bluuebunny/crossref_metadata_2025 huggingface dataset:
Is FCGR2A a susceptibility gene to systemic lupus erythematosus in Chinese?
Authors: Zhou XJ , Lv JC , Qin LX , Yang HZ , Yu F , Zhao MH , Zhang H
Published: July 2011

Recent genome-wide association scans and replication studies reinforce that FCGR2A is a susceptibility gene in systemic lupus erythematosus (SLE) in Caucasians. However, previous case control studies denied such conclusions in Chinese people. Besides genetic heterogeneity among different ethnicities, copy number variation (CNV), non-homogenous phenotypes and insufficient power may be confounders. We performed a case control study with 1066 Chinese (589 SLE patients and 477 healthy controls) and a meta-analysis based on 2328 SLE patients and 2313 healthy controls. FCGR2A CNV and FCGR2A131H/R [rs1801274] were detected by TaqMan assays. No variation of copy numbers of FCGR2A gene was found in Chinese. A further case control study suggested a dose–response character for FCGR2A131H/R and it affected disease activity, severity and prognosis. Finally, meta-analysis indicated FCGR2A that was a susceptibility gene to SLE in Chinese with an odds ratio of 1.094 and population attributable risk proportion of (PARP) 0.031. By an integrative strategy, we validate that FCGR2A bears no population-specific CNV. FCGR2A131H/R contributes to SLE susceptibility in Chinese, and affects disease activity, severity and prognosis. The undetected association in Chinese derives from under-power rather than any methodological obstacle due to CNV or population-specific genetic effect.
Impact of systemic lupus erythematosus on ovarian reserve in premenopausal women: Evaluation by using anti-Muellerian hormone
Authors: Lawrenz B , Henes JC , Henes M , Neunhoeffer E , Schmalzing M , Fehm T , Kïtter I
Published: July 2011

Systemic lupus erythematosus (SLE) is an autoimmune disease which may negatively influence fertility. Treatment with cyclophosphamide can damage the ovaries. The ovarian function can also be reduced by autoimmune oophoritis in lupus patients. We analysed the influence of SLE on the ovarian reserve against disease intensity and duration of illness. We determined the ovarian reserve in 33 premenopausal SLE patients without previous cyclophosphamide-treatment by measuring the anti-Muellerian hormone (AMH) and compared these with the AMH values of 33 age-matched healthy controls. Numbers of children and miscarriages were reported. Disease intensity of the SLE patients was determined using SLEDAI and ECLAM and duration of illness was taken into account. We found that the AMH values in the SLE group were significantly lower than in the healthy control group. No significant differences between the groups regarding number of children and miscarriages were noted and no correlation between the AMH value and the duration of illness or the SLEDAI as an indicator of disease activity was found. Despite mild disease activity SLE patients had a significantly lower ovarian reserve than age-matched healthy women. This could be a sign that SLE itself has a negative influence on the ovarian reserve.
Studies on the Shape Frozen/Recovery Behaviors of SMP-based Sandwich Structure
Authors: Li Z. F. , Wang Z. D.
Published: July 2011

Shape memory polymers (SMPs) are polymers that can change between temporary and permanent shapes via a programmed thermo-mechanical cycle. However, the stiffness and shape recovery stress of SMPs are much low as compared with shape memory alloys and ceramics. This article aims to improve their stiffness and shape recovery stress by utilization of sandwich structures. Two types of SMP-based sandwich beams, aluminum/SM-polyurethane/aluminum, and steel/SM-polyurethane/steel were considered. Theoretical solutions were proposed in describing the shape frozen/recovery behaviors, which include mechanical loading at an above temperature, frozen fixture by decreasing the temperature to be lower than Tg, and shape recovery through reheating the temperature to be higher than Tg. The results confirm that SMP-based sandwich structure can significantly improve the shape recovery stress and meanwhile realize an acceptable shape fixture rate.
The Town–Country Antithesis and the Environment
Authors: Thomas Clement Matthew
Published: July 2011

Current sociological interest in “real utopias” demands a critical evaluation of potential academic contributions to the subject. The following is a sociological critique of the real utopian project of abolishing the antithesis between town and country. The analysis uncovers a fundamental dilemma in theorizing how to transform this antithesis. On one hand, social and natural scientists have acknowledged that modern urbanization and the urban–rural divide contribute to the creation of a rift in the relationship between humans and the natural environment. On the other hand, modern cities, based on arguments about the efficiency of urban density, are defended by a wide variety of scholars. Nevertheless, in turning to a socioecological framework of analysis based on the work of Marx and Engels and metabolic rift theory, this dilemma can be resolved. This framework emphasizes that modern cities are the result of interdependent development, which is expressed through the antithesis between town and country. This antithesis is the intervening mechanism in which the metabolic rift is spatially observed and carried out. That the ecological rift is now planetary demands a real utopian project in which dramatically different social and spatial relations are theorized.
Mapping Police Stress
Authors: Hickman Matthew J. , Fricas Jennifer , Strom Kevin J. , Pope Mark W.
Published: July 2011

