bluuebunny/crossref_metadata_2025 huggingface dataset:
Microstructure evolution of ZK40 magnesium alloy during high strain rate compression deformation at elevated temperatures
Authors: Yan H-G , Wu Y-Z , Chen J-H , Zhu S-Q , Liu Z-W , Tian J
Published: June 2010

Microstructure evolution of the homogenised ZK40 magnesium alloy was investigated during compression in the temperature range of 250–400°C and at the strain rate range of 0·01–50 s−1. At a higher strain rate (⩾10 s−1), dynamic recrystallisation developed extensively at grain boundaries and twins, resulting in a more homogeneous microstructure than the other conditions. The hot deformation characteristics of ZK40 exhibited an abnormal relationship with the strain rate, i.e., the hot workability increased with increasing the strain rate. However, the dynamic recrystallisation grain size was almost the same with increasing the temperature at the strain rate of 10 s−1, while it increased obviously at the strain rates of 20 and 50 s−1. Therefore, hot deformation at the strain rate of 10 s−1 and temperature range of 250–400°C was desirable and feasible for the ZK40 alloy.
Infection as a comorbidity of COPD
Authors: Sethi S.
Published: June 2010

The normal lung has several defence mechanisms to deal with microorganisms. Lower respiratory infections in the absence of lung disease are therefore relatively infrequent as compared with upper respiratory tract infections in healthy adults. In the setting of chronic obstructive pulmonary disease (COPD), lower respiratory tract infections, both acute and chronic, occur with increased frequency. As these infections contribute considerably to the clinical course of the patient with COPD, they constitute a significant comorbidity in COPD. Recurrent acute infections by bacterial and/or viral pathogens are now clearly linked with the occurrence of exacerbations of COPD. In addition, the occurrence of pneumonia in COPD has received considerable recent attention as it appears to be increased by the use of inhaled corticosteroids. The role of chronic infection in the pathogenesis of COPD is an active area of research with several different types of pathogens potentially implicated. Additionally, COPD patients with HIV infection have a more rapidly progressive decline in lung function than non-HIV-infected patients. Enhanced understanding of the host–pathogen interaction is needed to better prevent and treat respiratory tract infection in COPD.
Discharge planning and management for patients with chronic respiratory failure using home mechanical ventilation
Authors: Piper A.
Published: June 2010

Educational aims

To identify some of the clinical issues associated with the safe and effective care of the patient using home ventilatory support.

To recognise those patients and clinical situations where problems related to home ventilation are more likely to occur.

To assist in developing discharge plans to improve quality of care for patients using long-term home ventilation.

The use of home mechanical ventilation (HMV) to manage chronic respiratory failure (CRF) is becoming increasingly prevalent, and is usually delivered by means of a mask interface and pressure preset device. Although the transition from initial acclimatisation and prescription of ventilation to long-term home use is fairly straightforward for many patients with respiratory failure, issues such as nutrition, progressive ventilatory dependence and psychosocial problems can arise. Anticipating these problems and identifying resources and procedures that can reduce the negative impact of complex care carried out in the home is important for the long-term success and safety of HMV.
Medical aerosols: ins and outs of inhalation therapy
Authors: Radic S. , Salonini E.
Published: June 2010

The “Medical aerosols: ins and outs of inhalation therapy” ERS School Course was held in Amsterdam, the Netherlands in November 2009. The course aimed to provide state-of-the-art knowledge in understanding basic aerosol science, key issues of treating diseased airways, patient-related factors influencing efficacy of aerosol therapy and specific pharmacokinetic/dynamic issues related to aerosol medicine. The course also emphasised regulatory issues and important factors on how to instruct and monitor the technical skills of patients.

ERS School Courses are aimed at all health professionals within the respiratory field and provide participants with high-quality information and hands-on session, leading to improvements in the daily clinical practice of all attendants. An important aspect of School Courses is the chance for delegates to meet and discuss their current clinical problems with experts in the field and also network with other delegates and make new contacts from around the world. This review gives the perspectives of two delegates from the course working in the field of aerosol medicine.
Transcriptome analysis in non-model species: a new method for the analysis of heterologous hybridization on microarrays
Authors: Degletagne Cyril , Keime Céline , Rey Benjamin , de Dinechin Marc , Forcheron Fabien , Chuchana Paul , Jouventin Pierre , Gautier Christian , Duchamp Claude
Published: June 2010

Background

Recent developments in high-throughput methods of analyzing transcriptomic profiles are promising for many areas of biology, including ecophysiology. However, although commercial microarrays are available for most common laboratory models, transcriptome analysis in non-traditional model species still remains a challenge. Indeed, the signal resulting from heterologous hybridization is low and difficult to interpret because of the weak complementarity between probe and target sequences, especially when no microarray dedicated to a genetically close species is available.

