bluuebunny/crossref_metadata_2025 huggingface dataset:
“My Home Is My Castle”
Authors: McIntosh Alison J. , Lynch Paul , Sweeney Majella
Published: August 2010

The intrinsic nature of small tourism business provision has rarely been captured in previous literature, but it has recently gained momentum within scholarly discourse exploring the role of the “home” in tourism and hospitality. This article contributes an examination of the commercial homestay host in New Zealand with a particular focus on the hosts’ personal relationship with their “commercial home.” The article reports the findings of in-depth interviews conducted with commercial homestay hosts in New Zealand. Findings allude to the tyranny of the homestay hosts in their tourism hosting role, their oppressive social need, self-marginalization, and distinctive identity—one that is notably defiant of other commercial hospitality and tourism business norms. In contrast, previous studies rarely showcase the personal perspectives, conscious defiance, or marginalization of commercial hospitality provision. Consequences for understanding the tourism and hospitality phenomenon of commercial home hosting are thus discussed.
N‐acetyltransferase‐2 (NAT2) Gene Polymorphisms and Enzyme Activity in Serbs: Unprecedented High Prevalence of Rapid Acetylators in a White Population
Authors: Djordjevic Natasa , Carrillo Juan Antonio , Ueda Nobuhisa , Gervasini Guillermo , Fukasawa Takashi , Suda Akira , Jankovic Slobodan , Aklillu Eleni
Published: August 2010

The aim of this study was to investigate N‐acetyltransferase 2 (NAT2) genetic polymorphism and enzyme activity in Serbs, and to examine the influence of NAT2 genotype, sex, and smoking on the phenotype. Genotyping for 190C>T, 282C>T, 341T>C, 403C>G, 411T>A, 481C>T, 590G>A, 803A>G, and 857G>A in the NAT2 gene, was performed in 140 healthy Serbs. NAT2 activity was determined as AFMU/(AFMU + 1X + 1U) urinary ratio in 100 subjects using caffeine as a probe. The most frequent NAT2 haplotypes were NAT2*5B (38.2%), NAT2*6A (26.0%), and NAT2*4 (24.4%). The log‐transformed NAT2 activity indices exhibited trimodal distribution with 9%, 36%, and 55% of slow, intermediate, and rapid acetylators, respectively. Significant NAT2 genotype‐phenotype correlation was observed (P < .0001). The frequency of NAT1*10 and NAT1*11 were 27.5% and 6.9%, respectively. There was no significant influence of sex or cigarette smoking on NAT2 enzyme activity. Eight subjects displayed rapid NAT2 acetylators phenotype despite being homozygous for NAT2 slow alleles, and NAT1 fast acetylators genotype (NAT1*10 and NAT1*11) had no implication. In contrast to other white populations described hitherto, rapid acetylator is the predominant NAT2 phenotype in Serbs. NAT2 genotype, but not sex and cigarette smoking, influence enzyme activity. NAT1 fast acetylators genotypes do not contribute for NAT2 genotype‐phenotype discordance.
The Origins and Restriction of Efficiency in Public Administration
Authors: Rutgers Mark R. , van der Meer Hendriekje
Published: August 2010

This article is primarily a study in the history of the concept of efficiency. It is argued that efficiency originated in Aristotelian ideas about causality and acquired a broad, substantive meaning of “moving force.” This meaning of the term was dominant well into 20th-century studies of public administration. In the course of the 20th century, however, efficiency became predominantly understood as “technical efficiency”: a ratio between resources and results. This connotation is especially clear in the explicit “textbook” definitions of efficiency. Nevertheless, we claim that the substantive meaning of efficiency is still around, and even at the heart of much criticism of efficiency. Technical efficiency obscures that efficiency in public administration is to be assessed in the light of public values. Efficiency as signifying the necessity of having capable operative administrative agents constitutes one of the, if not the, core value of the field.
Market-Based Government and the Decline of Organizational Ethics
Authors: Adams Guy B. , Balfour Danny L.
Published: August 2010

This article discusses ethical challenges posed by market-based government and the degree to which contracting enhances or diminishes government’s ability to ensure that organizations that deliver public services adhere to ethical practices and public values, such as lawfulness, transparency, and accountability. A case study of an organization—Blackwater (now, Xe)—vividly illustrates the considerable difficulty in achieving ethical organizations when so many basic functions are outsourced, with few or ineffective regulatory controls, to private organizations. Because some of these challenges can perhaps best be addressed at the organizational level, we conclude by proposing a typology of organizational ethics in matrix form, according to the organization’s relative standing on the two dimensions of compliance and social responsibility.
Heteroglossic Representations of Scientific Uncertainty
Authors: Kewell Beth
Published: August 2010

