
Authors: Poelmans Steven , Beham Barbara
Published: June 2008

Organizational efforts of adopting, designing, and implementing work‐family policies converge into single, discretionary decisions of supervisors whether or not to ‘allow’ these policies to specific employees under their supervision. These decisions are referred to as allowance decisions. In order to close a theoretical gap in current work‐family literature, we present an integrated, conceptual model of managerial allowance decisions. We develop propositions regarding factors that influence a supervisor's allowance decision at three different levels of analysis and behavioural outcomes in employees. Building on organizational justice theory, moderating effects of employees' fairness perceptions of allowance decisions are discussed. Finally, we outline implications for future research and recommendations for managers in organizations.
Understanding the factors that promote employability orientation: The impact of employability culture, career satisfaction, and role breadth self‐efficacy
Authors: Nauta Aukje , van Vianen Annelies , van der Heijden Beatrice , van Dam Karen , Willemsen Marja
Published: June 2008

This study among 702 Dutch employees working in the health care and welfare sector examined individual and organizational factors that are related to workers' employability orientation and turnover intention. Additionally, push and pull motives were examined of employees who aimed to leave their job. Results indicated that a strong employability culture adds extra variance over and above individual factors such as career satisfaction and role breadth self‐efficacy in the explanation of employability orientation, turnover intention, and push motives of employees who aim to leave their job. That is, employability culture is positively related to employability orientation, but negatively related to turnover intention and to push motives of those who aim to leave. Pull motives of employees who want to leave are explained by individual factors only, such as career dissatisfaction and role breadth self‐efficacy, but not by employability culture. These findings suggest that organizations that need to adapt to changing environments should implement a strong employability culture, because such a culture stimulates employability orientations among their employees while simultaneously decreasing turnover intentions.
Relating to voices: Exploring the relevance of this concept to people who hear voices
Authors: Chin Jasmine T. , Hayward Mark. , Drinnan Ange.
Published: June 2008

Objectives Conceptualizing interactions between voice hearers and their voices as a ‘relationship’ has recently become an area of psychological inquiry. To date the literature exploring the details of a hearer–voice relationship has arguably privileged the researchers' account of voice hearing at the expense of the individual's explanatory framework and perspective. The present study aimed to establish the perspectives of voice hearers regarding any ‘relationship’ they may have developed with their voices.

Method. In‐depth interviews were conducted with 10 service users who had heard voices for at least 12 months. The interviews were transcribed and analysed using interpretative phenomenological analysis (IPA).

Results. Analysis resulted in five major themes, three of which are discussed here: Defining the ‘other’ which detailed the personification process; ‘Me vs. the Voice’ which explored oppositional positioning between participants and their voice and strategies employed to retain power and ‘the Voice and Me’ which considered the union that was apparent, as well as participants' rejection of a relational concept. The concept of a ‘relationship’ was both accepted and rejected by participants. Acceptance of relating was relative to the poverty of social relationships. Rejections were considered in terms of preservation of self‐hood, conflict with personal explanatory models and constructions of the term ‘relationship’.

Conclusions. This study has provided evidence that supports new developments in working relationally with voices. Working within this frame may help to emphasize hearers' strengths whilst ameliorating distress. However, this concept needs to be posed as a possible rather than an established conceptualization.
Synergistic Tissue Counterstaining and Image Segmentation Techniques for Accurate, Quantitative Immunohistochemistry
Authors: Zehntner Simone P. , Chakravarty M. Mallar , Bolovan Rozica J. , Chan Christopher , Bedell Barry J.
Published: June 2008