Results

We show here that transcriptome analysis in a species genetically distant from laboratory models is made possible by usingMAXRS, a new method of analyzing heterologous hybridization on microarrays. This method takes advantage of the design of several commercial microarrays, with different probes targeting the same transcript. To illustrate and test this method, we analyzed the transcriptome of king penguin pectoralis muscle hybridized to Affymetrix chicken microarrays, two organisms separated by an evolutionary distance of approximately 100 million years. The differential gene expression observed between different physiological situations computed byMAXRSwas confirmed by real-time PCR on 10 genes out of 11 tested.

Conclusions

MAXRSappears to be an appropriate method for gene expression analysis under heterologous hybridization conditions.
Escherichia coli phylogenetic group determination and its application in the identification of the major animal source of fecal contamination
Authors: Carlos Camila , Pires Mathias M , Stoppe Nancy C , Hachich Elayse M , Sato Maria IZ , Gomes Tânia AT , Amaral Luiz A , Ottoboni Laura MM
Published: June 2010

Background

Escherichia coli strains are commonly found in the gut microflora of warm-blooded animals. These strains can be assigned to one of the four main phylogenetic groups, A, B1, B2 and D, which can be divided into seven subgroups (A0, A1, B1, B22, B23, D1 and D2), according to the combination of the three genetic markers chuA, yjaA and DNA fragment TspE4.C2. Distinct studies have demonstrated that these phylo-groups differ in the presence of virulence factors, ecological niches and life-history. Therefore, the aim of this work was to analyze the distribution of these E. coli phylo-groups in 94 human strains, 13 chicken strains, 50 cow strains, 16 goat strains, 39 pig strains and 29 sheep strains and to verify the potential of this analysis to investigate the source of fecal contamination.

Results

The results indicated that the distribution of phylogenetic groups, subgroups and genetic markers is non-random in the hosts analyzed. Strains from group B1 were present in all hosts analyzed but were more prevalent in cow, goat and sheep samples. Subgroup B23 was only found in human samples. The diversity and the similarity indexes have indicated a similarity between the E. coli population structure of human and pig samples and among cow, goat and sheep samples. Correspondence analysis using contingence tables of subgroups, groups and genetic markers frequencies allowed the visualization of the differences among animal samples and the identification of the animal source of an external validation set. The classifier tools Binary logistic regression and Partial least square -- discriminant analysis, using the genetic markers profile of the strains, differentiated the herbivorous from the omnivorous strains, with an average error rate of 17%.

Conclusions

This is the first work, as far as we are aware, that identifies the major source of fecal contamination of a pool of strains instead of a unique strain. We concluded that the analysis of the E. coli population structure can be useful as a supplementary bacterial source tracking tool.
Primary myxofibrosarcoma of the parotid: case report
Authors: Li Xu , Chen Xin , Shi Zhao-Hui , Chen Yang , Ye Jing , Qiao Li , Qiu Jian-Hua
Published: June 2010

Background

Myxofibrosarcoma is common in the extremities of elderly people and is characterized by a high frequency of local recurrence.

Case presentation

We report a 37 year old female who presented with a 4-month history of facial pain and a 3-month history of painful progressive swelling in the preauricular area. She underwent a total parotidectomy. The tumor was histopathologically and immunohistochemically diagnosed as a low-grade myxofibrosarcoma. The patient was free of disease 9 months after surgery with uneventful post-operative clinical course.

Conclusions

Parotid area swelling should always alert doctors. To our knowledge, this is the first case of parotid myxofibrosarcoma. It should be added to the differential diagnosis of diseases of the parotid. We have to recognize this disease and seek adequate treatment for it.
Rapid Health and Needs assessments after disasters: a systematic review
Authors: Korteweg Helena A , van Bokhoven Irene , Yzermans CJ , Grievink Linda
Published: June 2010

Background

Publichealth care providers, stakeholders and policy makers request a rapid insight into health status and needs of the affected population after disasters. To our knowledge, there is no standardized rapid assessment tool for European countries. The aim of this article is to describe existing tools used internationally and analyze them for the development of a workable rapid assessment.

Methods

A review was conducted, including original studies concerning a rapid health and/or needs assessment. The studies used were published between 1980 and 2009. The electronic databasesof Medline, Embase, SciSearch and Psychinfo were used.

Results

Thirty-three studies were included for this review. The majority of the studies was of US origin and in most cases related to natural disasters, especially concerning the weather. In eighteen studies an assessment was conducted using a structured questionnaire, eleven studies used registries and four used both methods. Questionnaires were primarily used to asses the health needs, while data records were used to assess the health status of disaster victims.

