bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting disease associated modules and prioritizing active genes based on high throughput data
Authors: Qiu Yu-Qing , Zhang Shihua , Zhang Xiang-Sun , Chen Luonan 
Published: January 2010

Abstract

Background
The accumulation of high-throughput data greatly promotes computational investigation of gene function in the context of complex biological systems. However, a biological function is not simply controlled by an individual gene since genes function in a cooperative manner to achieve biological processes. In the study of human diseases, rather than to discover disease related genes, identifying disease associated pathways and modules becomes an essential problem in the field of systems biology.

Results
In this paper, we propose a novel method to detect disease related gene modules or dysfunctional pathways based on global characteristics of interactome coupled with gene expression data. Specifically, we exploit interacting relationships between genes to define a gene's active score function based on the kernel trick, which can represent nonlinear effects of gene cooperativity. Then, modules or pathways are inferred based on the active scores evaluated by the support vector regression in a global and integrative manner. The efficiency and robustness of the proposed method are comprehensively validated by using both simulated and real data with the comparison to existing methods.

Conclusions
By applying the proposed method to two cancer related problems, i.e. breast cancer and prostate cancer, we successfully identified active modules or dysfunctional pathways related to these two types of cancers with literature confirmed evidences. We show that this network-based method is highly efficient and can be applied to a large-scale problem especially for human disease related modules or pathway extraction. Moreover, this method can also be used for prioritizing genes associated with a specific phenotype or disease.
Chemosensitization of cancer cells by siRNA using targeted nanogel delivery
Authors: Dickerson Erin B , Blackburn William H , Smith Michael H , Kapa Laura B , Lyon L Andrew , McDonald John F 
Published: January 2010

Abstract

Background
Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics.

Methods
We report here the use of core/shell hydrogel nanoparticles (nanogels) functionalized with peptides that specially target the EphA2 receptor to deliver small interfering RNAs (siRNAs) targeting EGFR. Expression of EGFR was determined by immunoblotting, and the effect of decreased EGFR expression on chemosensitization of ovarian cancer cells after siRNA delivery was investigated.

Results
Treatment of EphA2 positive Hey cells with siRNA-loaded, peptide-targeted nanogels decreased EGFR expression levels and significantly increased the sensitivity of this cell line to docetaxel (P < 0.05). Nanogel treatment of SK-OV-3 cells, which are negative for EphA2 expression, failed to reduce EGFR levels and did not increase docetaxel sensitivity (P > 0.05).

Conclusion
This study suggests that targeted delivery of siRNAs by nanogels may be a promising strategy to increase the efficacy of chemotherapy drugs for the treatment of ovarian cancer. In addition, EphA2 is a viable target for therapeutic delivery, and the siRNAs are effectively protected by the nanogel carrier, overcoming the poor stability and uptake that has hindered clinical advancement of therapeutic siRNAs.
Selective unresponsiveness to the inhibition of p38 MAPK activation by cAMP helps L929 fibroblastoma cells escape TNF-α-induced cell death
Authors: Wang Jing , Tang Ruihong , Lv Ming , Zhang Jiyan , Shen Beifen 
Published: January 2010

Abstract

Background
The cyclic AMP (cAMP) signaling pathway has been reported to either promote or suppress cell death, in a cell context-dependent manner. Our previous study has shown that the induction of dynein light chain (DLC) by cAMP response element-binding protein (CREB) is required for cAMP-mediated inhibition of mitogen-activated protein kinase (MAPK) p38 activation in fibroblasts, which leads to suppression of NF-κB activity and promotion of tumor necrosis factor-α (TNF-α)-induced cell death. However, it remains unknown whether this regulation is also applicable to fibroblastoma cells.

