bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of HIF-1alpha activity by homeodomain-interacting protein kinase-2 correlates with sensitization of chemoresistant cells to undergo apoptosis
Authors: Nardinocchi Lavinia , Puca Rosa , Sacchi Ada , D'Orazi Gabriella 
Published: January 2009

AbstractBackgroundHomeodomain-interacting protein kinase-2 (HIPK2), a transcriptional co-repressor with apoptotic function, can affect hypoxia-inducible factor 1 (HIF-1) transcriptional activity, through downmodulation of its HIF-1α subunit, in normoxic condition. Under hypoxia, a condition often found in solid tumors, HIF-1α is activated to induce target genes involved in chemoresistance, inhibition of apoptosis and tumor progression. Here, we investigated whether the HIPK2 overexpression could downregulate HIF-1α expression and activity in tumor cells treated with hypoxia-mimicking condition, and evaluated whether HIPK2-dependent downregulation of HIF-1α could sensitize chemoresistant tumor cells to adriamycin (ADR)-induced apoptosis.MethodsTumor cell lines carrying wild-type p53, siRNA p53, or mutant p53 were overexpressed with HIPK2 (full length or catalytic inactive mutant) and treated with cobalt chloride (CoCl2) to mimic hypoxia, in the presence or absence of ADR treatment. HIF-1α expression was measured by semiquantitative reverse-transcriptase (RT)-PCR and Western immunoblotting and HIF-1 activity was evaluated by luciferase assay using reporter plasmid containing hypoxia response elements (HREs) upstream of luciferase gene. HIF-1 target genes, including multidrug resistance 1 (MDR1) and the antiapoptotic Bcl2 were determined by RT-PCR. Cell survival and apoptosis were measured by colony assay and cleavage of the caspase-3 substrate PARP, respectively.ResultsOverexpression of HIPK2 resulted in downmodulation of cobalt-stabilized HIF-1α protein and HIF-1α mRNA levels, with subsequent inhibition of HIF-1 transcriptional activity. MDR1 and Bcl-2 gene expression was downmodulated by HIPK2 overexpression in cobalt-treated cells. Inhibition of HIF-1 transcriptional activity was dependent on HIPK2 catalytic activity. HIPK2 overexpression did not induce per se apoptosis of cobalt-treated cells, on the contrary it sensitized cobalt-treated cells to ADR-induced apoptosis, regardless of their p53 status.ConclusionThe ability of HIPK2 to restore the apoptosis-inducing potential of chemotherapeutic drug in hypoxia-mimicking condition and therefore to sensitize chemoresistant tumor cells suggests that HIPK2 may induce fundamental alterations in cell signaling pathways, involving or not p53 function. Thus potential use of HIPK2 is promising for cancer treatment by potentiating cytotoxic therapies, regardless of p53 cell status.
Inhibition of lentivirus replication by aqueous extracts of Prunella vulgaris
Authors: Brindley Melinda A , Widrlechner Mark P , McCoy Joe-Ann , Murphy Patricia , Hauck Cathy , Rizshsky Ludmila , Nikolau Basil , Maury Wendy 
Published: January 2009

Abstract

Background
Various members of the mint family have been used historically in Chinese and Native American medicine. Many of these same family members, including Prunella vulgaris, have been reported to have anti-viral activities. To further characterize the anti-lentiviral activities of P. vulgaris, water and ethanol extractions were tested for their ability to inhibit equine infectious anemia virus (EIAV) replication.

Results
Aqueous extracts contained more anti-viral activity than did ethanol extracts, displaying potent anti-lentiviral activity against virus in cell lines as well as in primary cell cultures with little to no cellular cytotoxicity. Time-of-addition studies demonstrated that the extracts were effective when added during the first four h of the viral life cycle, suggesting that the botanical constituents were targeting the virion itself or early entry events. Further analysis revealed that the extracts did not destroy EIAV virion integrity, but prevented viral particles from binding to the surface of permissive cells. Modest levels of anti-EIAV activity were also detected when the cells were treated with the extracts prior to infection, indicating that anti-EIAV botanical constituents could interact with both viral particles and permissive cells to interfere with infectivity. Size fractionation of the extract demonstrated that eight of the nine fractions generated from aqueous extracts displayed anti-viral activity. Separation of ethanol soluble and insoluble compounds in the eight active fractions revealed that ethanol-soluble constituents were responsible for the anti-viral activity in one fraction whereas ethanol-insoluble constituents were important for the anti-viral activity in two of the other fractions. In three of the five fractions that lost activity upon sub-fractionation, anti-viral activity was restored upon reconstitution of the fractions, indicating that synergistic anti-viral activity is present in several of the fractions.