Conclusions

Methods most commonly used were face to face interviews and data extracted from existing registries. Ideally, a rapid assessment tool is needed which does not add to the burden of disaster victims. In this perspective, the use of existing medical registries in combination with a brief questionnaire in the aftermath of disasters is the most promising. Since there is an increasing need for such a tool this approach needs further examination.
Positive Association between Aspirin-Intolerant Asthma and Genetic Polymorphisms of FSIP1: a Case-Case Study
Authors: Kim Jason Yongha , Kim Jeong Hyun , Park Tae Joon , Bae Joon Seol , Lee Jin Sol , Pasaje Charisse Flerida , Park Byung Lae , Cheong Hyun Sub , Park Jong-Sook , Park Sung-Woo , Uh Soo-Taek , Kim Mi-Kyeong , Choi Inseon S , Cho Sang Heon , Choi Byoung Whui , Park Choon-Sik , Shin Hyoung Doo
Published: June 2010

Background

Aspirin-intolerant asthma (AIA), which is caused by non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, causes lung inflammation and reversal bronchi reduction, leading to difficulty in breathing. Aspirin is known to affect various parts inside human body, ranging from lung to spermatogenesis. FSIP1, also known as HDS10, is a recently discovered gene that encodes fibrous sheath interacting protein 1, and is regulated by amyloid beta precursor protein (APP). Recently, it has been reported that a peptide derived from APP is cleaved by α disintegrin and metalloproteinase 33 (ADAM33), which is an asthma susceptibility gene. It has also been known that the FSIP1 gene is expressed in airway epithelium.

Objectives

Aim of this study is to find out whether FSIP1 polymorphisms affect the onset of AIA in Korean population, since it is known that AIA is genetically affected by various genes.

Methods

We conducted association study between 66 single nucleotide polymorphisms (SNPs) of the FSIP1 gene and AIA in total of 592 Korean subjects including 163 AIA and 429 aspirin-tolerant asthma (ATA) patients. Associations between polymorphisms of FSIP1 and AIA were analyzed with sex, smoking status, atopy, and body mass index (BMI) as covariates.

Results

Initially, 18 SNPs and 4 haplotypes showed associations with AIA. However, after correcting the data for multiple testing, only one SNP showed an association with AIA (corrected P-value = 0.03, OR = 1.63, 95% CI = 1.23-2.16), showing increased susceptibility to AIA compared with that of ATA cases. Our findings suggest that FSIP1 gene might be a susceptibility gene for aspirin intolerance in asthmatics.

Conclusion

Although our findings did not suggest that SNPs of FSIP1 had an effect on the reversibility of lung function abnormalities in AIA patients, they did show significant evidence of association between the variants in FSIP1 and AIA occurrence among asthmatics in a Korean population.
The transcription factor 7-like 2 (TCF7L2) polymorphism may be associated with focal arteriolar narrowing in Caucasians with hypertension or without diabetes: the ARIC Study
Authors: Yan Yu , Klein Ronald , Heiss Gerardo , Girman Cynthia J , Lange Ethan M , Klein Barbara E , Rose Kathryn M , Boerwinkle Eric , Pankow James S , Brancati Frederick L , Ballantyne Christie M , Köttgen Anna , North Kari E
Published: June 2010

Background

Transcription factor 7-like 2 (TCF7L2) has emerged as a consistently replicated susceptibility gene for type 2 diabetes, however, whether the TCF7L2 gene also has similar effects on the retinal microvasculature is less clear. We therefore aimed to investigate the association between the transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism and retinal microvascular phenotypes in the Atherosclerosis Risk in Communities (ARIC) Study (1993-1995).

Methods

This was a population-based, cross-sectional study of 10,320 middle-aged African American (n = 2,199) and Caucasian (n = 8,121) men and women selected from four United States communities to examine the association between TCF7L2 rs7903146 polymorphism and retinal microvascular signs (retinopathy, focal arteriolar narrowing, arteriovenous nicking, arteriolar and venular calibers). Photographs on one randomly selected eye were graded for presence of retinal microvascular signs and used to measure retinal vessel calibres.

Results

After adjusting for age, sex, study center, mean arterial blood pressure, total serum cholesterol, triglycerides, and other covariates, few associations of TCF7L2 rs7903146 and retinal microvascular signs were noted. TCF7L2 rs7903146 T risk allele was significantly associated with focal arteriolar narrowing in Caucasians with hypertension [odds ratio (OR)CT vs. CC (95% CI) = 1.25 (1.09-1.44); ORTT vs. CC = 1.56 (1.18-2.06); P = 0.002] and in Caucasians without diabetes [OR CT vs. CC = 1.18 (1.06-1.32); OR TT vs. CC = 1.40 (1.12, 1.75); P = 0.003]. No significant association of the TCF7L2 rs7903146 polymorphism and retinal vascular signs was noted among African American individuals.

Conclusions

TCF7L2 rs7903146 is not consistently associated with retinal microvascular signs. However, we report an association between the TCF7L2 rs7903146 polymorphism and focal arteriolar narrowing in Caucasians with hypertension or without diabetes. Further research in other large, population-based studies is needed to replicate these findings.
High cell density cultivation and recombinant protein production with Escherichia coli in a rocking-motion-type bioreactor
Authors: Glazyrina Julia , Materne Eva-Maria , Dreher Thomas , Storm Dirk , Junne Stefan , Adams Thorsten , Greller Gerhard , Neubauer Peter
Published: June 2010

