bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinome profiling of myxoid liposarcoma reveals NF-kappaB-pathway kinase activity and Casein Kinase II inhibition as a potential treatment option
Authors: Willems Stefan M , Schrage Yvonne M , Bruijn Inge H Briaire-de , Szuhai Karoly , Hogendoorn Pancras CW , Bovée Judith VMG 
Published: September 2010

Abstract

Background
Myxoid liposarcoma is a relatively common malignant soft tissue tumor, characterized by a (12;16) translocation resulting in a FUS-DDIT3 fusion gene playing a pivotal role in its tumorigenesis. Treatment options in patients with inoperable or metastatic myxoid liposarcoma are relatively poor though being developed and new hope is growing.

Results
Using kinome profiling and subsequent pathway analysis in two cell lines and four primary cultures of myxoid liposarcomas, all of which demonstrated a FUS-DDIT3 fusion gene including one new fusion type, we aimed at identifying new molecular targets for systemic treatment. Protein phosphorylation by activated kinases was verified by Western Blot and cell viability was measured before and after treatment of the myxoid liposarcoma cells with kinase inhibitors. We found kinases associated with the atypical nuclear factor-kappaB and Src pathways to be the most active in myxoid liposarcoma. Inhibition of Src by the small molecule tyrosine kinase inhibitor dasatinib showed only a mild effect on cell viability of myxoid liposarcoma cells. In contrast, inhibition of the nuclear factor-kappaB pathway, which is regulated by the FUS-DDIT3 fusion product, in myxoid liposarcoma cells using casein kinase 2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) showed a significant decrease in cell viability, decreased phosphorylation of nuclear factor-kappaB pathway proteins, and caspase 3 mediated apoptosis. Combination of dasatinib and TBB showed an enhanced effect.

Conclusion
Kinases associated with activation of the atypical nuclear factor-kappaB and the Src pathways are the most active in myxoid liposarcoma in vitro and inhibition of nuclear factor-kappaB pathway activation by inhibiting casein kinase 2 using TBB, of which the effect is enhanced by Src inhibition using dasatinib, offers new potential therapeutic strategies for myxoid liposarcoma patients with advanced disease.
Modelling biochemical networks with intrinsic time delays: a hybrid semi-parametric approach
Authors: von Stosch Moritz , Peres Joana , de Azevedo Sebastião Feyo , Oliveira Rui 
Published: September 2010

AbstractBackgroundThis paper presents a method for modelling dynamical biochemical networks with intrinsic time delays. Since the fundamental mechanisms leading to such delays are many times unknown, non conventional modelling approaches become necessary. Herein, a hybrid semi-parametric identification methodology is proposed in which discrete time series are incorporated into fundamental material balance models. This integration results in hybrid delay differential equations which can be applied to identify unknown cellular dynamics.ResultsThe proposed hybrid modelling methodology was evaluated using two case studies. The first of these deals with dynamic modelling of transcriptional factor A in mammalian cells. The protein transport from the cytosol to the nucleus introduced a delay that was accounted for by discrete time series formulation. The second case study focused on a simple network with distributed time delays that demonstrated that the discrete time delay formalism has broad applicability to both discrete and distributed delay problems.ConclusionsSignificantly better prediction qualities of the novel hybrid model were obtained when compared to dynamical structures without time delays, being the more distinctive the more significant the underlying system delay is. The identification of the system delays by studies of different discrete modelling delays was enabled by the proposed structure. Further, it was shown that the hybrid discrete delay methodology is not limited to discrete delay systems. The proposed method is a powerful tool to identify time delays in ill-defined biochemical networks.
Endovascular covered stenting for the management of post-percutaneous nephrolithotomy renal pseudoaneurysm: a case report
Authors: Philippou Prodromos , Moraitis Konstantinos , El-Husseiny Tamer , Wazait Hassan , Masood Junaid , Buchholz Noor 
Published: September 2010

Abstract

Introduction
Intrarenal pseudoaneurysm is a rare, yet clinically significant, complication of percutaneous nephrolithotomy. A high index of clinical suspicion is necessary in order to recognize pseudoaneurysm as the cause of delayed bleeding after percutaneous nephrolithotomy and angiography confirms the diagnosis which allows endovascular management.