The Bristol Inquiry is arguably one of the most important cases of judicial medical investigation held in the United Kingdom (UK), which continues to raise important insights into the social construction of medical and scientific risks. As a way of marking the inquiry’s tenth anniversary year, this article returns to an important conversation held between noted pediatric cardiothoracic and cardiovascular specialists, on days 49 and 50 of the inquiry’s proceedings. Their conversance principally describes a pathway of scientific advancement across four decades (c. the mid-1960s to 1999). Risks, and the avoidance of medical error (iatrogenesis), represent important subtopics of the ensuing historical narrative, within which the experts describe opportunities for error as diminishing in-line with paradigmatic advancement. The telling of this story of risk mitigation involves the expurgation of considerable sensitivities to scientific uncertainty. In analyzing this example of expert scientific witness testimony, the article primarily considers how representations of uncertainty are formulated in language. The article concludes that, in this instance, the social construction of risk and uncertainty were heteroglossically premised upon language catalysts, cognitive metaphors, and logic-based mathematical rubrics.
Visual field expansion after visual restoration therapy
Authors: Marshall Randolph S , Chmayssani Mohamad , O'Brien Katherine A , Handy Catherine , Greenstein Vivienne C
Published: August 2010

Objective: To determine whether visual field expansion occurs with visual restoration therapy (VRT), using fundus-controlled microperimetry to assess visual fields.

Design: This longitudinal cohort analysis assesses patients’ visual fields before and after visual restoration therapy using microperimetry and standard high-resolution perimetry.

Subjects: Seven patients with stroke-induced homonymous field cuts were studied.

Intervention: Visual restoration therapy is a computerized, home-based treatment aimed at reducing the size of the visual field defect of stroke patients with hemianopia through repetitive stimulation of the visual borderzone adjacent to the blind field. During twice-daily therapy for three months patients maintain central fixation while responding to eccentrically placed stimuli in the visual borderzone. The programme is adjusted monthly to changes in the patient’s visual field. Controversy exists as to whether expansion of visual fields measured at home with high-resolution perimetry is due to inadvertent eye movements and therefore would overrepresent the treatment’s effect.

Main measures: Microperimentry uses an infrared camera to track retinal vessels so that any shift or movement between the reference image and the real-time fundus image corrects the stimulus position, thus delivering stimuli to known retinal locations, and allowing accurate assessment of visual fields independent of eye movements.

Results: There was an average improvement in stimulus detection rate by microperimetry of 12.5% (range —1.4% to 38.9%, P =0.033). Six of 7 patients had ≥ 3% improvement in stimulus detection by home-based perimetry.

Conclusion: Our results demonstrate modest but real expansion in visual fields following visual restoration therapy which is not due to eye movements.
A comparison of the discrete and dimensional models of emotion in music
Authors: Eerola Tuomas , Vuoskoski Jonna K.
Published: August 2010

The primary aim of the present study was to systematically compare perceived emotions in music using two different theoretical frameworks: the discrete emotion model, and the dimensional model of affect. A secondary aim was to introduce a new, improved set of stimuli for the study of music-mediated emotions. A large pilot study established a set of 110 film music excerpts, half were moderately and highly representative examples of five discrete emotions (anger, fear, sadness, happiness and tenderness), and the other half moderate and high examples of the six extremes of three bipolar dimensions (valence, energy arousal and tension arousal). These excerpts were rated in a listening experiment by 116 non-musicians. All target emotions of highly representative examples in both conceptual sets were discriminated by self-ratings. Linear mapping techniques between the discrete and dimensional models revealed a high correspondence along two central dimensions that can be labelled as valence and arousal, and the three dimensions could be reduced to two without significantly reducing the goodness of fit. The major difference between the discrete and categorical models concerned the poorer resolution of the discrete model in characterizing emotionally ambiguous examples. The study offers systematically structured and rich stimulus material for exploring emotional processing.
Moved by music: A typology of music listeners
Authors: Ter Bogt Tom F.M. , Mulder Juul , Raaijmakers Quinten A.W. , Nic Gabhainn Saoirse
Published: August 2010

A typology of music listeners was constructed on the basis of importance attributed to music and four types of music use: mood enhancement; coping with problems; defining personal identity; and marking social identity. Three Listener Groups were identified through Latent Class Analysis of internet survey data of 997 Dutch respondents, aged 12—29. High-Involved listeners (19.7%) experienced music as a very important medium and used music most often for mood enhancement, coping with distress, identity construction and social identity formation. Medium- (74.2%) and Low- Involved (6.1%) listeners formed two distinct groups with less intense importance/use patterns Furthermore, High-Involved listeners reported that they liked a broad range of genres (Pop, Rock, High Brow, Urban and Dance) and experienced the most intense positive affect when listening. However, both High- and Medium-Involved listeners also reported more negative affects (anger and sadness) when listening, compared to the Low-Involved group. Even the Low-Involved group listened frequently to music and used music as a mood enhancer. Generally, people who are ‘moved by music’, either positively or negatively, use it for mood enhancement and coping more often. Therefore, the High-Involved group seems to benefit most from music’s capacity to enliven and enlighten life.
Acute Achilles Tendon Rupture
Authors: Nilsson-Helander Katarina , Grävare Silbernagel Karin , Thomeé Roland , Faxén Eva , Olsson Nicklas , Eriksson Bengt I. , Karlsson Jon
Published: August 2010

Background

There is no consensus regarding the optimal treatment for patients with acute Achilles tendon rupture. Few randomized controlled studies have compared outcomes after surgical or nonsurgical treatment with both groups receiving early mobilization.

Purpose

This study was undertaken to compare outcomes of patients with acute Achilles tendon rupture treated with or without surgery using early mobilization and identical rehabilitation protocols.

