bluuebunny/crossref_metadata_2025 huggingface dataset:
Consumption, Pleasure and Politics
Authors: Sassatelli Roberta , Davolio Federica
Published: July 2010

A growing field of research is documenting the political investment of the consumer. Yet, consumers are invested of political responsibilities in many different ways, which respond to different visions of politics and consumption, culture and the economy. In this article we critically explore the particular stance of an increasingly international actor such as Slow Food, placing it in the context of current debates on the scope of alternative food networks and on the moral boundaries of the market. Starting from the Slow Food core in Bra, Italy, and through a variety of qualitative sources, both primary (interviews) and secondary (publications, public speeches), we show that while Slow Food contributes to the current political investment of the consumer, it does so in distinctive ways which bear witness to its gastronomic origin and middle-class constituency. Slow Food rhetoric works out a politically-thick vision of taste refinement: its imagined consumer is an ‘eco-gastronome’, someone who adds ecological concerns onto a continuously trained aesthetic appreciation of food. The article considers the scope of what Slow Food has defined as the ‘right to pleasure’ in the face of a tension between inclusion and exclusion running through contemporary consumer culture. It concludes by exploring Slow Food’s current shifts towards issues such as economic growth, access to resources and environmental protection — crucial in defining the complex world of critical consumption — through a politico-aesthetic problematization of food consumption.
Gambling, Capitalism and the State
Authors: Young Martin
Published: July 2010

In this article I explore the relationships between commercial gambling and late capitalism. In particular, I am interested in the societal forces that produce gambling as a contemporary form of consumption, which I define as the state-sanctioned commodification of chance.As a theoretical entry point, I employ the typology of games devised by French sociologist Roger Caillois in his 1961 volume Man, Play, Games . Specifically, I develop Caillois’s distinction between competitive or agônistic games (the ancient Greek word meaning contest or challenge) and those based on chance or alea (the ancient Greek for playing at a game of chance of any kind). I extend these categories beyond a concern with the individual game to explore the tensions between the increasingly aleatory trends of the risk society, the agônistic forces of gambling production (i.e. the state and industry) and the aleatory nature of individual consumption. I argue that the expansion of gambling products is due to the state’s own position as aleatory subject within late capitalism. I suggest that the concern with the risk minimization of the risk society and the massive expansion of alea through gambling are dialectically related. In other words, the risk society produces a corollary — a demand for risk — in the production of alea.This contradiction is resolved through the consumption of alea as a form of controllable, bounded, and individualized risk, one that is able to be consumed free of the broader global anxieties of the risk society. Finally, I argue that aleatory consumption itself opens up the possibility of a series of misrecognitions between production and consumption, ones that, in combination with the ideology of chance, conceal the agônistic realm of production by enabling consumers to adopt individualized orientations towards consumption.
Imsukuhum Kulhum!
Authors: Peterson Mark Allen
Published: July 2010

At the turn of the millennium, Pokémon was perhaps the commodity phenomenon, dominating global children’s markets. Universalist explanations for Pokémon tend to ignore the myriad ways people actually encounter Pokémon in concrete situations, ways that include not only the purchasing and playing of games and collecting of objects but everyday social performances with and around these toys, games and activities. In this article, I will compare and contrast Pokémon’s reception in three upper middle class Egyptian families whose appropriations of Pokémon were shaped by Pokémon’s global indexicality, yet also shaped by forms of transnational Islam, through which people resist and seek to establish limits to Westernization. I argue that these processes are mediated by metadiscourses about Pokémon through which people articulated the meanings of their appropriations of Pokémon and integrated them into local systems of social relations.
An Inclusive Strategy of Teaching Diversity
Authors: Thomas Kecia M. , Ny Mia Tran  , Dawson Bryan L.
Published: July 2010

The article argues that many forms of diversity instruction, be it in the classroom or a conference room, have promoted an appreciation of differences without simultaneously promoting inclusion. Therefore, we advocate that diversity instruction should take a strategic approach to cultivating an appreciation of inclusion as well as diversity through considering the structure of the instruction, the authors of the work chosen, as well as who delivers the instruction. In essence, we present an alternative diversity teaching strategy that incorporates a value for inclusion.
Real Men Don’t Eat Quiche
Authors: Gal David , Wilkie James
Published: July 2010

Everyday items are imbued with subtle yet pervasive gender associations. For instance, sour dairy products and products with rounded edges tend to be perceived as relatively feminine, whereas meat and products with sharp edges tend to be perceived as relatively masculine. In a series of studies, we find that men are more likely to choose gender-congruent options (masculine foods and angular-shaped items) when they have unconstrained time and attentional resources than when these resources are constrained. In contrast, women’s choices tend to not be affected by time or attentional resource availability. Our findings suggest that men experience a conflict between their relatively intrinsic preferences and gender norms and that they tend to forgo their intrinsic preferences to conform to a masculine gender identity (when they have sufficient resources to incorporate gender norm information in their choices). Women, on the other hand, appear to be less concerned with making gender-congruent choices.
Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition
Authors: Leong Sai Mun , Tan Ban Xiong , Bte Ahmad Baidah , Yan Tie , Chee Lai Yuen , Ang Swee Tin , Tay Kian Ghee , Koh Liang Piu , Yeoh Allen Eng Juh , Koay Evelyn Siew-Chuan , Mok Yu-Keung , Lim Tit Meng
Published: July 2010

