bluuebunny/crossref_metadata_2025 huggingface dataset:
Two hosts and a caller: Analysing call sequences in a dual-host radio talkback setting
Authors: Ames Kate
Published: April 2013

Investigation into the impact of the stages of a radio call on host–caller interaction has traditionally been conducted in single host scenarios, whereby one host interacts with one caller. Further, this analysis has often been done in the context of talk radio that is designed to promote a sense of conflict in order to entertain its audience. However, what of dual or multi-host scenarios, where a number of hosts are co-participants when interacting with callers? This article considers a talkback segment within a chat-based program in which two studio-based hosts are involved in conversation with callers. It considers previous research into call sequence as applied to this scenario and reveals that rather than working to challenge the caller, the hosts work together to enable the callers to challenge the hosts but in a way that orients to sociability rather than conflict.
Antihyperglycemic Drug Gymnema sylvestre Also Shows Anticancer Potentials in Human Melanoma A375 Cells via Reactive Oxygen Species Generation and Mitochondria-Dependent Caspase Pathway
Authors: Chakraborty Debrup , Ghosh Samrat , Bishayee Kausik , Mukherjee Avinaba , Sikdar Sourav , Khuda-Bukhsh Anisur Rahman
Published: April 2013

Objective. Ethanolic extract of G ymnema sylvestre (GS) leaves is used as a potent antidiabetic drug in various systems of alternative medicine, including homeopathy. The present study was aimed at examining if GS also had anticancer potentials, and if it had, to elucidate its possible mechanism of action. Methods. We initially tested possible anticancer potential of GS on A375 cells (human skin melanoma) through MTT assay and determined cytotoxicity levels in A375 and normal liver cells; we then thoroughly studied its apoptotic effects on A375 cells through protocols such as Hoechst 33258, H2DCFDA, and rhodamine 123 staining and conducted ELISA for cytochrome c, caspase 3, and PARP activity levels; we determined the mRNA level expression of cytochrome c, caspase 3, Bcl2, Bax, PARP, ICAD, and EGFR signaling genes through semiquantitative reverse transcriptase polymerase chain reaction and conducted Western blot analysis of caspase 3 and PARP. We also analyzed cell cycle events, determined reactive oxygen species accumulation, measured annexin V-FITC/PI and rhodamine 123 intensity by flow cytometry. Results. Compared with both normal liver cells and drug-untreated A375, the mortality of GS-treated A375 cells increased in a dose-dependent manner. Additionally, GS induced nuclear DNA fragmentation and showed an increased level of mRNA expression of apoptotic signal related genes cytochrome c, caspase 3, PARP, Bax, and reduced expression level of ICAD, EGFR, and the anti-apoptotic gene Bcl2. Conclusion. Overall results indicate GS to have significant anticancer effect on A375 cells apart from its reported antidiabetic effect, indicating possibility of its palliative use in patients with symptoms of both the diseases.
Traumatic amputations
Authors: Clasper Jon , Ramasamy Arul
Published: April 2013

Traumatic amputations remain one of the most emotionally disturbing wounds of conflict, as demonstrated by their frequent use in films to illustrate the horrors of war. Unfortunately, they remain common injuries, particularly following explosions, and, in addition, many survivors require primary amputation for unsalvageable injuries or to save their life. A third group, late amputations, is being increasingly recognised, often as a result of the sequelae of complex foot injuries. This article will look at the epidemiology of these injuries and their acute management, complications and outcome.
Discerning Rejection of Technology
Authors: Rama Murthy Sudhir , Mani Monto
Published: April 2013

Technology is innate to modern society and primarily embodies human intellect. It greatly influences development, societal functioning, and sociotechnical transitions. Rapid technological advancements, made possible with advancement in science, human ingenuity, and competitive markets, provide human society with affordable and unlimited choice. A society can be viewed, with an individual as the fundamental unit, or as a community, or state/nation. In one view, sustainability can be viewed through a matrix of societal, economic, and environmental configurations associated with the three societal levels. Technological advancement and complexity can either remain simple and amenable to the user or, as emerging in recent years, may daunt the user to keep away. While the phenomenon of technology adoption (acceptance) in society has been well appreciated, the increasingly characteristic phenomenon of technology rejection is yet to be understood and studied. Technology rejection is not merely a negation of its acceptance, and hence requires to be discerned carefully. Rejection also does not imply in its totality, but varies in terms of its kind and/or intensiveness. While rejection is discernable at all these three levels of society, this study remains focused at the level of the user (individual). It attempts to discern rejection of technology and discusses its distinctness from technology acceptance through an exhaustive literature study. The article initially discusses the technology–society nexus and provides a preliminary technology–user interface model leading to a detailed discussion into the determinants of technology rejection.
Examining the Relationship Between Key Visual Characteristics of Urban Plazas and Aesthetic Response
Authors: Ferdous Farhana
Published: April 2013