Case presentation
We present a case of a 65-year old Caucasian woman who underwent percutaneous nephrolithotomy in the supine position for a two centimetre renal calculus. The postoperative course was complicated by persistent bleeding due to a renal pseudoaneurysm. The vascular lesion was successfully managed by endovascular exclusion through the use of a covered stent graft. We report the first successful use of this method for the management of iatrogenic pseudoaneurysm in a branch of the left renal artery and we focus on the imaging findings, technical details, advantages and limitations of this technique.

Conclusion
As a result of its high efficacy, interventional radiology has largely replaced open surgery for the management of renal pseudoaneurysm related to percutaneous nephrolithotomy. Recent technical advancements have allowed the use of covered stent grafts as an alternative to embolisation for the angiographic management of visceral artery pseudoaneurysm located in other organs. This novel technique allows the endovascular exclusion of the pseudoaneurysm, without compromising arterial supply to the end-structures - an advantage of critical importance in organs supplied by segmental arteries - in the absence of collateral vasculature, such as the kidney.
Barriers to accessing highly active antiretroviral therapy by HIV‐positive women attending an antenatal clinic in a regional hospital in western Uganda
Authors: Duff Putu , Kipp Walter , Wild T Cameron , Rubaale Tom , Okech‐Ojony Joa 
Published: September 2010

BackgroundThe aim of this study was to describe barriers to accessing and accepting highly active antiretroviral therapy (HAART) by HIV‐positive mothers in the Ugandan Kabarole District's Programme for the Prevention of Mother to Child Transmission‐Plus (PMTCT‐Plus).MethodsOur study was a qualitative descriptive exploratory study using thematic analysis. Individual in‐depth interviews (n = 45) were conducted with randomly selected HIV‐positive mothers who attended this programme, and who: (a) never enrolled in HAART (n = 17); (b) enrolled but did not come back to receive HAART (n = 2); (c) defaulted/interrupted HAART (n = 14); and (d) are currently adhering to HAART (n = 12). A focus group was also conducted to verify the results from the interviews.ResultsResults indicated that economic concerns, particularly transport costs from residences to the clinics, represented the greatest barrier to accessing treatment. In addition, HIV‐related stigma and non‐disclosure of HIV status to clients' sexual partners, long waiting times at the clinic and suboptimal provider‐patient interactions at the hospital emerged as significant barriers.ConclusionsThese barriers to antiretroviral treatment of pregnant and post‐natal women need to be addressed in order to improve HAART uptake and adherence for this group of the population. This would improve their survival and, at the same time, drastically reduce HIV transmission from mother to child.
Receptor conversion in distant breast cancer metastases
Authors: Hoefnagel Laurien DC , van de Vijver Marc J , van Slooten Henk-Jan , Wesseling Pieter , Wesseling Jelle , Westenend Pieter J , Bart Joost , Seldenrijk Cornelis A , Nagtegaal Iris D , Oudejans Joost , van der Valk Paul , van der Groep Petra , de Vries Elisabeth GE , van der Wall Elsken , van Diest Paul J 
Published: September 2010

Abstract
Introduction
When breast cancer patients develop distant metastases, the choice of systemic treatment is usually based on tissue characteristics of the primary tumor as determined by immunohistochemistry (IHC) and/or molecular analysis. Several previous studies have shown that the immunophenotype of distant breast cancer metastases may be different from that of the primary tumor (receptor conversion), leading to inappropriate choice of systemic treatment. The studies published so far are however small and/or methodologically suboptimal. Therefore, definite conclusions that may change clinical practice could not yet be drawn. We therefore aimed to study receptor conversion for estrogen receptor alpha (ERα), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in a large group of distant (non-bone) breast cancer metastases by re-staining all primary tumors and metastases with current optimal immunohistochemical and in situ hybridization methods on full sections.

Methods
A total of 233 distant breast cancer metastases from different sites (76 skin, 63 liver, 43 lung, 44 brain and 7 gastro-intestinal) were IHC stained for ERα, PR and HER2, and expression was compared to that of the primary tumor. HER2 in situ hybridization (ISH) was done in cases of IHC conversion or when primary tumors or metastases showed an IHC 2+ result.

