bluuebunny/crossref_metadata_2025 huggingface dataset:
Propofolversuspropofol plus hydrocodone for flexible bronchoscopy: a randomised study
Authors: Schlatter L. , Pflimlin E. , Fehrke B. , Meyer A. , Tamm M. , Stolz D.
Published: February 2011

Propofol and the combination of a benzodiazepine and an opiate have been established for sedation in flexible bronchoscopy. It is as yet unknown whether propofol in combination with an opiate is superior to propofol alone to suppress cough during the procedure.

300 consecutive patients undergoing flexible bronchoscopy at a tertiary care university hospital were randomly allocated to receive either the combination propofol and hydrocodone or propofol alone in a double-blind fashion. The primary end-point was the cough score during the procedure as estimated by the physician using a visual analogue scale.

Demographics were similar in both groups. Compared with propofol alone, median (interquartile range) cough scores assessed by physicians, nurses and patients were significantly lower in the group randomised to the combination propofol and hydrocodone (2.5 (1.5–4.0)versus2.0 (1.0–3.0), respectively, p=0.011). Additionally, patients receiving the combination required significantly lower doses of propofol than those receiving propofol alone (200 mg (140–280)versus260 mg (180–350), p<0.0001). Complex examinations, including bronchoalveolar lavage or transbronchial biopsy, benefited more from additional opiate. The duration of the procedure, time to discharge and complication rate were similar in both groups.

The combination of propofol and hydrocodone is safe and superior to propofol alone for cough suppression in flexible bronchoscopy.
Airway inflammation is augmented by obesity and fatty acids in asthma
Authors: Scott H.A. , Gibson P.G. , Garg M.L. , Wood L.G.
Published: February 2011

Obesity and asthma are associated, but the mechanism(s) of the association have yet to be elucidated. The aim of this study was to assess airway inflammation in relation to obesity and plasma fatty acids in males and females with and without asthma.

Obese (n=68) and nonobese (n=47) adults with asthma, and obese (n=16) and nonobese (n=63) healthy controls had induced sputum and venous blood samples analysed for inflammatory markers.

There was a positive interaction between obesity and asthma on sputum neutrophil percentage (p=0.012) and C-reactive protein level (p=0.003). Although sputum eosinophil percentage was elevated in asthma (p=0.001), there was no effect of obesity (p=0.16). Sputum neutrophil percentage was positively associated with body mass index in females with asthma (β=1.015, 95% CI 0.258–1.772; p=0.009) and neutrophilic asthma was present in a greater proportion of obese compared with non-obese females (42.9%versus16.2%; p=0.017). In males with asthma, sputum neutrophil percentage was positively associated with total plasma saturated fatty acids (β=0.108, 95% CI 0.036–0.180; p=0.004) and negatively with monounsaturated fatty acids (β= -0.068, 95% CI -0.131– -0.005; p=0.035).

This was the first study to demonstrate an increase in neutrophilic airway inflammation in obese asthma. This relationship was significant only in females with asthma. In males, saturated and monounsaturated fatty acids were important predictors of neutrophilic airway inflammation in asthma.
Evaluation of moxifloxacin for the treatment of tuberculosis: 3 years of experience
Authors: Pranger A.D. , van Altena R. , Aarnoutse R.E. , van Soolingen D. , Uges D.R.A. , Kosterink J.G.W. , van der Werf T.S. , Alffenaar J.W.C.
Published: February 2011

Moxifloxacin (MFX) is a powerful second-line anti-tuberculosis (TB) agent, but the optimal dose has not yet been established and long-term safety data are scarce.

We retrospectively reviewed the medical charts of TB patients treated at the Tuberculosis Centre Beatrixoord, University Medical Centre Groningen (Haren, the Netherlands) receiving MFX 400 mg once daily as part of their TB treatment between January 1 2006 and January 1 2009. Safety data and drug–drug interactions were evaluated. Efficacy was predicted based on the area under the concentration–time curve up to 24 h post-dosage (AUC0–24h)/minimal inhibitory concentration (MIC) ratio.

89 patients were treated with a median dose of 6.9 mg·kg−1MFX once daily for a median period of 74 days. Discontinuation of therapy occurred in only three patients due to gastrointestinal side-effects and hypersensitivity. Pharmacokinetic analysis showed an AUC0–24h/MIC ratio <100 in eight out of 16 patients. A large variation in protein binding affected the unbound AUC0–24hconsiderably.

These data show that MFX treatment was well tolerated in 89 patients receiving a dose of 400 mg once daily for a prolonged period. Considering the variability in (un)bound AUC0–24h/MIC ratio, therapeutic drug monitoring is recommended in selected patients (i.e.rifampicin co-medication; MIC ≥0.25 mg·L−1) to assess optimal therapy.
The functional expression of extracellular calcium-sensing receptor in rat pulmonary artery smooth muscle cells
Authors: Li Guang-wei , Wang Qiu-shi , Hao Jing-hui , Xing Wen-jing , Guo Jin , Li Hong-zhu , Bai Shu-zhi , Li Hong-xia , Zhang Wei-hua , Yang Bao-feng , Yang Guang-dong , Wu Ling-yun , Wang Rui , Xu Chang-qing
Published: February 2011

Background

The extracellular calcium-sensing receptor (CaSR) belongs to family C of the G protein coupled receptors. Whether the CaSR is expressed in the pulmonary artery (PA) is unknown.