Methods
Intracellular cAMP was determined in L929 fibroblastoma cells after treatment of the cells with various cAMP elevation agents. Effects of cAMP in the presence or absence of the RNA synthesis inhibitor actinomycin D or small interfering RNAs (siRNAs) against CREB on TNF-α-induced cell death in L929 cells were measured by propidium iodide (PI) staining and subsequent flow cytomety. The activation of p38 and c-Jun N-terminal protein kinase (JNK), another member of MAPK superfamily, was analyzed by immunoblotting. JNK selective inhibitor D-JNKi1 and p38 selective inhibitor SB203580 were included to examine the roles of JNK and p38 in this process. The expression of DLC or other mediators of cAMP was analyzed by immunoblotting. After ectopic expression of DLC with a transfection marker GFP, effects of cAMP on TNF-α-induced cell death in GFP+ cells were measured by PI staining and subsequent flow cytomety.

Results
Elevation of cAMP suppressed TNF-α-induced necrotic cell death in L929 fibroblastoma cells via CREB-mediated transcription. The pro-survival role of cAMP was associated with selective unresponsiveness of L929 cells to the inhibition of p38 activation by cAMP, even though cAMP significantly inhibited the activation of JNK under the same conditions. Further exploration revealed that the induction of DLC, the major mediator of p38 inhibition by cAMP, was impaired in L929 cells. Enforced inhibition of p38 activation by using p38 specific inhibitor or ectopic expression of DLC reversed the protection of L929 cells by cAMP from TNF-α-induced cell death.

Conclusion
These data suggest that the lack of a pro-apoptotic pathway in tumor cells leads to a net survival effect of cAMP.
The sigmoid volvulus: surgical timing and mortality for different clinical types
Authors: Cirocchi Roberto , Farinella Eriberto , La Mura Francesco , Morelli Umberto , Trastulli Stefano , Milani Diego , Di Patrizi Micol S , Rossetti Barbara , Spizzirri Alessandro , Galanou Ioanna , Kopanakis Konstandinos , Mecarelli Valerio , Sciannameo Francesco 
Published: January 2010

Abstract

Background
In western countries intestinal obstruction caused by sigmoid volvulus is rare and its mortality remains significant in patients with late diagnosis. The aim of this work is to assess what is the correct surgical timing and how the prognosis changes for the different clinical types.

Methods
We realized a retrospective clinical study including all the patients treated for sigmoid volvulus in the Department of General Surgery, St Maria Hospital, Terni, from January 1996 till January 2009. We selected 23 patients and divided them in 2 groups on the basis of the clinical onset: patients with clear clinical signs of obstruction and patients with subocclusive symptoms. We focused on 30-day postoperative mortality in relation to the surgical timing and procedure performed for each group.

Results
In the obstruction group mortality rate was 44% and it concerned only the patients who had clinical signs and symptoms of peritonitis and that were treated with a sigmoid resection (57%). Conversely none of the patients treated with intestinal derotation and colopexy died. In the subocclusive group mortality was 35% and it increased up to 50% in those patients with a late diagnosis who underwent a sigmoid resection.

Conclusions
The mortality of patients affected by sigmoid volvulus is related to the disease stage, prompt surgical timing, functional status of the patient and his collaboration with the clinicians in the pre-operative decision making process. Mortality is higher in both obstructed patients with generalized peritonitis and patients affected by subocclusion with late diagnosis and surgical treatment; in both scenarios a Hartmann's procedure is the proper operation to be considered.
Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associated with outcome in early arthritis patients: a cohort study
Authors: Ursum Jennie , Bos Wouter H , van Dillen Nancy , Dijkmans Ben AC , van Schaardenburg Dirkjan 
Published: January 2010

Abstract
Introduction
To investigate whether baseline levels of anti-citrullinated protein antibody (ACPA) or IgM rheumatoid factor (IgM-RF) and changes in the year thereafter are associated with disease activity, functional and radiographic outcome in early arthritis patients, and provide additional information over baseline autoantibody status.

Methods
In 545 early arthritis patients ACPA and IgM-RF levels, disease activity (DAS28), the Health Assessment Questionnaire (HAQ) and Sharp/Van der Heijde Score (SHS) were assessed annually. Baseline status, levels and first-year changes of the autoantibodies were associated with these measures at the two-year follow-up and sub-analysed according to autoantibody status.