In up to one-third of patients with acute myeloid leukemia, a C-terminal frame-shift mutation results in abnormal and abundant cytoplasmic accumulation of the usually nucleoli-bound protein nucleophosmin (NPM), and this is thought to function in cancer pathogenesis. Here, we demonstrate a gain-of-function role for cytoplasmic NPM in the inhibition of caspase signaling. The NPM mutant specifically inhibits the activities of the cell-death proteases, caspase-6 and -8, through direct interaction with their cleaved, active forms, but not the immature procaspases. The cytoplasmic NPM mutant not only affords protection from death ligand-induced cell death but also suppresses caspase-6/-8–mediated myeloid differentiation. Our data hence provide a potential explanation for the myeloid-specific involvement of cytoplasmic NPM in the leukemogenesis of a large subset of acute myeloid leukemia.
Adult hematopoietic stem cells require NKAP for maintenance and survival
Authors: Pajerowski Anthony G. , Shapiro Michael J. , Gwin Kimberly , Sundsbak Rhianna , Nelson-Holte Molly , Medina Kay , Shapiro Virginia Smith
Published: July 2010

Steady-state hematopoiesis is sustained through differentiation balanced with proliferation and self-renewal of hematopoietic stem cells (HSCs). Disruption of this balance can lead to hematopoietic failure, as hematopoietic differentiation without self-renewal leads to loss of the HSC pool. We find that conditional knockout mice that delete the transcriptional repressor NKAP in HSCs and all hematopoietic lineages during embryonic development exhibit perinatal lethality and abrogation of hematopoiesis as demonstrated by multilineage defects in lymphocyte, granulocyte, erythrocyte and megakaryocyte development. Inducible deletion of NKAP in adult mice leads to lethality within 2 weeks, at which point hematopoiesis in the bone marrow has halted and HSCs have disappeared. This hematopoietic failure and lethality is cell intrinsic, as radiation chimeras reconstituted with inducible Mx1-cre NKAP conditional knockout bone marrow also succumb with a similar time course. Even in the context of a completely normal bone marrow environment using mixed radiation chimeras, NKAP deletion results in HSC failure. NKAP deletion leads to decreased proliferation and increased apoptosis of HSCs, which is likely due to increased expression of the cyclin-dependent kinase inhibitors p21Cip1/Waf1 and p19Ink4d. These data establish NKAP as one of a very small number of transcriptional regulators that is absolutely required for adult HSC maintenance and survival.
Targeting FVIII expression to endothelial cells regenerates a releasable pool of FVIII and restores hemostasis in a mouse model of hemophilia A
Authors: Shi Qizhen , Fahs Scot A. , Kuether Erin L. , Cooley Brian C. , Weiler Hartmut , Montgomery Robert R.
Published: July 2010

The natural cell type(s) that synthesize and release factor VIII (FVIII) into the circulation are still not known with certainty. In vitro studies indicate that artificial expression of FVIII in endothelial cells produces an intracellular pool of FVIII that can be mobilized together with its carrier protein, von Willebrand factor (VWF), by agonists. Here, we show that expression of human B-domain deleted FVIII (hFVIII) in the vascular endothelium of otherwise FVIII-deficient mice results in costorage of FVIII and VWF in endothelial Weibel-Palade bodies and restores normal levels and activity of FVIII in plasma. Stored FVIII was mobilized into the circulation by subcutaneous administration of epinephrine. Human FVIII activity in plasma was strictly dependent on the presence of VWF. Endothelial-specific expression of hFVIII rescued the bleeding diathesis of hemophilic mice lacking endogenous FVIII. This hemostatic function of endothelial cell–derived hFVIII was suppressed in the presence of anti-FVIII inhibitory antibodies. These results suggest that targeting FVIII expression to endothelial cells may establish a releasable pool of FVIII and normalize plasma FVIII level and activity in hemophilia A, but does not prevent the inhibitory effect of anti-FVIII antibodies on the hemostatic function of transgene-derived hFVIII as is seen with platelet-derived FVIII expression.
Priming innate immune responses to infection by cyclooxygenase inhibition kills antibiotic-susceptible and -resistant bacteria
Authors: Stables Melanie J. , Newson Justine , Ayoub Samir S. , Brown Jeremy , Hyams Catherine J. , Gilroy Derek W.
Published: July 2010

