bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liposomal trichostatin A: therapeutic potential in hormone-dependent and -independent breast cancer xenograft models
Authors: Urbinati Giorgia , Marsaud Véronique , Nicolas Valérie , Vergnaud-Gauduchon Juliette , Renoir Jack-Michel 
Published: March 2011

Abstract

Background: Trichostatin A (TSA) is one of the most potent histone deacetylase inhibitors (HDACi) in vitro but it lacks biological activity in vivo when injected intravenously owing to its fast metabolism.

Materials and methods: TSA was incorporated into Stealth® liposomes (TSA-lipo) at a high loading and its anticancer activity was evaluated in several types of breast cancer cells and xenografts.

Results: In estrogen receptor α (ERα)-positive MCF-7 and T47-D cells, TSA induced a long-term degradation of cyclin A and a proteasome-dependent loss of ERα and cyclin D1, allowed derepression of p21WAF1/CIP1, HDAC1 and RhoB GTPase, concomitantly with blockade in G2/M of the cell cycle and apoptosis induction. In MDA-MB-231 (MDA) and SKBr-3 cells, TSA increased ERα mRNA and p21WAF1/CIP1 protein expression, but decreased cyclin A with a G2/M blockade and cleavage of polyADP-ribose polymerase (PARP). No significant restoration of any ER protein was noticed in any cells. TSA-lipo markedly inhibited tumor growth in MCF-7 and MDA cells xenografts following intravenous injection. Their anticancer effects were characterized by inhibition of Ki-67 labeling, the inhibition of tumor vasculature and an increase of p21WAF1/CIP1 in both tumors. In MCF-7 cell tumors, enhanced RhoB accumulation in the cytoplasm of epithelial cells was noticed, inversely to ERα that was strongly decreased.

Conclusion: Such anticancer activity of TSA-lipo is exp-lained by the protection provided by HDACi encapsulation and by the strong tumor accumulation of the nanocarriers as revealed by fluorescence confocal microscopy experi-ments. Together with its lack of toxicity, the enhanced stability of TSA-lipo in vivo justifies its development for therapeutic use in the treatment estradiol-dependent and -independent breast cancers.
Progesterone and cortisol levels in sporadic amyotrophic lateral sclerosis (sALS): correlation with prognostic factors
Authors: Monachelli Gisella Gargiulo , Meyer Maria , Rodríguez Gabriel , Garay Laura , Sica Roberto E. , De Nicola Alejandro F. , Deniselle Maria Claudia González 
Published: March 2011

Abstract
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder. Worse prognostic factors in ALS are: (a) advanced age, (b) bulbar onset, and (c) short time between onset and diagnosis. Progesterone (PROG) has been associated with neuroprotective and promyelinating activities in injury, ischemia and degeneration of the central and peripheral nervous system. Cortisol is connected to the response to stress situations and could contribute to neuronal damage. The goals of this study were: (i) to investigate whether PROG levels are modified by ALS prognostic factors and (ii) to determine whether cortisol follows the same pattern. We determined serum steroid levels in 27 patients with sporadic ALS (sALS) and 21 controls. Both steroid hormones showed significantly increased levels in ALS patients versus controls (mean±SEM: PROG ALS vs. control: 0.54±0.05 vs. 0.39±0.04 ng/mL, p<0.05; cortisol ALS vs. control: 17.02±1.60 vs. 11.83±1.38 μg/dL, p<0.05).1 A trend towards higher levels of PROG were demonstrated in spinal onset patients compared with bulbar onset (p=0.07), positive correlation with survival time (RRho=0.43, p=0.04) and a trend towards significance with time to diagnosis (RRho=0.36, p=0.06). These correlations have not been demonstrated for cortisol. Elevated serum steroid levels in sALS were probably due to hyperfunction of the hypothalamic-pituitary-adrenal axis. However, only PROG correlated with better prognostic factors. Future studies will determine if the different behavior of PROG and cortisol relate to any particular role they might play during the course of this motor neuron degenerative disease.

