bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human immunodeficiency virus and human papilloma virus - why HPV-induced lesions do not spontaneously resolve and why therapeutic vaccination can be successful
Authors: van der Burg Sjoerd H , Palefsky Joel M 
Published: December 2009

AbstractHIV and HPV can both cause chronic infections and are acquired during sexual contact. HIV infection results in a progressive loss of CD4+ T cells that is associated with an increased prevalence of HPV infections, type-specific persistence and an increase in HPV-associated malignancies. On the one hand this illustrates the important role of HPV-specific CD4+ helper T-cell immunity, on the other it shows the Achilles heel of the HPV-specific immune response. The use of highly active antiretroviral therapy (HAART) results in a rapid reduction of HIV and a reconstitution of systemic CD4+ T-cell levels. The use of HAART thus has the potential to raise immunity to HPV but to the surprise of many, the incidence of HPV-induced diseases has increased rather than declined since the introduction of HAART. Here, the knowledge on how HPV-induced diseases develop in the face of a non-compromised immune system will be used to explain why the effect of HAART on HPV-induced diseases is modest at best. Furthermore, exciting new data in the field of therapeutic vaccines against HPV will be discussed as this may form a more durable and clinically successful therapeutic approach for the treatment of HPV-induced high-grade lesions in HIV-positive subjects on HAART.
Replication and drug resistant mutation of HIV-1 subtype B' (Thailand B) variants isolated from HAART treatment individuals in China
Authors: Sun Jianping , Ma Liying , Yu Xiaoling , Huang Yang , Yuan Lin , Shao Yiming 
Published: December 2009

AbstractBackgroundDrug resistant HIV-1 variants were emergent more and more in AIDS individuals with highly active antiretroviral therapy (HAART) treatment. Understanding the replication and drug resistant mutation of HIV-1 variants isolated from HAART treatment individuals of China could help to design appropriate therapeutic strategies for these individuals.MethodsUse GHOST cell lines to analysis the coreceptor usage of HIV-1 variants. Coculture with PBMCs to analysis the replication capacity. Use RT-PCR to analysis the drug resistant mutation ofpolgene.Results13 HIV-1 variants experienced HAART were included in this study. 5 HIV-1 variants used CCR5 coreceptor (R5), while 8 use both CCR5 and CXCR4 coreceptor (R5X4). The replication capacity of R5X4 variants was no difference with R5 variants in vitro without antiretroviral drugs. Compare the drug resistant mutation between first HIV-1 variants and fourth variants; there were 37 drug resistant mutations in first variants and 32 drug resistant mutations in fourth variants. Only 7 drug resistance mutations were lost after coculture for 4 weeks, and 2 drug resistance mutations were emerged.ConclusionThese data suggested that the drug resistant level could not reduce in vitro in absence of antiretroviral drugs in few weeks. And maybe helpful for these HAART experienced individuals when change antiretroviral drugs.
Acute dosing of latrepirdine (Dimebon™), a possible Alzheimer therapeutic, elevates extracellular amyloid-β levels in vitro and in vivo
Authors: Steele John W , Kim Soong H , Cirrito John R , Verges Deborah K , Restivo Jessica L , Westaway David , Fraser Paul , Hyslop Peter St George , Sano Mary , Bezprozvanny Ilya , Ehrlich Michelle E , Holtzman David M , Gandy Sam 
Published: December 2009

Abstract

Background
Recent reports suggest that latrepirdine (Dimebon™, dimebolin), a retired Russian antihistamine, improves cognitive function in aged rodents and in patients with mild to moderate Alzheimer's disease (AD). However, the mechanism(s) underlying this benefit remain elusive. AD is characterized by extracellular accumulation of the amyloid-β (Aβ) peptide in the brain, and Aβ-lowering drugs are currently among the most popular anti-amyloid agents under development for the treatment of AD. In the current study, we assessed the effect of acute dosing of latrepirdine on levels of extracellular Aβ using in vitro and in vivo experimental systems.