Study Design

Randomized, controlled trial; Level of evidence, 1.

Methods

Ninety-seven patients (79 men, 18 women; mean age, 41 years) with acute Achilles tendon rupture were treated and followed for 1 year. The primary end point was rerupturing. Patients were evaluated using the Achilles tendon Total Rupture Score (ATRS), functional tests, and clinical examination at 6 and 12 months after injury.

Results

There were 6 (12%) reruptures in the nonsurgical group and 2 (4%) in the surgical group (P = .377). The mean 6- and 12-month ATRS were 72 and 88 points in the surgical group and 71 and 86 points in the nonsurgical group, respectively. Improvements in ATRS between 6 and 12 months were significant for both groups, with no significant between-group differences. At the 6-month evaluation, the surgical group had better results compared with the nonsurgically treated group in some of the muscle function tests; however, at the 12-month evaluation there were no differences between the 2 groups except for the heel-rise work test in favor of the surgical group. At the 12-month follow-up, the level of function of the injured leg remained significantly lower than that of the uninjured leg in both groups.

Conclusion

The results of this study did not demonstrate any statistically significant difference between surgical and nonsurgical treatment. Furthermore, the study suggests that early mobilization is beneficial for patients with acute Achilles tendon rupture whether they are treated surgically or nonsurgically. The preferred treatment strategy for patients with acute Achilles tendon rupture remains a subject of debate. Although the study met the sample size dictated by the authors’ a priori power calculation, the difference in the rerupture rate might be considered clinically important by some.
Paradoxes of Solidarity: Democracy and Colonial Legacies in Swedish Popular Education
Authors: Dahlstedt Magnus , Nordvall Henrik
Published: August 2010

Over the years, there have been several attempts to spread the “Swedish model” of popular education, that is, study circles and folk high schools, to countries in other parts of the world. In this article, the authors analyze the large-scale project of establishing folk development colleges in Tanzania in the 1970s and 1980s, by emphasizing the ways in which Swedish popular educators have described the folk development college project. Theoretically, the article is based on a postcolonial framework, highlighting the continuing importance of the legacies of colonialism in today’s society. One of the main conclusions in the article is that in the process of “exporting” the idea of popular education to other parts of the world, there is an ongoing formation of national self-images in contrast to images of the Other, where there is a constant risk of reproducing ideas from a colonial past.
Protective potential of 17β-estradiol against co-exposure of 4-hydroxynonenal and 6-hydroxydopamine in PC12 cells
Authors: Siddiqui MA , Kashyap MP , Al-Khedhairy AA , Musarrat J. , Khanna VK , Yadav S. , Pant AB
Published: August 2010

4-hydroxynonenal (4-HNE) and 6-hydroxydopamine (6-OHDA)-mediated damage in dopaminergic neurons is well documented. Protective potential of steroidal hormone (17β-estradiol) has also been suggested. However, therapeutic potential of such promising hormone is hampered due to complex brain anatomy and physiology. Thus, the present investigations were studied to suggest the applicability of dopamine expressing PC12 cells as in vitro tool to screen the pharmacological potential of 17β-estradiol against 4-HNE and 6-OHDA. MTT assay was conducted for cytotoxicity assessment of both 4-HNE (1 μM to 50 μM) and 6-OHDA (10-4 to 10-7 M). Non-cytotoxic concentrations, that is, 4-HNE (1 μM) and 6-OHDA (10-6 M) were selected to study the synergetic/additive responses. PC12 cells were found to be more vulnerable towards co-exposure of individual exposure of 4-HNE and 6-OHDA, even at non-cytotoxic concentrations. Then, cells were subjected to pre-treatment (24 hours) of 17β-estradiol (1 μM), followed by a permutation of combinations of both 4-HNE and 6-OHDA. Pretreatment of 17β-estradiol was found to be significantly effective against the cytotoxic responses of 4-HNE and 6-OHDA, when the damage was at lower level. However, 17β-estradiol was found to be ineffective against higher concentrations. Physiological-specific responses of PC12 cells against 4-HNE/6-OHDA and 17β-estradiol suggest its applicability as first tier of screening tool.
Protective effects of organic solvent fractions from the seeds of Vigna radiata L. wilczek against antioxidant mechanisms
Authors: Chung Ill-Min , Yeo Min-A , Kim Sun-Jin , Moon Hyung-In
Published: August 2010

This study was conducted to evaluate the in vitro scavenging activity and inhibitory effect of low-density lipoprotein oxidation of pro-oxidant reactive species in response to treatment with organic solvent fractions from mung bean (seeds of Vigna radiata) extracts using various screening methods including biological and non-biological oxidants. The antioxidant activity of different organic solvent fractions from mung bean extracts were studied in vitro methods by evaluating the total phenol components, measuring the antioxidant activity by trolox equivalent antioxidant capacity, measuring the scavenging effects on reactive oxygen species and on reactive nitrogen species as well as measuring the inhibitory effect on Cu2+-induced human low-density lipoprotein oxidation. The mung bean extracts were found to have a potent scavenging activity against all of the reactive species tested as well as an inhibitory effect on low-density lipoprotein oxidation, the studied mung bean was revealed to be very effective against the evaluated pro-oxidant species, including reactive oxygen species and on reactive nitrogen species.
Grappling with Governance: The Emergence of Business Improvement Districts in a National Capital
Authors: Lewis Nathaniel M.
Published: August 2010