Results
The mean age was 52.7 years, 69% was female, at baseline 56% was ACPA positive, 47% IgM-RF positive. At the two-year follow-up the mean DAS28 was 2.88, and the median HAQ and SHS were 0.38 and 1, respectively. At one year, ACPA and IgM-RF levels had decreased by 31% and 56%, respectively. A switch from negative to positive occurred in 2% for ACPA and 3% for IgM-RF. Positive ACPA and RF status were both associated with SHS at two years (P < 0.001), but baseline levels only showed a minor correlation of ACPA with DAS28 and HAQ at two years. Level changes were not associated with the outcome parameters.

Conclusions
Baseline levels and first-year changes of ACPA and IgM-RF are hardly associated with outcome after two years. Seroconversion seldom occurs. Therefore, it does not appear useful to repeat ACPA or IgM-RF measurements.
Women and the Courts in the Control of Violence between Men: Evidence from a Parisian Neighborhood Under Louis XIV
Authors: Melish Jacob 
Published: January 2010

Exceptionally detailed court cases from a neighborhood in early modern Paris show that workingwomen routinely criticized and broke up men's fistfights and other violent altercations. The royal government was thus partly dependent on women to help regulate male behavior and maintain order. Forces empowering women here included the royal criminal courts, whose penalties for much intermale violence gave men an incentive to acquiesce to women's intervention; women's use of language and physical force; and the protection provided by their close male kin. These forces also empowered women in many other nondomestic relations with men. The article deepens our understanding of early modern gender relations, royal criminal courts, and community self-regulation, as well as of workingwomen's roles, sources of empowerment, goals, and contribution to a key aspect of the “civilizing process.”
Les procès judiciaires exceptionnellement détaillés d'un quartier populaire parisien durant l'Ancien régime documentent le rôle des ouvrières dans la critique et l'arrêt des altercations violentes entre hommes. Le gouvernement royal s'appuyait en partie sur les femmes pour régulariser les conduites masculines et maintenir l'ordre. En pénalisant la majorité des violences intermasculines, la cour de justice criminelle royale incitait indirectement les hommes à accepter l'intervention des femmes, dont le pouvoir était également soutenu par leur usage de la parole et de la force physique, et par la protection des hommes de leur famille. Ces méthodes renforçaient aussi la position des femmes face aux hommes dans d'autres situations en dehors du cadre domestique. Cet article approfondit notre connaissance des relations entre hommes et femmes et du rapport entre la justice criminelle royale et l'autorégulation d'une communauté sous l'Ancien Régime. Il permet aussi de mieux comprendre le statut et les raisons d'agir des femmes, et leur contribution à un aspect clé du « processus de civilisation ».
Suzanne, David, Judith, Isaac...: Given Names and Protestant Religious Identity in Eighteenth-Century Paris
Authors: Garrioch David 
Published: January 2010

The history of given names, and what they can tell us about individual and group identities, has attracted much attention in recent years. The existence of specifically Protestant given names is well documented in the early modern period, when they served as important markers of religious identity. This article looks at the evolution of given names in eighteenth-century Paris and the extent to which they continued to operate in this way. It suggests that given names provide some evidence of resistance to religious persecution, yet they also reveal an important change in the way religious identity was marked, a change that underpinned the growth of religious toleration in the city.
Les prénoms et leur signification, notamment en ce qui concerne les identités individuelles et collectives, ont attiré l'attention des historiens de l'époque moderne. La préférence chez les protestants pour les prénoms provenant de l'Ancien Testament est bien connue. Cet article examine les usages protestants et catholiques à Paris au XVIIIe siècle et conclut que la persistance des différences dans le choix des prénoms suggère une certaine résistance protestante à la culture dominante. Cependant, l'évolution des pratiques de prénomination indique également d'importants changements dans les identités confessionnelles qui préparent la tolérance religieuse.
How the Not-So-Powerless Prevail: Industrial Labor Market Demand and the Contours of Militancy in Mid-Twentieth-Century São Paulo, Brazil
Authors: French John D. 
Published: January 2010