Research on police stress has developed out of several theoretical frameworks, but the knowledge base is limited by a common reliance on self-report stress measures. This article describes an innovative approach to studying police stress that attempts to overcome some of these limitations by using direct, real-time, and spatially anchored measurement of an officer’s stress response (via heart rate) during shift work. A pilot study was conducted using a single officer to determine whether this methodology is feasible for future studies. The pilot study demonstrated that continuous heart rate measurement over the course of the test officer’s shift was possible and that these data could be placed in space-time context for purposes of exploring potential stress “hot spots.” Overall, the results indicate that the methodology is both feasible and suitable for systematic studies of police stress, with the potential to advance our understanding of when, where, and why officers experience stress. Potential benefits, limitations, challenges of implementation, and future directions are discussed.
Scale effects in metal-forming friction and lubrication
Authors: Nielsen P S , Paldan N A , Calaon M , Bay N
Published: July 2011

Downscaling of metal-forming operations from macro- to microscale implies significant changes caused by size effects. Among these, the friction increases as reported by researchers using indirect test methods such as the ring-compression test and double-cup-extrusion test. In this study, a new test equipment is developed for studies of the size effect in metal-forming friction in the range from macro- to microscale. Investigations confirm a significant friction increase when downscaling. Visual inspection of the workpieces shows this to be explained by the amount of open and closed lubricant pockets.
A theoretical investigation of the use of 2k factorial analysis to determine the effects of dimensional manufacturing tolerances on the stability of hydrodynamic journal bearing systems
Authors: Ogrodnik P J , Xu W , Goodwin M J , Bancroft G A
Published: July 2011

Manufacturing tolerances and deviations from design parameters are inevitable in real hydrodynamic journal bearing systems. Normally, the stability of the system is assessed on the design parameters alone; the effects of deviations are assumed to be negligible and only the effects of gross changes are considered. In isolation, a single deviation may not demonstrate a significant effect, but in combination with other deviations, the effect may be large. This study presents a 2 k factorial analysis of the effects of manufacturing tolerances on system stability. It is further used to determine which tolerance, or combination of tolerances, is the most significant. The results show that manufacturing tolerances, and combinations thereafter, do have a significant effect on system stability, and they influence the system stability in different ways. The study also identified a region where system stability is insensitive to deviations. To enable visualization of the effects, a modified Sommerfeld number and new stability map are presented. Furthermore, the overall philosophy of using a ‘design of experiments’ approach to the determination of system stability has been vindicated. A later paper will compare the results from this study to those from experimental results.
Characterization and properties of low-friction, multilayered Cr-doped diamond-like carbon coatings prepared by pulse biased filtered cathodic arc deposition
Authors: Bujak J , Michalczewski R
Published: July 2011

The aim of the article was to investigate the effect of pulsed high-voltage bias on phase composition, surface morphology, mechanical properties, and the tribological performance of the multilayered Cr/CrN/DLC coatings prepared by the filtered cathodic arc deposition (FCAD) process. The coatings were deposited using a laboratory arc source device equipped with two macroparticle filtering systems. All coatings were deposited at substrate temperatures below 200°C. Cr/CrN/DLC multilayered coatings were analysed using X-ray photoelectron spectroscopy, a glow discharge optical emission spectrometry technique, scratch testing, nano-indentation measurements (nano-hardness and Young's modulus), and optical microscopy. Tribological tests employing a ball-on-disc tribosystem were performed in dry friction conditions in an air-conditioned room (RH 50 per cent, 23°C). The results proved that the substrate bias voltage exerts a significant influence on the mechanical properties of the Cr/CrN/DLC multilayered coatings by the changing chemical composition of the DLC top layers. With an increase of bias voltage from 2 to 6 kV, the Cr content increases from 2 to 4 per cent and the sp2/sp3 ratio decreases from 1.06 to 0.44. The Cr-doped DLC multilayered coatings were characterized by a very smooth surface, a low friction coefficient (0.13–0.15), moderate hardness (8–11 GPa), and a Young's modulus of 95–130 GPa. Due to the moderate adhesion strength of DLC top layers, their wear resistance was not satisfactory for real applications. In each tribological test, the delaminating process of the DLC layers was observed after approximately 200–300 load cycles. To improve the mechanical properties and adhesion of a DLC layer, the optimization of the transition and DLC layers is achieved by changing the parameters of the physical vapour deposition process.
A ‘Confucian Long Peace’ in pre-Western East Asia?
Authors: Kelly Robert E.
Published: July 2011