Results
Using a 10% threshold, receptor conversion by IHC for ERα, PR occurred in 10.3%, 30.0% of patients, respectively. In 10.7% of patients, conversion from ER+ or PR+ to ER-/PR- and in 3.4% from ER-/PR- to ER+ or PR+ was found. Using a 1% threshold, ERα and PR conversion rates were 15.1% and 32.6%. In 12.4% of patients conversion from ER+ or PR+ to ER-/PR-, and 8.2% from ER-/PR- to ER+ or PR+ occurred. HER2 conversion occurred in 5.2%. Of the 12 cases that showed HER2 conversion by IHC, 5 showed also conversion by ISH. One further case showed conversion by ISH, but not by IHC. Conversion was mainly from positive in the primary tumor to negative in the metastases for ERα and PR, while HER2 conversion occurred equally both ways. PR conversion occurred significantly more often in liver, brain and gastro-intestinal metastases.

Conclusions
Receptor conversion by immunohistochemistry in (non-bone) distant breast cancer metastases does occur, is relatively uncommon for ERα and HER2, and is more frequent for PR, especially in brain, liver and gastro-intestinal metastases.
Processing of Anti-Müllerian Hormone Regulates Receptor Activation by a Mechanism Distinct from TGF-β
Authors: di Clemente Nathalie , Jamin Soazik P. , Lugovskoy Alexey , Carmillo Paul , Ehrenfels Christian , Picard Jean-Yves , Whitty Adrian , Josso Nathalie , Pepinsky R. Blake , Cate Richard L. 
Published: September 2010

AbstractTGF-β family ligands are translated as prepropeptide precursors and are processed into mature C-terminal dimers that signal by assembling a serine/threonine kinase receptor complex containing type I and II components. Many TGF-β ligands are secreted in a latent form that cannot bind their receptor, due to the pro-region remaining associated with the mature ligand in a noncovalent complex after proteolytic cleavage. Here we show that anti-Müllerian hormone (AMH), a TGF-β family ligand involved in reproductive development, must be cleaved to bind its type II receptor (AMHRII), but dissociation of the pro-region from the mature C-terminal dimer is not required for this initial interaction. We provide direct evidence for this interaction by showing that the noncovalent complex binds to a soluble form of AMHRII in an ELISA format and to AMHRII immobilized on Sepharose. Binding of the noncovalent complex to Sepharose-coupled AMHRII induces dissociation of the pro-region from the mature C-terminal dimer, whereas no dissociation occurs after binding to immobilized AMH antibodies. The pro-region cannot be detected after binding of the AMH noncovalent complex to AMHRII expressed on COS cells, indicating that pro-region dissociation may occur as a natural consequence of receptor engagement on cells. Moreover, the mature C-terminal dimer is more active than the noncovalent complex in stimulating Sma- and Mad-related protein activation, suggesting that pro-region dissociation contributes to the assembly of the active receptor complex. AMH thus exemplifies a new mechanism for receptor engagement in which interaction with the type II receptor promotes pro-region dissociation to generate mature ligand.
Experimental and Finite Element Analysis of the API RP60 Test
Authors: Harris Jason T. , Segall Albert E. , Hellmann John R. , Scheetz Barry E. , Koseski Ryan P. , Boyce Joshua M. 
Published: September 2010

Abstract
The compaction and fracture of brittle spherical particles in a cylindrical vessel were experimentally and numerically studied in the context of the American Petroleum Institute Recommended Practice 60 for proppants used in the hydraulic fracturing of oil and gas wells. Because pressures within the cylindrical vessel could not be directly measured, strain was experimentally determined via gauges along the outside surface. In addition, an epoxy resin was also injected at various loading stages to “freeze” the damage states for analysis. In addition, acoustic emissions were monitored in situ to determine damage signatures that could be correlated with the frozen test and strain measurement data. Experimental results were then compared to finite element simulations by using an assumed double-exponential pressure distribution applied to the inner face of the vessel. The results indicated that the assumed pressure distribution adequately described the loading state within the cylinder and revealed apparent stratification of damaged proppants near the top and bottom of the container. In addition, the damaged proppants and acoustic emission signatures showed that the damage increases progressively with the loading in distinct stages characterized by fracture and subsequent stress redistribution.
Pore Independent Crack Propagation of Glass-Alumina Functionally Graded Materials
Authors: Cheng-Long Yu , Hong-Tao Jiang , Li-Li Wang 
Published: September 2010