Quantitative analysis of digitized IHC-stained tissue sections is increasingly used in research studies and clinical practice. Accurate quantification of IHC staining, however, is often complicated by conventional tissue counterstains caused by the color convolution of the IHC chromogen and the counterstain. To overcome this issue, we implemented a new counterstain, Acid Blue 129, which provides homogeneous tissue background staining. Furthermore, we combined this counterstaining technique with a simple, robust, fully automated image segmentation algorithm, which takes advantage of the high degree of color separation between the 3-amino-9-ethyl-carbazole (AEC) chromogen and the Acid Blue 129 counterstain. Rigorous validation of the automated technique against manual segmentation data, using Ki-67 IHC sections from rat C6 glioma and β-amyloid IHC sections from transgenic mice with amyloid precursor protein (APP) mutations, has shown the automated method to produce highly accurate results compared with ground truth estimates based on the manually segmented images. The synergistic combination of the novel tissue counterstaining and image segmentation techniques described in this study will allow for accurate, reproducible, and efficient quantitative IHC studies for a wide range of antibodies and tissues.
An Optimized Method for Histological Detection of Dopaminergic Neurons in Drosophila melanogaster
Authors: Drobysheva Daria , Ameel Kristen , Welch Brandon , Ellison Esther , Chaichana Khan , Hoang Bryan , Sharma Shilpy , Neckameyer Wendi , Srinakevitch Irina , Murphy Kelley J. , Schmid Aloisia
Published: June 2008

Parkinson's disease (PD) affects >1 million Americans and is marked by the loss of dopaminergic neurons in the substantia nigra. PD has been linked to two causative factors: genetic risks (hereditary PD) and environmental toxins (idiopathic PD). In recent years, considerable effort has been devoted to the development of a Drosophila model of human PD that might be useful for examining the cellular mechanisms of PD pathology by genetic screening. In 2000, Feany and Bender reported a Drosophila model of PD in which transgenic flies expressing human mutant α-synuclein exhibited shortened life spans, dopaminergic losses, Parkinsonian behaviors, and Lewy bodies in surviving dopaminergic neurons. Since then, a number of studies have been published that validate the model or build on it; conversely, a number report an inability to replicate the results and suggest that most protocols for dopaminergic histology underreport the actual numbers of dopaminergic neurons in the insect brain. Here we report the optimization of dopaminergic histology in Drosophila and identification of new dopaminergic neurons, show the remarkable dendritic complexity of these neurons, and provide an updated count of these neurons in adult brains. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.
Myotube Formation on Micro-patterned Glass: Intracellular Organization and Protein Distribution in C2C12 Skeletal Muscle Cells
Authors: Yamamoto Daniel L. , Csikasz Robert I. , Li Yu , Sharma Gunjana , Hjort Klas , Karlsson Roger , Bengtsson Tore
Published: June 2008

Proliferation and fusion of myoblasts are needed for the generation and repair of multinucleated skeletal muscle fibers in vivo. Studies of myocyte differentiation, cell fusion, and muscle repair are limited by an appropriate in vitro muscle cell culture system. We developed a novel cell culture technique [two-dimensional muscle syncytia (2DMS) technique] that results in formation of myotubes, organized in parallel much like the arrangement in muscle tissue. This technique is based on UV lithography-produced micro-patterned glass on which conventionally cultured C2C12 myoblasts proliferate, align, and fuse to neatly arranged contractile myotubes in parallel arrays. Combining this technique with fluorescent microscopy, we observed alignment of actin filament bundles and a peri-nuclear distribution of glucose transporter 4 after myotube formation. Newly formed myotubes contained adjacently located MyoD-positive and MyoD-negative nuclei, suggesting fusion of MyoD-positive and MyoD-negative cells. In comparison, the closely related myogenic factor Myf5 did not exhibit this pattern of distribution. Furthermore, cytoplasmic patches of MyoD colocalized with bundles of filamentous actin near myotube nuclei. At later stages of differentiation, all nuclei in the myotubes were MyoD negative. The 2DMS system is thus a useful tool for studies on muscle alignment, differentiation, fusion, and subcellular protein localization.
Neuroglobin and Cytoglobin Distribution in the Anterior Eye Segment
Authors: Ostojić Jelena , Grozdanić Siniś , Syed Nasreen A. , Hargrove Mark S. , Trent James T. , Kuehn Markus H. , Kardon Randy H. , Kwon Young H. , Sakaguchi Donald S.
Published: June 2008