International Relations theory about East Asia has increasingly argued that East Asia before Western penetration enjoyed a protracted peace. As explanations, a Chinese military hegemony would fit realist theory fairly well, while a cultural peace based on shared Confucian norms would be a significant anomaly. A Confucian Long Peace challenges widely held, albeit Eurocentric, realist presumptions including the perils of anarchy, the arms-racing and misperception of the security dilemma, and the regularity of power balancing. This article therefore investigates, first, whether such a peace did in fact exist, and, second, whether this might be attributed to Confucianism. A cultural peace theory requires a strong anti-war cultural norm and a shared sense of community. Skepticism is established by examining three comparative cultural spaces that nonetheless did not enjoy a culturally informed peace: the classical Greek city-state system, early modern Christendom, and the contemporary Arab state system. All were deeply riven and competitive. Nevertheless, empirical investigation of the last Chinese (Qing) dynasty before the Western arrival (1644–1839) demonstrates that it was remarkably peaceful toward its Confucian neighbors, while more ‘normally’ exploiting its power asymmetry against non-Confucian ones. Process-tracing specialized Chinese practices toward fellow Confucians suggests that the low Confucian war finding emanates from cultural restraint.
Do electoral coalitions facilitate democratic consolidation in Africa?
Authors: Resnick Danielle
Published: July 2011

In a region where democratization has led to a proliferation of opposition parties, pre-electoral coalitions represent an obvious means by which to reduce excessive party fragmentation in Africa. However, this article examines whether such coalitions facilitate democratic consolidation in terms of contributing to incumbent turnovers as well as creating competitive, institutionalized party systems. Election data for all opposition coalitions formed in Africa’s electoral democracies since 2000 reveals that coalitions rarely result in incumbent defeat. In addition, I find that a sizeable share of a country’s total electoral volatility is often due to fluctuations in voting for opposition parties that enter and exit coalitions, indicating the inability of coalition members to build loyal constituencies and become institutionalized over time. I argue that this is because many of these coalitions are primarily office-seeking and consist of parties that are distinguished predominantly by the personality of their leaders rather than a distinct political programme that is relevant to the concerns of African citizens.
The Effect of Ventilation Types on Pollutant Removal in a Large Space Plant with Multiple Pollutant Sources
Authors: Huang Jeng-Ming , Hsu Shou-Ping , Wu Yu-Lieh , Chen Hung-Yuen , Wang Chi-Chuan
Published: July 2011

This study numerically investigated the influences of ventilation designs on pollutant removal in a large space with multiple pollutant sources. The types of ventilation include general displacement and local exhaust ventilation with either partitioned or non-partitioned working field. The study demonstrated that the outlet positions and outlet flow rate distribution for local exhaust ventilation are more important than those of the general displacement type. It would be more effective to design local exhaust by placing the outlets on the midstream and downstream of the machines rather than on all the machines. The results also demonstrated that the effect of local exhaust type would not be more superior to the general displacement type due to the large space in plant and multiple pollutant sources such as oil gas pollutant source, mist of metalworking fluid, etc.
Model-based Optimal Control of Outdoor Air Flow Rate of an Air-Conditioning System with Primary Air-Handling Unit
Authors: Sun Zhongwei , Wang Shengwei , Zhu Na
Published: July 2011

This paper presents a model-based outdoor air flow rate optimal control strategy for multi-zone variable air volume air-conditioning systems with the primary air-handling units. An adaptive optimisation algorithm is adopted for optimising the set point of the outdoor air flow rate to minimise the energy cost, which could compromise the energy consumption of the primary fan and the cooling energy saving by the cold outdoor air. The primary fan energy consumption can be predicted using a simplified incremental fan model and the main parameters of this model are identified online. The cooling energy saving by the outdoor air is estimated online using the enthalpies of the air streams. The lower limit of the outdoor air flow rate is determined by a CO2-based adaptive demand-controlled ventilation strategy using the dynamic multi-space equation to maintain the satisfied indoor air quality (IAQ). Tests were conducted to evaluate the performance of the control strategy applied to a practical building system in simulation environment. The results show that the proposed optimal control strategy can reduce energy consumption significantly, while maintaining a satisfactory IAQ.
How do South Australian consumers negotiate and respond to information in the media about food and nutrition?
Authors: Ward Paul R. , Henderson Julie , Coveney John , Meyer Samantha
Published: July 2011

The amount of information in the media about food and nutrition is increasing. As part of the risk society, consumers have a moral imperative to synthesize this information in order to manage their diet. This article explores how media information about food affects how consumers place trust in the food system and strategies adopted to manage conflicting nutritional information. Qualitative interviews were undertaken with 47 shoppers drawn from higher and lower socio-economic metropolitan and rural locations. There was an overriding trust in the Australian food system; however, participants talked about the impact of the large amounts of complex, confusing and often contradictory information. For some, this led to an active search for ‘truth’. For others it created uncertainty and anxiety, and for others a sense of paralysis or stasis. The findings are explored in relation to the production and consumption of risks in late modernity and the interrelationship between trust and risk.
When Are Teachers Motivated to Work Beyond Retirement Age? The Importance of Support, Change of Work Role and Money
Authors: Matthijs Bal P. , Visser Michel S.
Published: July 2011