Abstract
Extensive interviews and confidential police and judicial records are used to explore the life of Marcos Andreotti (1910–1984), a lifelong Communist labor leader active in the industrial ABC region of greater São Paulo. The intensified persecution faced by Andreotti in the early Cold War years is placed within the trajectory of Andreotti’s working life as a skilled electrician. The labor market demand for skilled workers, it is shown, provided the foundation for Andreotti’s sustained militancy and decisively shaped his philosophy of shop floor organizing based on a dialectic between the skilled and the unskilled. This essay sheds new light on the poorly understood foundations of working-class political and labor militancy, while highlighting unexpected continuities between the era of Andreotti, before 1964, and the world of the “New Unionism” in the late 1970s, which began in ABC under the leadership of Brazil’s current president, Luiz Inácio Lula da Silva.
Normalisierung auf Umwegen. Polen in den politischen Konzeptionen Willy Brandts 1939-1966
Authors: Behring Rainer 
Published: January 2010

Vorspann
Willy Brandts Kniefall vor dem Mahnmal im Warschauer Ghetto ist in die Geschichte eingegangen. Aber hat der deutsche Bundeskanzler sich wirklich für Polen interessiert? Wie intensiv und seit wann? Der Kölner Historiker Rainer Behring stellt diese Fragen und kommt zu einem irritierenden Befund: Brandts Blick nach Osten ging über Polen hinweg und richtete sich vor allem auf die Sowjetunion, die in seinen Augen lange keine Bedrohung für die Freiheit Polens darstellte. Das änderte sich erst 1947/48, als der Sozialdemokrat mit linkssozialistisch-revolutionärer Vergangenheit alle Illusionen über Moskau verlor. Polen gewann in Brandts Vorstellungswelt nun langsam eigenes Gewicht, auch wenn keine Rede davon sein kann, dass von solchen Einsichten ein gerader Weg zur Aussöhnung und zum Warschauer Vertrag von 1970 führte.
Frühe biografische Texte zu Hitler. Zur Bewertung der autobiografischen Teile in Mein Kampf
Authors: Plöckinger Othmar 
Published: January 2010

Vorspann
Dass es eine der Grundanstrengungen von Hitlers Leben gewesen sei, die eigene Person zu verhüllen wie zu verklären, schrieb schon Joachim Fest. Kaum eine Person der Weltgeschichte habe sich so konsequent stilisiert und im Persönlichen unauffindbar gemacht wie er. Wie aber verlief dieser Prozess, wann begann er? Welche Aspekte seiner Biografie wurden von Hitler in den Vordergrund geschoben, welche abgeschwächt und welche ganz verschwiegen? Und welche Rolle spielte schließlich Hitlers Umgebung bei der Ausbildung von Topoi, die seit 1933 zum Allgemeingut einer ganzen Gesellschaft werden sollten?
Amerika und die Neuordnung Europas vor dem Marshallplan (1940-1944)
Authors: Heyde Veronika 
Published: January 2010

Vorspann
Die Vereinigten Staaten taten sich lange schwer mit Europa. Wie sollten sich ihre Beziehungen zum Alten Kontinent gestalten, und wie konnte man Europa nach dem Zweiten Weltkrieg so organisieren, dass von dort nicht bald wieder eine Gefahr für die Welt ausging? Über diese Fragen berieten im Auftrag von Präsident Roosevelt schon während des Krieges die klügsten Köpfe. Veronika Heyde, eine Mitarbeiterin des Instituts für Zeitgeschichte, zeichnet diese Beratungen nach und kommt dabei zu dem Ergebnis, dass man in Amerika der Idee eines geeinten Europa zunächst voller Skepsis begegnete; erst der Marshallplan brachte die Wende.
Iron Age Landscape and Rural Habitat in the Edetan Territory, Iberia (4th–3rd centuries BC)
Authors: Rosado Helena Bonet , Parreño Consuelo Mata , Martín Andrea Moreno 
Published: January 2010