Methods

The expression and distribution of CaSR were detected by RT-PCR, Western blotting and immunofluorescence. PA tension was detected by the pulmonary arterial ring technique, and the intracellular calcium concentration ([Ca2+]i) was detected by a laser-scanning confocal microscope.

Results

The expressions of CaSR mRNA and protein were found in both rat pulmonary artery smooth muscle cells (PASMCs) and PAs. Increased levels of [Ca2+]o (extracellular calcium concentration) or Gd3+ (an agonist of CaSR) induced an increase of [Ca2+]i and PAs constriction in a concentration-dependent manner. In addition, the above-mentioned effects of Ca2+ and Gd3+ were inhibited by U73122 (specific inhibitor of PLC), 2-APB (specific antagonist of IP3 receptor), and thapsigargin (blocker of sarcoplasmic reticulum calcium ATPase).

Conclusions

CaSR is expressed in rat PASMCs, and is involved in regulation of PA tension by increasing [Ca2+]i through G-PLC-IP3 pathway.
Estimating developmental states of tumors and normal tissues using a linear time-ordered model
Authors: Zhang Bo , Chen Beibei , Wu Tao , Xuan Zhenyu , Zhu Xiaopeng , Chen Runsheng
Published: February 2011

Background

Tumor cells are considered to have an aberrant cell state, and some evidence indicates different development states appearing in the tumorigenesis. Embryonic development and stem cell differentiation are ordered processes in which the sequence of events over time is highly conserved. The "cancer attractor" concept integrates normal developmental processes and tumorigenesis into a high-dimensional "cell state space", and provides a reasonable explanation of the relationship between these two biological processes from theoretical viewpoint. However, it is hard to describe such relationship by using existed experimental data; moreover, the measurement of different development states is also difficult.

Results

Here, by applying a novel time-ordered linear model based on a co-bisector which represents the joint direction of a series of vectors, we described the trajectories of development process by a line and showed different developmental states of tumor cells from developmental timescale perspective in a cell state space. This model was used to transform time-course developmental expression profiles of human ESCs, normal mouse liver, ovary and lung tissue into "cell developmental state lines". Then these cell state lines were applied to observe the developmental states of different tumors and their corresponding normal samples. Mouse liver and ovarian tumors showed different similarity to early development stage. Similarly, human glioma cells and ovarian tumors became developmentally "younger".

Conclusions

The time-ordered linear model captured linear projected development trajectories in a cell state space. Meanwhile it also reflected the change tendency of gene expression over time from the developmental timescale perspective, and our finding indicated different development states during tumorigenesis processes in different tissues.
DNA moves sequentially towards the nuclear matrix during DNA replication in vivo
Authors: Rivera-Mulia Juan Carlos , Hernández-Muñoz Rolando , Martínez Federico , Aranda-Anzaldo Armando
Published: February 2011

Background

In the interphase nucleus of metazoan cells DNA is organized in supercoiled loops anchored to a nuclear matrix (NM). There is varied evidence indicating that DNA replication occurs in replication factories organized upon the NM and that DNA loops may correspond to the actual replicons in vivo. In normal rat liver the hepatocytes are arrested in G0 but they synchronously re-enter the cell cycle after partial-hepatectomy leading to liver regeneration in vivo. We have previously determined in quiescent rat hepatocytes that a 162 kbp genomic region containing members of the albumin gene family is organized into five structural DNA loops.

Results

In the present work we tracked down the movement relative to the NM of DNA sequences located at different points within such five structural DNA loops during the S phase and after the return to cellular quiescence during liver regeneration. Our results indicate that looped DNA moves sequentially towards the NM during replication and then returns to its original position in newly quiescent cells, once the liver regeneration has been achieved.

Conclusions

Looped DNA moves in a sequential fashion, as if reeled in, towards the NM during DNA replication in vivo thus supporting the notion that the DNA template is pulled progressively towards the replication factories on the NM so as to be replicated. These results provide further evidence that the structural DNA loops correspond to the actual replicons in vivo.
Identification of errors introduced during high throughput sequencing of the T cell receptor repertoire
Authors: Nguyen Phuong , Ma Jing , Pei Deqing , Obert Caroline , Cheng Cheng , Geiger Terrence L
Published: February 2011

Background

Recent advances in massively parallel sequencing have increased the depth at which T cell receptor (TCR) repertoires can be probed by >3log10, allowing for saturation sequencing of immune repertoires. The resolution of this sequencing is dependent on its accuracy, and direct assessments of the errors formed during high throughput repertoire analyses are limited.

Results

We analyzed 3 monoclonal TCR from TCR transgenic, Rag-/- mice using Illumina® sequencing. A total of 27 sequencing reactions were performed for each TCR using a trifurcating design in which samples were divided into 3 at significant processing junctures. More than 20 million complementarity determining region (CDR) 3 sequences were analyzed. Filtering for lower quality sequences diminished but did not eliminate sequence errors, which occurred within 1-6% of sequences. Erroneous sequences were pre-dominantly of correct length and contained single nucleotide substitutions. Rates of specific substitutions varied dramatically in a position-dependent manner. Four substitutions, all purine-pyrimidine transversions, predominated. Solid phase amplification and sequencing rather than liquid sample amplification and preparation appeared to be the primary sources of error. Analysis of polyclonal repertoires demonstrated the impact of error accumulation on data parameters.

