bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrated functional genomic study of acute phenobarbital exposure in the rat
Authors: Waterman Claire L , Currie Richard A , Cottrell Lisa A , Dow Jacky , Wright Jayne , Waterfield Catherine J , Griffin Julian L 
Published: January 2010

AbstractBackgroundNon-genotoxic carcinogens are notoriously difficult to identify as they do not damage DNA directly and have diverse modes of action, necessitating long term in vivo studies. The early effects of the classic rodent non-genotoxic hepatocarcinogen phenobarbital have been investigated in the Fisher rat using a combination of metabolomics and transcriptomics, to investige early stage mechanistic changes that are predictive of longer term pathology.ResultsLiver and blood plasma were profiled across 14 days, and multivariate statistics used to identify perturbed pathways. Both metabolomics and transcriptomics detected changes in the liver which were dose dependent, even after one day of exposure. Integration of the two datasets associated perturbations with specific pathways. Hepatic glycogen was decreased due to a decrease in synthesis, and plasma triglycerides were decreased due to an increase in fatty acid uptake by the liver. Hepatic succinate was increased and this was associated with increased heme biosynthesis. Glutathione synthesis was also increased, presumably in response to oxidative stress. Liquid Chromatography Mass Spectrometry demonstrated a remodeling of lipid species, possibly resulting from proliferation of the smooth endoplasmic reticulum.ConclusionsThe data fusion of metabolomic and transcriptomic changes proved to be a highly sensitive approach for monitoring early stage changes in altered hepatic metabolism, oxidative stress and cytochrome P450 induction simultaneously. This approach is particularly useful in interpreting changes in metabolites such as succinate which are hubs of metabolism.
Virulence regulator AphB enhances toxR transcription in Vibrio cholerae
Authors: Xu Xiao , Stern Andrew M , Liu Zhi , Kan Biao , Zhu Jun 
Published: January 2010

Abstract

Background

Vibrio cholerae is the causative agent of cholera. Extensive studies reveal that complicated regulatory cascades regulate expression of virulence genes, the products of which are required for V. cholerae to colonize and cause disease. In this study, we investigated the expression of the key virulence regulator ToxR under different conditions.

Results
We found that compared to that of wild type grown to stationary phase, the toxR expression was lower in an aphB mutant strain. AphB has been previously shown to be a key virulence regulator that is required to activate the expression of tcpP. When expressed constitutively, AphB is able to activate the toxR promoter. Furthermore, gel shift analysis indicates that AphB binds toxR promoter region directly. We also characterize the effect of AphB on the levels of the outer membrane porins OmpT and OmpU, which are known to be regulated by ToxR.

Conclusions
Our data indicate that V. cholerae possesses an additional regulatory loop that use AphB to activate the expression of two virulence regulators, ToxR and TcpP, which together control the expression of the master virulence regulator ToxT.
A few strong connections: optimizing information retention in neuronal avalanches
Authors: Chen Wei , Hobbs Jon P , Tang Aonan , Beggs John M 
Published: January 2010

Abstract

Background
How living neural networks retain information is still incompletely understood. Two prominent ideas on this topic have developed in parallel, but have remained somewhat unconnected. The first of these, the "synaptic hypothesis," holds that information can be retained in synaptic connection strengths, or weights, between neurons. Recent work inspired by statistical mechanics has suggested that networks will retain the most information when their weights are distributed in a skewed manner, with many weak weights and only a few strong ones. The second of these ideas is that information can be represented by stable activity patterns. Multineuron recordings have shown that sequences of neural activity distributed over many neurons are repeated above chance levels when animals perform well-learned tasks. Although these two ideas are compelling, no one to our knowledge has yet linked the predicted optimum distribution of weights to stable activity patterns actually observed in living neural networks.

Results
Here, we explore this link by comparing stable activity patterns from cortical slice networks recorded with multielectrode arrays to stable patterns produced by a model with a tunable weight distribution. This model was previously shown to capture central features of the dynamics in these slice networks, including neuronal avalanche cascades. We find that when the model weight distribution is appropriately skewed, it correctly matches the distribution of repeating patterns observed in the data. In addition, this same distribution of weights maximizes the capacity of the network model to retain stable activity patterns. Thus, the distribution that best fits the data is also the distribution that maximizes the number of stable patterns.