Inhibition of cyclooxygenase (COX)–derived prostaglandins (PGs) by nonsteroidal anti-inflammatory drugs (NSAIDs) mediates leukocyte killing of bacteria. However, the relative contribution of COX1 versus COX2 to this process, as well as the mechanisms controlling it in mouse and humans, are unknown. Indeed, the potential of NSAIDs to facilitate leukocyte killing of drug-resistant bacteria warrants investigation. Therefore, we carried out a series of experiments in mice and humans, finding that COX1 is the predominant isoform active in PG synthesis during infection and that its prophylactic or therapeutic inhibition primes leukocytes to kill bacteria by increasing phagocytic uptake and reactive oxygen intermediate-mediated killing in a cyclic adenosine monophosphate (cAMP)-dependent manner. Moreover, NSAIDs enhance bacterial killing in humans, exerting an additive effect when used in combination with antibiotics. Finally, NSAIDs, through the inhibition of COX prime the innate immune system to mediate bacterial clearance of penicillin-resistant Streptococcus pneumoniae serotype 19A, a well-recognized vaccine escape serotype of particular concern given its increasing prevalence and multi-antibiotic resistance. Therefore, these data underline the importance of lipid mediators in host responses to in-fection and the potential of inhibitors of PG signaling pathways as adjunc-tive therapies, particularly in the con-text of antibiotic resistance.
The methylated N-terminal tail of RCC1 is required for stabilisation of its interaction with chromatin by Ran in live cells
Authors: Hitakomate Ekarat , Hood Fiona E , Sanderson Helen S , Clarke Paul R
Published: July 2010

Background

Regulator of chromosome condensation 1 (RCC1) is the guanine nucleotide exchange factor for Ran GTPase. Localised generation of Ran-GTP by RCC1 on chromatin is critical for nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Both the N-terminal tail of RCC1 and its association with Ran are important for its interaction with chromatin in cells. In vitro, the association of Ran with RCC1 induces a conformational change in the N-terminal tail that promotes its interaction with DNA.

Results

We have investigated the mechanism of the dynamic interaction of the α isoform of human RCC1 (RCC1α) with chromatin in live cells using fluorescence recovery after photobleaching (FRAP) of green fluorescent protein (GFP) fusions. We show that the N-terminal tail stabilises the interaction of RCC1α with chromatin and this function can be partially replaced by another lysine-rich nuclear localisation signal. Removal of the tail prevents the interaction of RCC1α with chromatin from being stabilised by RanT24N, a mutant that binds stably to RCC1α. The interaction of RCC1α with chromatin is destabilised by mutation of lysine 4 (K4Q), which abolishes α-N-terminal methylation, and this interaction is no longer stabilised by RanT24N. However, α-N-terminal methylation of RCC1α is not regulated by the binding of RanT24N. Conversely, the association of Ran with precipitated RCC1α does not require the N-terminal tail of RCC1α or its methylation. The mobility of RCC1α on chromatin is increased by mutation of aspartate 182 (D182A), which inhibits guanine-nucleotide exchange activity, but RCC1αD182A can still bind nucleotide-free Ran and its interaction with chromatin is stabilised by RanT24N.

Conclusions

These results show that the stabilisation of the dynamic interaction of RCC1α with chromatin by Ran in live cells requires the N-terminal tail of RCC1α. α-N-methylation is not regulated by formation of the binary complex with Ran, but it promotes chromatin binding through the tail. This work supports a model in which the association of RCC1α with chromatin is promoted by a conformational change in the α-N-terminal methylated tail that is induced allosterically in the binary complex with Ran.
Genomic patterns of nucleotide diversity in divergent populations of U.S. weedy rice
Authors: Reagon Michael , Thurber Carrie S , Gross Briana L , Olsen Kenneth M , Jia Yulin , Caicedo Ana L
Published: July 2010

Background

Weedy rice (red rice), a conspecific weed of cultivated rice (Oryza sativaL.), is a significant problem throughout the world and an emerging threat in regions where it was previously absent. Despite belonging to the same species complex as domesticated rice and its wild relatives, the evolutionary origins of weedy rice remain unclear. We use genome-wide patterns of single nucleotide polymorphism (SNP) variation in a broad geographic sample of weedy, domesticated, and wildOryzasamples to infer the origin and demographic processes influencing U.S. weedy rice evolution.

Results

We find greater population structure than has been previously reported for U.S. weedy rice, and that the multiple, genetically divergent populations have separate origins. The two main U.S. weedy rice populations share genetic backgrounds with cultivatedO. sativavarietal groups not grown commercially in the U.S., suggesting weed origins from domesticated ancestors. Hybridization between weedy groups and between weedy rice and local crops has also led to the evolution of distinct U.S. weedy rice populations. Demographic simulations indicate differences among the main weedy groups in the impact of bottlenecks on their establishment in the U.S., and in the timing of divergence from their cultivated relatives.

Conclusions

Unlike prior research, we did not find unambiguous evidence for U.S. weedy rice originating via hybridization between cultivated and wildOryzaspecies. Our results demonstrate the potential for weedy life-histories to evolve directly from within domesticated lineages. The diverse origins of U.S. weedy rice populations demonstrate the multiplicity of evolutionary forces that can influence the emergence of weeds from a single species complex.
Impact of Body Mass Index on the relationship of epicardial adipose tissue to metabolic syndrome and coronary artery disease in an Asian population
Authors: Park Jin-Sun , Ahn Sung-Gyun , Hwang Jung-Won , Lim Hong-Seok , Choi Byoung-Joo , Choi So-Yeon , Yoon Myeong-Ho , Hwang Gyo-Seung , Tahk Seung-Jea , Shin Joon-Han
Published: July 2010

Background

In a previous study, we demonstrated that the thickness of epicardial adipose tissue (EAT), measured by echocardiography, was increased in patients with metabolic syndrome (MS) and coronary artery disease (CAD). Several studies on obese patients, however, failed to demonstrate any relationship between EAT and CAD. We hypothesized that body mass index (BMI) affected the link between EAT and MS and CAD.