Urban plazas as public spaces occur in every town and city around the world; however, some plazas are more user-friendly and successful than others. This study examined that “aesthetics” also have a significant impact to determine the extent of success of urban plazas and urban open spaces in combination with other quantitative factors, such as centrality of location, provision of services, and amenities. In addition, this research sought to focus on the relationship between visual characteristics and aesthetic response to urban plazas. Photo elicitation and focus interviews were conducted to identify key visual characteristics as well as to examine aesthetic responses to those characteristics. Eight plazas and designed urban open spaces in Dhaka, Bangladesh, featured in the main study, and research methods included a structured questionnaire to collect data and used semantic differential rating scales as a measuring instrument. Outcomes from this research indicate that a positive aesthetic response was linked to specific visual characteristics of urban plazas, suggesting that this information could be used to more effectively refurbish existing and design new urban plazas as public spaces.
Intercultural Capital
Authors: Pöllmann Andreas
Published: April 2013

Drawing from Pierre Bourdieu’s conceptual “toolbox”, this article focuses on intercultural capital as an increasingly significant type of cultural capital and marker of sociocultural distinction. It first introduces different forms of intercultural capital, with a particular interest in the potential benefits of its embodiment. Subsequently, the critical question as to why some people can be considered as better positioned to realize intercultural capital than others is being addressed. The remainder of the discussion looks at possible operational “measures” for the concept of intercultural capital and how these may be applied to examine the conditions and potential impact of its realization.
Empirical Test of an Agricultural Landscape Model
Authors: Cooke Ira R. , Mattison Elizabeth H. A. , Audsley Eric , Bailey Alison P. , Freckleton Robert P. , Graves Anil R. , Morris Joe , Queenborough Simon A. , Sandars Daniel L. , Siriwardena Gavin M. , Trawick Paul , Watkinson Andrew R. , Sutherland William J.
Published: April 2013

Developing models to predict the effects of social and economic change on agricultural landscapes is an important challenge. Model development often involves making decisions about which aspects of the system require detailed description and which are reasonably insensitive to the assumptions. However, important components of the system are often left out because parameter estimates are unavailable. In particular, measurements of the relative influence of different objectives, such as risk, environmental management, on farmer decision making, have proven difficult to quantify. We describe a model that can make predictions of land use on the basis of profit alone or with the inclusion of explicit additional objectives. Importantly, our model is specifically designed to use parameter estimates for additional objectives obtained via farmer interviews. By statistically comparing the outputs of this model with a large farm-level land-use data set, we show that cropping patterns in the United Kingdom contain a significant contribution from farmer’s preference for objectives other than profit. In particular, we found that risk aversion had an effect on the accuracy of model predictions, whereas preference for a particular number of crops grown was less important. While nonprofit objectives have frequently been identified as factors in farmers’ decision making, our results take this analysis further by demonstrating the relationship between these preferences and actual cropping patterns.
Spirometry: step by step
Authors: Moore V.C.
Published: April 2013

Educational aims

To give an overview of what spirometry is, how to perform it and how to interpret it.

To discuss the quality criteria to produce acceptable and reproducible results.

To discuss the use of spirometry in the workplace.

Spirometry is easy to perform once trained and can be performed anywhere. It is useful for detecting early change and disease progression. Quality is important to ensure useful and reproducible results, otherwise results may be incorrectly interpreted. Training from a reputable centre should be undertaken to ensure the measures are understood as well as how to get the best results out of the patient.
A bright single-cell resolution live imaging reporter of Notch signaling in the mouse
Authors: Nowotschin Sonja , Xenopoulos Panagiotis , Schrode Nadine , Hadjantonakis Anna-Katerina
Published: April 2013

Background

Live imaging provides an essential methodology for understanding complex and dynamic cell behaviors and their underlying molecular mechanisms. Genetically-encoded reporter expressing mouse strains are an important tool for use in live imaging experiments. Such reporter strains can be engineered by placing cis-regulatory elements of interest to direct the expression of desired reporter genes. If these cis-regulatory elements are downstream targets, and thus activated as a consequence of signaling pathway activation, such reporters can provide read-outs of the signaling status of a cell. The Notch signaling pathway is an evolutionary conserved pathway operating in multiple developmental processes as well as being the basis for several congenital diseases. The transcription factor CBF1 is a central evolutionarily conserved component of the Notch signaling pathway. It binds the active form of the Notch receptor (NICD) and subsequently binds to cis-regulatory regions (CBF1 binding sites) in the promoters of Notch responsive genes. In this way, CBF1 binding sites represent a good target for the design of a Notch signaling reporter.

Results

To generate a single-cell resolution Notch signaling reporter, we used a CBF responsive element to direct the expression of a nuclear-localized fluorescent protein. To do this, we linked 4 copies of a consensus CBF1 binding site to the basal simian virus 40 (SV40) promoter, placed this cassette in front of a fluorescent protein fusion comprising human histone H2B linked to the yellow fluorescent protein (YFP) Venus, one of the brightest available YFPs. We used the CBF:H2B-Venus construct to generate both transgenic embryonic mouse stem (ES) cell lines and a strain of transgenic mice that would report Notch signaling activity.