Conclusions
We conclude that local cortical networks are very likely to use a highly skewed weight distribution to optimize information retention, as predicted by theory. Fixed distributions impose constraints on learning, however. The network must have mechanisms for preserving the overall weight distribution while allowing individual connection strengths to change with learning.
A tutorial on pilot studies: the what, why and how
Authors: Thabane Lehana , Ma Jinhui , Chu Rong , Cheng Ji , Ismaila Afisi , Rios Lorena P , Robson Reid , Thabane Marroon , Giangregorio Lora , Goldsmith Charles H 
Published: January 2010

AbstractPilot studies for phase III trials - which are comparative randomized trials designed to provide preliminary evidence on the clinical efficacy of a drug or intervention - are routinely performed in many clinical areas. Also commonly know as "feasibility" or "vanguard" studies, they are designed to assess the safety of treatment or interventions; to assess recruitment potential; to assess the feasibility of international collaboration or coordination for multicentre trials; to increase clinical experience with the study medication or intervention for the phase III trials. They are the best way to assess feasibility of a large, expensive full-scale study, and in fact are an almost essential pre-requisite. Conducting a pilot prior to the main study can enhance the likelihood of success of the main study and potentially help to avoid doomed main studies. The objective of this paper is to provide a detailed examination of the key aspects of pilot studies for phase III trials including: 1) the general reasons for conducting a pilot study; 2) the relationships between pilot studies, proof-of-concept studies, and adaptive designs; 3) the challenges of and misconceptions about pilot studies; 4) the criteria for evaluating the success of a pilot study; 5) frequently asked questions about pilot studies; 7) some ethical aspects related to pilot studies; and 8) some suggestions on how to report the results of pilot investigations using the CONSORT format.
Variable viral clearance despite adequate ganciclovir plasma levels during valganciclovir treatment for cytomegalovirus disease in D+/R- transplant recipients
Authors: Perrottet Nancy , Manuel Oriol , Lamoth Frédéric , Venetz Jean-Pierre , Sahli Roland , Decosterd Laurent A , Buclin Thierry , Pascual Manuel , Meylan Pascal 
Published: January 2010

Abstract

Background
Valganciclovir, the oral prodrug of ganciclovir, has been demonstrated equivalent to iv ganciclovir for CMV disease treatment in solid organ transplant recipients. Variability in ganciclovir exposure achieved with valganciclovir could be implicated as a contributing factor for explaining variations in the therapeutic response. This prospective observational study aimed to correlate clinical and cytomegalovirus (CMV) viral load response (DNAemia) with ganciclovir plasma concentrations in patients treated with valganciclovir for CMV infection/disease.

Methods
Seven CMV D+/R- transplant recipients (4 kidney, 2 liver and 1 heart) were treated with valganciclovir (initial dose was 900-1800 mg/day for 3-6.5 weeks, followed by 450-900 mg/day for 2-9 weeks). DNAemia was monitored by real time quantitative PCR and ganciclovir plasma concentration was measured at trough (Ctrough) and 3 h after drug administration (C3h) by HPLC.

Results
Four patients presented with CMV syndrome, two had CMV tissue-invasive disease after prophylaxis discontinuation, and one liver recipient was treated pre-emptively for asymptomatic rising CMV viral load 5 weeks post-transplantation in the absence of prophylaxis. CMV DNAemia decreased during the first week of treatment in all recipients except in one patient (median decrease: -1.2 log copies/mL, range: -1.8 to 0) despite satisfactory ganciclovir exposure (AUC0-12 = 48 mg·h/L, range for the 7 patients: 40-118 mg·h/L). Viral clearance was obtained in five patients after a median of time of 34 days (range: 28-82 days). Two patients had recurrent CMV disease despite adequate ganciclovir exposure (65 mg·h/L, range: 44-118 mg·h/L).