1Conversion factors from conventional units to SI units: Progesterone ng/mL to nmol/L=3.18 Cortisol μg/dL to nmol/L=27.59
Antihormone induced compensatory signalling in breast cancer: an adverse event in the development of endocrine resistance
Authors: Gee Julia M.W. , Nicholson Robert I. , Barrow Denise , Dutkowski Carol M. , Goddard Lindy , Jordan Nicola J. , McClelland Richard A. , Knowlden Janice M. , Francies Hayley E. , Hiscox Stephen E. , Hutcheson Iain R. 
Published: March 2011

AbstractUsing MCF7 breast cancer cells, it has been shown that antihormones promote expression/activity of oestrogen-repressed tyrosine kinases, notably EGFR, HER2 and Src. These inductive events confer responsiveness to targeted inhibitors (e.g., gefitinib, trastuzumab, saracatinib). We observed that these antihormone-induced phenomena are common to ER+HER2– and ER+HER2+ breast cancer models in vitro, where targeting of EGFR, HER2 or Src alongside antihormone improves antitumour response and delays/prevents endocrine resistance. Such targeted inhibitors also subvert acquired endocrine resistant cells which retain increased EGFR, HER2 and Src (e.g., TAMR and FASR models derived after 6–12 months of tamoxifen or Faslodex treatment). Thus, antihormone-induced tyrosine kinases comprise “compensatory signalling” crucial in limiting maximal initial antihormone response and subsequently driving acquired resistance in vitro. However, despite such convincing preclinical findings from our group and others, clinical trials examining equivalent antigrowth factor strategies have proved relatively disappointing. Our new studies deciphering underlying causes reveal that further antihormone-promoted events could be pivotal in vivo. Firstly, Faslodex induces HER3 and HER4 which sensitise ER+ cells to heregulin, a paracrine growth factor that overcomes endocrine response and diminishes antitumour effect of agents targeting EGFR, HER2 or Src alongside antihormone. Secondly, extended antihormone exposure (experienced by ER+ cells prior to adjuvant clinical relapse) can “reprogramme” the compensatory kinase profile in vitro, hindering candidate antigrowth factor targeting of endocrine resistance. Faslodex resistant cells maintained with this antihormone for 3 years in vitro lose EGFR/HER2 dependency, gaining alternative mitogenic/invasion kinases. Deciphering these previously unrecognised antihormone-induced events could provide superior treatments to control endocrine relapse in the clinic.
The agent-instrument-place “polysemy” of the suffix ‑tor in Romance
Authors: Rainer Franz 
Published: March 2011

Abstract
The Latin suffix ‑tor was purely agentive, while its Romance counterparts, in the standard languages, all also have an instrumental, and some additionally a locative meaning. Traditionally, this state of affairs has been attributed to a meaning extension during the Proto-Romance stage, when instruments are said to have been conceptualized metaphorically as agents. It is the aim of this paper to show that there has never been any such meaning extension. It will be argued that the multifunctionality of Romance ‑tor is due instead to a combination of factors such as sound change, borrowing, ellipsis, and analogy.
A Temporal Comparison of the Effects of Unemployment and Job Insecurity on Wellbeing
Authors: Burchell Brendan 
Published: March 2011

Analyses of individuals’ working lives make a variety of assumptions about the relationship between time, wellbeing and economic stress. Some assume that stress will accumulate in adverse environments, leading to chronic effects of, for instance, long-term unemployment or job insecurity. Other studies emphasize the acute effects of changes per se, and assume adaptation. This paper examines how employees respond both to acute and chronic job insecurity. This paper will use two datasets. The first is from a survey of over 300 UK employees employed in 26 companies; this dataset included both qualitative and quantitative data, at both employer and employee levels. The second dataset consisted of longitudinal data from the British Household Panel Survey. It was found that the unexpected announcement of job insecurity can cause a sudden and marked spike in psychological symptoms. Looking at longer-term effect for prolonged periods of job insecurity, wellbeing (i.e. symptoms of anxiety and depression) continues to deteriorate for at least a year, with no sign of leveling off or recovery. This is in contrast to the findings on long-term unemployment, where there is evidence of adaptation and slight improvements in psychological wellbeing after six months. The reasons for these opposing patterns between job insecurity and unemployment are discussed in terms of the challenge for individuals attempting to cope with perceived future uncertainty during the prolonged recovery from the current recession.
Porous Poly(ε‐caprolactone) Nerve Guide Filled with Porous Gelatin Matrix for Nerve Tissue Engineering
Authors: Tonda‐Turo Chiara , Audisio Chiara , Gnavi Sara , Chiono Valeria , Gentile Piergiorgio , Raimondo Stefania , Geuna Stefano , Perroteau Isabelle , Ciardelli Gianluca 
Published: March 2011