Conclusion

By using multiple CBF1 binding sites together with a subcellular-localized, genetically-encoded fluorescent protein, H2B-Venus, we have generated a transgenic strain of mice that faithfully recapitulates Notch signaling at single-cell resolution. This is the first mouse reporter strain in which individual cells transducing a Notch signal can be visualized. The improved resolution of this reporter makes it ideal for live imaging developmental processes regulated by the Notch signaling pathway as well as a short-term lineage tracer of Notch expressing cells due to the perdurance of the fluorescent reporter. Taken together, the CBF:H2B-Venus mouse strain is a unique tool to study and understand the morphogenetic events regulated by the Notch signaling pathway.
Ectopic expression of AtPAD4broadens resistance of soybean to soybean cyst and root-knot nematodes
Authors: Youssef Reham M , MacDonald Margaret H , Brewer Eric P , Bauchan Gary R , Kim Kyung-Hwan , Matthews Benjamin F
Published: April 2013

Background

The gene encoding PAD4 (PHYTOALEXIN-DEFICIENT4) is required in Arabidopsis for expression of several genes involved in the defense response to Pseudomonas syringae pv. maculicola. AtPAD4 (Arabidopsis thaliana PAD4) encodes a lipase-like protein that plays a regulatory role mediating salicylic acid signaling.

Results

We expressed the gene encoding AtPAD4 in soybean roots of composite plants to test the ability of AtPAD4 to deter plant parasitic nematode development. The transformed roots were challenged with two different plant parasitic nematode genera represented by soybean cyst nematode (SCN; Heterodera glycines) and root-knot nematode (RKN; Meloidogyne incognita). Expression of AtPAD4 in soybean roots decreased the number of mature SCN females 35 days after inoculation by 68 percent. Similarly, soybean roots expressing AtPAD4 exhibited 77 percent fewer galls when challenged with RKN.

Conclusions

Our experiments show that AtPAD4 can be used in an economically important crop, soybean, to provide a measure of resistance to two different genera of nematodes.
Changes in age distribution of hemorrhagic fever with renal syndrome: an implication of China’s expanded program of immunization
Authors: He Xiaozhou , Wang Shiwen , Huang Xiaoxia , Wang Xiaofang
Published: April 2013

Background

Vaccination against hemorrhagic fever with renal syndrome (HFRS) has been applied successfully for more than 20 years in China, and since 2008, the government has implemented the Expanded Program of Immunization (EPI) in regions with high incidence. In this study, we analyzed the EPI-related changes in age distribution in reported cases of HFRS and proposed new recommendations for prevention and control of the disease.

Methods

Data relating to incidence of HFRS, geographical location and age distribution were collected through the China Information System for Disease Control and Prevention (CISDCP) from 2005 to 2010. Excel and SPSS 18.0 software, χ2 tests and descriptive methodology were used for analysis of the data.

Results

A total 75 434 HFRS cases were reported in 28 provinces in China between 2005 and 2010. The majority of HFRS cases occurred in adults aged 30 to 55 and this group accounted for 68.3% of the total. With the implementation of the immunization program, HFRS age distribution has clearly changed in recent years. The proportion of HFRS cases among individuals targeted by EPI (16–60 years of age) decreased from 86.9% in 2005 to 81.9% in 2010. However, the proportion of cases among the non-vaccinated group aged <16 and >60 had increased from 13.1% in 2005 to 18.1% in 2010. Notably, in the >60 age group the proportion rose from 8.8% in 2005 to 14.7% in 2010. These differences were statistically significant.

Conclusion

HFRS vaccination has played an important role in HFRS control and prevention in China. However, since the proportion of HFRS cases over 60 years old has increased significantly since EPI was implemented, it is recommended that the age limit for vaccination be reconsidered. This finding may have practical implications for more effective HFRS vaccination in the future.
Stable expression plasmids for Streptomyces based on a toxin-antitoxin system
Authors: Sevillano Laura , Díaz Margarita , Santamaría Ramón I
Published: April 2013

Background

Bacteria included in the genus Streptomyces exhibit several attractive characteristics that make them adequate hosts for the heterologous expression of proteins. One of them is that some of its species have a high secretion capacity and hence the protein of interest could be released to the culture supernatant, facilitating downstream processing. To date, all the expression vectors described for these bacteria contain antibiotic resistance genes as selection markers. However, the use of antibiotics to produce proteins at industrial level is currently becoming more restricted owing to the possibility of contamination of the final product. In this report, we describe the use of the S. lividans yefM/yoeBsl toxin-antitoxin system to develop a stable plasmid expression system.

Results

In order to use the yefM/yoeBsl system to stabilize expression plasmids in Streptomyces, a S. lividans mutant strain that contained only the toxin gene (yoeBsl) in its genome and the antitoxin gene (yefMsl) located in a temperature-sensitive plasmid was constructed and used as host. This strain was transformed with an expression plasmid harbouring both the antitoxin gene and the gene encoding the protein of interest. Thus, after elimination of the temperature-sensitive plasmid, only cells with the expression plasmid were able to survive. On using this system, two proteins - an α-amylase from S. griseus and a xylanase from S. halstedii - were overproduced without the addition of antibiotic to the culture medium. The production of both proteins was high, even after long incubations (8 days), and after serial subcultures, confirming the stability of the plasmids without antibiotic selection.