Business improvement districts (BIDs) constitute a relatively new mode of urban governance in which business and property owners pay surtaxes for collectivized, privatized maintenance and development services in their respective neighborhoods. Although they are typically considered an innovative means of improving urban areas—or at the very least a benign intervention of business owners to draw new consumers—the case of Washington, D.C., shows that BIDs are also an increasingly entrenched neo-liberal institution promoted by state restructuring and interurban competition. Given local conditions, such as a permissive legislative environment and fragmented governance, the proliferation, size, and influence of D.C.’s BIDs pose concerns about institutional accountability, socioeconomic inequality, and sustainability of services. Using a mixed-methods approach that integrates urban governance theory, performance metrics, and interviews with BID and D.C. government officials, this study finds that Washington’s BIDs have promoted revitalization but also pose concerns about limited public accountability, exacerbated socioeconomic and spatial inequalities, and further retreat of the municipal government.
When does self-control matter? The interaction between morality and self-control in crime causation
Authors: Wikström Per-Olof H. , Svensson Robert
Published: September 2010

In this paper we will test one of the key assumptions of Situational Action Theory: that individuals’ (law-relevant) morality is more fundamental to their crime involvement than their ability to exercise self-control. We specifically hypothesize that, for individuals with a strong morality, their capability to exercise self-control plays less of a role in their crime involvement than it does for individuals with a weak morality, whose capability to exercise self-control may substantially influence their engagement in crime. To test this hypothesis we use data from the Peterborough Youth Study (PYS), a cross-sectional survey of 1957 adolescents aged 14—15 from the UK city of Peterborough. The findings support the main hypothesis: young people with a strong (law-relevant) morality do not engage in crime, regardless of their ability to exercise self-control. However, among those with a weaker (law-relevant) morality, their ability to exercise self-control is an important factor in their crime involvement.
Comparing Criminal Careers of Organized Crime Offenders and General Offenders
Authors: van Koppen M. Vere , de Poot Christianne J. , Blokland Arjan A. J.
Published: September 2010

Organized crime differs substantially from high-volume crime, at least theoretically. But do offenders differ as well? This study makes an extensive comparison between offenders who engage in organized crime at a particular moment in their lives and general offenders, based on various dimensions of their criminal careers. Many organized crime offenders do not have judicial contacts before adulthood. Surprisingly, this turns out to be the case for the comparison group as well. However, organized crime offenders do more often have previous judicial contacts, and those previous contacts are also far more serious. These general findings are robust; they also hold when the comparisons are restricted to organized crime offenders and general offenders who have engaged in drug crimes and fraud cases.
Linking Screening for Emotional and Behavioral Problems to Problem-Solving Efforts: An Adaptive Model of Behavioral Assessment
Authors: Volpe Robert J. , Briesch Amy M. , Chafouleas Sandra M.
Published: September 2010

This paper addresses several objectives of the special issue on universal screening by addressing gaps in the current research base concerning universal screening for mental, emotional, and behavioral health and by providing a framework for addressing the limitations of extant approaches. Specifically, an adaptive model of behavioral assessment (AMBA) is proposed as a conceptual framework for linking screening and progress monitoring and designing tier 2 interventions.
Screening Young Children’s Risk for Mental Health Problems: A Review of Four Measures
Authors: Feeney-Kettler Kelly A. , Kratochwill Thomas R. , Kaiser Ann P. , Hemmeter Mary Louise , Kettler Ryan J.
Published: September 2010

Accurate identification of young children at risk for mental health problems is a key step in establishing early childhood preventive intervention programs. Without psychometrically valid identification procedures, children in need of early intervention may not be identified and may not receive appropriate care. This article provides a review of universal screening measures to help teachers, school psychologists, and other mental health professionals make informed decisions about selecting tools to assist in identifying preschool-age children at risk for mental health problems. A review of the literature on broadband measures designed to screen the social and emotional functioning of children age 3 to 5 years old yielded three published measures that met predetermined inclusionary criteria. An additional unpublished measure was also included. Selected measures were reviewed according to the Standards for Educational and Psychological Testing. Special attention was given to predictive validity indices, including sensitivity, specificity, positive predictive value, and negative predictive value. The results of the review provided information on the measures that were most psychometrically sound and cost-effective for screening young children for mental health problems. Recommendations are made for routine screening, so young children can be referred for prevention programming before their problems worsen and negatively affect their development.
The role of synovitis in osteoarthritis
Authors: Wenham Claire Y. J. , Conaghan Philip G.
Published: August 2010