Background

Single-use rocking-motion-type bag bioreactors provide advantages compared to standard stirred tank bioreactors by decreased contamination risks, reduction of cleaning and sterilization time, lower investment costs, and simple and cheaper validation. Currently, they are widely used for cell cultures although their use for small and medium scale production of recombinant proteins with microbial hosts might be very attractive. However, the utilization of rocking- or wave-induced motion-type bioreactors for fast growing aerobic microbes is limited because of their lower oxygen mass transfer rate. A conventional approach to reduce the oxygen demand of a culture is the fed-batch technology. New developments, such as the BIOSTAT® CultiBag RM system pave the way for applying advanced fed-batch control strategies also in rocking-motion-type bioreactors. Alternatively, internal substrate delivery systems such as EnBase® Flo provide an opportunity for adopting simple to use fed-batch-type strategies to shaken cultures. Here, we investigate the possibilities which both strategies offer in view of high cell density cultivation of E. coli and recombinant protein production.

Results

Cultivation of E. coli in the BIOSTAT® CultiBag RM system in a conventional batch mode without control yielded an optical density (OD600) of 3 to 4 which is comparable to shake flasks. The culture runs into oxygen limitation. In a glucose limited fed-batch culture with an exponential feed and oxygen pulsing, the culture grew fully aerobically to an OD600 of 60 (20 g L-1 cell dry weight). By the use of an internal controlled glucose delivery system, EnBase® Flo, OD600 of 30 (10 g L-1 cell dry weight) is obtained without the demand of computer controlled external nutrient supply. EnBase® Flo also worked well in the CultiBag RM system with a recombinant E. coli RB791 strain expressing a heterologous alcohol dehydrogenase (ADH) to very high levels, indicating that the enzyme based feed supply strategy functions well for recombinant protein production also in a rocking-motion-type bioreactor.

Conclusions

Rocking-motion-type bioreactors may provide an interesting alternative to standard cultivation in bioreactors for cultivation of bacteria and recombinant protein production. The BIOSTAT® Cultibag RM system with the single-use sensors and advanced control system paves the way for the fed-batch technology also to rocking-motion-type bioreactors. It is possible to reach cell densities which are far above shake flasks and typical for stirred tank reactors with the improved oxygen transfer rate. For more simple applications the EnBase® Flo method offers an easy and robust solution for rocking-motion-systems which do not have such advanced control possibilities.
Reptin is required for the transcription of telomerase reverse transcriptase and over-expressed in gastric cancer
Authors: Li Wenjuan , Zeng Jiping , Li Qiao , Zhao Li , Liu Tiantian , Björkholm Magnus , Jia Jihui , Xu Dawei
Published: June 2010

Background

Telomerase is activated in oncogenesis, which confers an immortal phenotype to cancer cells. The AAA + ATPase Reptin is required for telomerase biogenesis by maintaining telomerase RNA (hTER) stability and is aberrantly expressed in certain cancers. Given its role in chromatin remodeling and transcription regulation, we determined the effect of Reptin on the transcription of the telomerase reverse transcriptase (hTERT) gene, a key component of the telomerase complex and its expression in gastric cancer.

Results

Knocking down Reptin or its partner Pontin using small interfering RNA in gastric and cervical cancer cells led to significant decreases in hTERT mRNA, but hTERT promoter activity was inhibited in only Reptin-depleted cells. Reptin interacted with the c-MYC oncoprotein and its stimulatory effect on the hTERT promoter was significantly dependent on functional E-boxes in the promoter. Moreover, Reptin bound to the hTERT proximal promoter and the loss of the Reptin occupancy led to dissociation of c-MYC from the hTERT promoter in Reptin-depleted cells. Reptin inhibition dramatically impaired clonogenic potential of gastric cancer cells by inducing cell growtharrest and over-expression of Reptin was observed in primary gastric cancer specimens.

Conclusions

The hTERT gene is a direct target of Reptin, and hTERT transcription requires constitutive expression of Reptin and its cooperation with c-MYC. Thus, Reptin regulates telomerase at two different levels. This finding, together with the requirementof Reptin for the clonogenic potential of cancer cells and its over-expression in gastriccancer and other solid tumors, suggests that Reptin may be a putative therapeutic target.
Knock down of HIF-1α in glioma cells reduces migration in vitro and invasion in vivo and impairs their ability to form tumor spheres
Authors: Méndez Olga , Zavadil Jiri , Esencay Mine , Lukyanov Yevgeniy , Santovasi Daniel , Wang Shu-Chi , Newcomb Elizabeth W , Zagzag David
Published: June 2010

Background

Glioblastoma (GBM) is the most common and malignant primary intracranial human neoplasm. GBMs are characterized by the presence of extensive areas of necrosis and hypoxia. Hypoxia and its master regulator, hypoxia inducible factor 1 (HIF-1) play a key role in glioma invasion.