Conclusions

This is the first report that describes the use of a toxin-antitoxin system to maintain high -copy plasmids in Streptomyces. This finding could be a valuable tool for using Streptomyces as a host to produce proteins at the industrial and pharmaceutical levels without the use of antibiotics in the production step.
An N-terminal domain helical motif of Prototype Foamy Virus Gag with dual functions essential for particle egress and viral infectivity
Authors: Reh Juliane , Stange Annett , Götz Anne , Rönitz Marlene , Große Arend , Lindemann Dirk
Published: April 2013

Background

Foamy viruses (FVs) have developed a unique budding strategy within the retrovirus family. FV release requires co-expression and a highly specific interaction between capsid (Gag) and glycoprotein (Env), which cannot be complemented by heterologous Env proteins. The interaction domain in FV Env has been mapped in greater detail and resides mainly in the N-terminal tip of the cytoplasmic domain of the Env leader peptide subunit. In contrast, the corresponding domain within Gag is less well defined. Previous investigations suggest that it is located within the N-terminal part of the protein.

Results

Here we characterized additional Gag interaction determinants of the prototype FV (PFV) isolate using a combination of particle release, GST pull-down and single cycle infectivity analysis assays. Our results demonstrate that a minimal PFV Gag protein comprising the N-terminal 129 aa was released into the supernatant, whereas proteins lacking this domain failed to do so. Fine mapping of domains within the N-terminus of PFV Gag revealed that the N-terminal 10 aa of PFV Gag were dispensable for viral replication. In contrast, larger deletions or structurally deleterious point mutations in C-terminally adjacent sequences predicted to harbor a helical region abolished particle egress and Gag – Env protein interaction. Pull-down assays, using proteins of mammalian and prokaryotic origin, support the previous hypothesis of a direct interaction of both PFV proteins without requirement for cellular cofactors and suggest a potential direct contact of Env through this N-terminal Gag domain. Furthermore, analysis of point mutants within this domain in context of PFV vector particles indicates additional particle release-independent functions for this structure in viral replication by directly affecting virion infectivity.

Conclusions

Thus, our results demonstrate not only a critical function of an N-terminal PFV Gag motif for the essential capsid - glycoprotein interaction required for virus budding but also point out additional functions that affect virion infectivity.
Stress responses, vitagenes and hormesis as critical determinants in aging and longevity: Mitochondria as a “chi”
Authors: Cornelius Carolin , Perrotta Rosario , Graziano Antonio , Calabrese Edward J , Calabrese Vittorio
Published: April 2013

Understanding mechanisms of aging and determinants of life span will help to reduce age-related morbidity and facilitate healthy aging. Average lifespan has increased over the last centuries, as a consequence of medical and environmental factors, but maximal life span remains unchanged. Extension of maximal life span is currently possible in animal models with measures such as genetic manipulations and caloric restriction (CR). CR appears to prolong life by reducing reactive oxygen species (ROS)-mediated oxidative damage. But ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways. By sensing the intracellular nutrient and energy status, the functional state of mitochondria, and the concentration of ROS produced in mitochondria, the longevity network regulates life span across species by coordinating information flow along its convergent, divergent and multiply branched signaling pathways, including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–response, challenges long-standing beliefs about the nature of the dose–response in a lowdose zone, having the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Here we focus on possible signaling mechanisms involved in the activation of vitagenes resulting in enhanced defense against energy and stress resistance homeostasis dysiruption with consequent impact on longevity processes.
Toxicity and outcomes of thoracic re-irradiation using stereotactic body radiation therapy (SBRT)
Authors: Reyngold Marsha , Wu Abraham J , McLane Amanda , Zhang Zhigang , Hsu Meier , Stein Nicholas F , Zhou Ying , Ho Alice Y , Rosenzweig Kenneth E , Yorke Ellen D , Rimner Andreas
Published: April 2013

Background

Patients treated for a thoracic malignancy carry a significant risk of developing other lung lesions. Locoregional control of intrathoracic recurrences is challenging due to the impact of prior therapies on normal tissues. We examined the safety and efficacy of thoracic re-irradiation using high-precision image-guided stereotactic body radiation therapy (SBRT).

Methods

Records of 39 patients with prior intra-thoracic conventionally fractionated radiation therapy (RT) who underwent SBRT for a subsequent primary, recurrent or metastatic lung tumor from 11/2004 to 7/2011 were retrospectively reviewed.

Results

Median dose of prior RT was 61 Gy (range 30–80 Gy). Median biologically effective prescription dose (α/β = 10) (BED10) of SBRT was 70.4 Gy (range 42.6-180 Gy). With a median followup of 12.6 months among survivors, 1- and 2-year actuarial local progression-free survival (LPFS) were 77% and 64%, respectively. Median recurrence-free (RFS) and overall survival (OS) were 13.8 and 22.0 months, respectively. Patients without overlap of high-dose regions of the primary and re-irradiation plans were more likely to receive a BED10 ≥100 Gy, which was associated with higher LPFS (hazard ratio, [HR] = 0.18, p = 0.04), RFS ([HR] = 0.31, p = 0.038) and OS ([HR] = 0.25, p = 0.014). Grade 2 and 3 pulmonary toxicity was observed in 18% and 5% of patients, respectively. Other grade 2–4 toxicities included chest wall pain in 18%, fatigue in 15% and skin toxicity in 5%. No grade 5 events occurred.