Conclusion
Our findings indicate that multiple Prunella constituents have profound anti-viral activity against EIAV, providing additional evidence of the broad anti-viral abilities of these extracts. The ability of the aqueous extracts to prevent entry of viral particles into permissive cells suggests that these extracts may function as promising microbicides against lentiviruses.
Genotoxic responses to titanium dioxide nanoparticles and fullerene in gpt delta transgenic MEF cells
Authors: Xu An , Chai Yunfei , Nohmi Takehiko , Hei Tom K 
Published: January 2009

Abstract

Background
Titanium dioxide (TiO2) nanoparticles and fullerene (C60) are two attractive manufactured nanoparticles with great promise in industrial and medical applications. However, little is known about the genotoxic response of TiO2 nanoparticles and C60 in mammalian cells. In the present study, we determined the mutation fractions induced by either TiO2 nanoparticles or C60 in gpt delta transgenic mouse primary embryo fibroblasts (MEF) and identified peroxynitrite anions (ONOO-) as an essential mediator involved in such process.

Results
Both TiO2 nanoparticles and C60 dramatically increased the mutation yield, which could be abrogated by concurrent treatment with the endocytosis inhibitor, Nystatin. Under confocal scanning microscopy together with the radical probe dihydrorhodamine 123 (DHR 123), we found that there was a dose-dependent formation of ONOO- in live MEF cells exposed to either TiO2 nanoparticles or C60, and the protective effects of antioxidants were demonstrated by the nitric oxide synthase (NOS) inhibitor, NG-methyl-L-arginine (L-NMMA). Furthermore, suppression of cyclooxygenase-2 (COX-2) activity by using the chemical inhibitor NS-398 significantly reduced mutation frequency of both TiO2 nanoparticles and C60.

Conclusion
Our results provided novel information that both TiO2 nanoparticles and C60 were taken up by cells and induced kilo-base pair deletion mutations in a transgenic mouse mutation system. The induction of ONOO- may be a critical signaling event for nanoparticle genotoxicity.
Novel multicellular organotypic models of normal and malignant breast: tools for dissecting the role of the microenvironment in breast cancer progression
Authors: Holliday Deborah L , Brouilette Kellie T , Markert Anja , Gordon Linda A , Jones J Louise 
Published: January 2009

Abstract
Introduction
There is increasing recognition of the role of the microenvironment in the control of both normal and tumour cell behaviour. In the breast, myoepithelial cells and fibroblasts can influence tumour cell behaviour, with myoepithelial cells exhibiting a broad tumour-suppressor activity while fibroblasts frequently promote tumour growth and invasion. This study describes the development of physiologically relevant three-dimensional heterotypic culture systems containing mixed normal or tumour-derived breast populations and shows how such models can be used to dissect the interactions that influence cell behaviour.

Methods
Populations of luminal cells, myoepithelial cells and fibroblasts were isolated from normal and malignant breast tissue, characterised and compared with immortalised cell lines. Co-localisation of normal and malignant luminal cells with myoepithelial cells alone or with either normal or tumour-derived fibroblasts was studied. Cultures were grown for seven days, and then gels were fixed and whole gel immunofluorescence carried out to assess co-localisation and polarisation. The potential role of matrix metalloproteinases (MMP) or hepatocyte growth factor(HGF)-c-met signalling in disrupting cellular organisation was investigated by incorporating inhibitors into cultures either alone or in combination.

Results
Over a culture period of seven days, myoepithelial cells organised themselves around luminal cell populations forming dual-cell co-units. Characterisation of co-units showed established basal polarity and differentiation analogous to their in vivo counterparts. Tumour cell co-units revealed subtle differences to normal co-units including disruption of basement membrane and loss of β4-integrin, as described in ductal carcinoma in situ (DCIS) in vivo. Inclusion of normal fibroblasts had no influence on co-unit formation; however, inclusion of tumour-associated fibroblasts lead to disruption of co-unit organisation, and this was significantly inhibited in the presence of MMP and/or c-met inhibitors.