AbstractThe preparation and characterization of PCL guides filled with a porous matrix of a freeze‐dried, genipin‐crosslinked gelatin sponge (GL/GP) is described. Porous guides are obtained by dip coating a rotating mandrel with a PCL/PEO blend solution followed by PEO solvent extraction. PCL/PEO 60/40 is selected as the optimal composition to obtain model porous membranes with suitable morphological properties to ensure nutrient permeation and moderate stiffness. GL/GP sponges show increased mechanical strength and water stability, compared to uncrosslinked GL sponges. GL/GP in the form of films, sponges and internal fillers support the in vitro adhesion and proliferation of Schwann like cells.
Effective PEGylation of Iron Oxide Nanoparticles for High Performance In Vivo Cancer Imaging
Authors: Liu Dongfang , Wu Wei , Ling Jingjing , Wen Song , Gu Ning , Zhang Xizhi 
Published: March 2011

AbstractA practical and effective strategy for synthesizing PEGylated superparamagnetic iron oxide nanoparticles (SPIONs) is established. In this strategy, poly(acrylic acid) (PAA) is combined with SPIONs via multiple coordination between the carboxylic groups of PAA and SPIONs, which introduces abundant carboxylic groups, then, α,ω‐diamino PEG is linked to SPIONs via the amidation of the carboxylic groups. The synthesized PEGylated SPIONs exhibit no cytotoxicity and high resistance to phagocytosis by macrophages in vitro as well as low uptake by the liver and spleen in vivo, which makes the SPIONs highly efficient in tumor imaging by magnetic resonance imaging (MRI) at a relatively low dose of SPIONs. These outstanding properties are largely due to the significant shielding effect of the dense PEG coating as well as the net neutral surface of the PEGylated SPIONs in physiological conditions. In summary, the PEGylated SPIONs prepared by this strategy exhibit great application potential in tumor imaging as MRI contrast agents targeting through enhanced permeability and retention (EPR) effect.
Reversible Electroaddressing of Self‐assembling Amino‐Acid Conjugates
Authors: Liu Yi , Kim Eunkyoung , Ulijn Rein V. , Bentley William E. , Payne Gregory F. 
Published: March 2011

AbstractThe triggered assembly of organic and biological materials in response to imposed electrical signals (i.e., electroaddressing) provides interesting opportunities for applications in molecular electronics, biosensing and nanobiotechnology. Recent studies have shown that the conjugation of aromatic moieties to short peptides often yields hydrogelator compounds that can be triggered to self‐assemble over a hierarchy of length scales in response to a reduction in pH. Here, we examined the capabilities of fluorenyl‐9‐methoxycarbonyl‐phenylalanine (Fmoc‐Phe) to electrodeposit in response to an electrochemically‐induced pH gradient generated at the anode surface. We report that the electrodeposition of Fmoc‐Phe; is rapid (minutes), can be spatially controlled in normal and lateral directions, and can be reversed by applying a brief cathodic current. Further more, we show that Fmoc‐Phe can be simultaneously deposited on one electrode address (anode) while it is being cathodically stripped from a separate electrode address of the same chip. Finally, we demonstrate that these capabilities can be extended for electroaddressing within microfluidic channels. The reversible assembly/disassembly of molecular gelators (Fmoc‐amino acids and Fmoc‐peptides) in response to spatiotemporally imposed electrical signals offers unique opportunities for electroaddressing that should be especially valuable for lab‐on‐a‐chip applications.
Domains Beyond the Grain Boundary
Authors: Ivry Yachin , Chu Daping , Scott James F. , Durkan Colm 
Published: March 2011

AbstractThin films of inorganic materials are used in diverse applications, typically in polycrystalline form due to their relatively simple production. We have used enhanced piezoresponse force microscopy to investigate the domain distribution within neighbouring grains in thin polycrystalline films of the ferroelectric–ferroelastic system lead zirconate titanate (PZT). We demonstrate that domains are organized into areas with a correlated alignment of the ferroelastic and ferroelectric domains, spanning multiple grain boundaries. We present five typical arrangements of such structures: azimuthal, radial, gradient, and short‐ and long‐ range linear domain organizations. Moreover, we discuss the mechanical and electrical constraints that dictate these structures.
Development of a simultaneous continuum and noncontinuum state estimator with application on a distillation process
Authors: Olanrewaju Moshood J. , Huang Biao , Afacan Artin 
Published: March 2011