Results

To further elucidate the functional role of HIF-1α in glioma cell migration in vitro and in invasion in vivo, we used a shRNA approach to knock down HIF-1α expression complemented with genome-wide expression profiling, performed in both normoxic and hypoxic conditions. Our data show that knock down of HIF-1α in glioma cells significantly impairs their migration in vitro as well as their ability to invade into the brain parenchyma in vivo. Next, we assessed the role that HIF-1α plays in maintaining the characteristics of cancer stem cells (CSCs). By using the tumor sphere forming assay, we demonstrate that HIF-1α plays a role in the survival and self-renewal potential of CSCs. Finally, expression profiling experiments in glioma cells provided detailed insight into a broad range of specific biological pathways and processes downstream of HIF-1α. We discuss the role of these processes in the migratory and invasive properties, as well as the stem cell biology of glioblastomas

Conclusions

Our data show that knock down of HIF-1α in human and murine glioma cells impairs their migration in vitro and their invasion in vivo. In addition, our data suggest that HIF-1α plays a role in the survival and self-renewal potential of CSCs and identify genes that might further elucidate the role of HIF-1α in tumor migration, invasion and stem cell biology.
Measuring the neighborhood environment: associations with young girls' energy intake and expenditure in a cross-sectional study
Authors: Leung Cindy W , Gregorich Steven E , Laraia Barbara A , Kushi Lawrence H , Yen Irene H
Published: June 2010

Background

Neighborhood environments affect children's health outcomes. Observational methods used to assess neighborhoods can be categorized as indirect, intermediate, or direct. Direct methods, involving in-person audits of the neighborhoods conducted by trained observers, are recognized as an accurate representation of current neighborhood conditions. The authors investigated the associations of various neighborhood characteristics with young girls' diet and physical activity.

Methods

This study is based on a subset of participants in the Cohort Study of Young Girls' Nutrition, Environment and Transitions (CYGNET). In-person street audits were conducted within 215 girls' residential neighborhoods using a modified St. Louis Audit Tool. From the street audit data, exploratory factor analysis revealed five neighborhood scales: "mixed residential and commercial," "food and retail," "recreation," "walkability," and "physical disorder." A Neighborhood Deprivation Index was also derived from census data. The authors investigated if the five neighborhood scales and the Neighborhood Deprivation Index were associated with quartiles of total energy intake and expenditure (metabolic equivalent (MET) hours/week) at baseline, and whether any of these associations were modified by race/ethnicity.

Results

After adjustment for demographic characteristics, there was an inverse association between prevalence of "food and retail" destinations and total energy intake (for a one quartile increase, OR = 0.84, 95% CI 0.74, 0.96). Positive associations were also observed between the "recreation" and "walkability" scales with physical activity among Hispanic/Latina girls (for a one quartile increase in MET, OR = 1.94, 95% CI 1.31, 2.88 for recreation; OR = 1.71, 95% CI 1.11, 2.63 for walkability). Among African-American girls, there was an inverse association between "physical disorder" and physical activity (OR = 0.31, 95% CI 0.12, 0.80).

Conclusions

These results suggest that neighborhood food and retail availability may be inversely associated with young girls' energy intakes in contrast to other studies' findings that focused on adults. There is considerable variation in neighborhoods' influences on young girls' physical activity behaviors, particularly for young girls of different racial/ethnic backgrounds.
5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention: summary of key research and implications for policy and practice ‐ Introduction
Authors: Kort Rodney
Published: June 2010

19‐22 July 2009, 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2009), Cape Town, South Africa
5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention: summary of key research and implications for policy and practice – Basic sciences
Authors: Mascolinli Mark , Kort Rodney
Published: June 2010

Basic science studies at the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2009) provided important new information that has implications not only for treatment, but also for better understanding the complex dynamics of HIV infection, epidemiology, and the impact of biology and genetics on vulnerability to HIV infection, disease progression and the risk of vertical transmission. There was renewed interest in strategies on how to eliminate residual viremia, bolster the immune system and potentially achieve viral eradication given recent evidence that antiretroviral therapy (ART) is effective at minimizing viral reservoirs if administered early in acute infection.

19‐22 July 2009, 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2009), Cape Town, South Africa
5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention: summary of key research and implications for policy and practice – Clinical sciences
Authors: Mascolinli Mark , Kort Rodney
Published: June 2010

Studies in several sub‐Saharan African countries demonstrated that the expansion of antiretroviral therapy (ART) access is not only beneficial for people living with HIV, but also results in significant declines in tuberculosis and malaria incidence and prevalence, bolstering arguments for earlier and increased ART access and contributing to a growing understanding of co‐epidemic dynamics. Several studies demonstrated that using standard triple‐drug ART in resource‐limited settings can reduce vertical transmission by as much as less than 1% if continued throughout breastfeeding.

The Nevirapine Resistance Study (NEVEREST) results provided proof of concept that nevirapine could be used as part of a paediatric second‐line regimen, despite exposure to nevirapine prophylaxis for vertical transmission, following successful suppression on a lopinavir/ritonavir‐based regimen. A South African study found that high pre‐treatment levels of inflammatory and coagulation markers were strong predictors of death, reflecting similar findings in high‐income countries and reinforcing the shift towards viewing HIV as a chronic, inflammatory disease. An early study of a new integrase inhibitor (S/GSK1349572) indicated strong potency and limited cross‐resistance with raltegravir, the only integrase inhibitor currently approved for treatment.