Conclusions
Valganciclovir treatment for CMV infection/disease in D+/R- transplant recipients can thus result in variable viral clearance despite adequate ganciclovir plasma concentrations, probably correlating inversely with anti-CMV immune responses after primary infection.
Tocotrienols are good adjuvants for developing cancer vaccines
Authors: Abdul Hafid Sitti Rahma , Radhakrishnan Ammu Kutty , Nesaretnam Kalanithi 
Published: January 2010

AbstractBackgroundDendritic cells (DCs) have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours.MethodsIn this study we have used tocotrienol-rich fraction (TRF), a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF) and DC pulsed with tumour lysate from 4T1 cells (DC+TL). Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF) while two groups of animal which were supplemented daily with carrier oil (control) and with TRF (TRF). After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour.ResultsOur study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF) injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF) compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8) and natural killer cells (NK) were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice.ConclusionOur study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.
Impact of clinical urgency, physician supply and procedural capacity on regional variations in wait times for coronary angiography
Authors: Wijeysundera Harindra C , Stukel Therese A , Chong Alice , Natarajan Madhu K , Alter David A 
Published: January 2010

Abstract

Background
Despite universal health care, there continues to be regional access disparities to coronary angiography in Canada. Our objective was to evaluate the extent to which demand-side factors such as clinical urgency/need, and supply-side factors, as reflected by differences in physician and procedural supply account for these inequalities.

Methods
Our cohort consisted of 74,254 consecutive patients referred for coronary angiography in Ontario, Canada between April 1st 2005 and March 31st 2006, divided into three urgency strata based on a clinical urgency scale. Cox-proportional hazard models were developed, adjusting for age, gender, socioeconomic status (SES), region, and urgency score, with greater hazard ratios (HR) indicating shorter wait times. To evaluate mediators of any residual wait-time differences, we examined the influence of the regional supply of cath lab facilities, invasive cardiologists and general practitioners (GP).

Results
We found that the urgency score was a significant predictor of wait time in all three strata (urgent patients: HR 1.61 for each unit increase in patient urgency (95% Confidence interval (CI) 1.55-1.67); semi-urgent patients: HR 1.55 (95% CI 1.44-1.68); elective patients: HR 1.13 (95% CI 1.08-1.18)). After accounting for clinical need/urgency, regional wait time differences persisted; these were most consistently associated with variation in cath lab supply. The impact of invasive cardiologist supply was restricted to urgent patients while that of GP supply was confined to semi-urgent and elective patients.

Conclusion
We found that there remained significant regional disparities in access to coronary angiography after accounting for clinical need. These disparities are partially explained by variations in supply of both procedural capacity and physician services, most notably in elective and semi-urgent patients.
Bronchial Fistula Associated with Sunitinib in a Patient Previously Treated with Radiation Therapy
Authors: Basille Damien , Andrejak Michel , Bentayeb Houcine , Kanaan Marc , Fournier Clément , Lecuyer Emmanuelle , Boutemy Marie , Garidi Réda , Douadi Youcef , Dayen Charles 
Published: January 2010