This article investigates the factors influencing the motivation to continue working after retirement among a sample of Dutch teachers. Based on previous research, it was proposed that teachers will be motivated to work after their legal retirement age when organizational support, possibilities to change work roles and financial needs are high. Moreover, based on conversation of resources theory, it was expected that these factors would interact with each other, with the strongest effects for combinations of high support, high change of work role and high financial needs. A survey was distributed among 123 teachers working in a high school in the Netherlands. Moderated hierarchical regression analysis showed that organizational support and change of work role were positively related to motivation to continue working. However, contrary to hypothesis, organizational support and change of work role interacted negatively, such that organizational support was only positively related to motivation to continue working for those who wanted to conduct the same kind of work after their retirement. This article shows that organizations should focus on offering support to their teachers in their decisions for working after retirement, and on offering possibilities for changes in the tasks they conduct.
Aspirations to and Perceptions of Secondary Headship: Contrasting Female Teachers’ and Headteachers’ Perspectives
Authors: Smith Joan M.
Published: July 2011

This article reports on some of the findings of a wider, life history study of the factors affecting the career decisions of 40 female secondary school teachers, including 10 female headteachers. As a part of this, insights were sought into why women continue to be proportionally under-represented in secondary headship posts in UK secondary schools. Interview evidence indicated that the majority of female teachers in the study harboured a set of negative perceptions of school leadership and rejected headship as a career option. In this article, I contrast these negative perceptions with the positive picture of headship painted by the female headteachers. The headteachers in this study were driven by a strong sense of values relating to pupil achievement, and saw themselves as agents of change who needed to occupy positions of power in order to enact their principles to maximum effect. Drawing on the narratives of the 10 headteachers, I discuss their positive, agentic perspectives on school leadership, underpinned by essentially child-centred values. I argue that a more proactive approach to promoting this positive view of school leadership may be key to encouraging women (and presumably some men) who have previously rejected headship as a career, to reconsider.
Inflammation-induced up-regulation of TLR2 expression in human endothelial cells is independent of differential methylation in the TLR2 promoter CpG island
Authors: Diesel Britta , Ripoche Nadège , Risch Rebecca T , Tierling Sascha , Walter Jörn , Kiemer Alexandra K
Published: July 2011

Toll-like receptors play an important role in endothelial inflammation; however, little is known on the mechanisms regulating their expression. Differential promoter DNA methylation is an increasingly recognized mechanism that determines a switch between gene silencing and gene transcription. We hypothesized that epigenetic mechanisms are involved in the regulation of endothelial TLR2 expression because of the localization of the TLR2 promoter on a CpG-island. Resting human umbilical vein endothelial cells (HUVECs) displayed rather low TLR2 mRNA expression, while a strong expression increase occurred under inflammatory conditions. We examined the TLR2 promoter methylation pattern in resting HUVECs and compared it to cells treated either with the inflammatory cytokine TNF-α or the DNA-demethylating agent 5-azacytidine. DNA bisulfite conversion was followed by either genomic sequencing or single nucleotide primer extension (SNuPE) HPLC. Results of both techniques showed a low- or non-methylated TLR2 promoter in resting HUVECs and no alteration of the methylation pattern under inflammatory conditions. Whereas 5-azacytidine significantly increased the mRNA expression of the epigenetically regulated gene H19, TLR2 expression was not affected. Taken together, employing different methodological approaches, our data show no implication of methylation pattern changes in inflammatory induction of TLR2 expression in human endothelial cells.
Phenotypic and functional profiles of CRIg (Z39Ig)-expressing macrophages in the large intestine
Authors: Tanaka Masashi , Nagai Taku , Usami Makoto , Hasui Kazuhisa , Takao Sonshin , Matsuyama Takami
Published: July 2011

Intestinal macrophages (Mϕ) play significant roles in maintaining homeostasis by the efficient elimination of foreign particles in the large intestine. However, functional complement receptors have not been fully identified. In this study, we showed that a complement receptor of the Ig superfamily (CRIg, also known as Z39Ig), a receptor for complement fragments (C3b and iC3b), was expressed on a subset of intestinal Mϕ in murine and human large intestine. When abilities of uptake of antigens of murine CRIg+ Mϕ were examined, intestinal CRIg+ Mϕ displayed less endocytic and similar phagocytic abilities compared to resident peritoneal F4/80+CRIg− Mϕ and F4/80+CRIg+ Mϕ. Additionally, we found that a significant portion of C3b-dependent phagocytosis by large intestinal Mϕ involves CRIg, emphasizing the importance of efficient mechanisms to eliminate foreign particles in the large intestine. On the other hand, intestinal Mϕ from 2,4,6-trinitrobenzene sulfonic acid-treated mice had decreased CRIg expression but increased CD11b expression, implying some contribution to the removal of immune complexes. This study will shed new light on opsonization and phagocytosis by large intestinal Mϕ.
Sindbis virus induced phosphorylation of IRF3 in human embryonic kidney cells is not dependent on mTOR
Authors: Dhanushkodi Nisha R , Mohankumar Vidyarani , Raju Ramaswamy
Published: July 2011