19‐22 July 2009, 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2009), Cape Town, South Africa
Bedside measurement of changes in lung impedance to monitor alveolar ventilation in dependent and non-dependent parts by electrical impedance tomography during a positive end-expiratory pressure trial in mechanically ventilated intensive care unit patients
Authors: Bikker Ido G , Leonhardt Steffen , Reis Miranda Dinis , Bakker Jan , Gommers Diederik
Published: June 2010

Introduction

As it becomes clear that mechanical ventilation can exaggerate lung injury, individual titration of ventilator settings is of special interest. Electrical impedance tomography (EIT) has been proposed as a bedside, regional monitoring tool to guide these settings. In the present study we evaluate the use of ventilation distribution change maps (ΔfEIT maps) in intensive care unit (ICU) patients with or without lung disorders during a standardized decremental positive end-expiratory pressure (PEEP) trial.

Methods

Functional EIT (fEIT) images and PaO2/FiO2 ratios were obtained at four PEEP levels (15 to 10 to 5 to 0 cm H2O) in 14 ICU patients with or without lung disorders. Patients were pressure-controlled ventilated with constant driving pressure. fEIT images made before each reduction in PEEP were subtracted from those recorded after each PEEP step to evaluate regional increase/decrease in tidal impedance in each EIT pixel (ΔfEIT maps).

Results

The response of regional tidal impedance to PEEP showed a significant difference from 15 to 10 (P = 0.002) and from 10 to 5 (P = 0.001) between patients with and without lung disorders. Tidal impedance increased only in the non-dependent parts in patients without lung disorders after decreasing PEEP from 15 to 10 cm H2O, whereas it decreased at the other PEEP steps in both groups.

Conclusions

During a decremental PEEP trial in ICU patients, EIT measurements performed just above the diaphragm clearly visualize improvement and loss of ventilation in dependent and non-dependent parts, at the bedside in the individual patient.
Composition and regulation of maternal and zygotic transcriptomes reflects species-specific reproductive mode
Authors: Shen-Orr Shai S , Pilpel Yitzhak , Hunter Craig P
Published: June 2010

Background

Early embryos contain mRNA transcripts expressed from two distinct origins; those expressed from the mother's genome and deposited in the oocyte (maternal) and those expressed from the embryo's genome after fertilization (zygotic). The transition from maternal to zygotic control occurs at different times in different animals according to the extent and form of maternal contributions, which likely reflect evolutionary and ecological forces. Maternally deposited transcripts rely on post-transcriptional regulatory mechanisms for precise spatial and temporal expression in the embryo, whereas zygotic transcripts can use both transcriptional and post-transcriptional regulatory mechanisms. The differences in maternal contributions between animals may be associated with gene regulatory changes detectable by the size and complexity of the associated regulatory regions.

Results

We have used genomic data to identify and compare maternal and/or zygotic expressed genes from six different animals and find evidence for selection acting to shape gene regulatory architecture in thousands of genes. We find that mammalian maternal genes are enriched for complex regulatory regions, suggesting an increase in expression specificity, while egg-laying animals are enriched for maternal genes that lack transcriptional specificity.

Conclusions

We propose that this lack of specificity for maternal expression in egg-laying animals indicates that a large fraction of maternal genes are expressed non-functionally, providing only supplemental nutritional content to the developing embryo. These results provide clear predictive criteria for analysis of additional genomes.
Nothing in Evolution Makes Sense Except in the Light of DNA
Authors: Kalinowski Steven T. , Leonard Mary J. , Andrews Tessa M.
Published: June 2010

Natural selection is one of the most important concepts for biology students to understand, but students frequently have misconceptions regarding how natural selection operates. Many of these misconceptions, such as a belief in “Lamarckian” evolution, are based on a misunderstanding of inheritance. In this essay, we argue that evolution instructors should clarify the genetic basis of natural selection by discussing examples of DNA sequences that affect fitness. Such examples are useful for showing how natural selection works, for establishing connections between genetics and evolution, and for creating cognitive conflict within students having misconceptions. We describe several examples of genes that instructors might use during lectures, and present preliminary evidence from our classroom that an evolution curriculum rich in DNA sequences is effective at reducing student misconceptions of natural selection.
Editorial: CD8 T cells cut back on calcium intake in the lungs
Authors: Fulton Ross B , Varga Steven M
Published: June 2010

The commentary focuses on the regulation of effector T cells in the lung.
Editorial: Biased agonism in chemoattractant receptor signaling
Authors: Ye Richard D
Published: June 2010

Selective induction of neutrophil responses by chemoattractants reflects biased agonistic activities of the ligands and is modulated at several levels in chemoattractant receptor signaling.
Phase I Study of Single-Agent Anti–Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates
Authors: Brahmer Julie R. , Drake Charles G. , Wollner Ira , Powderly John D. , Picus Joel , Sharfman William H. , Stankevich Elizabeth , Pons Alice , Salay Theresa M. , McMiller Tracee L. , Gilson Marta M. , Wang Changyu , Selby Mark , Taube Janis M. , Anders Robert , Chen Lieping , Korman Alan J. , Pardoll Drew M. , Lowy Israel , Topalian Suzanne L.
Published: June 2010

Purpose

Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti–PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates.