Objective: To report a case of bronchial fistula associated with sunitinib in a patient previously treated with radiation therapy. Case Summary: A 40-year-old man with renal cell cancer diagnosed in 2005 and initially treated by radical nephrectomy presented in March 2007 with a recurrence with cerebral, mediastinal, and lung metastases. A thoracic computed tomography (CT) scan showed a subcarinal tumor obstructing the bronchus intermedius. The patient was initially treated with cerebral and thoracic radiotherapy and then with sunitinib 50 mg/day (4 weeks on, 2 weeks off). Two months after the beginning of treatment, a CT scan revealed a dramatic reduction in the size of the tumor, associated with a bronchial fistula. This was confirmed by flexible bronchoscopy, which showed complete necrosis of the tumor and a large perforation of the bronchus intermedius. Sunitinib was immediately withdrawn and antibiotic prophylaxis was instituted. It was not possible to place an endobronchial stent. Two weeks later, flexible bronchoscopy revealed the reappearance of a yellowish mass protruding into the bronchus intermedius (40% obstruction). A few months later, the obstruction of the bronchus intermedius progressed to 90% and was associated with a contralateral obstruction of the left mainstem bronchus (20%). A rigid bronchoscopy was then performed to clear the obstruction and an endobronchial stent was placed, with satisfactory initial results. In February 2008, the patient presented with new bronchial obstruction under the endobronchial stent but refused a rigid bronchoscopy and died in March 2008. Discussion: Sunitinib, a multitarget tyrosine kinase inhibitor with antiangiogenic and antitumoral activities, has been approved for the treatment of advanced renal cell carcinoma. This treatment is generally well tolerated. Serious complications may occur, however. According to the Naranjo probability scale, the bronchial fistula was possibly related to sunitinib treatment. Conclusions: This is a rare case of a bronchial perforation leading to a fistula associated with sunitinib treatment after mediastinal radiation therapy. Clinicians may consider strict follow-up of patients with proximal lung metastases treated with sunitinib (CT scan and, if appropriate, placement of an endobronchial stent).
Experimental Investigation of Preheated Jatropha Oil Fuelled Direct Injection Compression Ignition Engine—Part 2: Engine Durability and Effect on Lubricating Oil
Authors: Agarwal Avinash Kumar , Dhar Atul 
Published: January 2010

Abstract
Straight vegetable oil utilization as diesel engine fuel has the advantage of eliminating the energy, time, and cost involved in biodiesel production. Since straight vegetable oils have relatively higher viscosity compared to mineral diesel, they have to be modified to bring their combustion related properties closer to mineral diesel. In this study, a heat exchanger was used to utilize the waste heat of engine exhaust gas for reducing the viscosity of jatropha oil, and the performance, emission, and combustion characteristics are described in the first part of the paper. Carbon deposits, wear of vital engine parts, and the effect of jatropha oil on lubricating oil properties were analyzed in long-term endurance test for 512 h. The effect on lubricating oil of heated jatropha oil (J100) as well as 50 % blend of jatropha oil (J50) were compared with mineral diesel by comparing the lubricant’s density, viscosity, flash point, carbon residue, ash content, copper corrosion, and pentane and benzene insoluble measurements after an interval of every 128 h. Wear of the cylinder liner, diameter of piston, piston rings, gudgeon pin, and small and big-end bearings for J100 and J50 were measured vis-à-vis mineral diesel. Jatropha oil fuelled engine first undergoes lowering of lubricating oil viscosity followed by severe vegetable oil initiated oxidation of lubricating oil base-stock and thus the life of the lubricating oil gets depleted in approximately 400 h. The wear of J50 fuelled engine liner is found to be relatively lower compared to mineral diesel fuelled engine.
Glass Formation and Mechanical Properties of Ti–Cu–Ni Alloys with High Ti Content
Authors: Zhang S. G. , Hu G. H. , Meng Q. G. , Li J. G. 
Published: January 2010

Abstract
A series of Ti–Cu–Ni alloys with Ti content as high as 50–70 at. % expected to possess potential high glass-forming ability (GFA) was designed according to the ε criterion (Xia, M. X., Zhang, S. G., Ma, C. L., and Li, J. G., “Evaluation of Glass-Forming Ability for Metallic Glasses Based on Order-Disorder Competition,” Appl. Phys. Lett. Vol. 89, 2006, pp. 091917-1–091917-3) and were prepared by melt spinning and suck casting methods. The samples were examined by X-ray diffractometry, differential scanning calorimetry, optical microscopy, scanning electronic microscopy, and quasistatic compression test. The GFA of the melt-spun ribbons is enhanced with increasing ε. Ti58Cu32Ni10 alloy with the maximum designed ε value of 0.542 exhibits best GFA with a glass transition temperature of 627 K and a wide supercooled liquid region of 45 K. However, this alloy failed to form a fully glassy rod of 1 mm in diameter. Room temperature compression tests reveal that the 1 mm diameter Ti58Cu32Ni10 glass composite exhibits work-hardening characteristic, with ultimate compressive stress of 2418 MPa, yielding stress σ0.2 of 1448 MPa and about 7.8 % plastic strain. The combination of high strength and ductility was attributed to a dendritic TiCu(Ni) network embedded in the hard glass matrix.
Initiation Behavior of Crack Originated from Non-Metallic Inclusion in Rolling Contact Fatigue
Authors: Tsunekage Norimasa , Hashimoto Kazuya , Fujimatsu Takeshi , Hiraoka Kazuhiko 
Published: January 2010