The mammalian target of rapamycin (mTOR) plays critical roles in immunity. We previously showed that infection of human embryonic kidney (HEK) cells with Sindbis virus (SIN), an enveloped RNA alphavirus, profoundly suppresses Akt/mTOR signaling, and host translation late during infection. To understand how SIN mediated suppression of mTOR affects innate response, we analyzed phosphorylation of interferon regulatory factor 3 (IRF3) and expression of two antiviral genes. Here we show strong phosphorylation of IRF3, and an increase in mRNA levels for antiviral genes interferon stimulated gene (ISG)56 and interferon gamma inducible protein (IP)-10 when intracellular viral RNA levels are high during late infection. The mTOR inhibitors rapamycin and torin1 do not block, but mildly upregulate these responses. Even after prolonged treatment with Ly294002, the PI3K inhibitor only partially blocks SIN induced phosphorylation of IRF3. While Ly294002 treatment downregulated the SIN induced expression of ISG56 mRNA levels, it had no effect on SIN induced upregulation of IP-10 expression. These results point to SIN replication-mediated activation of IRF3, independent of mTOR function, when host protein synthesis is severely suppressed by virus infection.
This is Your Portfolio on Winter
Authors: Kramer Lisa A. , Weber J. Mark
Published: July 2011

This study found that people who suffer from seasonal affective disorder (SAD) displayed financial risk aversion that varied across the seasons as a function of seasonally changing affect. The SAD-sufferers had significantly stronger preferences for safe choices during the winter than non-SAD-sufferers, and they did not differ from non-SAD-sufferers during the summer. The effect of SAD on risk aversion in the winter was mediated by depression.
Do-Gooder Derogation
Authors: Minson Julia A. , Monin Benoît
Published: July 2011

Two studies document do-gooder derogation (the putting down of morally motivated others), by studying the reactions of meat eaters to vegetarians. In Study 1, 47% of participants freely associated negative terms with vegetarians and the valence of the words was negatively related to how much participants expected vegetarians to see themselves as morally superior to nonvegetarians. In Study 2, we manipulated the salience of anticipated moral reproach by varying whether participants reported these expectations before or after rating vegetarians. As predicted, participants rated vegetarians less positively after imagining their moral judgment of meat eaters. These studies empirically document the backlash reported by moral minorities and trace it back to resentment by the mainstream against feeling morally judged.
Narcissism, Well-Being, and Observer-Rated Personality Across the Lifespan
Authors: Hill Patrick L. , Roberts Brent W.
Published: July 2011

Previous studies have noted that narcissists do, in some cases, experience benefits. The current study adds to this discussion by examining whether age might moderate the links between narcissism and a self-reported benefit (life satisfaction) and an observer-reported benefit (observer ratings of personality). In a sample of college students and their family members ( N = 807), the authors demonstrate that narcissism positively correlates with life satisfaction for adolescents and emerging adults, but not for adult participants. In addition, the relationship between narcissism and observer-reported neuroticism was weakly negative for undergraduate students, but significant and positive for their mothers. Taken together, these results suggest that narcissism is more beneficial for adolescents and emerging adults than for adults. Both sets of analyses also pointed to the importance of studying narcissism as a multifaceted construct. Findings are discussed with respect to personality development theories that emphasize adult role adoption.
Emerging new approaches for the treatment of acute promyelocytic leukemia
Authors: Park Jae , Jurcic Joseph G. , Rosenblat Todd , Tallman Martin S.
Published: July 2011

The introduction of all-trans retinoic acid (ATRA) in the late 1980s combined with anthracycline-based chemotherapy has revolutionized the prognosis of acute promyelocytic leukemia (APL) with more than 90% complete response rates and cure rates of approximately 80%. The subsequent advent of arsenic trioxide (ATO) in 1990s and progress in the treatment of APL have changed its course from a highly fatal to a highly curable disease. Despite the dramatic improvement in clinical outcome of APL, treatment failure still occurs due most often to early death. Relapse has become increasingly less frequent, most commonly occurring in patients with high-risk disease. A major focus of research for the past decade has been to develop risk-adapted and rationally targeted nonchemotherapy treatment strategies to reduce treatment-related morbidity and mortality to low- and intermediate-risk or older patients while targeting more intensive or alternative therapy to those patients at most risk of relapse. In this review, emerging new approaches to APL treatment with special emphasis on strategies to reduce early deaths, risk-adapted therapy during induction, consolidation and maintenance, as well as an overview of current and future clinical trials in APL will be discussed.
Estimation of surface roughness for turning operations using image texture features
Authors: Gadelmawla E S
Published: July 2011

Measuring surface roughness is vital to quality control of the machined workpiece. In recent years, vision systems have made image analysis easier and more flexible for measuring surface roughness by using texture features. In this paper, the texture features of the grey-level co-occurrence matrix (GLCM) have been utilized to estimate surface roughness of specimens machined by turning operations. The relationship between GLCM texture features and surface roughness has been investigated to discover which texture features can be used to estimate surface roughness. The correlation coefficient between each texture feature and the arithmetic average height ( Ra) was calculated and discussed. The investigation showed that six texture features are highly correlated with Ra. Therefore, these texture features were used to estimate surface roughness for similar specimens with known values of Ra. The results showed that the maximum percentage of error between the actual Ra and the estimated Ra was about ±7 per cent.
Investigation of cutting force and temperature of end-milling Ti–6Al–4V with different minimum quantity lubrication (MQL) parameters
Authors: Liu Z Q , Cai X J , Chen M , An Q L
Published: July 2011

Different parameters (air pressure, quantity of minimum quantity lubrication (MQL) oil, position of nozzle, etc.) of an MQL system have different effects on the milling force and milling temperature. The cutting force and cutting temperature, which are closely related to lubrication and coolant, play significant roles in improving/reducing the cutting quality of a workpiece and extending/shortening the tool life.