Patients and Methods

Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non–small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti–PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy.

Results

Anti–PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti–PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells ≥ 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment.

Conclusion

Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.
J. B. S. Haldane's Last Years: His Life and Work in India (1957–1964)
Authors: Dronamraju Krishna
Published: June 2010

J. B. S. Haldane (1892–1964) was an outstanding scientist and a polymath who contributed significantly to physiology, genetics, biochemistry, statistics, biometry, cosmology, and philosophy, although he himself possessed no formal qualifications in any branch of science. His early science training was provided by his father, Oxford University physiologist J. S. Haldane, and the rest was self-taught. The author came to know him well as his student during his last years, which were spent in India (1957–1964). Haldane's unique intellectual qualities and the research undertaken by his associates in India during those years are described.
Evaluation of a Point-of-Care Blood Analyzer for Use in Determination of Select Hematological Indices in the Seminole Killifish
Authors: DiMaggio Matthew A , Ohs Cortney L , Petty B Denise
Published: June 2010

Conventional methodologies for hematological analysis are gradually being replaced with new technologies. Point-of-care blood analyzers are both efficient and user friendly. As the use of such technologies becomes more pervasive in current literature, investigations into the accuracy and reliability of point-of-care analyzers for evaluating fish hematological indices are warranted. The purpose of this study was to evaluate a point-of-care blood analyzer (i-STAT®) and chosen cartridge (E3+) against conventionally accepted instrumentation (CAI) for use in determination of hematocrit, sodium, potassium, and chloride values in Seminole killifish Fundulus seminolis. Whole blood, a whole-blood heparin dilution, and undiluted plasma were analyzed in the point-of-care unit to determine hematological parameters of interest. The Bland–Altman method for assessing agreement between two methods of clinical measurement was used as well as calculations of correlation coefficients and two-tailed paired Student's t-tests. Generally, mean values obtained from CAI were higher than those from the i-STAT using whole blood, heparin-diluted blood, and plasma. Significant differences (P ≤ 0.05) were observed between all means analyzed by t-tests. When compared with CAI results, none of the blood index values generated by the i-STAT in these experiments could be considered reliable.
Avian use of introduced plants: Ornithologist records illuminate interspecific associations and research needs
Authors: Aslan Clare E. , Rejmánek Marcel
Published: June 2010

Introduced species have the potential to impact processes central to the organization of ecological communities. Although hundreds of nonnative plant species have naturalized in the United States, only a small percentage of these have been studied in their new biotic communities. Their interactions with resident (native and introduced) bird species remain largely unexplored. As a group, citizen scientists such as ornithologists possess a wide range of experiences. They may offer insights into the prevalence and form of bird interactions with nonnative plants on a broad geographic scale. We surveyed 173 ornithologists from four U.S. states, asking them to report observations of bird interactions with nonnative plants. The primary goal of the survey was to obtain information useful in guiding future empirical research. In all, 1143 unique bird–plant interactions were reported, involving 99 plant taxa and 168 bird species. Forty‐seven percent of reported interactions concerned potential dispersal (feeding on seeds or fruits). Remaining “habitat interactions” involved bird use of plants for nesting, perching, woodpecking, gleaning, and other activities. We utilized detrended correspondence analysis to ordinate birds with respect to the plants they reportedly utilize. Results illuminate the new guilds formed by these interactions. We assessed the existing level of knowledge about invasiveness of those plants reported most often in feeding interactions, identifying information gaps for biological invasions research priority. To exemplify the usefulness of citizen science data, we utilized survey results to guide field research on invasiveness in some of these plant species and observed both qualitatively and quantitatively strong agreement between survey reports and our empirical data. Questionnaire reports are therefore heuristically informative for the fields of both avian ecology and invasion biology.
Simultaneous modeling of habitat suitability, occupancy, and relative abundance: African elephants in Zimbabwe
Authors: Martin Julien , Chamaillé-Jammes Simon , Nichols James D. , Fritz Hervé , Hines James E. , Fonnesbeck Christopher J. , MacKenzie Darryl I. , Bailey Larissa L.
Published: June 2010