Conclusions

Caution is needed in interpreting repertoire data due to potential contamination with mis-sequence reads. However, a high association of errors with phred score, high relatedness of erroneous sequences with the parental sequence, dominance of specific nt substitutions, and skewed ratio of forward to reverse reads among erroneous sequences indicate approaches to filter erroneous sequences from repertoire data sets.
Relapse according to antipsychotic treatment in schizophrenic patients: a propensity-adjusted analysis
Authors: Millier Aurelie , Sarlon Emmanuelle , Azorin Jean-Michel , Boyer Laurent , Aballea Samuel , Auquier Pascal , Toumi Mondher
Published: February 2011

Objective

To compare the rate of relapse as a function of antipsychotic treatment (monotherapy vs. polypharmacy) in schizophrenic patients over a 2-year period.

Methods

Using data from a multicenter cohort study conducted in France, we performed a propensity-adjusted analysis to examine the association between the rate of relapse over a 2-year period and antipsychotic treatment (monotherapy vs. polypharmacy).

Results

Our sample consisted in 183 patients; 50 patients (27.3%) had at least one period of relapse and 133 had no relapse (72.7%). Thirty-eight (37.7) percent of the patients received polypharmacy. The most severely ill patients were given polypharmacy: the age at onset of illness was lower in the polypharmacy group (p = 0.03). Patients that received polypharmacy also presented a higher general psychopathology PANSS subscore (p = 0.04) but no statistically significant difference was found in the PANSS total score or the PANSS positive or negative subscales. These patients were more likely to be given prescriptions for sedative drugs (p < 0.01) and antidepressant medications (p = 0.03). Relapse was found in 23.7% of patients given monotherapy and 33.3% given polypharmacy (p = 0.16). After stratification according to quintiles of the propensity score, which eliminated all significant differences for baseline characteristics, antipsychotic polypharmacy was not statistically associated with an increase of relapse: HR = 1.686 (0.812; 2.505).

Conclusion

After propensity score adjustment, antipsychotic polypharmacy is not statistically associated to an increase of relapse. Future randomised studies are needed to assess the impact of antipsychotic polypharmacy in schizophrenia.
Ambulatory oxygen: why do COPD patients not use their portable systems as prescribed? A qualitative study
Authors: Arnold Elizabeth , Bruton Anne , Donovan-Hall Maggie , Fenwick Angela , Dibb Bridget , Walker Elizabeth
Published: February 2011

Background

Patients with COPD on long term oxygen therapy frequently do not adhere to their prescription, and they frequently do not use their ambulatory oxygen systems as intended. Reasons for this lack of adherence are not known. The aim of this study was to obtain in-depth information about perceptions and use of prescribed ambulatory oxygen systems from patients with COPD to inform ambulatory oxygen design, prescription and management.

Methods

A qualitative design was used, involving semi-structured face-to-face interviews informed by a grounded theory approach. Twenty-seven UK community-dwelling COPD patients using NHS prescribed ambulatory systems were recruited. Ambulatory oxygen systems comprised cylinders weighing 3.4 kg, a shoulder bag and nasal cannulae.

Results

Participants reported that they: received no instruction on how to use ambulatory oxygen; were uncertain of the benefits; were afraid the system would run out while they were using it (due to lack of confidence in the cylinder gauge); were embarrassed at being seen with the system in public; and were unable to carry the system because of the cylinder weight. The essential role of carers was also highlighted, as participants with no immediate carers did not use ambulatory oxygen outside the house.

Conclusions

These participants highlighted previously unreported problems that prevented them from using ambulatory oxygen as prescribed. Our novel findings point to: concerns with the lack of specific information provision; the perceived unreliability of the oxygen system; important carer issues surrounding managing and using ambulatory oxygen equipment. All of these issues, as well as previously reported problems with system weight and patient embarrassment, should be addressed to improve adherence to ambulatory oxygen prescription and enhance the physical and social benefits of maintaining mobility in this patient group. Increased user involvement in both system development and service provision planning, could have avoided many of the difficulties highlighted by this study.
Induction of strain-transcendent antibodies to placental-type isolates with VAR2CSA DBL3 or DBL5 recombinant proteins
Authors: Avril Marion , Cartwright Megan M , Hathaway Marianne J , Smith Joseph D
Published: February 2011

Background

Pregnancy associated malaria is a severe clinical syndrome associated with sequestration of Plasmodium falciparum-infected erythrocytes in the placenta. Placental binding is mediated by VAR2CSA, which adheres to chondroitin sulphate A (CSA). VAR2CSA is a large and polymorphic protein that has six Duffy binding-like (DBL) domains. There is still limited understanding as to how effective individual VAR2CSA domains are at generating inhibitory antibodies or the number of domain variants needed for universal vaccine coverage.

Methods

To investigate the immunogenic properties of single domain VAR2CSA recombinant proteins, rats or rabbits were immunized with five of the six VAR2CSA domains produced in Pichia pastoris. Immune plasma was analysed against a geographically diverse panel of CSA-binding lab lines to assess antibody breadth and inhibitory activity.

Results

Of the five domains, DBL3, and to a lesser extent DBL5, induced antibodies that cross-reacted on five diverse CSA-binding parasite lines by flow cytometry. By comparison, anti-DBL6 antibodies were highly strain-specific and anti-DBL1 and anti-DBL4 antibodies were poorly reactive by flow cytometry. From this series of recombinant proteins, adhesion-blocking activity was restricted to a single rat immunized against a DBL4 recombinant protein.