Conclusions
To the best of the authors' knowledge, this study describes for the first time a co-culture model comprising three major components of normal and malignant breast: luminal cells, myoepithelial cells and stromal fibroblasts. These cells organise into structures recapitulating normal and DCIS breast, with homing of myoepithelial cells around the luminal population. Importantly, differences are exhibited between these systems reflecting those described in tissues, including a central role for tumour-associated fibroblasts and MMPs in mediating disruption of normal structures. These findings support the value of these models in dissecting normal and tumour cell behaviour in an appropriate microenvironment.
The clinical significance of below-knee great saphenous vein reflux following endovenous laser ablation of above-knee great saphenous vein
Authors: Theivacumar N S , Darwood R J , Dellegrammaticas D , Mavor A I D , Gough M J 
Published: January 2009

Aims The standard technique for endovenous laser ablation (EVLA) for varicose veins due to great saphenous vein (GSV) reflux involves obliteration of the above-knee (AK) GSV. This study assesses the significance of persistent below-knee (BK) GSV reflux following such therapy. Methods Sixty-nine limbs (64 patients) with varicosities and GSV reflux underwent AK-EVLA. Post treatment, GSV reflux (ultrasound: six, 12 weeks) and Aberdeen varicose vein severity scores (AVVSS, 12 weeks) were assessed, and residual varicosities treated with foam sclerotherapy (six weeks). Results The untreated BK-GSV remained patent in all limbs. Ultrasound showed normal antegrade flow in 34/69 (49%, Group A), flash reflux <1 s in 7/69 (10%, Group B) and >1 s reflux in 28/69 (41%, Group C). Although AVVSS improved in all groups ( P < 0.001): A: 14.6 (8.4–19.3) versus 2.8 (0.5–4.4), B: 13.9 (7.5–20.1) versus 3.7 (2.1–6.8), C: 15.1 (8.9–22.5) versus 8.1 (5.3–12.6) the improvement was less in Group C ( P < 0.001 versus A and B) and was associated with a greater requirement (A: 4/34 [12%]; B: 1/7 [14%]; C: 25/28 [89%]) for sclerotherapy (persisting varicosities) ( P < 0.001). Conclusion Although AK-GSV EVLA improves symptoms regardless of persisting BK reflux, the latter appears responsible for residual symptoms and a greater need for sclerotherapy for residual varicosities.
Meta-analysis of subfascial endoscopic perforator vein surgery (SEPS) for chronic venous insufficiency
Authors: Luebke T , Brunkwall J 
Published: January 2009

Objectives The degree of benefits and risks, and the role of subfascial endoscopic perforator vein surgery (SEPS) in the management for chronic venous insufficiency (CVI) remains uncertain. Methods A multiple health database search was performed including Medline, Embase, Ovid, Cochrane Database of Systematic Reviews, and Cochrane Database of Abstracts of Reviews of Effectiveness, on all studies published between 1985 and 2008 that reported on health outcomes in patients with CVI treated with SEPS and comparing this therapy with the conventional Linton procedure. Three studies, which compared SEPS with conventional surgery, were included in the present meta-analysis. Results Between SEPS and Linton groups, there was a significant lower rate of wound infections for SEPS (odds ratio [OR] 0.06 [95% confidence interval (CI) 0.02 to 0.25]) and a significantly reduced hospital stay for SEPS (OR –8.96 [95% CI –11.62 to –6.30]). In addition, SEPS was associated with a significant reduced rate of recurrent ulcers (mean follow-up 21 months) (OR 0.15 [95% CI 0.04–0.62]). There was no significant difference between the groups in the following dimensions: rate of hospital re-admission (OR 0.21 [95% CI 0.03 –1.31]), death at six months (OR 3.00 [95% CI 0.11–78.27]), ulcer healing rate at four months (OR 0.44 [95% CI 0.09–2.12]), and the rate of deep vein thrombosis (DVT) (OR 0.35 [95% CI 0.01–8.85]). Conclusion From the level of evidence available by now it seems that SEPS, used as a part of a treatment regimen for severe CVI, benefits most patients in the short term regarding ulcer healing and the prevention of ulcer recurrence. It can be safely performed with less early postoperative complications compared with the Linton procedure. However, further prospective randomized trials are required to define the long-term benefits of SEPS.
Energy Efficient and Eco-friendly Intensively Quenched Limited Hardenability Low Alloy Steels
Authors: Kobasko Nikolai I. 
Published: January 2009