AbstractThis study focuses on the development and application of a hybrid moving horizon estimator (HMHE) to achieve simultaneous estimation of both continuum and noncontinuum states in a constrained switching dynamic system. One of the major issues in a moving horizon estimation approach is the development of an arrival cost to summarize the effect of past and a prior information. In this work, we have developed a generalized arrival cost, which accounts for both continuum and noncontinuum states. A generalized hybrid state estimator, which can be used as a stand‐alone continuum state estimator, or as a simultaneous continuum and noncontinuum state estimator, is developed. The effects of constraints, process, and measurement noise levels, as well as a moving horizon length on the simultaneous estimation of both the continuum and noncontinuum states are analyzed. The effectiveness of the HMHE is demonstrated through simulation studies, while its practical reliability is tested by conducting experimental studies on a distillation column. © 2011 American Institute of Chemical Engineers AIChE J, 2012
Understanding the influence of the ionic liquid composition and the surrounding phase nature on the stability of supported ionic liquid membranes
Authors: Hernández‐Fernández Francisco J. , de los Ríos Antonia P. , Tomás‐Alonso Francisca , Palacios José M. , Víllora Gloria 
Published: March 2011

AbstractThe industrial application of supported liquid membranes (SLMs) is still limited due to concerns about their stability. In a previous work, the selective separation of the substrates and products of a transesterification reaction was successfully carried out using Nylon membranes impregnated with ionic liquids (ILs). This article analyses the effect of both the IL composition and the nature of the surrounding phase on the stability of these SLMs to design highly stable supported ionic liquid systems. For this purpose, the stability of SLMs based on several ILs after immersion for a week in different feed/receiving phases was characterized using scanning electron microscopy combined with energy dispersive X‐ray (SEM‐EDX). The differential migration of the ILs observed from the membrane toward the surrounding phases was found to be correlated with the solubility of the ILs in the contacting phases. It was observed that SLM stability increased as the polarity of the solvent used as receiving phase decreased and as the hydrophilic character of the ILs used as liquid phase increased. Furthermore, the polymeric support was found to have a strongly stabilizing effect because losses of IL after immersion in a given surrounding phase were much lower than that derived from the solubility of the IL in this phase. © 2011 American Institute of Chemical Engineers AIChE J, 2012
Targeting the p53 pathway to protect the neonatal ischemic brain
Authors: Nijboer Cora H. , Heijnen Cobi J. , van der Kooij Michael A. , Zijlstra Jitske , van Velthoven Cindy T.J. , Culmsee Carsten , van Bel Frank , Hagberg Henrik , Kavelaars Annemieke 
Published: March 2011

AbstractObjective:To investigate whether inhibition of mitochondrial p53 association using pifithrin‐μ (PFT‐μ) represents a potential novel neuroprotective strategy to combat perinatal hypoxic‐ischemic (HI) brain damage.Methods:Seven‐day‐old rats were subjected to unilateral carotid artery occlusion and hypoxia followed by intraperitoneal treatment with PFT‐μ, an inhibitor of p53 mitochondrial association or PFT‐α an inhibitor of p53 transcriptional activity. Cerebral damage, sensorimotor and cognitive function, apoptotic pathways (cytosolic cytochrome c, Smac/DIABLO, active caspase 3), and oxidative stress (lipid peroxidation and PARP‐1 cleavage) were investigated.Results:PFT‐μ treatment completely prevented the HI‐induced increase in mitochondrial p53 association at 3 hours and reduced neuronal damage at 48 hours post‐HI. PFT‐μ had long‐term (6–10 weeks post‐HI) beneficial effects as sensorimotor and cognitive outcome improved and infarct size was reduced by ∼79%. Neuroprotection by PFT‐μ treatment was associated with strong inhibition of apoptotic pathways and reduced oxidative stress. Unexpectedly, PFT‐μ also inhibited HI‐induced upregulation of p53 target genes. However, the neuroprotective effect of inhibiting only p53 transcriptional activity by PFT‐α was significantly smaller and did not involve reduced oxidative stress.Interpretation:We are the first to show that prevention of mitochondrial p53 association by PFT‐μ strongly improves functional outcome and decreases lesion size after neonatal HI. PFT‐μ not only inhibits mitochondrial release of cytochrome c, but also inhibits oxidative stress. We propose that as a consequence nuclear accumulation of p53 and transcription of proapoptotic target genes are prevented. In conclusion, targeting p53 mitochondrial association by PFT‐μ may develop into a novel and powerful neuroprotective strategy. ANN NEUROL 2011;00:000–000
Paper 1: The EUROCAT network—organization and processes†
Authors: Boyd Patricia A. , Haeusler Martin , Barisic Ingeborg , Loane Maria , Garne Ester , Dolk Helen 
Published: March 2011