Conclusions

Single domain VAR2CSA recombinant proteins produced in P. pastoris had limited efficacy in eliciting adhesion blocking antibody responses, but VAR2CSA DBL3 and DBL5 domains contain strain-transcendent epitopes that can be targeted by vaccination and may have application for vaccine development.
In vitro susceptibility to quinine and microsatellite variations of the Plasmodium falciparum Na+/H+ exchanger (Pfnhe-1) gene: the absence of association in clinical isolates from the Republic of Congo
Authors: Briolant Sébastien , Pelleau Stéphane , Bogreau Hervé , Hovette Philippe , Zettor Agnès , Castello Jacky , Baret Eric , Amalvict Rémy , Rogier Christophe , Pradines Bruno
Published: February 2011

Background

Quinine is still recommended as an effective therapy for severe cases of Plasmodium falciparum malaria, but the parasite has developed resistance to the drug in some cases. Investigations into the genetic basis for quinine resistance (QNR) suggest that QNR is complex and involves several genes, with either an additive or a pairwise effect. The results obtained when assessing one of these genes, the plasmodial Na+/H+ exchanger, Pfnhe-1, were found to depend upon the geographic origin of the parasite strain. Most of the associations identified have been made in Asian strains; in contrast, in African strains, the influence of Pfnhe on QNR is not apparent. However, a recent study carried out in Kenya did show a significant association between a Pfnhe polymorphism and QNR. As genetic differences may exist across the African continent, more field data are needed to determine if this association exists in other African regions. In the present study, association between Pfnhe and QNR is investigated in a series of isolates from central Africa.

Methods

The sequence analysis of the polymorphisms at the Pfnhe-1 ms4760 microsatellite and the evaluation of in vitro quinine susceptibility (by isotopic assay) were conducted in 74 P. falciparum isolates from the Republic of Congo.

Results

Polymorphisms in the number of DNNND or NHNDNHNNDDD repeats in the Pfnhe-1 ms4760 microsatellite were not associated with quinine susceptibility.

Conclusions

The polymorphism in the microsatellite ms4760 in Pfnhe-1 that cannot be used to monitor quinine response in the regions of the Republic of Congo, where the isolates came from. This finding suggests that there exists a genetic background associated with geographic area for the association that will prevent the use of Pfnhe as a molecular marker for QNR. The contribution of Pfnhe to the in vitro response to quinine remains to be assessed in other regions, including in countries with different levels of drug pressure.
Soluble Frizzled-7 receptor inhibits Wnt signaling and sensitizes hepatocellular carcinoma cells towards doxorubicin
Authors: Wei Wei , Chua Mei-Sze , Grepper Susan , So Samuel K
Published: February 2011

Background

There are limited therapeutic options for hepatocellular carcinoma (HCC), the most common liver malignancy worldwide. Recent studies have identified the Frizzled-7 receptor (FZD7), important for activation of Wnt-mediated signaling, as a potential therapeutic target for HCC and other cancers.

Methods

We hypothesized that the extracellular domain of FZD7 (sFZD7) would be a clinically more relevant therapeutic modality than previously studied approaches to target FZD7. We expressed and purified sFZD7 from E. coli, and tested its functional activity to interact with Wnt3, its ability to inhibit Wnt3-mediated signaling, and its potential for combinatorial therapy in HCC.

Results

sFZD7 pulled down Wnt3 from Huh7 cells, and decreased β-catenin/Tcf4 transcriptional activity in HCC cells.In vitro, sFZD7 dose-dependently decreased viability of three HCC cell lines (HepG2, Hep40, and Huh7, all with high FZD7 and Wnt3 mRNA), but had little effect on normal hepatocytes from three donors (all with low level FZD7 and Wnt3 mRNA). When combined with doxorubicin, sFZD7 enhanced the growth inhibitory effects of doxorubicin against HCC cellsin vitro, and against Huh7 xenograftsin vivo. Reduced expressions of c-Myc, cyclin D1, and survivin were observedin vitroandin vivo. Additionally, sFZD7 altered the levels of phosphorylated AKT and ERK1/2 induced by doxorubicin treatmentin vitro, suggesting that several critical pathways are involved in the chemosensitizing effect of sFZD7.

Conclusions

We propose that sFZD7 is a feasible therapeutic agent with specific activity, which can potentially be combined with other chemotherapeutic agents for the improved management of HCC.
In vitro study of the PLA2 inhibition and antioxidant activities of Aloe vera leaf skin extracts
Authors: Kammoun Maher , Miladi Sonia , Ali Yassine Ben , Damak Mohamed , Gargouri Youssef , Bezzine Sofiane
Published: February 2011

Background

In the present work we determined the total phenolic content ofAloe veraleaf skin (AVLS) extracts by using various solvents (hexane, chloroform-ethanol (1/1), ethyl acetate, butanol and water). We have also evaluated the antioxidant and the anti-PLA2 properties of these extracts by measuring their inhibition potency on the human pro-inflammatory phospholipase A2 (group IIA).

Results

The water extract exhibits the highest inhibitory effect with an IC50= 0.22 mg/ml and interestingly no effect was observed on the digestive phospholipase A2 (group IB) even at a concentration of 5 mg/ml. Antioxidant activities were also analyzed and the most active extracts were observed when using chloroform ethanol (1/1) and ethyl acetate (IC50= 0.274 and 0.326 mg/ml, respectively). Analysis of the total phenolic content reveals that the water extract, with the best anti-PLA2 effect, was poor in phenolic molecules (2 mg GAE/g). This latter value has to be compared with the chloroform-ethanol and the ethyl acetate extracts (40 and 23.8 mg GAE/g, respectively), mostly responsible for the antioxidant activity.