The present work investigates experimentally the effects of different MQL parameters (air pressure, quantity of oil consumed, and position of the nozzle) in end-milling titanium alloy (Ti–6Al–4V). The experimental results show that the penetrating ability of MQL oil mist has a significant effect on the milling forces and milling temperatures. When the values of air pressure and spraying distance were either too large or too small, it is not good for oil mist to penetrate into the contact zones. The spraying angle of the nozzle position has a minimal impact on the penetration ability. Conversely, the amount of oil delivery is the most important part of MQL application. The minimum quantity of oil consumption can be obtained. The results will help to select optimum MQL parameters in end-milling titanium alloy.
Fc gamma receptor IIb on target B cells promotes rituximab internalization and reduces clinical efficacy
Authors: Lim Sean H. , Vaughan Andrew T. , Ashton-Key Margaret , Williams Emily L. , Dixon Sandra V. , Chan H. T. Claude , Beers Stephen A. , French Ruth R. , Cox Kerry L. , Davies Andrew J. , Potter Kathleen N. , Mockridge C. Ian , Oscier David G. , Johnson Peter W. M. , Cragg Mark S. , Glennie Martin J.
Published: July 2011

The anti-CD20 mAb rituximab is central to the treatment of B-cell malignancies, but resistance remains a significant problem. We recently reported that resistance could be explained, in part, by internalization of rituximab (type I anti-CD20) from the surface of certain B-cell malignancies, thus limiting engagement of natural effectors and increasing mAb consumption. Internalization of rituximab was most evident in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), but the extent of internalization was heterogeneous within each disease. Here, we show that the inhibitory FcγRIIb on target B cells promotes this process and is largely responsible for the observed heterogeneity across a range of B-cell malignancies. Internalization correlated strongly with FcγRIIb expression on normal and malignant B cells, and resulted in reduced macrophage phagocytosis of mAb-coated targets. Furthermore, transfection of FcγRIIb into FcγRIIb negative Ramos cells increased internalization of rituximab in a dose-dependent manner. Target-cell FcγRIIb promoted rituximab internalization in a cis fashion and was independent of FcγRIIb on neighboring cells. It became phosphorylated and internalized along with CD20:anti-CD20 complexes before lysosomal degradation. In MCL patients, high FcγRIIb expression predicted less durable responses after rituximab-containing regimens. Therefore, target-cell FcγRIIb provides a potential biomarker of response to type I anti-CD20 mAb.
Therapeutic efficacy of FTY720 in a rat model of NK-cell leukemia
Authors: Liao Aijun , Broeg Kathleen , Fox Todd , Tan Su-Fern , Watters Rebecca , Shah Mithun Vinod , Zhang Lucy Q. , Li Yongping , Ryland Lindsay , Yang Jun , Aliaga Cesar , Dewey Alden , Rogers Andrew , Loughran Kelly , Hirsch Leah , Jarbadan Nancy Ruth , Baab Kendall Thomas , Liao Jason , Wang Hong-Gang , Kester Mark , Desai Dhimant , Amin Shantu , Loughran Thomas P. , Liu Xin
Published: July 2011

NK-cell leukemia is a clonal expansion of NK cells. The illness can occur in an aggressive or chronic form. We studied cell lines from human and rat NK-cell leukemias (aggressive NK-cell leukemia) as well as samples from patients with chronic NK-cell leukemia to investigate pathogenic mechanisms. Here we report that Mcl-1 was overexpressed in leukemic NK cells and that knockdown of Mcl-1 induced apoptosis in these leukemic cells. In vitro treatment of human and rat NK leukemia cells with FTY720 led to caspase-dependent apoptosis and decreased Mcl-1 expression in a time- and-dose-dependent manner. These biologic effects could be inhibited by blockade of reactive oxygen species generation and the lysosomal degradation pathway. Lipidomic analyses after FTY720 treatment demonstrated elevated levels of sphingosine, which mediated apoptosis of leukemic NK cells in vitro. Importantly, systemic administration of FTY720 induced complete remission in the syngeneic Fischer rat model of NK-cell leukemia. Therapeutic efficacy was associated with decreased expression of Mcl-1 in vivo. These data demonstrate that therapeutic benefit of FTY720 may result from both altered sphingolipid metabolism as well as enhanced degradation of a key component of survival signaling.
Monoclonal antibody blockade of IL-2 receptor α during lymphopenia selectively depletes regulatory T cells in mice and humans
Authors: Mitchell Duane A. , Cui Xiuyu , Schmittling Robert J. , Sanchez-Perez Luis , Snyder David J. , Congdon Kendra L. , Archer Gary E. , Desjardins Annick , Friedman Allan H. , Friedman Henry S. , Herndon James E. , McLendon Roger E. , Reardon David A. , Vredenburgh James J. , Bigner Darell D. , Sampson John H.
Published: July 2011