Abstract
Recently, it has been generally accepted that flaking life is dependent on the size of non-metallic inclusion under proper condition in bearing use. Statistics of extreme values to predict the maximum non-metallic inclusion size and ultrasonic test to assess large non-metallic inclusions in a large volume are widely used as practical methods for the evaluation of bearing steel cleanliness. Murakami’s formula is well known, which describes the relationship between non-metallic inclusion size and fatigue strength. However, the formula cannot be directly applied to rolling contact fatigue because of the difference in applied stress mode. While the equation was invented to predict the fatigue limit in principal stress mode, rolling contact fatigue is mainly caused by shear stress. It is expected that the condition of bearing use will be more critical due to the downsizing tendency in various industrial or automotive machine units. Thus the research on the flaking mechanism becomes more important from the viewpoint of global ecology because that is beneficial to the improvement in bearing life and methods for cleanliness evaluation. Due to the difficulty in experimental observation, however, the details of the flaking mechanism in rolling contact fatigue caused by non-metallic inclusion has not yet been clarified. Focusing on the relationship between non-metallic inclusion and initiation of the crack, the flaking mechanism is proposed in this paper.
Two New Species of Choreutinula (Collembola: Hypogastruridae) from America and China
Authors: Palacios-Vargas José G , Castaño-Meneses Gabriela , Gao Yang 
Published: January 2010

Abstract
Two new species of Choreutinula Paclt 1944 are described and illustrated. One American, from North Dakota, which differs from other species by the presence of 4+4 setae on ventral tube and small setae p3 on Abd. V. The other species is from China, resembles Choreutinula inermis (Tullberg, 1871), is the second species of the genus recorded from Asia, and it differs from other species by the presence of 4+4 setae on ventral tube, as the American species, but shows nine tubercles between setae p1-p1 on Abd. IV and has the unguiculus as a minute bristle. A key for the six species now known in the genus is given.
Life History Studies of Homalodisca vitripennis (Hemiptera: Cicadellidae), a Vector of Pierce's Disease of Grapevine
Authors: Lauzière Isabelle , Sétamou Mamoudou 
Published: January 2010

Abstract
Homafodisca vitripennis (Germar) (Hemiptera: Cicadellidae) vectors Xylella fastidiosa, a bacterium causing Pierce's disease in grapevine. The development and reproductive biology of this economically important insect species were studied under greenhouse and laboratory conditions during the spring—summer and fall—winter and at different rearing densities. The greenhouse was heated during the cool months to match summer temperatures and photoperiods were enhanced artificially. Longevity was affected by sex and season, with winter individuals living significantly longer than summer males (6.5-fold) and females (two-fold). Vitellogenesis was delayed in fall female H. vitripennis and a higher variability in lifetime fecundities was also observed. Longevity and the factors influencing it such as environmental conditions and availability of food sources are key factors determining fecundity in H. vitripennis. Offspring performance (developmental time, survival) was moderate during the cool months, although development of nymphs to adulthood was ≈13% greater. Rearing densities affected developmental time, survival, and egg production. Egg production per capita was higher in winter adults and the largest egg output was obtained at a rearing density of 100 nymphs per cage. Data presented herein suggest that nymph and adult H. vitripennis have evolved to ensure that only resistant stages are exposed to seasonal hazards. Captive adult females entered reproductive diapause in the fall as wild females would and despite warm greenhouse temperatures and long photoperiods and nymphal development decreased three- to six-fold during the fall-winter depending on rearing densities. These traits may be critical for the species to perpetuate in its native range.