Conclusion

A significant correlation was established between the total phenolic content and the antioxidant capacity but not with the anti PLA2 activity. Results from phytochemical screening suggest that the anti PLA2 molecules were probably catechin tannins compounds.
Biochemical isolation and purification of ovulation-inducing factor (OIF) in seminal plasma of llamas
Authors: Ratto Marcelo H , Delbaere Louis TJ , Leduc Yvonne A , Pierson Roger A , Adams Gregg P
Published: February 2011

Background

The objective of the present study was to isolate and purify the protein fraction(s) of llama seminal plasma responsible for the ovulation-inducing effect of the ejaculate.

Methods

Semen collected from male llamas by artificial vagina was centrifuged and the seminal plasma was harvested and stored frozen. Seminal plasma was thawed and loaded onto a Type 1 macro-prep ceramic hydroxylapatite column and elution was carried out using a lineal gradient with 350 mM sodium phosphate. Three protein fractions were identified clearly (Fractions A, B, and C), where a prominent protein band with a mass of 14 kDa was identified in Fraction C. Fraction C was loaded into a sephacryl gel filtration column for further purification using fast protein liquid chromatography (FPLC). Isocratic elution resulted in 2 distinct protein fractions (Fractions C1 and C2). An in vivo bioassay (n = 10 to 11 llamas per group) was used to determine the ovarian effect of each fraction involving treatment with saline (negative control), whole seminal plasma (positive control), or seminal plasma Fractions A, B or C2. Ultrasonography was done to detect ovulation and CL formation, and blood samples were taken to measure plasma progesterone and LH concentrations.

Results

Ovulation and CL formation was detected in 0/10, 10/11, 0/10, 2/11, and 10/11 llamas treated with saline, whole seminal plasma, Fractions A, B and C2 respectively (P < 0.001). A surge in circulating concentrations of LH was detected within 2 hours only in llamas treated with either whole seminal plasma or Fraction C2. Plasma progesterone concentration and CL diameter profiles were greatest (P < 0.05) in llamas treated with Fraction C2.

Conclusion

Ovulation-inducing factor was isolated from llama seminal plasma as a 14 kDa protein molecule that elicits a preovulatory LH surge followed by ovulation and CL formation in llamas, suggesting an endocrine effect at the level of the hypothalamus (release of GnRH) or the pituitary (gonadotrophs).
Decentralization of the provision of health services to people living with HIV/AIDS in rural China: the case of three counties
Authors: Zhang Xiulan , Miège Pierre , Zhang Yurong
Published: February 2011

This study is based on a large-scale household survey and in-depth interviews of key informants that was conducted in villages in three counties of two provinces in China. We assess the new decentralized service provision system for people living with HIV/AIDS in rural populations in China. Since 2003, new social assistance schemes, and, more importantly, decentralization of routine treatment and care to community health stations, were progressively implemented in rural areas most affected by the HIV/AIDS epidemic. Though some problems remain, such as persistent discrimination towards infected patients and the lack of sufficient training of medical staff, the new decentralized pattern of service provision has lowered barriers to health access and alleviated economic pressure on affected households.
On the direct insulator-quantum Hall transition in two-dimensional electron systems in the vicinity of nanoscaled scatterers
Authors: Liang Chi-Te , Lin Li-Hung , Kuang Yoa Chen , Lo Shun-Tsung , Wang Yi-Ting , Lou Dong-Sheng , Kim Gil-Ho , Yuan-Huei Chang , Ochiai Yuichi , Aoki Nobuyuki , Chen Jeng-Chung , Lin Yiping , Chun-Feng Huang , Lin Sheng-Di , Ritchie David A
Published: February 2011

A direct insulator-quantum Hall (I-QH) transition corresponds to a crossover/transition from the insulating regime to a high Landau level filling factor ν > 2 QH state. Such a transition has been attracting a great deal of both experimental and theoretical interests. In this study, we present three different two-dimensional electron systems (2DESs) which are in the vicinity of nanoscaled scatterers. All these three devices exhibit a direct I-QH transition, and the transport properties under different nanaoscaled scatterers are discussed.
Near-surface processing on AlGaN/GaN heterostructures: a nanoscale electrical and structural characterization
Authors: Greco Giuseppe , Giannazzo Filippo , Frazzetto Alessia , Raineri Vito , Roccaforte Fabrizio
Published: February 2011

The effects of near-surface processing on the properties of AlGaN/GaN heterostructures were studied, combining conventional electrical characterization on high-electron mobility transistors (HEMTs), with advanced characterization techniques with nanometer scale resolution, i.e., transmission electron microscopy, atomic force microscopy (AFM) and conductive atomic force microscopy (C-AFM). In particular, a CHF3-based plasma process in the gate region resulted in a shift of the threshold voltage in HEMT devices towards less negative values. Two-dimensional current maps acquired by C-AFM on the sample surface allowed us to monitor the local electrical modifications induced by the plasma fluorine incorporated in the material.