Conclusions

SBRT can be safely and successfully administered to patients with prior thoracic RT. Dose reduction for cases with direct overlap of successive radiation fields results in acceptable re-treatment toxicity profile.
Nadir CA-125 level as prognosis indicator of high-grade serous ovarian cancer
Authors: Xu Xia , Wang Yan , Wang Fang , Jia Lizhou , Zhou Yiqin , Deng Fei , Qu Junwei , Zhou Bifang , Meng Aifeng , Fu Bole , Chen Xiaoxiang , Qian Zhiying , Wang Jinhua
Published: April 2013

Purpose

The capacity of nadir CA-125 levels to predict the prognosis of epithelial ovarian cancer remains controversial. This study aimed to explore whether the nadir CA-125 serum levels could predict the durations of overall survival (OS) and progression free survival (PFS) in patients with high-grade serous ovarian cancer (HG-SOC) from the USA and PRC.

Materials and methods

A total of 616 HG-SOC patients from the MD Anderson Cancer Center (MDACC, USA) between 1990 and 2011 were retrospectively analyzed. The results of 262 cases from the Jiangsu Institute of Cancer Research (JICR, PRC) between 1992 and 2011 were used to validate the MDACC data. The CA-125 immunohistochemistry assay was performed on 280 tissue specimens. The Cox proportional hazards model and the log-rank test were used to assess the associations between the clinicopathological characteristics and duration of survival.

Results

The nadir CA-125 level was an independent predictor of OS and PFS (p < 0.01 for both) in the MDACC patients. Lower nadir CA-125 levels (≤10 U/mL) were associated with longer OS and PFS (median: 61.2 and 16.8 months with 95% CI: 52.0–72.4 and 14.0–19.6 months, respectively) than their counterparts with shorter OS and PFS (median: 49.2 and 10.5 months with 95% CI: 41.7–56.7 and 6.9–14.1 months, respectively). The nadir CA-125 levels in JICR patients were similarly independent when predicting the OS and PFS (p < 0.01 for both). Nadir CA-125 levels less than or equal to 10 U/mL were associated with longer OS and PFS (median: 59.9 and 15.5 months with 95% CI: 49.7–70.1 and 10.6–20.4 months, respectively), as compared with those more than 10 U/mL (median: 42.0 and 9.0 months with 95% CI: 34.4–49.7 and 6.6–11.2 months, respectively). Baseline serum CA-125 levels, but not the CA-125 expression in tissues, were associated with the OS and PFS of HG-SOC patients in the MDACC and JICR groups. However, these values were not independent. Nadir CA-125 levels were not associated with the tumor burden based on second-look surgery (p = 0.09). Patients who achieved a pathologic complete response had longer OS and PFS (median: 73.7 and 20.7 months with 95% CI: 63.7–83.7 and 9.5–31.9 months, respectively) than those with residual tumors (median: 34.6 and 10.6 months with 95% CI: 6.9–62.3 and 4.9–16.3 months, respectively).

Conclusions

The nadir CA-125 level was an independent predictor of OS and PFS in HG-SOC patients. Further prospective studies are required to clinically optimize the chances for a complete clinical response of HG-SOC cases with higher CA-125 levels (>10 U/mL) at the end of primary treatment.
The effects of the semirecumbent position on hemodynamic status in patients on invasive mechanical ventilation: prospective randomized multivariable analysis
Authors: Göcze Ivan , Strenge Felix , Zeman Florian , Creutzenberg Marcus , Graf Bernhard M , Schlitt Hans J , Bein Thomas
Published: April 2013

Introduction

Adopting the 45° semirecumbent position in mechanically ventilated critically ill patients is recommended, as it has been shown to reduce the incidence of ventilator-associated pneumonia. Although the benefits to the respiratory system are clear, it is not known whether elevating the head of the bed results in hemodynamic instability. We examined the effect of head of bed elevation (HBE) on hemodynamic status and investigated the factors that influence mean arterial pressure (MAP) and central venous oxygen saturation (ScvO2) when patients were positioned at 0°, 30°, and 45°.

Methods

Two hundred hemodynamically stable adults on invasive mechanical ventilation admitted to a multidisciplinary surgical intensive care unit were recruited. Patients' characteristics included catecholamine and sedative doses, the original angle of head of bed elevation (HBE), the level of positive end expiratory pressure (PEEP), duration and mode of mechanical ventilation. A sequence of HBE positions (0°, 30°, and 45°) was adopted in random order, and MAP and ScvO2 were measured at each position. Patients acted as their own controls. The influence of degree of HBE and of the covariables on MAP and ScvO2 was analyzed by using liner mixed models. Additionally, uni- and multivariable logistic regression models were used to indentify risk factors for hypotension during HBE, defined as MAP <65 mmHg.

Results

Changing HBE from supine to 45° caused significant reductions in MAP (from 83.8 mmHg to 71.1 mmHg, P < 0.001) and ScvO2 (76.1% to 74.3%, P < 0.001). Multivariable modeling revealed that mode and duration of mechanical ventilation, the norepinephrine dose, and HBE had statistically significant influences. Pressure-controlled ventilation was the most influential risk factor for hypotension when HBE was 45° (odds ratio (OR) 2.33, 95% confidence interval (CI), 1.23 to 4.76, P = 0.017).