Lymphodepletion augments adoptive cell transfer during antitumor immunotherapy, producing dramatic clinical responses in patients with malignant melanoma. We report that the lymphopenia induced by the chemotherapeutic agent temozolomide (TMZ) enhances vaccine-driven immune responses and significantly reduces malignant growth in an established model of murine tumorigenesis. Unexpectedly, despite the improved antitumor efficacy engendered by TMZ-induced lymphopenia, there was a treatment related increase in the frequency of immunosuppressive regulatory T cells (TRegs; P = .0006). Monoclonal antibody (mAb)–mediated inhibition of the high-affinity IL-2 receptor α (IL-2Rα/CD25) during immunotherapy in normal mice depleted TRegs (73% reduction; P = .0154) but also abolished vaccine-induced immune responses. However, during lymphodepletion, IL-2Rα blockade decreased TRegs (93% reduction; P = .0001) without impairing effector T-cell responses, to augment therapeutic antitumor efficacy (66% reduction in tumor growth; P = .0024). Of clinical relevance, we also demonstrate that anti–IL-2Rα mAb administration during recovery from lymphodepletive TMZ in patients with glioblastoma reduced TReg frequency (48% reduction; P = .0061) while permitting vaccine-stimulated antitumor effector cell expansion. To our knowledge, this is the first report of systemic antibody-mediated TReg depletion during lymphopenia and the consequent synergistic enhancement of vaccine-driven cellular responses, as well as the first demonstration that anti–IL-2Rα mAbs function differentially in nonlymphopenic versus lymphopenic contexts.
Nonoverlapping functions for Notch1 and Notch3 during murine steady-state thymic lymphopoiesis
Authors: Shi Jianjun , Fallahi Mohammad , Luo Jun-Li , Petrie Howard T.
Published: July 2011

Notch1 signaling is absolutely essential for steady-state thymic lymphopoiesis, but the role of other Notch receptors, and their potential overlap with the function of Notch1, remains unclear. Here we show that like Notch1, Notch3 is differentially expressed by progenitor thymocytes, peaking at the DN3 progenitor stage. Using mice carrying a gene-trapped allele, we show that thymic cellularity is slightly reduced in the absence of Notch3, although progression through the defined sequence of TCR-αβ development is normal, as are NKT and TCRγδ cell production. The absence of a profound effect from Notch3 deletion is not explained by residual function of the gene-trapped allele because insertion mapping suggests that the targeted allele would not encode functional signaling domains. We also show that although Notch1 and Notch3 are coexpressed on some early intrathymic progenitors, the relatively mild phenotype seen after Notch3 deletion does not result from the compensatory function of Notch1, nor does Notch3 function explain the likewise mild phenotype seen after conditional (intrathymic) deletion of Notch1. Our studies indicate that Notch1 and Notch3 carry out nonoverlapping functions during thymocyte differentiation, and that while Notch1 is absolutely required early in the lymphopoietic process, neither receptor is essential at later stages.
Serum ceruloplasmin protein expression and activity increases in iron-deficient rats and is further enhanced by higher dietary copper intake
Authors: Ranganathan Perungavur N. , Lu Yan , Jiang Lingli , Kim Changae , Collins James F.
Published: July 2011

Increases in serum and liver copper content are noted during iron deficiency in mammals, suggesting that copper-dependent processes participate during iron deprivation. One point of intersection between the 2 metals is the liver-derived, multicopper ferroxidase ceruloplasmin (Cp) that is important for iron release from certain tissues. The current study sought to explore Cp expression and activity during physiologic states in which hepatic copper loading occurs (eg, iron deficiency). Weanling rats were fed control or low iron diets containing low, normal, or high copper for ∼ 5 weeks, and parameters of iron homeostasis were measured. Liver copper increased in control and iron-deficient rats fed extra copper. Hepatic Cp mRNA levels did not change; however, serum Cp protein was higher during iron deprivation and with higher copper consumption. In-gel and spectrophotometric ferroxidase and amine oxidase assays demonstrated that Cp activity was enhanced when hepatic copper loading occurred. Interestingly, liver copper levels strongly correlated with Cp protein expression and activity. These observations support the possibility that liver copper loading increases metallation of the Cp protein, leading to increased production of the holo enzyme. Moreover, this phenomenon may play an important role in the compensatory response to maintain iron homeostasis during iron deficiency.
Regulation of fibrinolysis by S100A10 in vivo
Authors: Surette Alexi P. , Madureira Patricia A. , Phipps Kyle D. , Miller Victoria A. , Svenningsson Per , Waisman David M.
Published: July 2011