The results are compared with a recently introduced gate control processing: the local rapid thermal oxidation process of the AlGaN layer. By this process, a controlled thin oxide layer on surface of AlGaN can be reliably introduced while the resistance of the layer below increase locally.
Synthesis and magnetic properties of single-crystalline Na2-

x
Mn8O16 nanorods
Authors: Lan Changyong , Gong Jiangfeng , Liu Shijiang , Yang Shaoguang
Published: February 2011

The synthesis of single-crystalline hollandite-type manganese oxides Na2-
x
Mn8O16 nanorods by a simple molten salt method is reported for the first time. The nanorods were characterized by powder X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and a superconducting quantum interference device magnetometer. The magnetic measurements indicated that the nanorods showed spin glass behavior and exchange bias effect at low temperatures. The low-temperature magnetic behaviors can be explained by the uncompensated spins on the surface of the nanorods.
Expression of sphingosine kinase 1 in amoeboid microglial cells in the corpus callosum of postnatal rats
Authors: Lin Haiyan , Baby Nimmi , Lu Jia , Kaur Charanjit , Zhang Chuansen , Xu Jiajun , Ling Eng-Ang , Dheen S Thameem
Published: February 2011

Sphingosine kinase 1 (SphK1), a key enzyme responsible for phosphorylating sphingosine into sphingosine-1-phosphate (S1P) has been shown to be expressed in monocytes and monocyte-derived peripheral macrophages. This study demonstrates SphK1 immunoexpression in amoeboid microglial cells (AMC), a nascent monocyte-derived brain macrophage in the corpus callosum of developing rat brain. SphK1 immunofluorescence expression, which appeared to be weak in AMC in normal brain, was markedly induced by lipopolysaccharide (LPS) or hypoxia treatment. Western blot analysis also showed increased expression level of SphK1 in the corpus callosum rich in AMC after LPS treatment. Detection of SphK1 mRNA and its upregulation after LPS treatment was confirmed in primary culture AMC by RT-PCR. Administration of N, N-dimethylsphingosine (DMS), a specific inhibitor of SphK1, effectively reduced upregulated SphK1 immunoexpression in AMC bothin vivoandin vitro. This was corroborated by western blot which showed a decrease in SphK1 protein level of callosal tissue with DMS pretreatment. Remarkably, LPS-induced upregulation of the transcription factor NFκB was suppressed by DMS. We conclude that SphK1 expression in AMC may be linked to regulation of proinflammatory cytokinesviaan NFκB signaling pathway.
Bioinformatic analyses identifies novel protein-coding pharmacogenomic markers associated with paclitaxel sensitivity in NCI60 cancer cell lines
Authors: Eng Lawson , Ibrahim-zada Irada , Jarjanazi Hamdi , Savas Sevtap , Meschian Mehran , Pritchard Kathleen I , Ozcelik Hilmi
Published: February 2011

Background

Paclitaxel is a microtubule-stabilizing drug that has been commonly used in treating cancer. Due to genetic heterogeneity within patient populations, therapeutic response rates often vary. Here we used the NCI60 panel to identify SNPs associated with paclitaxel sensitivity. Using the panel's GI50 response data available from Developmental Therapeutics Program, cell lines were categorized as either sensitive or resistant. PLINK software was used to perform a genome-wide association analysis of the cellular response to paclitaxel with the panel's SNP-genotype data on the Affymetrix 125 k SNP array. FastSNP software helped predict each SNP's potential impact on their gene product. mRNA expression differences between sensitive and resistant cell lines was examined using data from BioGPS. Using Haploview software, we investigated for haplotypes that were more strongly associated with the cellular response to paclitaxel. Ingenuity Pathway Analysis software helped us understand how our identified genes may alter the cellular response to paclitaxel.

Results

43 SNPs were found significantly associated (FDR < 0.005) with paclitaxel response, with 10 belonging to protein-coding genes (CFTR, ROBO1, PTPRD, BTBD12, DCT, SNTG1, SGCD, LPHN2, GRIK1, ZNF607). SNPs in GRIK1, DCT, SGCD and CFTR were predicted to be intronic enhancers, altering gene expression, while SNPs in ZNF607 and BTBD12 cause conservative missense mutations. mRNA expression analysis supported these findings as GRIK1, DCT, SNTG1, SGCD and CFTR showed significantly (p < 0.05) increased expression among sensitive cell lines. Haplotypes found in GRIK1, SGCD, ROBO1, LPHN2, and PTPRD were more strongly associated with response than their individual SNPs.

Conclusions

Our study has taken advantage of available genotypic data and its integration with drug response data obtained from the NCI60 panel. We identified 10 SNPs located within protein-coding genes that were not previously shown to be associated with paclitaxel response. As only five genes showed differential mRNA expression, the remainder would not have been detected solely based on expression data. The identified haplotypes highlight the role of utilizing SNP combinations within genomic loci of interest to improve the risk determination associated with drug response. These genetic variants represent promising biomarkers for predicting paclitaxel response and may play a significant role in the cellular response to paclitaxel.
Larval migration in PERL chambers as an in vitro model for percutaneous infection stimulates feeding in the canine hookworm Ancylostoma caninum
Authors: Franke Daniela , Strube Christina , Epe Christian , Welz Claudia , Schnieder Thomas
Published: February 2011

Background

Ancylostoma caninum third-stage larvae are the non-feeding infective stage of this parasite and are able to infect potential hosts via different infection routes. Since percutaneous infection is one of the most important routes and skin penetration is the first step into parasitic life, an existing in vitro model for percutaneous migration was modified and evaluated. The main parameter used to evaluate migration was the migration ratio (migrated larvae as a percentage of total number of larvae recovered). Additionally, the skin lag was calculated, expressing the percentage of larvae remaining in the skin and therefore not being recovered. Since initiation of feeding is proposed to be an important step in the transition from free-living to parasitic A. caninum larvae, feeding assays were performed with in vitro percutaneously migrated larvae. Additionally, infective larvae of A. caninum were activated via serum-stimulation and feeding behaviour was analysed and compared between percutaneously migrated and serum-stimulated larvae.