This article focuses on the rural organisation and the settlement pattern of the Iberian Iron Age city
of Edeta. Ongoing research into its macro-spatial organisation has revealed the existence of different
functions and internal features within the settlements and their relation to a wider and more integrated
space: the territory. Based on excavation and survey data, we present new questions and analytical
categories in order to approach issues related to territory formation and the emergence of socio-economic
complexity in the Iron Age societies of ancient eastern Iberia.
The Effect of Passive Opium Smoking on Cardiovascular Indices of Rabbits with Normal and Ischemic Hearts
Authors: Joukar Siyavash , Najafipour Hamid , Malekpour-Afshar Reza , Mirzaeipour Fatemeh , Nasri Hamid Reza 
Published: January 2010

Some Asian people believe that opium can protect the cardiovascular system. To assess this belief, we investigated the effect of passive opium smoking (POS) on cardiovascular indices in rabbits with ischemic and non-ischemic hearts.
Rabbits (n = 43) were divided into control (CTL), short term opium (SO) and long term opium (LO) groups. SO and LO groups were exposed to opium smoking for 3 days and 4 weeks, respectively. ECG, blood pressure (BP), left ventricular pressure and cardiac troponin I levels were recorded. Isoproterenol (ISO) was injected to induce cardiac ischemia and after 4 h the above variables were measured along with cardiac histopathology assessment.
All groups showed significant increments in troponin I level (P < 0.05) except the CTL group. This trend was more obvious in ISO-treated groups. Mean arterial pressure (MAP) significantly decreased in all groups (p< 0.05) except the LO group. Opium exposure attenuated ISO-induced myodegeneration but augmented tissue congestion and hemorrhage.
In conclusion, higher troponin I serum level and ECG changes were found in passive opium smoking groups. This evidence is against the belief that opium can protect the cardiovascular system.
Downregulation of the Longevity-Associated Protein Sirtuin 1 in Insulin Resistance and Metabolic Syndrome: Potential Biochemical Mechanisms
Authors: de Kreutzenberg Saula Vigili , Ceolotto Giulio , Papparella Italia , Bortoluzzi Alessia , Semplicini Andrea , Man Chiara Dalla , Cobelli Claudio , Fadini Gian Paolo , Avogaro Angelo 
Published: January 2010

OBJECTIVE
Sirtuins (SIRTs) are NAD+-dependent deacetylases that regulate metabolism and life span. We used peripheral blood mononuclear cells (PBMCs) to determine ex vivo whether insulin resistance/metabolic syndrome influences SIRTs. We also assessed the potential mechanisms linking metabolic alterations to SIRTs in human monocytes (THP-1) in vitro.

RESEARCH DESIGN AND METHODS
SIRT1-SIRT7 gene and protein expression was determined in PBMCs of 54 subjects (41 with normal glucose tolerance and 13 with metabolic syndrome). Insulin sensitivity was assessed by the minimal model analysis. Subclinical atherosclerosis was assessed by carotid intima-media thickness (IMT). In THP-1 cells exposed to high glucose or fatty acids in vitro, we explored SIRT1 expression, p53 acetylation, Jun NH2-terminal kinase (JNK) activation, NAD+ levels, and nicotinamide phosphoribosyltransferase (NAMPT) expression. The effects of SIRT1 induction by resveratrol and of SIRT1 gene silencing were also assessed.

RESULTS
In vivo, insulin resistance and metabolic syndrome were associated with low PBMC SIRT1 gene and protein expression. SIRT1 gene expression was negatively correlated with carotid IMT. In THP-1 cells, high glucose and palmitate reduced SIRT1 and NAMPT expression and reduced the levels of intracellular NAD+ through oxidative stress. No effect was observed in cells exposed to linoleate or insulin. High glucose and palmitate increased p53 acetylation and JNK phosphorylation; these effects were abolished in siRNA SIRT1–treated cells. Glucose- and palmitate-mediated effects on NAMPT and SIRT1 were prevented by resveratrol in vitro.

CONCLUSIONS
Insulin resistance and subclinical atherosclerosis are associated with SIRT1 downregulation in monocytes. Glucotoxicity and lypotoxicity play a relevant role in quenching SIRT1 expression.