AbstractThe European Surveillance of Congenital Anomalies (EUROCAT) is a network of population‐based congenital anomaly registries in Europe, funded by the European Union, which has been in operation for more than 30 years. It currently surveys more than 1.7 million births per year, including 31% of births in the European Union, and includes almost all population‐based European congenital anomaly registries as its members. EUROCAT member registries collect data, ascertained from multiple sources, on all major structural congenital and chromosomal anomalies. EUROCAT surveillance relates to three areas: prevalence, primary prevention, and prenatal screening.This article describes the history of EUROCAT and gives an overview of the current methodology and work of EUROCAT covering the database content and management, coding and classification of anomalies, core surveillance, prevalence tables, statistical monitoring.The monitoring of new developments in prenatal diagnosis, medication during pregnancy, use of folic acid, and investigation of clusters and exposures are overseen by working groups responsible for organizing research and producing regular reports. The EUROCAT Web site includes current data on prevalence rates and prenatal detection rates—an example of information useful to clinicians, public health service managers, and patients. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.
One‐step enzyme extraction and immobilization for biocatalysis applications
Authors: Cassimjee Karim Engelmark , Kourist Robert , Lindberg Diana , Wittrup Larsen Marianne , Thanh Nguyen Hong , Widersten Mikael , Bornscheuer Uwe T. , Berglund Per 
Published: March 2011

AbstractAn extraction/immobilization method for HIs6‐tagged enzymes for use in synthesis applications is presented. By modifying silica oxide beads to be able to accommodate metal ions, the enzyme was tethered to the beads after adsorption of Co(II). The beads were successfully used for direct extraction of C. antarctica lipase B (CalB) from a periplasmic preparation with a minimum of 58% activity yield, creating a quick one‐step extraction‐immobilization protocol. This method, named HisSi Immobilization, was evaluated with five different enzymes [Candida antarctica lipase B (CalB), Bacillus subtilis lipase A (BslA), Bacillus subtilis esterase (BS2), Pseudomonas fluorescence esterase (PFE), and Solanum tuberosum epoxide hydrolase 1 (StEH1)]. Immobilized CalB was effectively employed in organic solvent (cyclohexane and acetonitrile) in a transacylation reaction and in aqueous buffer for ester hydrolysis. For the remaining enzymes some activity in organic solvent could be shown, whereas the non‐immobilized enzymes were found inactive. The protocol presented in this work provides a facile immobilization method by utilization of the common His6‐tag, offering specific and defined means of binding a protein in a specific location, which is applicable for a wide range of enzymes.
Molecular dynamic simulation of wild type and mutants of the polymorphic amyloid NNQNTF segments of elk prion: Structural stability and thermodynamic of association
Authors: Berhanu Workalemahu M. , Masunov Artëm E. 
Published: March 2011

AbstractA hexapeptide with amino acid sequence NNQNTF from the elk prion protein forms amyloid fibrils. Here we use molecular dynamic simulations of the oligomers and their single point glycine mutants to study their stability. In an effort to probe the structural stability and association thermodynamic in a realistic environment, all wildtype of NNQNTF polymorphic forms with different size and their corresponding double layer 5 strands single point glycine mutants were subjected to a total of 500 ns of explicit‐solvent molecular dynamics (MD) simulation. Our results show that the structural stability of the NNQNTF oligomers increases with increasing the number of β‐strands for double layers. Our results also demonstrated that hydrophobic interaction is the principle driving force to stabilize the adjacent β‐strands while the steric zipper is responsible for holding the neighboring β‐sheet layers together. We used MM‐PBSA approach free energy calculations to determine the role of nonpolar effects, electrostatics and entropy in binding. Nonpolar effects remained consistently more favorable in wild type and mutants reinforcing the importance of hydrophobic effects in protein‐protein binding. While entropy systematically opposed binding in all cases, there was no observed trend in the entropy difference between wildtype and glycine mutant. Free energy decomposition shows residues situated at the interface were found to make favorable contributions to the peptide‐peptide association. The study of the wild type and mutants in an explicit solvent may provide valuable insight for amyloid aggregation inhibitor design efforts. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 573–590, 2011.