Abstract
Low and limited hardenability (LH) steels are plain carbon steels characterized by a low content of alloying elements (Cr, Ni, Mo, W, V, etc.). The use of LH steels with an intensive quenching method allows full elimination of the carburization process for a variety of steel parts, such as, gear and bearing products, tools, low-wear parts for different applications. This is based on the steel super strengthening phenomenon and creation of high residual compressive stresses at the surface of intensively quenched steel parts. Both of these factors allow replacing expensive alloy steels with plain carbon steels. The unique characteristic of limited hardenability steels is that these alloys only harden to a shallow depth when heated and quenched. The main idea of this paper involves the creation of the optimal depth of a hardened shell which provides optimal stress distribution in quenched steel parts. Since the LH steel core does not harden significantly, a relatively high ductility of the core is maintained. The grain sizes of LH steels are greater than ASTM 8. Several patents on LH steels have been issued in Europe. A number of technical papers utilizing LH steels for gears and bearing products have been published in the UkrainePapers published by and available from Intensive Technologies Ltd, Kyiv, Ukraine: http://www.itl.kiev.ua and Russia. Elimination of carburizing saves energy and prevents the emissions of thousands of tons of CO2 gases. Furthermore, the high level of compressive surface residual stresses and the steel super strengthening phenomenon eliminates the need for secondary shot peening or surface induction operations. Also, carburized alloy steels can be successfully replaced by LH steels to increase service life and decrease materials cost.
Evaluation of Semicircular Bending Test for Determining Tensile Strength and Stiffness Modulus of Asphalt Mixtures
Authors: Huang Likui , Cao Keming , Zeng Menglan 
Published: January 2009

Abstract
The semicircular bending (SCB) test has been shown to possess several advantages over other tests in characterizing asphalt mixtures in previous studies. This research study evaluates the SCB test for determining the tensile strength and stiffness modulus of the paving material with numerical simulation and laboratory experimentation. An analytical model describing the tensile stress at the middle point of the lower surface of the specimen in the SCB test was developed based on the plane assumption in mechanics of materials. Analysis using the finite element method indicated that the error induced by the model was within 2 %. Laboratory experiment carried out on three types of asphalt mixtures at various temperatures showed that the strength of the material by the SCB test was nearly 50 % higher on average than that by the flexural beam bending (FBB) test due to such factors as complexities in stress and strain states as well as nonlinearity and viscoelasticity of the material. Laboratory experiment also showed that the stiffness moduli for 10–40 % of maximum load from the FBB test and from the SCB test were in a well-defined linear relationship with differences less than 10 %. In addition, based on finite element analysis, a practical approach for determining stiffness modulus of asphalt mixtures using deflection at the middle point of the lower surface of the specimen in the SCB test was established.
Coexistence of hydrogen and polyanions in multinary main group element hydrides
Authors: Häussermann Ulrich 
Published: January 2009

Abstract
Multinary hydrides based on mixtures of s- and p-block metals are often not fully hydrogenated, but possess a polymeric anion which is formed by the p-block component upon reduction by the s-block metals. Hydrogen may occur hydridic and exclusively coordinated by s-block metal ions (Zintl phase hydrides), or be incorporated in the polymeric anion where it acts as a covalently bonded terminating ligand (polyanionic hydrides). The current state of Zintl phase hydrides and polyanionic hydrides is reviewed with an emphasis on crystal structures and bonding principles.
Structural transitions induced by hydrogen absorption in metallic hydrides
Authors: Latroche Michel J. 
Published: January 2009

Abstract
Intermetallic compounds are able to store reversibly large amount of hydrogen. The hydride formation usually takes place through a two-phase domain for which an equilibrium plateau is observed between the metallic phase and its hydride. Such phase transformation induces important structural changes such as volume expansion (either isotropic and anisotropic), symmetry lowering, hydrogen ordering and phase transitions. In some cases, change of the electronic structure, from metallic to iono-covalent state, is reported. Finally, amorphization can occur leading to disproportionation of the parent compound. In this overview we give some examples of these different behaviors to illustrate the fascinating structural properties of these materials that are of potential interest from the fundamental point of view and for practical applications like energy storage either by solid-gas or electrochemical routes.
Hydrogen induced site depopulation in the LaMgNi4-hydrogen system
Authors: Chotard Jean-Noël , Sheptyakov Denis , Yvon Klaus 
Published: January 2009