This study provides a detailed description of immunolocalization of two oxygen-binding proteins, neuroglobin (Ngb) and cytoglobin (Cygb), in the anterior segment of healthy human and canine eyes. Specific antibodies against Ngb and Cygb were used to examine their distribution patterns in anterior segment structures including the cornea, iris, trabecular meshwork, canal of Schlemm, ciliary body, and lens. Patterns of immunoreactivity (IR) were imaged with confocal scanning laser and conventional microscopy. Analysis of sectioned human and canine eyes showed Ngb and Cygb IR in the corneal epithelium and endothelium. In the iris, Ngb and Cygb IR was localized to the anterior border and the stroma, iridal sphincter, and dilator muscle. In the iridocorneal angle, Ngb and Cygb were detected in endothelial cells of the trabecular meshwork and canal of Schlemm in human. In the ciliary body, Ngb and Cygb IR was localized to the non-pigmented ciliary epithelium of the pars plana and pars plicata and in ciliary body musculature. Ngb and Cygb distribution was similar and colocalized within the same structures of healthy human and canine anterior eye segments. Based on their immunolocalization and previously reported biochemical features, we hypothesize that Ngb and Cygb may function as scavengers of reactive oxygen species. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.
Pericellular Hyaluronan Coat Visualized in Live Cells With a Fluorescent Probe Is Scaffolded by Plasma Membrane Protrusions
Authors: Rilla Kirsi , Tiihonen Riikka , Kultti Anne , Tammi Markku , Tammi Raija
Published: June 2008

Many cell types wear up to 20-μm-wide hyaluronidase-sensitive surface coats, detected by exclusion of sedimenting particles like fixed erythrocytes. The structure of the coat is enigmatic, being apparently too thick to be accounted by random coils or even extended chains of just hyaluronan attached to cell surface. We have shown that hyaluronan synthesis enforced by green fluorescent protein-hyaluronan synthase transfection creates microvillous protrusions. The idea that the plasma membrane protrusions rather than hyaluronan alone is responsible for the exclusion space was studied with a fluorescent probe for hyaluronan and a dye with membrane affinity, applied to live cell cultures. Mesothelial and smooth muscle cells, fibroblasts, and chondrocytes, all known for their endogenously active hyaluronan synthesis, showed hyaluronan-coated plasma membrane protrusions, barely visible in phase contrast microscopy. Treatment with hyaluronidase and inhibition of hyaluronan synthesis caused retraction of the protrusions unless they were attached to substratum. Hyaluronan and the exclusion space were reduced, but did not disappear, by purified hyaluronan hexasaccharides that compete with hyaluronan attached to CD44. The results suggest that slender plasma membrane protrusions are an inherent feature of hyaluronan coats, form their scaffold, and largely result from ongoing hyaluronan synthesis in their plasma membrane. This manuscript contains online supplemental material at www.jhc.org . Please visit this article online to view these materials.
Improvement of radioactive liquid waste treatment efficiency by sequential cationic and anionic ion exchangers
Authors: Borai E. H. , Hilal M. A. , Attallah M. F. , Shehata F. A.
Published: June 2008

Various types of liquid radioactive wastes are released from different nuclear activities. The treatment efficiencies of these wastes depend highly on the physical and chemical composition of each waste such as pH, TDS and electrical conductivity. The treatment efficiency of some radionuclides with different valency states (such as 134Cs, 65Zn, 60Co and 152+154Eu) was tested based on the absorption capacity of cationic exchanger (KY-2) functionlized with polystyrene sulphonic group. The competitive adsorption on cationic exchanger was investigated by mono radionuclide and multi radionuclides wastes. The influence of the presence of various anionic complexants in the rad-waste on the adsorption capacity and hence the treatment efficiency was quantitatively studied using weakly base aminated anionic exchanger (AN-31). The enhancement in decontamination factor of each radionuclide is mostly attributed to the high adsorption capacity of the cationic resin in addition to the complexation capability of the radionuclide with the different complexant existed in the waste solution. The complex formation improved the decontamination factor through indirect adsorption of the anionic species on the subsequent anionic exchanger during the treatment process. The results showed that the removal percentages are around 50% for 134Cs, 60Co, 65Zn and 152,154Eu, without complexant compound. Significant enhancements of the removal percentages >85% were obtained for 60Co, 65Zn and 152,154Eu, respectively, on addition of manganese sulphate while maximum removal percentage (75.3±0.7%) is obtained for 134Cs when using 0.1 M citric acid as a complexing agent.
Formation and hydrolysis of polynuclear Th(IV) complexes – a nano-electrospray mass-spectrometry study
Authors: Walther C. , Fuss M. , Büchner S.
Published: June 2008