Osteoarthritis (OA) is the most common form of arthritis worldwide yet there is still a lack of effective treatments for this condition. Increasingly, attention has turned to the role of the synovium in OA as it is now recognized, in part from the use of modern imaging techniques, that synovitis is both common and associated with pain. This offers a target for treatment, for both symptom and potential structure modification. In this review we discuss the evidence for histological and imaging-detected synovitis and the current role of antisynovial therapies in OA.
Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome
Authors: Göhring Gudrun , Michalova Kyra , Beverloo H. Berna , Betts David , Harbott Jochen , Haas Oskar A. , Kerndrup Gitte , Sainati Laura , Bergstraesser Eva , Hasle Henrik , Starý Jan , Trebo Monika , van den Heuvel-Eibrink Marry M. , Zecca Marco , van Wering Elisabeth R. , Fischer Alexandra , Noellke Peter , Strahm Brigitte , Locatelli Franco , Niemeyer Charlotte M. , Schlegelberger Brigitte
Published: August 2010

To identify cytogenetic risk factors predicting outcome in children with advanced myelodysplastic syndrome, overall survival of 192 children prospectively enrolled in European Working Group of Myelodysplastic Syndrome in Childhood studies was evaluated with regard to karyotypic complexity. Structurally complex constitutes a new definition of complex karyotype characterized by more than or equal to 3 chromosomal aberrations, including at least one structural aberration. Five-year overall survival in patients with more than or equal to 3 clonal aberrations, which were not structurally complex, did not differ from that observed in patients with normal karyotype. Cox regression analysis revealed the presence of a monosomal and structurally complex karyotype to be strongly associated with poor prognosis (hazard ratio = 4.6, P < .01). Notably, a structurally complex karyotype without a monosomy was associated with a very short 2-year overall survival probability of only 14% (hazard ratio = 14.5; P < .01). The presence of a structurally complex karyotype was the strongest independent prognostic marker predicting poor outcome in children with advanced myelodysplastic syndrome.
The challenge of targeting EGFR: experience with gefitinib in nonsmall cell lung cancer
Authors: Armour A.A. , Watkins C.L.
Published: September 2010

As the first approved epidermal growth factor receptor (EGFR)-targeted therapy for nonsmall cell lung cancer (NSCLC), the clinical development of gefitinib was complex. Advances in scientific understanding of the target biology during its clinical development enabled the identification of a biomarker to define patients most likely to derive benefit from gefitinib. Initial phase II trials showed clinically meaningful anti-tumour activity in 12–18% of unselected pretreated patients with advanced NSCLC at the optimum biological dose (250 mg). Subgroup analyses of these and subsequent phase III trials in unselected patients suggested thatEGFRmutation and some clinical characteristics associated with a higher incidence ofEGFRmutation (Asian ethnicity, adenocarcinoma histology, never-smoking and female sex) were linked with increased response to gefitinib. Consequently, the IRESSA Pan-Asia Study (IPASS) was conducted in never-smokers or former light-smokers in East Asia who had adenocarcinoma of the lung. IPASS showed thatEGFRmutation was the strongest predictor of improved progression-free survival (mutation-positive subgroup hazard ratio (HR) 0.48, 95% CI 0.36–0.64 (p<0.001, n = 261); mutation-negative subgroup HR 2.85, 95% CI 2.05–3.98 (p<0.001, n = 176); interaction test p<0.001) with gefitinibversuscarboplatin/paclitaxel as first-line therapy for advanced NSCLC. Important lessons for the development of future personalised medicines are discussed.
Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC
Authors: Lin Zhong-Zhe , Jeng Yung-Ming , Hu Fu-Chang , Pan Hung-Wei , Tsao Hsin-Wei , Lai Po-Lin , Lee Po-Huang , Cheng Ann-Lii , Hsu Hey-Chi
Published: August 2010

Background

To investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC).

Methods

The Aurora B and Aurora A mRNA level was measured in 160 HCCs and the paired nontumorous liver tissues by reverse transcription-polymerase chain reaction. Mutations of the p53 and β-catenin genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of exon 2 to exon 11 of p53 and exon 3 of β-catenin. Anticancer effects of AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and Hep3B cell lines.

Results

Aurora B was overexpressed in 98 (61%) of 160 HCCs and in all 7 HCC cell lines examined. The overexpression of Aurora B was associated with Aurora A overexpression (P = 0.0003) and p53 mutation (P = 0.002) and was inversely associated with β-catenin mutation (P = 0.002). Aurora B overexpression correlated with worse clinicopathologic characteristics. Multivariate analysis confirmed that Aurora B overexpression was an independent poor prognostic factor, despite its interaction with Aurora A overexpression and mutations of p53 and β-catenin. In Huh-7 and Hep3B cells, AZD1152-HQPA induced proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle disturbance, and apoptosis.

Conclusion

Aurora B overexpression is an independent molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora B kinase selective inhibitors are potential therapeutic agents for HCC treatment.
Mathematics, Thermodynamics, and Modeling to Address Ten Common Misconceptions about Protein Structure, Folding, and Stability
Authors: Robic Srebrenka
Published: September 2010

To fully understand the roles proteins play in cellular processes, students need to grasp complex ideas about protein structure, folding, and stability. Our current understanding of these topics is based on mathematical models and experimental data. However, protein structure, folding, and stability are often introduced as descriptive, qualitative phenomena in undergraduate classes. In the process of learning about these topics, students often form incorrect ideas. For example, by learning about protein folding in the context of protein synthesis, students may come to an incorrect conclusion that once synthesized on the ribosome, a protein spends its entire cellular life time in its fully folded native confirmation. This is clearly not true; proteins are dynamic structures that undergo both local fluctuations and global unfolding events. To prevent and address such misconceptions, basic concepts of protein science can be introduced in the context of simple mathematical models and hands-on explorations of publicly available data sets. Ten common misconceptions about proteins are presented, along with suggestions for using equations, models, sequence, structure, and thermodynamic data to help students gain a deeper understanding of basic concepts relating to protein structure, folding, and stability.
Quietism in German Mysticism and Philosophy
Authors: Magee Glenn Alexander
Published: September 2010