Results
We evaluated extracellular levels of Aβ in three experimental systems, under basal conditions and after treatment with latrepirdine. Mouse N2a neuroblastoma cells overexpressing Swedish APP were incubated for 6 hr in the presence of either vehicle or vehicle + latrepirdine (500pM-5 μM). Synaptoneurosomes were isolated from TgCRND8 mutant APP-overexpressing transgenic mice and incubated for 0 to 10 min in the absence or presence of latrepirdine (1 μM or 10 μM). Drug-naïve Tg2576 Swedish mutant APP overexpressing transgenic mice received a single intraperitoneal injection of either vehicle or vehicle + latrepirdine (3.5 mg/kg). Picomolar to nanomolar concentrations of acutely administered latrepirdine increased the extracellular concentration of Aβ in the conditioned media from Swedish mutant APP-overexpressing N2a cells by up to 64% (p = 0.01), while a clinically relevant acute dose of latrepirdine administered i.p. led to an increase in the interstitial fluid of freely moving APP transgenic mice by up to 40% (p = 0.01). Reconstitution of membrane protein trafficking and processing is frequently inefficient, and, consistent with this interpretation, latrepirdine treatment of isolated TgCRND8 synaptoneurosomes involved higher concentrations of drug (1-10 μM) and led to more modest increases in extracellular Aβx-42 levels (+10%; p = 0.001); of note, however, was the observation that extracellular Aβx-40 levels did not change.

Conclusions
Here, we report the surprising association of acute latrepirdine dosing with elevated levels of extracellular Aβ as measured in three independent neuron-related or neuron-derived systems, including the hippocampus of freely moving Tg2576 mice. Given the reported association of chronic latrepirdine treatment with improvement in cognitive function, the effects of chronic latrepirdine treatment on extracellular Aβ levels must now be determined.
Ranges of control in the transcriptional regulation of Escherichia coli
Authors: Sonnenschein Nikolaus , Hütt Marc-Thorsten , Stoyan Helga , Stoyan Dietrich 
Published: December 2009

Abstract

Background
The positioning of genes in the genome is an important evolutionary degree of freedom for organizing gene regulation. Statistical properties of these distributions have been studied particularly in relation to the transcriptional regulatory network. The systematics of gene-gene distances then become important sources of information on the control, which different biological mechanisms exert on gene expression.

Results
Here we study a set of categories, which has to our knowledge not been analyzed before. We distinguish between genes that do not participate in the transcriptional regulatory network (i.e. that are according to current knowledge not producing transcription factors and do not possess binding sites for transcription factors in their regulatory region), and genes that via transcription factors either are regulated by or regulate other genes. We find that the two types of genes ("isolated" and "regulatory" genes) show a clear statistical repulsion and have different ranges of correlations. In particular we find that isolated genes have a preference for shorter intergenic distances.

Conclusions
These findings support previous evidence from gene expression patterns for two distinct logical types of control, namely digital control (i.e. network-based control mediated by dedicated transcription factors) and analog control (i.e. control based on genome structure and mediated by neighborhood on the genome).
The transcription factor RBP-J is essential for retinal cell differentiation and lamination
Authors: Zheng Min-Hua , Shi Ming , Pei Zhe , Gao Fang , Han Hua , Ding Yu-Qiang 
Published: December 2009

Abstract

Background
The highly ordered vertebrate retina is composed of seven cell types derived from a common pool of retinal progenitor cells (RPCs), and is a good model for the studies of cell differentiation and interaction during neural development. Notch signaling plays a pivotal role in retinogenesis in mammals, but the full scope of the functions of Notch pathway, and the underlying molecular mechanisms, remain unclear.

Results
In this study, we conditionally knocked out RBP-J, the critical transcription factor downstream to all four Notch receptors, in RPCs of mouse retina at different developmental stages. Disruption of RBP-J at early retinogenesis resulted in accelerated RPCs differentiation, but only photoreceptors and ganglion cells were overrepresented, with other neuronal populations diminished. Similarly, deletion of RBP-J at early postnatal days also led to overproduction of photoreceptors, suggesting that RBP-J governed RPCs specification and differentiation through retinogenesis. In all the RBP-J deletion models, the retinal laminar structures were distorted by the formation of numerous rosette-like structures, reminiscent of β-catenin deficient retina. Indeed, we found that these rosettes aligned with gaps in β-catenin expression at the apical surface of the retina. By in vivo electroporation-mediated transfection, we demonstrated that lamination defects in RBP-J deficient retinae were rescued by overexpressing β-catenin.