Polynuclear hydroxide complexes play an important role for the hydrolysis of tetravalent thorium ions in aqueous solution, in particular for Th(IV) concentrations exceeding some [Th(IV)]=10−4 M. Consequently, these polymers must be considered when describing hydrolysis of Th(IV) or dissolution processes of Th(IV) solids. In the past, considerable efforts were made to obtain equilibrium formation constants of these polymers and different stoichiometries for dimers, tetramers and hexamers have been suggested. However, most information was obtained from indirect methods, in particular, from potentiometric titrations. In the present work, we present an approach of directly quantifying polymeric metal hydroxide complexes in solution. By nano-electrospray mass-spectrometry the degrees of polymerization, i.e. the numbers of Th4+ ions and the numbers of hydroxide ligands, and as a consequence, also the charges of the complexes are measured. All mono- and polynuclear species which are present in solution are quantified simultaneously down to species contributing less than 0.1% of the total [Th(IV)] concentration. Solutions of [Th(IV)]=6×10−6–10−1 M are investigated in HCl at [H+]=10−4–0.1 M. More than 30 different polymeric complexes are observed with the general trend of increasing number of hydroxide ligands with decreasing acidity. A surprising finding is the presence of the pentamer Th5(OH)y

z +, which was not described in the literature before. With decreasing Th(IV) concentration the stability field of polymers narrows continuously until polymers can no longer be detected below [Th(IV)]=10−5 M.
Preparation and evaluation of [67Ga]-DTPA-β-1–24-corticotrophin in normal rats
Authors: Jalilian A. R. , Shanehsazzadeh S. , Akhlaghi M. , Garoosi J. , Rajabifar S. , Tavakoli M. B.
Published: June 2008

β-1–24-corticotrophin was successively labeled with [67Ga]-gallium chloride after residulation with freshly prepared cyclic DTPA-dianhydride. The best results of the conjugation were obtained by the addition of 1 ml of a β-1–24-corticotrophin pharmaceutical solution (1 mg/mL, pH=6.5) to a glass tube pre-coated with DTPA-dianhydride (0.01 mg) at 25 °C with continuous mild stirring for 30 min. Radio-thin layer chromatography showed an overall radiochemical purity of >90% at optimized conditions after labeling. HPLC showed a radiochemical purity more than 95% (specific activity =300–500 MBq/mg, labeling efficiency 77%). The stability of the radioconjugate was tested in presence of human serum at 37 °C. Preliminary in vivo studies in normal rats were performed to determine the biodistribution of the radioimmunoconjugate up to 30 min. Lungs showed to have the major tracer uptake which is consistent with the natural distribution of ACTH receptors in human body. Pretreatment of animals with cold peptide following labeled compound administration reduced lung uptake at least 10 and 3 times after 15 and 30 min, respectively, as well as significant decrease in adrenal uptake after 15 min. These data support the specific receptor binding of the radiolabeled compound. This tracer can be used in detection of ACTH receptor in lung and adrenal malignancies.
Frenulotomy for Breastfeeding Infants With Ankyloglossia: Effect on Milk Removal and Sucking Mechanism as Imaged by Ultrasound
Authors: Geddes Donna T. , Langton Diana B. , Gollow Ian , Jacobs Lorili A. , Hartmann Peter E. , Simmer Karen
Published: June 2008

OBJECTIVE. There is evidence that infants with ankyloglossia can experience breastfeeding difficulties including poor attachment to the breast, suboptimal weight gain, and maternal nipple pain, which may lead to early weaning of the infant. No studies have investigated the cause of these breastfeeding difficulties. The objective of this study was to determine the effectiveness of frenulotomy in infants experiencing persistent breastfeeding difficulties despite professional assistance by measuring changes in milk transfer and tongue movement during breastfeeding before and after frenulotomy.