A contribution to the sixth installment of the Common Knowledge symposium “Apology for Quietism,” this article argues that a strong strain of quietism runs through German intellectual history, from medieval mystics such as Eckhart to the main line of modern philosophers, including Kant, Fichte, Hegel, Schopenhauer, Nietzsche, Wittgenstein, and Heidegger. Magee treats each of these in turn, establishing case by case that the relation of the individual to the universal is the central issue of German thought, as it is of quietist thinking generally. The identity of the universal varies; sometimes it is said to be God, sometimes the moral law, and sometimes reason (whether human reason or an objective reason inherent in the nature of the world). The process of grappling with how human beings must orient themselves toward the universal very often issues in conclusions that are quietistic: we are enjoined to acquiesce to the universal, and to accept the world as its manifestation. And such, Magee argues, is the case throughout the mainstream German intellectual tradition.
The recruitment of acetylated and unacetylated tropomyosin to distinct actin polymers permits the discrete regulation of specific myosins in fission yeast
Authors: Coulton Arthur T. , East Daniel A. , Galinska-Rakoczy Agnieszka , Lehman William , Mulvihill Daniel P.
Published: September 2010

Tropomyosin (Tm) is a conserved dimeric coiled-coil protein, which forms polymers that curl around actin filaments in order to regulate actomyosin function. Acetylation of the Tm N-terminal methionine strengthens end-to-end bonds, which enhances actin binding as well as the ability of Tm to regulate myosin motor activity in both muscle and non-muscle cells. In this study we explore the function of each Tm form within fission yeast cells. Electron microscopy and live cell imaging revealed that acetylated and unacetylated Tm associate with distinct actin structures within the cell, and that each form has a profound effect upon the shape and integrity of the polymeric actin filament. We show that, whereas Tm acetylation is required to regulate the in vivo motility of class II myosins, acetylated Tm had no effect on the motility of class I and V myosins. These findings illustrate a novel Tm-acetylation-state-dependent mechanism for regulating specific actomyosin cytoskeletal interactions.
Practitioner‐Customizable Clinical Information Systems: A Case Study to Ground Further Research and Development Opportunities
Authors: Morrison Cecily , Blackwell Alan F. , Vuylsteke Alain
Published: September 2010

The uptake of electronic records and information technology support in intensive care medicine has been slower than many people predicted. One of the engineering challenges to overcome has been the subtle, but important, variation in clinical practice in different units. A relatively recent innovation that addresses this challenge is practitioner‐customizable clinical information systems, allowing clinicians wide scope in adjusting their systems to suit their clinical practice. However, these systems present a significant design challenge, not only of added technical complexity, but in providing tools that support clinicians in doing many of the tasks of a software engineer. This paper reviews the use of a commercially available clinical information system that is intended to be practitioner‐customizable, and considers the further design and development of tools to support healthcare practitioners doing end‐user customization on their own clinical information systems.
Instrumented Indentation of Lung Reveals Significant Short Term Alteration in Mechanical Behavior with 100% Oxygen
Authors: Silva Maricris R. , Shen Hsuan-Tso , Marzban Ali , Gouldstone Andrew
Published: September 2010

In critical care, trauma, or other situations involving reduced lung function, oxygen is given to avoid hypoxia. It is known that under certain conditions and long time (several hours) exposure, oxygen is toxic to the lungs, the possible mechanisms being direct cellular damage or surfactant dysfunction. Our key objective was to investigate possible changes in lung function when exposed to 100% oxygen in the short term (several tidal volumes). We performed mechanical tests on lobar surfaces of excised mammalian lungs inflated with air or 100% oxygen, examining (i) stiffness, (ii) non‐linear mechanical response and (iii) induced alveolar deformation. Our results showed that within five tidal volumes of breathing 100% oxygen, lung mechanics are significantly altered. In addition, after five tidal volumes of laboratory air, lung mechanical behavior begins to return to pre‐oxygen levels, indicating some reversibility. These significant and short‐term mechanical effects of oxygen could be linked to oxygen toxicity.
A Randomized Exhaustive Propositionalization Approach for Molecule Classification
Authors: Samorani Michele , Laguna Manuel , DeLisle Robert Kirk , Weaver Daniel C.
Published: September 2010

Drug discovery is the process of designing compounds that have desirable properties, such as activity and nontoxicity. Molecule classification techniques are used along with this process to predict the properties of the compounds to expedite their testing. Ideally, the classification rules found should be accurate and reveal novel chemical properties, but current molecule representation techniques lead to less-than-adequate accuracy and knowledge discovery. This work extends the propositionalization approach recently proposed for multirelational data mining in two ways: it generates expressive attributes exhaustively, and it uses randomization to sample a limited set of complex (“deep”) attributes. Our experimental tests show that the procedure is able to generate meaningful and interpretable attributes from molecular structural data, and that these features are effective for classification purposes.
Influence of loading conditions on the measurement of mode I critical stress intensity factor for wood and medium-density fiberboard by the single-edge-notched tension test
Authors: Yoshihara Hiroshi
Published: September 2010