Conclusions

HBE to the 45° position is associated with significant decreases in MAP and ScvO2 in mechanically ventilated patients. Pressure-controlled ventilation, higher simplified acute physiology (SAPS II) score, sedation, high catecholamine, and PEEP requirements were identified as independent risk factors for hypotension after backrest elevation. Patients at risk may need positioning at 20° to 30° to overcome the negative effects of HBE, especially in the early phase of intensive care unit admission.
Development and validation of a robust automated analysis of plasma phospholipid fatty acids for metabolic phenotyping of large epidemiological studies
Authors: Wang Laura Yun , Summerhill Keith , Rodriguez-Canas Carmen , Mather Ian , Patel Pinal , Eiden Michael , Young Stephen , Forouhi Nita G , Koulman Albert
Published: April 2013

A fully automated, high-throughput method was developed to profile the fatty acids of phospholipids from human plasma samples for application to a large epidemiological sample set (n > 25,000). We report here on the data obtained for the quality-control materials used with the first 860 batches, and the validation process used. The method consists of two robotic systems combined with gas chromatography, performing lipid extraction, phospholipid isolation, hydrolysis and derivatization to fatty-acid methyl esters, and on-line analysis. This is the first report showing that fatty-acid profiling is an achievable strategy for metabolic phenotyping in very large epidemiological and genetic studies.
Shipmate Networks and Black Identities in the Marriage Files of Montevideo, 1768–1803
Authors: Borucki Alex
Published: April 2013

The experience of enslaved Africans in the Atlantic crossing redefined the meanings of the nomenclature emerging from the slave trade. Under violent conditions, captives developed networks with shipmates on board slave vessels. These ties survived for decades if shipmates stayed together in the same region, as they did in Montevideo. Shipmate ties represented a living connection for Africans not only with their experience in the Atlantic crossing but also with their homelands. Shipmates provided support to their fellows when they needed trusted associates, as the marriage files of Montevideo clearly demonstrate. Enslaved Africans commonly asked fellow shipmates to testify about their past when marrying into the Catholic Church. Marriage files contain data on the routes Africans took across the Atlantic and the Americas. They indicate the origins of the groom, bride, and witnesses, their shared itineraries, and how these itineraries changed over time. Thus they reveal patterns of geographical mobility and networks created by common experiences. Marriage files can be easily quantified, which allows us to track historical trends. At the same time, each file offers a unique story. A close reading of these stories contextualizes the experiences of slaves in the Catholic Americas and underscores common patterns in ways that lie beyond quantification.
MODERNIST Poetry's ENCOUNTER WITH EPISTEMIC MODELS OF VALUE
Authors: Altieri Charles
Published: April 2013

This article elaborates on the dilemma faced by modernist poets in seeking to define values in an intellectual context that was post-Romantic and post-epistemic. Pound and Stevens, for example, reacted strongly against the ways that Romantic writers had tried to tie the rhetorical elaboration of values to precise descriptions, as if description could still support values. Victorian writing tended to experience the effort to ground value in fact as a source of constant irony, given that the desired values refused to become manifest. Positivist philosophy and its literary allies asserted that values simply occupy a different and much more unstable realm than do facts. Having established these historical premises, the essay then concentrates on how Stevens and Pound, in challenging positivist assumptions, sought two different sources of value, each of which, however, placed value within the domain of experience. Pound's approach was Nietzschean, in that it was Nietzsche who had demonstrated how valuing precedes determinations about fact. Pound's capacity to make his early lyric poems seem to come out of nowhere and depend on linguistic invention alone for their power is shown to be a realization of Nietzschean strategies. Meanwhile, Stevens in his early work tried out a range of attitudes that seemed to him capable of defying fact, especially by approximating aphoristic self-assertion. Finally, Pound in his Cantos and Stevens from the late thirties onward developed self-reflexive versions of an analogical model of valuing that, as Dora Zhang has shown, shaped the response of novelists (James, Proust, and Woolf) to the same dilemma that modernist poets were facing. The essay closes with a reading of section XII of “An Ordinary Evening in New Haven” as a demonstration of Stevens's analogical mode.
Kuwait’s Modern Spectacle
Authors: al-Nakib Farah
Published: April 2013

This article examines the making of modern Kuwait City between 1950 and 1980 by complicating the popular “rags to riches” paradigm that permeates both official state discourse and much of the literature on Kuwait’s urban development. It argues that the “modern” city that replaced the demolished pre-oil town during the first three decades of oil urbanization was more of a spectacle than a lived reality. Although the state exerted much effort and expense between 1951 and 1971 in planning for the development of a capital city to celebrate Kuwait’s newfound prosperity and progress, certain unexpected consequences of rapid oil wealth significantly hindered the production of the rational and usable city the state was hoping for. As such, state development projects from the early 1960s onward focused more on how the city looked than on how it actually worked, creating an urban spectacle that gave a distinct impression that Kuwait was a rapidly modernizing city despite the fact that, behind the scenes, it was stagnating. Al-Nakib’s article examines particular development projects produced between 1950 and the Iraqi invasion of 1990 that contributed to this spectacle of modernity and have led to the misguided though common assumption that oil modernization in Kuwait was a linear, smooth, successful, and virtually overnight leap from ancient to modern, chaos to order.
The Politics and Ideology of Urban Development in Iraq’s Oil City
Authors: Bet-Shlimon Arbella
Published: April 2013