Methods

We consecutively enrolled 643 patients (302 males, 341 females; 59 ± 11 years), who underwent echocardiography and coronary angiography. The EAT thickness was measured on the free wall of the right ventricle at the end of diastole. All patients were divided into two groups: high BMI group, ≥27 kg/m2 (n = 165), and non-high BMI group, < 27 kg/m2 (n = 478).

Results

The median and mean EAT thickness of 643 patients were 3.0 mm and 3.1 ± 2.4 mm, respectively. In the non-high BMI group, the median EAT thickness was significantly increased in patients with MS compared to those without MS (3.5 vs. 1.9 mm, p < 0.001). In the high BMI group, however, there was no significant difference in the median EAT thickness between patients with and without MS (3.0 vs. 2.5 mm, p = 0.813). A receiver operating characteristic (ROC) curve analysis predicting MS revealed that the area under the curve (AUC) of the non-high BMI group was significantly larger than that of the high BMI group (0.659 vs. 0.506, p = 0.007). When compared to patients without CAD, patients with CAD in both the non-high and high BMI groups had a significantly higher median EAT thickness (3.5 vs. 1.5 mm, p < 0.001 and 4.0 vs. 2.5 mm, p = 0.001, respectively). However, an ROC curve analysis predicting CAD revealed that the AUC of the non-high BMI group tended to be larger than that of the high BMI group (0.735 vs. 0.657, p = 0.055).

Conclusions

While EAT thickness was significantly increased in patients with MS and CAD, the power of EAT thickness to predict MS and CAD was stronger in patients with BMI < 27 kg/m2. These findings showed that the measurement of EAT thickness by echocardiography might be especially useful in an Asian population with a non-high BMI, less than 27 kg/m2.
Production of biohydrogen by recombinant expression of [NiFe]-hydrogenase 1 in Escherichia coli
Authors: Kim Jaoon YH , Jo Byung Hoon , Cha Hyung Joon
Published: July 2010

Background

Hydrogenases catalyze reversible reaction between hydrogen (H2) and proton. Inactivation of hydrogenase by exposure to oxygen is a critical limitation in biohydrogen production since strict anaerobic conditions are required. While [FeFe]-hydrogenases are irreversibly inactivated by oxygen, it was known that [NiFe]-hydrogenases are generally more tolerant to oxygen. The physiological function of [NiFe]-hydrogenase 1 is still ambiguous. We herein investigated the H2 production potential of [NiFe]-hydrogenase 1 of Escherichia coli in vivo and in vitro. The hya A and hya B genes corresponding to the small and large subunits of [NiFe]-hydrogenase 1 core enzyme, respectively, were expressed in BL21, an E. coli strain without H2 producing ability.

Results

Recombinant BL21 expressing [NiFe]-hydrogenase 1 actively produced H2 (12.5 mL H2/(h·L) in 400 mL glucose minimal medium under micro-aerobic condition, whereas the wild type BL21 did not produce H2 even when formate was added as substrate for formate hydrogenlyase (FHL) pathway. The majority of recombinant protein was produced as an insoluble form, with translocation of a small fraction to the membrane. However, the membrane fraction displayed high activity (~65% of total cell fraction), based on unit protein mass. Supplement of nickel and iron to media showed these metals contribute essentially to the function of [NiFe]-hydrogenase 1 as components of catalytic site. In addition, purified E. coli [NiFe]-hydrogenase 1 using his6-tag displayed oxygen-tolerant activity of ~12 nmol H2/(min·mg protein) under a normal aeration environment, compared to [FeFe]-hydrogenase, which remains inactive under this condition.

Conclusions

This is the first report on physiological function of E. coli [NiFe]-hydrogenase 1 for H2 production. We found that [NiFe]-hydrogenase 1 has H2 production ability even under the existence of oxygen. This oxygen-tolerant property is a significant advantage because it is not necessary to protect the H2 production process from oxygen. Therefore, we propose that [NiFe]-hydrogenase can be successfully applied as an efficient biohydrogen production tool under micro-aerobic conditions.
The active commuting route environment scale (ACRES): development and evaluation
Authors: Wahlgren Lina , Stigell Erik , Schantz Peter
Published: July 2010

Background

Route environments can be a potentially important factor in influencing people's behaviours in relation to active commuting. To better understand these possible relationships, assessments of route environments are needed. We therefore developed a scale; the Active Commuting Route Environment Scale (ACRES), for the assessment of bicyclists' and pedestrians' perceptions of their commuting route environments. Here we will report on the development and the results of validity and reliability assessments thereof.

Methods

Active commuters (n = 54) were recruited when they bicycled in Stockholm, Sweden. Traffic planning and environmental experts from the Municipality of Stockholm were assembled to form an expert panel (n = 24). The active commuters responded to the scale on two occasions, and the expert panel responded to it once. To test criterion-related validity, differences in ratings of the inner urban and suburban environments of Greater Stockholm were compared between the experts and the commuters. Furthermore, four items were compared with existing objective measures. Test-retest reproducibility was assessed with three types of analysis: order effect, typical error and intraclass correlation.