Abstract
The LaMgNi4-hydrogen system was investigated by in-situ neutron powder diffraction and pressure-composition isotherm measurements at 100 °C and hydrogen (deuterium) pressures of up 50 bar. The system displays three hydride phases that have distinctly different hydrogen plateau pressures and H atom distributions. The cubic α-LaMgNi4H0.75 phase forms below 0.01 bar hydrogen pressure and H atoms fill one type of tetrahedral Ni4 interstices. The orthorhombic distorted β-LaMgNiH3.7 phase forms at about 3 bar hydrogen pressure and H atoms fill both tetrahedral LaNi3 and triangular bi-pyramidal La2MgNi2 interstices. Interestingly, tetrahedral Ni4 interstices are no longer occupied. Finally, the most hydrogen rich γ-LaMgNi4H4.85 phase forms above 20 bar. It has again cubic symmetry and H atoms continue to occupy triangular bi-pyramidal La2MgNi2 interstices while filling a new type of tetrahedral Ni4 interstices that are neither occupied in the α- nor in the β-phase. The tetrahedral LaNi3 interstices occupied in the β-phase are empty. Hydrogen induced depopulations of interstitial sites in metal hydrides are relatively rare and consistent with, but not entirely due to, the onset of repulsive H–H interactions at increasing hydrogen concentrations.
The nature of deuterium arrangements in YD3 and other rare-earth trideuterides
Authors: Udovic Terrence J. , Huang Qingzhen , Santoro Antonio , Rush John J. 
Published: January 2009

Abstract
The efficacy of different structural models for describing the observed neutron-powder-diffraction (NPD) measurements of bulk polycrystalline YD3 as well as other hexagonal rare-earth (i.e., Nd, Tb, Dy, Ho, Er, and Tm) trideuteride powders has been investigated via Rietveld refinement. Between the two possible structural configurations, centrosymmetric P-3c1 and noncentrosymmetric P63
cm, the latter can be excluded due to very high correlations found between the positions of the D sites. Hence, the true “diffraction-average” structure for YD3 and all other rare-earth deuterides studied is centrosymmetric (P-3c1). This seems to contrast with the prior evidence from first-principles calculations and various spectroscopic probes suggesting that the true local symmetry is not P-3c1, but rather, noncentrosymmetric. A possible way to reconcile the apparently conflicting conclusions from NPD and spectroscopic measurements is by assuming that the real structure is a twinned arrangement of nanosized, noncentrosymmetric configurations. For example, we demonstrate that the diffraction-average centrosymmetric P-3c1 structure can result from a superposition of individual, noncentrosymmetric P3c1 twins. A comparison of neutron vibrational spectra for YH3 and YD3 confirms that both compounds share similar structural arrangements.
The Fixation Probability of Rare Mutators in Finite Asexual Populations
Authors: Wylie C Scott , Ghim Cheol-Min , Kessler David , Levine Herbert 
Published: January 2009

Abstract
A mutator is an allele that increases the mutation rate throughout the genome by disrupting some aspect of DNA replication or repair. Mutators that increase the mutation rate by the order of 100-fold have been observed to spontaneously emerge and achieve high frequencies in natural populations and in long-term laboratory evolution experiments with Escherichia coli. In principle, the fixation of mutator alleles is limited by (i) competition with mutations in wild-type backgrounds, (ii) additional deleterious mutational load, and (iii) random genetic drift. Using a multiple-locus model and employing both simulation and analytic methods, we investigate the effects of these three factors on the fixation probability Pfix of an initially rare mutator as a function of population size N, beneficial and deleterious mutation rates, and the strength of mutations s. Our diffusion-based approximation for Pfix successfully captures effects ii and iii when selection is fast compared to mutation ($\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{{\mu}}/s{\ll}1\) \end{document}$). This enables us to predict the conditions under which mutators will be evolutionarily favored. Surprisingly, our simulations show that effect i is typically small for strong-effect mutators. Our results agree semiquantitatively with existing laboratory evolution experiments and suggest future experimental directions.