Bet-Shlimon’s article considers the question of how, in the urban arena of Kirkuk, oil acted as a catalyst for development projects in which political, economic, and ideological threads were inextricably intertwined. It contends that the presence of oil in Kirkuk created certain factors that shaped both the trajectory of urban development and its political implications. One of these factors was the presence of many foreign, especially British, workers and executives of the Iraq Petroleum Company (IPC). The company’s size also meant that a large number of the city’s residents worked for this foreign-owned enterprise, leading to labor organization and interventions by the company in order to promote capitalist ideals. Second, the fact that the oil industry had greater access to resources and materials than the Kirkuk municipality allowed the IPC to spearhead housing, water, and other infrastructural projects. Finally, as the site where Iraq’s oil wealth was produced, Kirkuk was of vital importance to the Iraqi and British governments, both of whom pressured the IPC to act in ways that would benefit their interests. Throughout these projects and the interactions that accompanied them, the IPC, British government, and Iraqi government operated on the assumption that urban development could counter the influence of communism and lead to the attainment of modernity.
A dynamic code of dorsal neural tube genes regulates the segregation between neurogenic and melanogenic neural crest cells
Authors: Nitzan Erez , Krispin Shlomo , Pfaltzgraff Elise R. , Klar Avihu , Labosky Patricia A. , Kalcheim Chaya
Published: April 2013

Understanding when and how multipotent progenitors segregate into diverse fates is a key question during embryonic development. The neural crest (NC) is an exemplary model system with which to investigate the dynamics of progenitor cell specification, as it generates a multitude of derivatives. Based on ‘in ovo’ lineage analysis, we previously suggested an early fate restriction of premigratory trunk NC to generate neural versus melanogenic fates, yet the timing of fate segregation and the underlying mechanisms remained unknown. Analysis of progenitors expressing a Foxd3 reporter reveals that prospective melanoblasts downregulate Foxd3 and have already segregated from neural lineages before emigration. When this downregulation is prevented, late-emigrating avian precursors fail to upregulate the melanogenic markers Mitf and MC/1 and the guidance receptor Ednrb2, generating instead glial cells that express P0 and Fabp. In this context, Foxd3 lies downstream of Snail2 and Sox9, constituting a minimal network upstream of Mitf and Ednrb2 to link melanogenic specification with migration. Consistent with the gain-of-function data in avians, loss of Foxd3 function in mouse NC results in ectopic melanogenesis in the dorsal tube and sensory ganglia. Altogether, Foxd3 is part of a dynamically expressed gene network that is necessary and sufficient to regulate fate decisions in premigratory NC. Their timely downregulation in the dorsal neural tube is thus necessary for the switch between neural and melanocytic phases of NC development.
Maternal Dead-End1 is required for vegetal cortical microtubule assembly during Xenopus axis specification
Authors: Mei Wenyan , Jin Zhigang , Lai Fangfang , Schwend Tyler , Houston Douglas W. , King Mary Lou , Yang Jing
Published: April 2013

Vertebrate axis specification is an evolutionarily conserved developmental process that relies on asymmetric activation of Wnt signaling and subsequent organizer formation on the future dorsal side of the embryo. Although roles of Wnt signaling during organizer formation have been studied extensively, it is unclear how the Wnt pathway is asymmetrically activated. In Xenopus and zebrafish, the Wnt pathway is triggered by dorsal determinants, which are translocated from the vegetal pole to the future dorsal side of the embryo shortly after fertilization. The transport of dorsal determinants requires a unique microtubule network formed in the vegetal cortex shortly after fertilization. However, molecular mechanisms governing the formation of vegetal cortical microtubule arrays are not fully understood. Here we report that Dead-End 1 (Dnd1), an RNA-binding protein required for primordial germ cell development during later stages of embryogenesis, is essential for Xenopus axis specification. We show that knockdown of maternal Dnd1 specifically interferes with the formation of vegetal cortical microtubules. This, in turn, impairs translocation of dorsal determinants, the initiation of Wnt signaling, organizer formation, and ultimately results in ventralized embryos. Furthermore, we found that Dnd1 binds to a uridine-rich sequence in the 3′-UTR of trim36, a vegetally localized maternal RNA essential for vegetal cortical microtubule assembly. Dnd1 anchors trim36 to the vegetal cortex in the egg, promoting high concentrations of Trim36 protein there. Our work thus demonstrates a novel and surprising function for Dnd1 during early development and provides an important link between Dnd1, mRNA localization, the microtubule cytoskeleton and axis specification.
The role of membrane-trafficking small GTPases in the regulation of autophagy
Authors: Bento Carla F. , Puri Claudia , Moreau Kevin , Rubinsztein David C.
Published: April 2013