Results

There was a concordance in sizes and directions of differences in ratings of inner urban and suburban environments between the experts and the commuters. Furthermore, both groups' ratings were in line with existing objectively measured differences between the two environmental settings. Order effects between test and retest were observed in 6 of 36 items. The typical errors ranged from 0.93 to 2.54, and the intraclass correlation coefficients ranged from 'moderate' (0.42) to 'almost perfect' (0.87).

Conclusions

The ACRES was characterized by considerable criterion-related validity and reasonable test-retest reproducibility.
Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R
Authors: Li Ge , Park Hyeon U , Liang Dong , Zhao Richard Y
Published: July 2010

Background

Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive.

Results

To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU) and ultraviolet light (UV) also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV.

Conclusions

These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.
Thermal Nociceptive Properties of Trigeminal Afferent Neurons in Rats
Authors: Cuellar Jason M , Manering Neil A , Klukinov Mikhail , Nemenov Michael I , Yeomans David C
Published: July 2010

Background:

Although nociceptive afferents innervating the body have been heavily studied form many years, much less attention has been paid to trigeminal afferent biology. In particular, very little is known concerning trigeminal nociceptor responses to heat, and almost nothing in the rat. This study uses a highly controlled and reproducible diode laser stimulator to investigate the activation of trigeminal afferents to noxious skin heating.

Results:

The results of this experiment demonstrate that trigeminal thermonociceptors are distinct from themonociceptors innervating the limbs. Trigeminal nociceptors have considerably slower action potential conduction velocities and lower temperature thresholds than somatic afferent neurons. On the other hand, nociceptors innervating both tissue areas separate into those that respond to short pulse, high rate skin heating and those that respond to long pulse, low rate skin heating.

Conclusions:

This paper provides the first description in the literature of the in vivo properties of thermonociceptors in rats. These finding of two separate populations aligns with the separation between C and A-delta thermonociceptors innervating the paw, but have significant differences in terms of temperature threshold and average conduction velocities. An understanding of the temperature response properties of afferent neurons innervating the paw skin have been critical in many mechanistic discoveries, some leading to new pain therapies. A clear understanding of trigeminal nociceptors may be similarly useful in the investigation of trigeminal pain mechanisms and potential therapies.
Acute lead intoxication in a female battery worker: Diagnosis and management
Authors: Dounias George , Rachiotis George , Hadjichristodoulou Christos
Published: July 2010

Lead is a significant occupational and environmental hazard. Battery industry is one of the settings related to lead intoxication. Published information on the use of oral chelating agents for the treatment of anaemia in the context of acute lead intoxication is limited. The patient was a 33 year immigrant female worker in a battery manufacture for 3 months. She complained for malaise that has been developed over the past two weeks. Pallor of skin and conjunctiva was the only sign found in physical examination. The blood test on admission revealed normochromic anaemia. Endoscopic investigation of the gastrointestinal system was negative for bleeding. The bone marrow biopsy was unrevealing.

At baseline no attention has been paid to patient's occupational history. Afterwards the patient's occupational history has been re-evaluated and she has been screened for lead intoxication. The increased levels of the lead related biomarkers of exposure and effect confirmed the diagnosis. The patient received an oral chelating agent and an improvement in clinical picture, and levels of haematological and lead related biochemical parameters have been recorded. No side effect and no rebound effect were observed. This case report emphasizes the importance of the occupational history in the context of the differential diagnosis. Moreover, this report indicates that lead remains a significant occupational hazard especially in the small scale battery industry
Increased activity and expression of histone deacetylase 1 in relation to tumor necrosis factor-alpha in synovial tissue of rheumatoid arthritis
Authors: Kawabata Tomoko , Nishida Keiichiro , Takasugi Koji , Ogawa Hiroko , Sada Kenei , Kadota Yasutaka , Inagaki Junko , Hirohata Satoshi , Ninomiya Yoshifumi , Makino Hirofumi
Published: July 2010

Introduction

The purpose of this study was to investigate the profile of histone deacetylase (HDAC) expression in the synovial tissue of rheumatoid arthritis (RA) compared with that of normal control and osteoarthritis (OA), and to examine whether there is a link between HDAC activity and synovial inflammation.

Methods

HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of total synovial tissue surgically obtained from normal, OA and RA joints. The level of cytoplasmic tumor necrosis factor a (TNFα) fraction was measured by ELISA. Total RNA of synovial tissue was used for RT-PCR of HDAC1-8. In synovial fibroblasts from RA (RASFs), the effects of TNFα on nuclear HDAC activity and class I HDACs (1, 2, 3, 8) mRNA expressions were examined by quantitative real-time PCR. The protein expression and distribution of class I HDACs were examined by Western blotting.

Results

Nuclear HDAC activity was significantly higher in RA than in OA and normal controls and correlated with the amount of cytoplasmic TNFα. The mRNA expression of HDAC1 in RA synovial tissue was higher than in OA and normal controls, and showed positive correlation with TNFα mRNA expression. The protein level of nuclear HDAC1 was higher in RA synovial tissue compared with OA synovial tissue. Stimulation with TNFα significantly increased the nuclear HDAC activity and HDAC1 mRNA expression at 24 hours and HDAC1 protein expression at 48 hours in RASFs.