The mode I critical stress intensity factorKIcfor wood and medium-density fiberboard (MDF) was obtained by conducting the single-edge-notched tension (SENT) test, designed for isotropic materials, under various loading conditions, and performing subsequent numerical analysis on the test data. The validity of the SENT test for this purpose was examined by conducting double cantilever beam (DCB) tests and comparing test data with those of the SENT tests. The best values ofKIcare obtained by conducting the SENT test under pin loading and introducing an additional crack length into the equations used for analyzing the test data.
Progressive NKCC1-Dependent Neuronal Chloride Accumulation during Neonatal Seizures
Authors: Dzhala Volodymyr I. , Kuchibhotla Kishore V. , Glykys Joseph C. , Kahle Kristopher T. , Swiercz Waldemar B. , Feng Guoping , Kuner Thomas , Augustine George J. , Bacskai Brian J. , Staley Kevin J.
Published: September 2010

Seizures induce excitatory shifts in the reversal potential for GABAA-receptor-mediated responses, which may contribute to the intractability of electro-encephalographic seizures and preclude the efficacy of widely used GABAergic anticonvulsants such as phenobarbital. We now report that, in intact hippocampi prepared from neonatal rats and transgenic mice expressing Clomeleon, recurrent seizures progressively increase the intracellular chloride concentration ([Cl−]i) assayed by Clomeleon imaging and invert the net effect of GABAAreceptor activation from inhibition to excitation assayed by the frequency of action potentials and intracellular Ca2+transients. These changes correlate with increasing frequency of seizure-like events and reduction in phenobarbital efficacy. The Na+–K+–2Cl−(NKCC1) cotransporter blocker bumetanide inhibited seizure-induced neuronal Cl−accumulation and the consequent facilitation of recurrent seizures. Our results demonstrate a novel mechanism by which seizure activity leads to [Cl−]iaccumulation, thereby increasing the probability of subsequent seizures. This provides a potential mechanism for the early crescendo phase of neonatal seizures.
GABABReceptor Modulation of Serotonin Neurons in the Dorsal Raphé Nucleus and Escalation of Aggression in Mice
Authors: Takahashi Aki , Shimamoto Akiko , Boyson Christopher O. , DeBold Joseph F. , Miczek Klaus A.
Published: September 2010

The serotonin (5-HT) system in the brain has been studied more than any other neurotransmitter for its role in the neurobiological basis of aggression. However, which mechanisms modulate the 5-HT system to promote escalated aggression is not clear. We here explore the role of GABAergic modulation in the raphé nuclei, from which most 5-HT in the forebrain originates, on escalated aggression in male mice. Pharmacological activation of GABAB, but not GABAA, receptors in the dorsal raphé nucleus (DRN) escalated aggressive behaviors. In contrast, GABA agonists did not escalate aggressive behaviors after microinjection into the median raphé nucleus. The aggression-heightening effect of the GABABagonist baclofen depended on the activation of 5-HT neurons in the DRN because it was blocked by coadministration of the 5-HT1Aagonist 8-OH-DPAT [((±)-8-hydroxy-2-(di-n-propylamino)tetralin) hydrobromide] (DPAT), which acts on autoreceptors and inhibits 5-HT neural activity.In vivomicrodialysis showed that GABABactivation in the DRN increased extracellular 5-HT level in the medial prefrontal cortex. This may be attributable to an indirect action via presynaptic GABABreceptors. The presynaptic GABABreceptors suppress Ca2+channel activity and inhibit neurotransmission, and the coadministration of N-type Ca2+channel blocker facilitated the effect of baclofen. These findings suggest that the indirect disinhibition of 5-HT neuron activity by presynaptic GABABreceptors on non-5-HT neurons in the DRN is one of the neurobiological mechanisms of escalated aggression.
Agrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity
Authors: Dietrich Marcelo O. , Antunes Catiele , Geliang Gan , Liu Zhong-Wu , Borok Erzsebet , Nie Yongzhan , Xu Allison W. , Souza Diogo O. , Gao Qian , Diano Sabrina , Gao Xiao-Bing , Horvath Tamas L.
Published: September 2010