Macroautophagy is a bulk degradation process characterised by the formation of double-membrane vesicles, called autophagosomes, which deliver cytoplasmic substrates for degradation in the lysosome. It has become increasingly clear that autophagy intersects with multiple steps of the endocytic and exocytic pathways, sharing many molecular players. A number of Rab and Arf GTPases that are involved in the regulation of the secretory and the endocytic membrane trafficking pathways, have been shown to play key roles in autophagy, adding a new level of complexity to its regulation. Studying the regulation of autophagy by small GTPases that are known to be involved in membrane trafficking is becoming a scientific hotspot and may provide answers to various crucial questions currently debated in the autophagy field, such as the origins of the autophagosomal membrane. Thus, this Commentary highlights the recent advances on the regulation of autophagy by membrane-trafficking small GTPases (Rab, Arf and RalB GTPases) and discusses their putative roles in the regulation of autophagosome formation, autophagosome-dependent exocytosis and autophagosome-lysosome fusion.
Context affects nestmate recognition errors in honey bees and stingless bees
Authors: Couvillon Margaret J. , Segers Francisca H.I.D. , Cooper-Bowman Roseanne , Truslove Gemma , Nascimento Daniela L. , Nascimento Fabio S. , Ratnieks Francis L.W.
Published: April 2013

Nestmate recognition studies, where a discriminator first recognises and then behaviourally discriminates (accept/reject) another individual, have used a variety of methodologies and contexts. This is potentially problematic because recognition errors in discrimination behaviour are predicted to be context-dependent. Here we compare the recognition decisions (accept/reject) of discriminators in two eusocial bees, Apis mellifera and Tetragonisca angustula, under different contexts. These contexts include natural guards at the hive entrance (control); natural guards held in plastic test arenas away from the hive entrance that vary either in the presence or absence of colony odour or the presence or absence of an additional nestmate discriminator; and, for the honey bee, the inside of the nest. For both honey bees and stingless bee guards, total recognition errors of behavioural discrimination made by guards (% nestmates rejected + % non-nestmates accepted) are much lower at the colony entrance (honey bee: 30.9%; stingless bee: 33.3%) than in the test arenas (honey bee: 60-86%; stingless bee: 61-81%; p < 0.001 for both). Within the test arenas, the presence of colony odour specifically reduced the total recognition errors in honey bees, although this reduction still fell short of bringing error levels down to what was found at the colony entrance. Lastly, in honey bees, the data show that the in-nest collective behavioural discrimination by c. 30 workers that contact an intruder is insufficient to achieve error-free recognition and is not as effective as the discrimination by guards at the entrance. Overall, these data demonstrate that context is a significant factor in a discriminators's ability to make appropriate recognition decisions and, additionally, should be considered when designing recognition study methodologies.
How does the "ancient" asexual Philodina roseola (Rotifera: Bdelloidea) handle potential UVB-induced mutations?
Authors: Fischer Claus , Ahlrichs Wilko H. , Buma Anita G. J. , van de Poll Willem H. , Bininda-Emonds Olaf R. P.
Published: April 2013

Like other obligate asexuals, bdelloid rotifers are expected to suffer from degradation of their genomes through processes including the accumulation of deleterious mutations. However, sequence-based analyses in this regard remain inconclusive. Instead of looking for historical footprints of mutations in these ancient asexuals, we directly examined the susceptibility and ability to repair point mutations by the bdelloid Philodina roseola Ehrenberg, 1832 by inducing cyclobutane-pyrimidine dimers (CPDs) via exposure to UVB radiation (280-320 nm). For comparison, we performed analogous experiments with the facultative asexual monogonont rotifer Brachionus rubens Ehrenberg, 1838. Different strategies were found for the two species. P. roseola appeared to shield itself from CPD induction through uncharacterized UV-absorbing compounds and, except for the genome reconstruction that occurs after desiccation, was largely unable to repair UVB-induced damage. By contrast, B. rubens was more susceptible to UVB-irradiation, but could repair all induced damage in about two hours. In addition, whereas UV-irradiation had a significant negative impact on the reproductive output of P. roseola, and especially so after desiccation, that of B. rubens was unaffected. Although the strategy of P. roseola might suffice under natural conditions where UVB-irradiation is less intense, the lack of any immediate CPD repair mechanisms in this species remains perplexing. It remains to be investigated how typical these results are for bdelloids as a group and therefore how reliant these animals are on desiccation-dependent genome repair to correct potential DNA damage given their obligate asexual lifestyle.
A Theoretical Framework for Real Time Release with NIR and Chemometrics
Authors: Skibsted Erik , Westerhuis Johan , Smilde Age , Witte D.T.
Published: April 2013

The increasing use of NIR and process data acquisition systems in industry facilitates the realisation of real time release (RTR). RTR is a system of pharmaceutical product release that provides assurance of the intended product quality based on the information collected during the manufacturing process and on the compliance with specific GMP requirements.1 RTR is product and process specific. The development of a RTR system begins with risk assessment and involves the use of designed experiments to determine how important process parameters afect critical quality attributes of a final product. Through process understanding and control of process variability, consistent quality may be achieved, and the need for final quality tests reduced or eliminated. In this column the authors summarise their approach to using NIR for successful RTR.