Conclusions
Our data indicate that RBP-J-mediated canonical Notch signaling governs retinal cell specification and differentiation, and maintains retinal lamination through the expression of β-catenin.
Reduced expression of cenp-e in human hepatocellular carcinoma
Authors: Liu Zijie , Ling Kang , Wu Xia , Cao Ju , Liu Bin , Li Suyan , Si Qiong , Cai Yan , Yan Chen , Zhang Yan , Weng Yaguang 
Published: December 2009

Abstract

Background
CENP-E, one of spindle checkpoint proteins, plays a crucial role in the function of spindle checkpoint. Once CENP-E expression was interrupted, the chromosomes can not separate procedurally, and may result in aneuploidy which is a hallmark of most solid cancers, such as hepatocellular carcinoma (HCC). We investigate the expression of CENP-E in human hepatocellular carcinoma,. and analyze the effect of low CENP-E expression on chromosome separation in normal liver cell line (LO2).

Methods
We determined its levels in HCC and para-cancerous tissues, human hepatocellular carcinoma-derived cell line (HepG2) and LO2 cell line using real time quantitative PCR (QPCR) and Western blot. Further to know whether reduction in CENP-E expression impairs chromosomes separation in LO2 cells. we knocked down CENP-E using shRNA expressing vector and then count the aneuploid in LO2 cells using chromosomal counts assay.

Results
We found that both CENP-E mRNA and protein levels were significantly reduced in HCC tissues and HepG2 cells compared with para-cancerous tissues and LO2 cells, respectively. A significantly-increased proportion of aneuploid in these down-knocked LO2 cells compared with those treated with control shRNA vector.

Conclusions
Together with other results, these results reveal that CENP-E expression was reduced in human HCC tissue, and low CENP-E expression result in aneuploidy in LO2 cells.
Interleukin-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates interleukin-17A and RORγt in γδ T cells
Authors: Cornelissen Ferry , Mus Adriana MC , Asmawidjaja Patrick S , van Hamburg Jan Piet , Tocker Joel , Lubberts Erik 
Published: December 2009

Abstract
Introduction
Interleukin (IL)-23 is essential for the development of various experimental autoimmune models. However, the role of IL-23 in non-autoimmune experimental arthritis remains unclear. Here, we examined the role of IL-23 in the non-autoimmune antigen-induced arthritis (AIA) model. In addition, the regulatory potential of IL-23 in IL-17A and retinoic acid-related orphan receptor gamma t (RORγt) expression in CD4+ and TCRγδ+ T cells was evaluated systemically as well as at the site of inflammation.

Methods
Antigen-induced arthritis was induced in wild-type, IL-23p19-deficient and IL-17 Receptor A - knockout mice. At different time points, synovial cytokine and chemokine expression was measured. At days 1 and 7 of AIA, splenocytes and joint-infiltrating cells were isolated and analyzed for intracellular IL-17A and interferon (IFN)-γ ex-vivo by flow cytometry. In splenic CD4+ and TCRγδ+ T cells gene expression was quantified by flow cytometry and quantitative PCR.

Results
IL-23 was critical for full-blown AIA. Lack of IL-23 did not prevent the onset of joint inflammation but stopped the progression to a destructive synovitis. IL-23 regulated IL-17A expression in CD4+ T cells in the spleen. Of note, IL-17A and IFN-γ expression was reduced in CD4+ T cells in the inflamed joints of IL-23p19-deficient mice. Interestingly, IL-23 was also critical for the induction of IL-17A and RORγt but not IFN-γ in TCRγδ+ T cells in the inflamed joints. The importance of the IL-23/IL-17 axis was further confirmed using IL-17 Receptor A knockout mice showing significantly milder AIA compared to control mice, with a disease course comparable to that of IL-23p19-deficient mice.

Conclusions
These data show that IL-23 is critical for full-blown expression of a non-autoimmune destructive arthritis and regulates the proportion of IL-17A and IFN-γ-positive CD4+ T cells at the site of inflammation. Furthermore, IL-23 regulates IL-17A and RORγt expression in TCRγδ T cells in arthritis. These findings indicate that regulating the IL-23 pathway may have therapeutic potential in non-autoimmune arthritis.
Combined effects of single nucleotide polymorphisms TP53 R72P and MDM2 SNP309, and p53 expression on survival of breast cancer patients
Authors: Schmidt Marjanka K , Tommiska Johanna , Broeks Annegien , van Leeuwen Flora E , Van't Veer Laura J , Pharoah Paul DP , Easton Douglas F , Shah Mitul , Humphreys Manjeet , Dörk Thilo , Reincke Scarlett A , Fagerholm Rainer , Blomqvist Carl , Nevanlinna Heli 
Published: December 2009

Abstract
Introduction
Somatic inactivation of the TP53 gene in breast tumors is a marker for poor outcome, and breast cancer outcome might also be affected by germ-line variation in the TP53 gene or its regulators. We investigated the effects of the germ-line single nucleotide polymorphisms TP53 R72P (215G>C) and MDM2 SNP309 (-410T>G), and p53 protein expression in breast tumors on survival.