Conclusions

Our results showed nuclear HDAC activity and expression of HDAC1 were significantly higher in RA than in OA synovial tissues, and they were upregulated by TNFα stimulation in RASFs. These data might provide important clues for the development of specific small molecule HDAC inhibitors.
Viscosity effects in vibratory mobilization of residual oil
Authors: Beresnev Igor A. , Deng Wen
Published: July 2010

The last decade has seen clarifications of the underlying capillary physics behind stimulation of oil production by seismic waves and vibrations. Computational studies have prevailed, however, and no viscous hydrodynamic theory of the phenomenon has been proposed. For a body of oil entrapped in a pore channel, viscosity effects are naturally incorporated through a model of two-phase core-annular flow. These effects are significant at the postmobilization stage, when the resistance of capillary forces is overcome and viscosity becomes the only force resisting an oil ganglion’s motion. A viscous equation of motion follows, and computational fluid dynamics (CFD) establishes the limits of its applicability. The theory allows inexpensive calculation of important geophysical parameters of reservoir stimulation for given pore geometries, such as the frequency and amplitude of vibrations needed to mobilize the residual oil. The theoretical mobilizing acceleration in seismic waves for a given frequency is accurate to within approximately 30% or better when checked against CFD. The advantages of the viscous theory over the inviscid one are twofold. The former can calculate complete time histories of forced displacement of an oil blob in a pore channel, including retardation by capillary forces, mobilization by vibrations, and an ensuing Haines jump. It also provides an approximately factor-of-two improvement in the calculation of the mobilizing acceleration needed to unplug a static ganglion.
Pediatric Phase I Trial and Pharmacokinetic Study of Vorinostat: A Children's Oncology Group Phase I Consortium Report
Authors: Fouladi Maryam , Park Julie R. , Stewart Clinton F. , Gilbertson Richard J. , Schaiquevich Paula , Sun Junfeng , Reid Joel M. , Ames Matthew M. , Speights Roseanne , Ingle Ashish M. , Zwiebel James , Blaney Susan M. , Adamson Peter C.
Published: July 2010

Purpose

The purpose of this study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of vorinostat administered as a single agent and in combination 13-cis retinoic acid (13cRA) in children with refractory solid tumors; to evaluate the tolerability of the solid tumor MTD in children with refractory leukemias; and to characterize the pharmacokinetics of a vorinostat suspension in children.

Patients and Methods

Vorinostat was administered orally daily starting at 180 mg/m2/d with escalations planned in 30% increments. Pharmacokinetic studies were performed with the initial dose. Acetyl-histone (H3) accumulation was assessed by Western blotting of peripheral blood mononuclear cells (PBMC).

Results

Sixty-four patients were enrolled on this multipart trial. In patients with solid tumors, the MTD was 230 mg/m2/d with dose-limiting neutropenia, thrombocytopenia, and hypokalemia at 300 mg/m2/d. DLTs observed with the combination of 13cRA and vorinostat included thrombocytopenia, neutropenia, anorexia, and hypertriglyceridemia, resulting in a MTD of vorinostat 180 mg/m2/d 4 times per week and 13cRA 80 mg/m2/dose twice per day, days 1 through 14 every 28 days. Wide interpatient variability was noted in vorinostat disposition, with area under the concentration-time curves at 230 mg/m2/d for the capsule (range, 1,415 to 9,291 ng/mL × hr) and oral suspension (range, 1,186 to 4,780 ng/mL × hr). Significant accumulation of acetylated H3 histone in PBMC was observed after administration of vorinostat, particularly at higher doses. One patient with neuroblastoma experienced a complete response to the combination.

Conclusion

In children with recurrent solid tumors, vorinostat is well-tolerated at 230 mg/m2/d, with a modest dose reduction being required when combining vorinostat with 13cRA. Drug disposition is similar to that observed in adults.
Phase II, Open-Label Study of Pazopanib or Lapatinib Monotherapy Compared With Pazopanib Plus Lapatinib Combination Therapy in Patients With Advanced and Recurrent Cervical Cancer
Authors: Monk Bradley J. , Mas Lopez Luis , Zarba Juan J. , Oaknin Ana , Tarpin Carole , Termrungruanglert Wichai , Alber Jacquelyn A. , Ding Jie , Stutts Melissa W. , Pandite Lini N.
Published: July 2010

Purpose

Pazopanib and lapatinib are tyrosine kinase inhibitors that target vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and c-Kit or epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2/neu), respectively. In cervical cancer, EGFR and HER2/neu overexpression and high microvascular density correlate with survival.

Patients and Methods

Patients with measurable stage IVB persistent/recurrent cervical carcinoma not amenable to curative therapy and at least one prior regimen in the metastatic setting were randomly assigned in a ratio of 1:1:1 to pazopanib at 800 mg once daily, lapatinib at 1,500 mg once daily, or lapatinib plus pazopanib combination therapy (lapatinib at 1,000 mg plus pazopanib at 400 mg once daily or lapatinib at 1,500 mg plus pazopanib at 800 mg once daily). Therapy continued until progression or withdrawal because of adverse events (AEs). Primary end point was progression-free survival (PFS), and secondary end points were overall survival (OS), response rate (RR), and safety. The futility boundary was crossed at the planned interim analysis for combination therapy compared with lapatinib therapy, and the combination was discontinued.