PATIENTS AND METHODS. Twenty-four mother-infant dyads (infant age: 33 ± 28 days) that were experiencing persistent breastfeeding difficulties despite receiving professional advice were recruited. Submental ultrasound scans (Acuson XP10) of the oral cavity were performed both before and ≥7 days after frenulotomy. Milk transfer, pain, and LATCH (latch, audible swallowing, type of nipple, comfort, and hold) scores were recorded before and after frenulotomy. Infant milk intake was measured by using the test-weigh method.

RESULTS. For all of the infants, milk intake, milk-transfer rate, LATCH score, and maternal pain scores improved significantly postfrenulotomy. Two groups of infants were identified on ultrasound. One group compressed the tip of the nipple, and the other compressed the base of the nipple with the tongue. These features either resolved or lessened in all except 1 infant after frenulotomy.

CONCLUSIONS. Infants with ankyloglossia experiencing persistent breastfeeding difficulties showed less compression of the nipple by the tongue postfrenulotomy, which was associated with improved breastfeeding defined as better attachment, increased milk transfer, and less maternal pain. In the assessment of breastfeeding difficulties, ankyloglossia should be considered as a potential cause.
Referring to Others in the Scientific Journal Article. A brief history
Authors: Banks David
Published: June 2008

Study of a corpus of 30 articles taken from the Philosophical Transactions of the Royal Society, and covering the period 1700-1980, shows that their writing contains features which betray the relationships that prevailed within the scientific community of their time. Some features, such as mention of the Ancients, die out quickly, while others, like giving the provenance of specimens, continue throughout the period. Praising others is common in the early articles but disappears as time goes on. There is some evidence of the epistolary form from which the scientific article developed. Critical remarks, particularly in the early years are accompanied by attempts to explain the supposed error. There is also evidence of the way the gentleman scientist, or virtuoso, gradually gives way to the professional.
Construing the ‘social gospel’ of Martin Luther King Jr.
Authors: Miller Donna R. , Turci Monica
Published: June 2008

This paper reports the findings of research into select linguistic resources construing what has been called the ‘social gospel’ of Martin Luther King Jr. (henceforth MLK): i.e., the secularized ‘here and now’ face of the typically other-worldly religious message of deliverance. For this purpose, the environment of the node word free* is investigated in 2 small, specially created, diachronic corpora of, firstly, his speeches (MLK1) and, for comparative purposes, his sermons (MLK2).
Gardeners’ Talk
Authors: Thomson Elizabeth , Cléirigh Chris , Head Lesley , Muir Pat
Published: June 2008

It is increasingly recognized that the major barriers to environmental sustainability are social, cultural and organizational rather than scientific. Environmental managers are acknowledging the importance of research into environmental attitudes and behaviours but have tended to use non-linguistic research methods. In this study, linguistic tools, particularly transitivity and appraisal analysis are used to investigate the kinds of attitudes and linguistic construals different groups of Australians have in relation to their own backyards and to the environment at large. Three interview transcripts of urban dwelling Australian citizens talking about their backyards and their environmental attitudes which were selected according to gardener type: non-native; general-native and committed-native gardener are analysed. The purpose is to examine the relationships between gardener type, attitudes towards the environment and the interviewees’ feelings of empowerment in relation to environmental practices as revealed by their language use. The analyses are compared to the methods of human geography to test the extent to which linguistic methodologies can inform or confirm the geographical approaches.