Abstract
Crack propagation of glass-alumina functionally graded materials prepared by a novel freeform fabrication method was investigated. Pores were intentionally introduced by partial decomposition of poly vinyl alcohol gel. Preferential distribution of pores adjacent the alumina particles is confirmed due to the integrated liquid-phase sintering process, especially the migration of the activated alumina interfaces towards the equilibrium state. Crack propagation and distribution were directly observed by scanning electron microscopy. Cracks propagate through the weakly bonded interfaces which finally cause the glass matrix to fracture. However, pores have little effect on the crack propagation.
Development of a Flattened Indirect Tension Test for Asphalt Concrete
Authors: Dave Eshan V. , Braham Andrew F. , Buttlar William G. , Paulino Glaucio H. 
Published: September 2010

Abstract
The indirect tension test (IDT) is frequently used in civil engineering because of its benefits over direct tension testing. In the mid-1990s, an IDT protocol was developed for evaluating tensile strength and creep properties of asphalt concrete mixtures, as specified by the American Association of State Highway Transportation Officials (AASHTO) in AASHTO T322. However, with the increased use of finer aggregate gradations and polymer modified asphalt binders in asphalt concrete mixtures, the validity of IDT strength results can be questioned in instances where significant crushing occurs under the narrow loading heads. Therefore, a new specimen configuration is proposed for indirect tension testing of asphalt concrete. In place of the standard loading heads, the specimen was trimmed to produce flat planes with parallel faces, creating a “flattened IDT.” A viscoelastic finite element analysis of the flattened configuration was performed to evaluate the optimal trimming width. In addition, the numerically determined geometry was verified by means of laboratory testing of three asphalt concrete mixtures in two flattened configurations. This integrated modeling and testing study showed that when using fine aggregate gradations and compliant asphalt binders, crushing is significantly reduced while maintaining tensile stresses near the center of the specimen. Furthermore, creep compliances were evaluated using the flattened IDT and compared with those obtained following AASHTO T322. Some variation was observed between the creep properties evaluated from the different geometries, particularly for higher compliance values. As a preliminary assessment, the flattened IDT seems to be a suitable geometry for the evaluation of indirect tensile strength of asphalt concrete. Further testing and analysis should be performed on the flattened IDT arrangement for evaluation of the creep compliance. This study provides an initial step towards a possible revision of the current AASHTO standard for IDT testing of asphalt concrete mixtures.
Askese und Wissenschaft – Thomas von Aquin und Max Weber im Vergleich
Authors: Krieger Gerhard , Krieger Gerhard 
Published: September 2010

Abstract
Asceticism and science are connected in Weber’s thought insofar as “asceticism” includes an attitude of job-related professionalization and this attitude in turn signifies capitalistic as well as scientific activity. In this way, asceticism has also an “innerworldly” nature, in contrast to the way it is depicted in Christianity or in other religions. In this (religious) sense, asceticism serves as a means to otherworldly completion, while its “innerworldly” meaning is entirely interior to itself. Insofar as for Weber, asceticism, independent from any religious sense, signifies scientific as well as economic activity, it is a “practical-rational” conduct of life in the sense of competence, enhancement, and perfection. This is the methodological basis for a reconsideration of Thomas Aquinas’ ideas on asceticism. Thomas, like Weber, uncouples the relation of otherworldly completion and asceticism and links this decoupling to the priority of perfection of asceticism. However Thomas, contrary to Weber, associates asceticism with the conditions innate to a particular way of life; in this sense, asceticism can determine human existence itself, insofar as it is realized both “outside the world in monastic communities” and also “within this world and for it”. With reference to the relation of science and asceticism, for Thomas as well as for Weber scientific activity is “ascetic” in the sense that it strives for perfection. However, in contrast to Weber, Thomas maintains that it is impossible for a subject to bring his scientific activity to a complete conclusion.
Voter Turnout, Information Acquisition and Education: Evidence from 15 European Countries
Authors: Borgonovi Francesca , d'Hombres Beatrice , Hoskins Bryony 
Published: September 2010