Methods
We pooled data from four breast cancer cohorts within the Breast Cancer Association Consortium for which both TP53 R72P and MDM2 SNP309 were genotyped and follow-up was available (n = 3,749). Overall and breast cancer-specific survival analyses were performed using Kaplan-Meier analysis and multivariate Cox's proportional hazards regression models.

Results
Survival of patients did not differ by carriership of either germ-line variant, R72P (215G>C) or SNP309 (-410G>T) alone. Immunohistochemical p53 staining of the tumor was available for two cohorts (n = 1,109 patients). Survival was worse in patients with p53-positive tumors (n = 301) compared to patients with p53-negative tumors (n = 808); breast cancer-specific survival: HR 1.6 (95% CI 1.2 to 2.1), P = 0.001. Within the patient group with p53-negative tumors, TP53 rare homozygous (CC) carriers had a worse survival than G-allele (GG/GC) carriers; actuarial breast cancer-specific survival 71% versus 80%, P = 0.07; HR 1.8 (1.1 to 3.1), P = 0.03. We also found a differential effect of combinations of the two germ-line variants on overall survival; homozygous carriers of the G-allele in MDM2 had worse survival only within the group of TP53 C-allele carriers; actuarial overall survival (GG versus TT/TG) 64% versus 75%, P = 0.001; HR (GG versus TT) 1.5 (1.1 to 2.0), P = 0.01. We found no evidence for a differential effect of MDM2 SNP309 by p53 protein expression on survival.

Conclusions
The TP53 R72P variant may be an independent predictor for survival of patients with p53-negative tumors. The combined effect of TP53 R72P and MDM2 SNP309 on survival is in line with our a priori biologically-supported hypothesis, that is, the role of enhanced DNA repair function of the TP53 Pro-variant, combined with increased expression of the Mdm2 protein, and thus overall attenuation of the p53 pathway in the tumor cells.
Modelling and characteristics of a fluid-driven bi-directional motor for an angular position-control system
Authors: Nakao Y , Ishikawa M 
Published: December 2009

A water-driven spindle was developed for use in ultra-precision machine tools. Features of this spindle are: (a) it utilizes water flow power to spin the spindle rotor and (b) it utilizes the water pressure to support the rotor. Bend flow channels are formed in the cross-sections of the spindle rotor so that the power of the water flow can be converted into driving power for spinning the rotor. This paper proposes a spindle structure similar to that of the water-driven spindle. A feature of the proposed spindle is that it can be driven in either rotational direction by switching the supply ports. By virtue of the feature of the proposed spindle, angular position control will become achievable by designing an appropriate control system. Prior to developing the angular position-controllable spindle, a testing device, named the fluid-driven bi-directional motor, was developed. This paper deals with the modelling of the motor that will be needed for designing the angular position control system. The derived mathematical model is then evaluated by comparison with the experimental results. It is then verified that the derived mathematical model is capable of representing the static as well as dynamic characteristics of the motor.
People With Intellectual Disabilities in Iceland: A Bourdieuean Interpretation of Self-Advocacy
Authors: Björnsdóttir Kristín , Jóhannesson IngólfurÁsgeir 
Published: December 2009

AbstractThere are many barriers to social participation in Iceland for people with intellectual disabilities. This article builds on qualitative research with young adults with intellectual disabilities. The purpose of this article is to develop an approach where the struggles over the meaning of social participation of people with intellectual disabilities are seen as social strategies. In the article, the authors suggest that people with intellectual disabilities are carving out a space where intellectual disability is gaining higher social status. They also posit that people with intellectual disabilities use several social strategies in the emerging field of self-advocacy for the purpose of improving their social position. Thus, the article contributes to a new social understanding of disability and how people with disabilities gain authority over their lives and experiences.
Optimal Management of Regional Water Supply Systems Using a Reduced Finite-Element Groundwater ModelOptimierte Bewirtschaftung von regionalen Wasserversorgungssystemen unter Nutzung eines reduzierten Finite-Elemente Grundwassermodells
Authors: Bernard Thomas , Krol Oliver , Linke Hartmut , Rauschenbach Thomas 
Published: December 2009