Results

Maximum skin migration levels of infective larvae were observed at temperatures above 32°C when larvae were placed on the epidermal side of skin for more than 12 hours. The medium beneath the skin had no effect on migration ratio, and no significant difference between the migration ratios through fresh and frozen/thawed skin was observed.

Maximum feeding levels of 93.2% were observed for percutaneously migrated larvae after 48 h incubation, whereas serum-stimulated larvae reached the maximum of 91.0% feeding larvae after 24 h.

Conclusions

The PERL chamber system was optimised and standardised as an in vitro model for percutaneous migration. The larvae recovered after percutaneous migration showed characteristic signs of activation similar to that of serum-stimulated larvae. The observed difference in time course of resumption of feeding indicates that percutaneously migrated larvae are not identical to serum-stimulated larvae, which are currently representing the model for early parasitic stages.
The combination of the entomopathogenic fungus Metarhizium anisopliae with the insecticide Imidacloprid increases virulence against the dengue vector Aedes aegypti (Diptera: Culicidae)
Authors: Paula Adriano R , Carolino Aline T , Paula Cátia O , Samuels Richard I
Published: February 2011

Background

Dengue fever transmitted by the mosquito Aedes aegypti, is one of the most rapidly spreading insect borne diseases, stimulating the search for alternatives to current control measures. The dengue vector A. aegypti has received less attention than anophelene species, although more than 2.5 billion people are at risk of infection worldwide. Entomopathogenic fungi are emerging as potential candidates for the control of mosquitoes. Here we continue our studies on the pathogenicity of the entomopathogenic fungus Metarhizium anisopliae against adult A. aegypti females. With the aim of further reducing mean survival times of A. aegypti exposed to fungus impregnated surfaces, a sub-lethal concentration of the neonicotinoid insecticide Imidacloprid (IMI) was added to fungal suspensions.

Results

A sub-lethal concentration of IMI that did not significantly alter the daily survival rates or mean survival percentages of mosquitoes was identified to be 0.1 ppm. This sub-lethal concentration was combined with M. anisopliae conidia (1 × 109 conidia mL-1). Both the combined treatment and the conidia alone were able to reduce the survival of A. aegypti compared with untreated or IMI treated mosquitoes. Importantly, mosquito survival following exposure to the combined treatment for 6 and 12 hrs was significantly reduced when compared with mosquitoes exposed to conidia alone.

Conclusions

This is the first time that a combination of an insecticide and an entomopathogenic fungus has been tested against A. aegypti. Firstly, the study showed the potential of IMI as an alternative to the currently employed pyrethroid adulticides. Secondly, as an alternative to applications of high concentrations of chemical insecticides, we suggest that adult A. aegypti could be controlled by surface application of entomopathogenic fungi and that the efficiency of these fungi could be increased by combining the fungi with ultra-low concentrations of insecticides, resulting in higher mortality following relatively short exposure times.
Imprisoned and imperiled: access to HIV and TB prevention and treatment, and denial of human rights, in Zambian prisons
Authors: Todrys Katherine W , Amon Joseph J , Malembeka Godfrey , Clayton Michaela
Published: February 2011

Background

Although HIV and tuberculosis (TB) prevalence are high in prisons throughout sub‐Saharan Africa, little research has been conducted on factors related to prevention, testing and treatment services.

Methods

To better understand the relationship between prison conditions, the criminal justice system, and HIV and TB in Zambian prisons, we conducted a mixed‐method study, including: facility assessments and in‐depth interviews with 246 prisoners and 30 prison officers at six Zambian prisons; a review of Zambian legislation and policy governing prisons and the criminal justice system; and 46 key informant interviews with government and non‐governmental organization officials and representatives of international agencies and donors.

Results

The facility assessments, in‐depth interviews and key informant interviews found serious barriers to HIV and TB prevention and treatment, and extended pre‐trial detention that contributed to overcrowded conditions. Disparities both between prisons and among different categories of prisoners within prisons were noted, with juveniles, women, pre‐trial detainees and immigration detainees significantly less likely to access health services.

Conclusions

Current conditions and the lack of available medical care in Zambia's prisons violate human rights protections and threaten prisoners' health. In order to protect the health of prisoners, prison‐based health services, linkages to community‐based health care, general prison conditions and failures of the criminal justice system that exacerbate overcrowding must be immediately improved. International donors should work with the Zambian government to support prison and justice system reform and ensure that their provision of funding in such areas as health services respect human rights standards, including non‐discrimination. Human rights protections against torture and cruel, inhuman or degrading treatment, and criminal justice system rights, are essential to curbing the spread of HIV and TB in Zambian prisons, and to achieving broader goals to reduce HIV and TB in Zambia.
Blood transfusion during cardiac surgery is associated with inflammation and coagulation in the lung: a case control study
Authors: Tuinman Pieter R , Vlaar Alexander P , Cornet Alexander D , Hofstra Jorrit J , Levi Marcel , Meijers Joost CM , Beishuizen Albertus , Schultz Marcus J , Groeneveld AB Johan , Juffermans Nicole P
Published: February 2011

Introduction

Blood transfusion is associated with increased morbidity and mortality in cardiac surgery patients, but cause-and-effect relations remain unknown. We hypothesized that blood transfusion is associated with changes in pulmonary and systemic inflammation and coagulation occurring in patients who do not meet the clinical diagnosis of transfusion-related acute lung injury (TRALI).