Results

Of 230 patients enrolled, 152 were randomly assigned to the monotherapy arms: pazopanib (n = 74) or lapatinib (n = 78). Most patients (62%) had recurrent cancer. Pazopanib improved PFS (hazard ratio [HR], 0.66; 90% CI, 0.48 to 0.91; P = .013) and OS (HR, 0.67; 90% CI, 0.46 to 0.99; P = .045). Median OS was 50.7 weeks and 39.1 weeks and RRs were 9% and 5% for pazopanib and lapatinib, respectively. The only grade 3 AE > 10% was diarrhea (11% pazopanib and 13% lapatinib). Grade 4 AEs were 9% (lapatinib) and 12% (pazopanib).

Conclusion

This study confirms the activity of antiangiogenesis agents in advanced and recurrent cervical cancer and demonstrates the benefit of pazopanib based on the prolonged PFS and favorable toxicity profile.
Matched Pair Analysis Comparing Surgery Followed By Radiotherapy and Radiotherapy Alone for Metastatic Spinal Cord Compression
Authors: Rades Dirk , Huttenlocher Stefan , Dunst Juergen , Bajrovic Amira , Karstens Johann H. , Rudat Volker , Schild Steven E.
Published: July 2010

Purpose

The appropriate treatment for MSCC is controversial. A small randomized trial showed that decompressive surgery followed by radiotherapy was superior to radiotherapy alone. That study was limited to highly selected patients. Additional studies comparing surgery plus radiotherapy to radiotherapy could better clarify the role of surgery.

Methods

Data from 108 patients receiving surgery plus radiotherapy were matched to 216 patients (1:2) receiving radiotherapy alone. Groups were matched for 11 potential prognostic factors and compared for post-treatment motor function, ambulatory status, regaining ambulatory status, local control, and survival. Subgroup analyses were performed for patients receiving adequate surgery (direct decompressive surgery plus stabilization of involved vertebrae), patients receiving laminectomy, patients with solid tumors, patients with solid tumors receiving adequate surgery, and patients with solid tumors receiving laminectomy.

Results

Improvement of motor function occurred in 27% of patients after surgery plus radiotherapy and 26% after radiotherapy alone (P = .92). Post-treatment ambulatory rates were 69% after surgery plus radiotherapy and 68% after radiotherapy alone (P = .99). Of the nonambulatory patients, 30% and 26%, respectively, (P = .86) regained ambulatory status after treatment. One-year local control rates were 90% after surgery plus radiotherapy and 91% after radiotherapy alone (P = .48). One-year overall survival rates were 47% and 40%, respectively (P = .50). The subgroup analyses did not show significant differences between both groups. Surgery-related complications occurred in 11% of patients.

Conclusion

In this study, the outcomes of the end points evaluated after radiotherapy alone appeared similar to those of surgery plus radiotherapy. A new randomized trial comparing both treatments is justified.
Preventing preterm birth: the past limitations and new potential of animal models
Authors: Ratajczak Christine K. , Fay Justin C. , Muglia Louis J.
Published: July 2010

The high rate of preterm birth in the USA and many other countries is a potential target for improving children’s immediate health and reducing the medical problems they face as adults. The acute complications for infants born prematurely often require intensive care management and are followed by long-lasting cognitive, sensory, motor, and cardiovascular deficits that substantially limit adult capabilities and survival. The inability to effectively reduce preterm birth stems from the failure to understand normal mechanisms of parturition in humans. Although studies from several model organisms help define the physiology of maintenance and termination of pregnancy, there are fundamental differences between species. For example, species regulate their production of progesterone, the crucial hormone in sustaining pregnancy, differently. This limits the extent to which models can provide meaningful information about the physiological mechanisms of human gestation. The growing wealth of sequenced mammalian genomes, computational comparative genomic tools and systems biology approaches provides new potential to utilize the divergence of DNA sequences and physiology between species to understand the genetic underpinnings of preterm birth.
Pax3 induces differentiation of juvenile skeletal muscle stem cells without transcriptional upregulation of canonical myogenic regulatory factors
Authors: Young Arthur P. , Wagers Amy J.
Published: July 2010

Pax3 is an essential myogenic regulator of fetal and embryonic development, but its role in postnatal myogenesis remains a topic of debate. We show that constitutive expression of Pax3 in postnatal, juvenile mouse skeletal muscle stem cells, a subset of the heterogeneous satellite cell pool highly enriched for myogenic activity, potently induces differentiation. This differentiation-promoting activity stands in contrast to the differentiation-inhibiting effects of Pax3 in the commonly used mouse myoblast cell line C2C12. Pax3 mRNA levels in distinct muscles correlate with the rate of myogenic differentiation of their muscle stem cells. Although Pax3 controls embryonic myogenesis through regulation of the canonical myogenic regulatory factors (MRFs) Myf-5, MyoD, myogenin and Mrf4, we find that in postnatal muscle stem cells, ectopic Pax3 expression fails to induce expression of any of these factors. Unexpectedly, overexpression of neither Myf-5 nor myogenin is sufficient to induce differentiation of juvenile stem cells; and knockdown of Myf-5, rather than inhibiting differentiation, promotes it. Taken together, our results suggest that there are distinct myogenic regulatory pathways that control the embryonic development, juvenile myogenesis and adult regeneration of skeletal myofibers.
p38γ regulates interaction of nuclear PSF and RNA with the tumour-suppressor hDlg in response to osmotic shock
Authors: Sabio Guadalupe , Cerezo-Guisado María I. , del Reino Paloma , Iñesta-Vaquera Francisco A. , Rousseau Simon , Arthur J. Simon C. , Campbell David G. , Centeno Francisco , Cuenda Ana
Published: July 2010