Abstract
The sustainable management of water resources and a reliable supply of safe drinking water will play a key role for the human prosperity in the following decades. This paper presents an optimal control approach for the management of water resources in a rapid developing region with critical water shortage. A model of the water allocation system is developed which considers both surface and groundwater resources and the distribution network. A reduced model of the complex spatially distributed 3D Finite Element groundwater model is applied. Hence the optimization problem, which is formulated as a large scale structured non-linear programming problem, can be solved with appropriate computation effort. The performance of the proposed concept is analyzed using realistic optimization scenarios.
Colloidal Synthesis of Silicon Nanocrystals Via Inverse Micelles Microemulsion
Authors: Teh Geok Bee , Nagalingam Saravanan , Tilley Richard D. , Ramesh S. , Lim Yun Seng 
Published: December 2009

Abstract
We describe here the synthesis and characterization of silicon nanocrystals prepared by using microemulsion technique which involved the formation of inverse micelles. Colloidal systems employing TOAB as the surfactant molecules were used to synthesise nanosized silicon nanocrystals. The initial reaction of silicon tetrachloride, SiCl4 with a strong reducing agent, NaBH4 produced Si nanocrystals with hydrogen terminated surfaces. The surfaces of the nanocrystals were then capped with 1-heptene which protected the silicon nanocrystals from oxidation. The resultant surface passivated silicon nanocrystals suspended in organic solvent were characterized by Fourier transform infrared spectroscopy, photoluminescence spectroscopy and high resolution transmission electron microscopy. This study provided direct evidence of ageing, stability of different surface passivation and the quantum confinement effect in nanosized silicon nanocrystals.
Phase Diagram for Ionic Liquids
Authors: Lewandowski Andrzej , Swiderska-Mocek Agnieszka 
Published: December 2009

Abstract
Dimensionless reduced melting point T* (thermal energy at the melting point related to the energy of Coulombic interaction) and volume V* (molar volume related to the volume occupied by ions) were calculated from experimental data available in the literature. Calculations were performed for a number of 1:1 valent salts, having melting points in the range from 254 K (room temperature ionic liquid [EtMeIm+][NTf2
−]) and 1268 K (NaF). While the reduced melting temperature was approximately constant (0.12 ± 0.03), the reduced molar volume differed considerably (0.255–1.050). Pairs of V*;T* parameters were used for the construction of a V* = f(T*) phase diagram, which showed one vertical line, indicating regions of salt existence in the solid and liquid states. All V*, T* points, calculated for salts of different melting points, were at the same line.
A Novel Room Temperature Molten Salt Electrolyte Based on LiBOB and 2-Oxazolidinone for Electrochemical Capacitors
Authors: Yang Zhenyu , Li Wei , Yu Shuxian , Zhang Ning , Gu Ningyu , Zhang Rongbin , Gao Lijun 
Published: December 2009

Abstract
In this paper, a novel room temperature molten salt electrolyte based on lithium bis(oxalato)borate (LiB(C2O4)2, LiBOB) and 2-Oxazolidinone (C3H5NO2, OZO) has been prepared as the electrolyte of electrochemical capacitors (EDLCs). The conductivity, thermal stability and electrochemical stability of the LiBOB-OZO electrolytes are investigated. It shows excellent thermal stability, high ionic conductivity (up to 10.4mS cm−1) and a wide electrochemical stability window (4.5 V). The temperature dependence of conductivity for the electrolytes follows the VFT equation, which demonstrates a solvent-assisted ionic conductivity mechanism. Based on it, a specific recipe of the LiBOB-OZO electrolytes (with a molar ratio of 1:6) is evaluated by cylic voltammetry, AC impedance spectroscopy, and galvanostatic charging-discharging in a test EDLC capacitor. It is found that the EDLC with the LiBOB-OZO complex electrolyte can be charged up to 2.5 V, the specific capacitance based on an activated carbon electrode can reach 92.5 F g−1 at 50°C, the equivalent series resistance (ESR) decreases sharply from 18.2 Ω at 30 °C to 7.2 Ω at 70 °C. Then, an EDLC of higher energy density and power density can be obtained，especially in the temperatures above 50 °C