Endothelial cells form the inner lining of vascular networks and maintain blood fluidity by inhibiting blood coagulation and promoting blood clot dissolution (fibrinolysis). Plasmin, the primary fibrinolytic enzyme, is generated by the cleavage of the plasma protein, plasminogen, by its activator, tissue plasminogen activator. This reaction is regulated by plasminogen receptors at the surface of the vascular endothelial cells. Previous studies have identified the plasminogen receptor protein S100A10 as a key regulator of plasmin generation by cancer cells and macrophages. Here we examine the role of S100A10 and its annexin A2 binding partner in endothelial cell function using a homozygous S100A10-null mouse. Compared with wild-type mice, S100A10-null mice displayed increased deposition of fibrin in the vasculature and reduced clearance of batroxobin-induced vascular thrombi, suggesting a role for S100A10 in fibrinolysis in vivo. Compared with wild-type cells, endothelial cells from S100A10-null mice demonstrated a 40% reduction in plasminogen binding and plasmin generation in vitro. Furthermore, S100A10-deficient endothelial cells demonstrated impaired neovascularization of Matrigel plugs in vivo, suggesting a role for S100A10 in angiogenesis. These results establish an important role for S100A10 in the regulation of fibrinolysis and angiogenesis in vivo, suggesting S100A10 plays a critical role in endothelial cell function.
Transcriptome characterization and polymorphism detection between subspecies of big sagebrush (Artemisia tridentata)
Authors: Bajgain Prabin , Richardson Bryce A , Price Jared C , Cronn Richard C , Udall Joshua A
Published: July 2011

Background

Big sagebrush (Artemisia tridentata) is one of the most widely distributed and ecologically important shrub species in western North America. This species serves as a critical habitat and food resource for many animals and invertebrates. Habitat loss due to a combination of disturbances followed by establishment of invasive plant species is a serious threat to big sagebrush ecosystem sustainability. Lack of genomic data has limited our understanding of the evolutionary history and ecological adaptation in this species. Here, we report on the sequencing of expressed sequence tags (ESTs) and detection of single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) markers in subspecies of big sagebrush.

Results

cDNA ofA. tridentatasspp.tridentataandvaseyanawere normalized and sequenced using the 454 GS FLX Titanium pyrosequencing technology. Assembly of the reads resulted in 20,357 contig consensus sequences in ssp.tridentataand 20,250 contigs in ssp.vaseyana. A BLASTx search against the non-redundant (NR) protein database using 29,541 consensus sequences obtained from a combined assembly resulted in 21,436 sequences with significant blast alignments (≤ 1e-15). A total of 20,952 SNPs and 119 polymorphic SSRs were detected between the two subspecies. SNPs were validated through various methods including sequence capture. Validation of SNPs in different individuals uncovered a high level of nucleotide variation in EST sequences. EST sequences of a third, tetraploid subspecies (ssp.wyomingensis) obtained by Illumina sequencing were mapped to the consensus sequences of the combined 454 EST assembly. Approximately one-third of the SNPs between sspp.tridentataandvaseyanaidentified in the combined assembly were also polymorphic within the two geographically distant ssp.wyomingensissamples.

Conclusion

We have produced a large EST dataset forArtemisia tridentata, which contains a large sample of the big sagebrush leaf transcriptome. SNP mapping among the three subspecies suggest the origin of ssp.wyomingensisvia mixed ancestry. A large number of SNP and SSR markers provide the foundation for future research to address questions in big sagebrush evolution, ecological genetics, and conservation using genomic approaches.
Comparison of indicators of material circumstances in the context of an epidemiological study
Authors: Nkosi Thomas Matukala , Parent Marie-Elise , Siemiatycki Jack , Pintos Javier , Rousseau Marie-Claude
Published: July 2011

Background

Since individual-level income is difficult to collect, investigators often rely on group-based measures derived from census data. No study has assessed the use of residential property values as an indicator of individual material circumstances. We aimed to compare two proxy indicators of material circumstances, one based on residential value and the other on median census tract income, to self-reported household income.

Methods

We used data from a case-control study (1996-2002), restricting analyses to 676 residents of the Island of Montreal for whom the three indicators were available. The degree of discrepancy between the residential value index, census income, and self-reported household income - each in 5 categories - was estimated, along with overall and weighted Kappas.

Results

When comparing residential value index and census income to self-reported household income, perfect concordance was observed for 38% and 30% of subjects, respectively; very good concordance, defined as ≤ 1 category difference, was observed for 76% and 69% of subjects, respectively. When compared to self-reported household income, overall and weighted Kappas showed stronger agreement with residential value index (weighted Kappa = 0.37, 95% CI: 0.32, 0.42) than with census income (weighted Kappa = 0.25, 95% CI: 0.20, 0.30).

Conclusions

A residential value index may provide a measure of material circumstances that is closer to self-reported household income than the commonly used census income. Each indicator presents advantages and disadvantages, and their choice may depend on study objectives and feasibility.