Methods

We performed a case control study in a mixed medical-surgical intensive care unit of a university hospital in the Netherlands. Cardiac surgery patients (n = 45) were grouped as follows: those who received no transfusion, those who received a restrictive transfusion (one two units of blood) or those who received multiple transfusions (at least five units of blood). Nondirected bronchoalveolar lavage fluid (BALF) and blood were obtained within 3 hours postoperatively. Normal distributed data were analyzed using analysis of variance and Dunnett's post hoc test. Nonparametric data were analyzed using the Kruskal-Wallis and Mann-Whitney U tests.

Results

Restrictive transfusion increased BALF levels of interleukin (IL)-1β and D-dimer compared to nontransfused controls (P < 0.05 for all), and IL-1β levels were further enhanced by multiple transfusions (P < 0.01). BALF levels of IL-8, tumor necrosis factor α (TNFα) and thrombin-antithrombin complex (TATc) were increased after multiple transfusions (P < 0.01, P < 0.001 and P < 0.01, respectively) compared to nontransfused controls, but not after restrictive transfusions. Restrictive transfusions were associated with increased pulmonary levels of plasminogen activator inhibitor 1 compared to nontransfused controls with a further increase after multiple transfusions (P < 0.001). Concomitantly, levels of plasminogen activator activity (PAA%) were lower (P < 0.001), indicating impaired fibrinolysis. In the systemic compartment, transfusion was associated with a significant increase in levels of TNFα, TATc and PAA% (P < 0.05).

Conclusions

Transfusion during cardiac surgery is associated with activation of inflammation and coagulation in the pulmonary compartment of patients who do not meet TRALI criteria, an effect that was partly dose-dependent, suggesting transfusion as a mediator of acute lung injury. These pulmonary changes were accompanied by systemic derangement of coagulation.
Growth Hormone Signaling in Human T47D Breast Cancer Cells: Potential Role for a Growth Hormone Receptor-Prolactin Receptor Complex
Authors: Xu Jie , Zhang Yue , Berry Philip A. , Jiang Jing , Lobie Peter E. , Langenheim John F. , Chen Wen Y. , Frank Stuart J.
Published: February 2011

GH receptor (GHR) and prolactin (PRL) receptor (PRLR) are structurally similar cytokine receptor superfamily members that are highly conserved among species. GH has growth-promoting and metabolic effects in various tissues in vertebrates, including humans. PRL is essential for regulation of lactation in mammals. Recent studies indicate that breast tissue bears GHR and PRLR and that both GH and PRL may impact development or behavior of breast cancer cells. An important facet of human GH (hGH) and human PRL (hPRL) biology is that although hPRL interacts only with hPRLR, hGH binds well to both hGHR and hPRLR. Presently, we investigated potential signaling effects of both hormones in the estrogen receptor- and progesterone receptor-positive human T47D breast cancer cell line. We found that this cell type expresses ample GHR and PRLR and responds well to both hGH and hPRL, as evidenced by activation of the Janus kinase 2/signal transducer and activator of transcription 5 pathway. Immunoprecipitation studies revealed specific GHR-PRLR association in these cells that was acutely enhanced by GH treatment. Although GH caused formation of disulfide-linked and chemically cross-linked GHR dimers in T47D cells, GH preferentially induced tyrosine phosphorylation of PRLR rather than GHR. Notably, both a GHR-specific ligand antagonist (B2036) and a GHR-specific antagonist monoclonal antibody (anti-GHRext-mAb) failed to inhibit GH-induced signal transducer and activator of transcription 5 activation. In contrast, although the non-GHR-specific GH antagonist (G120R) and the PRL antagonist (G129R) individually only partially inhibited GH-induced activation, combined treatment with these two antagonists conferred greater inhibition than either alone. These data indicate that endogenous GHR and PRLR associate (possibly as a GHR-PRLR heterodimer) in human breast cancer cells and that GH signaling in these cells is largely mediated by the PRLR in the context of both PRLR-PRLR homodimers and GHR-PRLR heterodimers, broadening our understanding of how these related hormones and their related receptors may function in physiology and pathophysiology.
America Abridged: Matthaeus Merian, Johann Ludwig Gottfried, and the Apotheosis of the De Bry Collection of Voyages
Authors: van Groesen Michiel
Published: February 2011

In 1631, Matthaeus Merian and Johann Ludwig Gottfried published a one-volume abridgment of the monumental America series issued by Theodor De Bry and his two sons. Historia Antipodum can be considered the apotheosis of the collection of voyages to the New World. This article argues that the abridgment, rather than the independent publication it is sometimes taken to be, was constructed with the same editorial strategy in mind as earlier De Bry volumes. Heathen beliefs in the western hemisphere were further emphasized, European superiority was visualized more clearly, and the predilection for spectacular images was stronger than ever. In many ways, the modifications Merian and Gottfried made to both texts and illustrations surpassed the changes made for the original volumes of America. In bringing together these representations in a single, affordable volume, Merian and Gottfried prolonged the influence of the De Bry collection and its carefully manipulated representations until well into the eighteenth century.