Sirt1 has been associated with various effects of calorie restriction, including an increase in lifespan. Here we show in mice that a central regulatory component in energy metabolism, the hypothalamic melanocortin system, is affected by Sirt1, which promotes the activity and connectivity of this system resulting in negative energy balance. In adult mice, the pharmacological inhibition of brain Sirt1 activity decreased Agrp neuronal activity and the inhibitory tone on the anorexigenic POMC neurons, as measured by the number of synaptic inputs to these neurons. When a Sirt1 inhibitor (EX-527) was injected either peripherally (i.p., 10 mg/kg) or directly into the brain (i.c.v., 1.5 nmol/mouse), it decreased both food intake during the dark cycle and ghrelin-induced food intake. This effect on feeding is mediated by upstream melanocortin receptors, because the MC4R antagonist, SHU9119, reversed Sirt1's effect on food intake. This action of Sirt1 required an appropriate shift in the mitochondrial redox state: in the absence of such an adaptation enabled by the mitochondrial protein, UCP2, Sirt1-induced cellular and behavioral responses were impaired. In accordance with the pharmacological results, the selective knock-out of Sirt1 in hypothalamic Agrp neurons through the use of Cre-Lox technology decreased electric responses of Agrp neurons to ghrelin and decreased food intake, leading to decreased lean mass, fat mass, and body weight. The present data indicate that Sirt1 has a central mode of action by acting on the NPY/Agrp neurons to affect body metabolism.
Norepinephrine Promotes Microglia to Uptake and Degrade Amyloid β Peptide through Upregulation of Mouse Formyl Peptide Receptor 2 and Induction of Insulin-Degrading Enzyme
Authors: Kong Yan , Ruan Lingfei , Qian Lihua , Liu Xiaolei , Le Yingying
Published: September 2010

Locus ceruleus (LC) is the main subcortical site of norepinephrine synthesis. In Alzheimer's disease (AD) patients and rodent models, degeneration of LC neurons and reduced levels of norepinephrine in LC projection areas are significantly correlated with the increase in amyloid plaques, neurofibrillary tangles, and severity of dementia. Activated microglia play a pivotal role in the progression of AD by either clearing amyloid β peptide (Aβ) deposits through uptake of Aβ or releasing cytotoxic substances and proinflammatory cytokines. Here, we investigated the effect of norepinephrine on Aβ uptake and clearance by murine microglia and explored the underlying mechanisms. We found that murine microglia cell line N9 and primary microglia expressed β2adrenergic receptor (AR) but not β1and β3AR. Norepinephrine and isoproterenol upregulated the expression of Aβ receptor mFPR2, a mouse homolog of human formyl peptide receptor FPR2, through activation of β2AR in microglia. Norepinephrine also induced mFPR2 expression in mouse brain. Activation of β2AR in microglia promoted Aβ42uptake through upregulation of mFPR2 and enhanced spontaneous cell migration but had no effect on cell migration in response to mFPR2 agonists. Furthermore, activation of β2AR on microglia induced the expression of insulin-degrading enzyme and increased the degradation of Aβ42. Mechanistic studies showed that isoproterenol induced mFPR2 expression through ERK1/2-NF-κB and p38-NF-κB signaling pathways. These findings suggest that noradrenergic innervation from LC is needed to maintain adequate Aβ uptake and clearance by microglia, and norepinephrine is a link between neuron and microglia to orchestrate the host response to Aβ in AD.
INCREASING THE VARIETY OF FOODS CONSUMED BY A PICKY EATER: GENERALIZATION OF EFFECTS ACROSS CAREGIVERS AND SETTINGS
Authors: Valdimarsdóttir Hildur , Halldórsdóttir Lilja Yr , Sigurådóttir Zuilma Gabriela
Published: September 2010

A multiple baseline across settings was used to evaluate the effects of differential reinforcement of alternative behavior, nonremoval of the fork (Hoch, Babbitt, Coe, Krell, & Hackbert, 1994), and stimulus fading on consumption of food rejected previously. The study was conducted in two separate settings, and caregivers were trained in the intervention technique to increase generalization to natural settings. Food variety increased in both settings.
Inhibition of Inflammatory Cytokine Secretion by Plant-Derived Compounds Inuviscolide and Tomentosin: The Role of NFκB and STAT1
Authors: Abrham Galya , Dovrat Sara , Bessler Hanna , Grossman Shlomo , Uri Nir , Bergman Margalit
Published: August 2010

The plant Inula viscosa has been shown to possess many important medicinal benefits, including
anti-inflammatory, anti-oxidant, anti-bacterial, and anti-fungal activities, but the plant metabolites that mediate these
effects and their mechanism of action are poorly understood. In a previous study, we demonstrated a reduced expression
of the p65 subunit of nuclear factor kappa B (NFκB) in melanoma cells treated with the purified sesquiterpene lactone
compounds, Inuviscolide (Inv) and Tomentosin (Tom), extracted from Inula viscosa leaves. In this study, we tested the invitro
effect of these purified compounds on the secretion of pro-inflammatory cytokines from human peripheral blood
mononuclear cells (PBMCs) upon stimulation with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA). Their
possible mechanism of action was also studied. The results showed that both agents caused decreased production of IL-2,
IL-1β, IFNγ, and slightly increased secretion of TNFα, whereas secretion of IL-6 was not affected. The elevated levels of
TNFα did not appear to affect the viability of human PBMCs. Western blot analysis revealed a reduction in the protein
level of both the transcription factor component p65/RelA of nuclear factor-κB (NFκB) and the signal transducer and
activator of transcription 1 (STAT1) through proteosomal degradation. However, no change was observed in the
expression level of the nuclear factor-κB component, p50 (NFκB), or the signal transducer and activator of transcription 3
(STAT3). Taken together, our results indicate the possible future use of these agents as an anti-inflammatory treatment in
cases where overstimulation of cytokine secretion is the basis for the pathological symptoms.