Activation of p38γ modulates the integrity of the complex formed by the human discs large protein (hDlg) with cytoskeletal proteins, which is important for cell adaptation to changes in environmental osmolarity. Here we report that, in response to hyperosmotic stress, p38γ also regulates formation of complexes between hDlg and the nuclear protein polypyrimidine tract-binding protein-associated-splicing factor (PSF). Following osmotic shock, p38γ in the cell nucleus increases its association with nuclear hDlg, thereby causing dissociation of hDlg-PSF complexes. Moreover, hDlg and PSF bind different RNAs; in response to osmotic shock, p38γ causes hDlg-PSF and hDlg-RNA dissociation independently of its kinase activity. These findings identify a novel nuclear complex and suggest a previously unreported function of p38γ, which is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment.
Role of progerin-induced telomere dysfunction in HGPS premature cellular senescence
Authors: Benson Erica K. , Lee Sam W. , Aaronson Stuart A.
Published: July 2010

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature-aging syndrome caused by a dominant mutation in the gene encoding lamin A, which leads to an aberrantly spliced and processed protein termed progerin. Previous studies have shown that progerin induces early senescence associated with increased DNA-damage signaling and that telomerase extends HGPS cellular lifespan. We demonstrate that telomerase extends HGPS cellular lifespan by decreasing progerin-induced DNA-damage signaling and activation of p53 and Rb pathways that otherwise mediate the onset of premature senescence. We show further that progerin-induced DNA-damage signaling is localized to telomeres and is associated with telomere aggregates and chromosomal aberrations. Telomerase amelioration of DNA-damage signaling is relatively rapid, requires both its catalytic and DNA-binding functions, and correlates in time with the acquisition by HGPS cells of the ability to proliferate. All of these findings establish that HGPS premature cellular senescence results from progerin-induced telomere dysfunction.
Geomagnetic Matching Algorithm Based on the Probabilistic Neural Network
Authors: Zhou J , Liu Y , Ge Z
Published: July 2010

In order to realize geomagnetism-aided navigation in the regions with insignificant geomagnetic characteristic, inspired by the pattern recognition idea, the geomagnetic matching problem was transformed into statistical pattern recognition and was analysed from the aspect of pattern recognition. A matching algorithm based on the probabilistic neural network (PNN) was proposed. The selection of training sample for the PNN, the relation between the parameter of the PNN, and the geomagnetic roughness were studied. Then a PNN was constructed for geomagnetic matching. Simulation results show that the proposed method can greatly improve the efficiency and achieve better performance than ordinary correlative matching algorithm. The accuracy of the matching method is less than the unit cell size of the geomagnetic map.
A Bivariate Fréchet Distribution and its Application to the Statistics of Two Successive Surf Parameters
Authors: Myrhaug D , Leira B J
Published: July 2010

A bivariate Fréchet distribution which is obtained by transforming a bivariate Rayleigh distribution is presented. The emphasis is on its application to the statistics of two successive surf parameters. The results are illustrated by estimating the probability of two successive spilling breakers and two successive plunging breakers on different slopes by using wave parameters corresponding to typical field conditions.
Application of an industrial robot in the sports domain: Simulating the ground contact phase of running
Authors: Ronkainen J A , El-Kati R F , Fleming P R , Forrester S E
Published: July 2010

Mechanical devices currently used to test sports equipment are limited to one or two degrees of freedom and cannot replicate complete human movements. The purpose of this study was to investigate the capabilities of a six-degrees-of-freedom industrial robot (iRobot) to replicate the ground contact phase of human running. The objectives were as follows: to quantify the repeatability of the iRobot system; to assess the ability of the system to replicate heelstrike running and forefoot running. High-speed video and force plate data were collected for a single-subject heelstrike running and forefoot running. The iRobot was programmed to replicate the two footstrikes and then to perform 500 cycles of each. System kinematics and ground contact forces were recorded every tenth cycle. The kinematic repeatability of the iRobot was extremely good (less than 2 mm mean standard deviation in all marker trajectories). The peak vertical ground reaction forces showed systemic trends specific to the footstrike; heelstrike 3 per cent decrease and forefoot 19 per cent increase over the 500 cycles. iRobot replication of the footstrikes met with some success, particularly for the forefoot running. The iRobot generated highly repeatable kinematics and demonstrated potential for applications within the footwear industry. A number of improvements to the system were identified which could further improve its ability to replicate human running.