Abstract
This article examines the impact of education on political participation in 15 European countries. We use data from the European Social Survey and find that education is positively associated with voter turnout and information acquisition about politics and currents affairs. However, when we use exogeneous changes in compulsory schooling to instrument education, we observe a statistically significant causal relationship in the case of information acquisition but not voter turnout.
Combined Effects of Ototoxic Solvents and Noise on Hearing in Automobile Plant Workers in Iran
Authors: Mohammadi Saber , Labbafinejad Yasser , Attarchi Mirsaeed 
Published: September 2010

Combined Effects of Ototoxic Solvents and Noise on Hearing in Automobile Plant Workers in IranExposure of workers to mixtures of organic solvents and to occupational noise is frequent in a number of industries. Recent studies suggest that exposure to both can cause a more severe hearing loss than exposure to noise alone. Our cross-sectional study included 411 workers of a large automobile plant divided in three groups. The first group included assembly workers exposed to noise alone; the second included workers in a new paint shop, who were exposed to a mixture of organic solvents at a permissible level; and the third group included paint shop workers exposed to both noise and higher than permissible levels of organic solvents in an old paint shop. These groups were compared in terms of low-frequency hearing loss (model 1; average hearing threshold >25 dB at 0.5 kHz, 1 kHz, and 2 kHz) and high-frequency hearing loss (model 2; average hearing threshold >25 dB at 3 kHz, 4 kHz, 6 kHz, and 8 kHz). High-frequency hearing loss was more common in workers exposed to a combination of noise and mixed organic solvents even at permissible levels than in workers exposed to noise alone even after correction for confounding variables. This study shows that combined exposure to mixed organic solvents and occupational noise can exacerbate hearing loss in workers. Therefore, an appropriate hearing protection programme is recommended, that would include short-interval audiometric examinations and efficient hearing protectors.
New European Commission Regulation on Variations to the Terms of Marketing Authorisation for Medicinal Products and its Impact on Croatian Legislation
Authors: Martinac Adrijana , Tomić Siniša , Šimičić Mirna 
Published: September 2010

New European Commission Regulation on Variations to the Terms of Marketing Authorisation for Medicinal Products and its Impact on Croatian LegislationVariations introduced to medicinal product documentation must not affect the quality, efficacy, and safety of the product. Croatian Medicinal Products Act and accompanying ordinances are largely aligned with the EU regulations. The EU has now tried to simplify the issue of variations with a new Regulation, creating differences in the definition of and approach to resolving certain types of variations between Croatia and the EU. These differences could hinder the approval procedure for variations in Croatia, particularly for medicines already approved in the EU. Amending the Croatian Ordinance on medicines already authorised in the EU would be one way of maintaining the efficiency of the Croatian regulatory system.
Cadmium and Selenium Interaction in Mammals
Authors: Lazarus Maja 
Published: September 2010

Međudjelovanje kadmija i selenija u sisavacaIzloženost kadmiju neizbježna je zbog njegove sveprisutnosti u okolišu kao prirodne sastavnice Zemljine kore i kao onečišćenja. Kadmij može izazvati toksične učinke u gotovo cijelom organizmu vezanjem za biološke strukture i nakupljanjem u tkivima, poticanjem stvaranja slobodnih radikala, kao i međudjelovanjem s esencijalnim elementima, često u obliku antagonizma. S druge strane, dodatnim unosom esencijalnih elemenata može se utjecati na raspodjelu i štetne učinke kadmija. Selenij je esencijalan mikroelement i antioksidans, a zbog svojstva vezanja za kadmij (kao i živu, arsen i druge toksične elemente) te uloge u detoksifikaciji, detaljnije se počelo istraživati međudjelovanje kadmija i selenija. U radu je dan pregled dosadašnjih saznanja o toksikokinetici i toksikodinamici kadmija, biokinetici i biodinamici selenija i mehanizmima njihova međudjelovanja proizašlih uglavnom iz istraživanja na životinjama i ograničenu broju istraživanja u ljudima. Različite doze i odnos doza, način i dužina izloženosti kadmiju i seleniju u pokusima na životinjama uzrok su često vrlo oprečnih rezultata istraživanja opisanih u literaturi. Buduća istraživanja međudjelovanja kadmija i selenija treba usmjeriti na osjetljive skupine stanovništva i na istraživanje mehanizama tog međudjelovanja. Doze i izloženost u pokusima na životinjama treba prilagoditi dugotrajnim i niskim razinama izloženosti koje su najčešće u ljudi.