The recent development of statistical models such as dynamic site occupancy models provides the opportunity to address fairly complex management and conservation problems with relatively simple models. However, surprisingly few empirical studies have simultaneously modeled habitat suitability and occupancy status of organisms over large landscapes for management purposes. Joint modeling of these components is particularly important in the context of management of wild populations, as it provides a more coherent framework to investigate the population dynamics of organisms in space and time for the application of management decision tools. We applied such an approach to the study of water hole use by African elephants in Hwange National Park, Zimbabwe. Here we show how such methodology may be implemented and derive estimates of annual transition probabilities among three dry‐season states for water holes: (1) unsuitable state (dry water holes with no elephants); (2) suitable state (water hole with water) with low abundance of elephants; and (3) suitable state with high abundance of elephants. We found that annual rainfall and the number of neighboring water holes influenced the transition probabilities among these three states. Because of an increase in elephant densities in the park during the study period, we also found that transition probabilities from low abundance to high abundance states increased over time. The application of the joint habitat–occupancy models provides a coherent framework to examine how habitat suitability and factors that affect habitat suitability influence the distribution and abundance of organisms. We discuss how these simple models can further be used to apply structured decision‐making tools in order to derive decisions that are optimal relative to specified management objectives. The modeling framework presented in this paper should be applicable to a wide range of existing data sets and should help to address important ecological, conservation, and management problems that deal with occupancy, relative abundance, and habitat suitability.
Optimal management strategies to control local population growth or population spread may not be the same
Authors: Shea Katriona , Jongejans Eelke , Skarpaas Olav , Kelly Dave , Sheppard Andy W.
Published: June 2010

The objective of most pest management programs is to “control” the pest species. However, optimal control of local abundance and population growth may require different management strategies than optimal control of spatial spread. We use coupled demographic–dispersal models to address the relative importance of different management approaches to these two main control objectives for the invasive thistle Carduus nutans. The models are parameterized with data from thistle populations in the native (France) and invaded ranges (Australia and New Zealand). We assess a wide range of commonly used management strategies for their absolute and relative impacts on population growth and spread in both invaded‐range scenarios.

The projected population growth rate in New Zealand is more than twice that in Australia, while the spread rate is more than four times the Australian value. In general, spread and growth are both most strongly affected by the same life cycle transitions; however, in a few cases certain vital rates disproportionately affect either spread or growth. The transition that represents the contribution of large rosettes in one year to the number of large rosettes in the following year (the large rosette–large rosette transition) in Australia is dominated by reproduction (rather than survival) and hence is relatively more important to spread than to population growth. In New Zealand, the small rosette–small rosette transition is also predominantly dispersal‐related. However, establishment of small plants from the seed bank contributes more to population growth than spread, as no dispersal is involved.

The fine‐resolution vital‐rate‐based modeling approach allows us to identify potentially novel optimal management strategies: approaches that reduce microsite availability show promise for reducing both population growth and spread, while strategies that affect dispersal parameters will affect spread. Additionally, the relative ranking of some biocontrol agents shifts depending on whether control of population growth or population spread is the desired outcome and therefore could alter which of the agents are preferred for release in a new area. The possibility of differences in ranked agent effectiveness has been predicted theoretically, but never before demonstrated using field data.
Impacts of individual tree species on carbon dynamics in a moist tropical forest environment
Authors: Russell Ann E. , Raich James W. , Arrieta Ricardo Bedoya , Valverde-Barrantes Oscar , González Eugenio
Published: June 2010

In the moist tropical forest biome, which cycles carbon (C) rapidly and stores huge amounts of C, the impacts of individual species on C balances are not well known. In one of the earliest replicated experimental sites for investigating growth of native tropical trees, we examined traits of tree species in relation to their effects on forest C balances, mechanisms of influence, and consequences for C sequestration. The monodominant stands, established in abandoned pasture in 1988 at La Selva Biological Station, Costa Rica, contained five species in a complete randomized block design. Native species were:Hieronyma alchorneoides,Pentaclethra macroloba,Virola koschnyi, andVochysia guatemalensis. The exotic species wasPinus patula. By 16 years, the lack of differences among species in some attributes suggested strong abiotic control in this environment, where conditions are very favorable for growth. These attributes included aboveground net primary productivity (ANPP), averaging 11.7 Mg C·ha−1·yr−1across species, and soil organic C (0–100 cm, 167 Mg C/ha). Other traits differed significantly, however, indicating some degree of biological control. InVochysiaplots, both aboveground biomass of 99 Mg C/ha, and belowground biomass of 20 Mg C/ha were 1.8 times that ofVirola(P= 0.02 and 0.03, respectively). Differences among species in overstory biomass were not compensated by understory vegetation. Belowground NPP of 4.6 Mg C·ha−1·yr−1inHieronymawas 2.4 times that ofPinus(P< 0.01). Partitioning of NPP to belowground components inHieronymawas more than double that ofPinus(P= 0.03). The canopy turnover rate inHieronymawas 42% faster than that ofVirola(P< 0.01). Carbon sequestration, highest inVochysia(7.4 Mg C·ha−1·yr−1,P= 0.02), averaged 5.2 Mg C·ha−1·yr−1, close to the annual per capita fossil fuel use in the United States of 5.3 Mg C. Our results indicated that differences in species effects on forest C balances were related primarily to differences in growth rates, partitioning of C among biomass components, tissue turnover rates, and tissue chemistry. Inclusion of those biological attributes may be critical for robust modeling of C cycling across the moist tropical forest biome.