bluuebunny/crossref_metadata_2025 huggingface dataset:
Rembrandts eerste reis naar Friesland
Authors: Broos Ben
Published: July 2010

On at least three occasions (in 1633, 1634 and in 1635) Rembrandt visited the village of Sint Annaparochie in Het Bildt, where Saskia Uylenburgh lived from her fourteenth to her twentieth year. Biographies of the artist discuss only the days surrounding his marriage to Saskia in the Frisian village on 22 June 1634. The present report concerns Rembrandt's very first visit to Friesland, in 1633. His last visit to Het Bildt can be dated to 12 July 1635, when Saskia served as witness at the baptism of her young niece Antje van Loo, the fourth child of her sister Hiskia Uylenburgh, who was married to Gerrit van Loo, Het Bildt's municipal secretary. Saskia was presumably also present with Rembrandt at the baptism of Hiskia's third child, Sophia, on 2 June 1633. On 8 June he drew his famous portrait of Saskia in silverpoint on parchment. In 1853, A. Wassenbergh, pastor of Sint Annaparochie, published the details on the baptisms of the Van Loo children in the church register, including the presence of Titia Uylenburgh as witness in 1633. The importance of this document has been underestimated. Titia had married François Coopal of Flushing. He turns out to have registered at Franeker's university (a veritable Uylenburgh bastion), which explains his marriage around 1628 to Saskia's sister Titia. Titia and/or her husband were also witnesses at the baptism of every one of Rembrandt and Saskia's children. The document that indirectly establishes Rem-brandt's presence in Sint Annaparochie from 2 to 8 June 1633 is important. Rembrandt carried with him a kind of sketchbook, of which three parchment leaves have survived. One of them shows his engagement portrait of Saskia. The two other sheets, drawn on both sides, feature three landscapes. The stylistic connection between these sheets and the then uncommon subject matter, the landscape, has been noted by Schatborn, Schneider and Van de Wetering. The type of farm depicted is not Dutch but more likely Frisian. The date on the portrait, 8 June 1633, is a sound benchmark for the dating of the landscapes. The second sheet was later substantially cropped to turn the studies of the heads on the back into the main depiction. The third sheet, a view of some farm's still has its original format. The back of this sheet shows a panorama with a view of a village. Until recently a matt obscured the correspondence in format with Saskia's portrait. The panoramic landscape deserves closer consideration because it must have been done in Sint Annaparochie and could therefore depict the surroundings of the village. 'Het Bildt' is depicted on a map in Schotanus' 1664 Beschryvinge ... van Frieslandt. The situation in Rembrandt's drawing corresponds closely with the plan of the area as reproduced on Schotanus' map: from left to right we see Sint Annaparochie, a copse of trees to the north of what the map calls 'Vogel', and, probably, Vrouwenparochie, with summarily indicated spire. In June of 1633, in my opinion, Rembrandt drew the surroundings of the village in which he was to marry Saskia in July of 1634.
Selbstdarstellung und Spezialistentum in der niederländischen Malerei des I7. Jahrhunderts - ein neuer Fund zur Biographie Hendrick van Steenwijcks d.J
Authors: Nicolaisen Jan
Published: July 2010

An inscription in a painting of I636 depicting a church interior by the painter Hendrick van Steenwijck the Younger in the Museum der bildenden Künste Leipzig (Maximilian Speck von Stern-burg Foundation, Inv.No. I62I) has not been read correctly until today. It deserves attention, since it turns out to be the artist's signature and the only surviving source of information about the place and date of Steenwijck the Younger's birth. It reads: H.V.S. nat(us). Ant(werpen).// Ao MDLXXX M(ens). Sept(embris). The inscription is part of an epitaph in which there is also a portrait of Steenwijck the Younger, resembling his portrait by Anton van Dyck in the portrait series of the "Iconographie" published around the same date. The article links this rare case of an artist's self-representation in a painting with the biographical situation of Steenwijck, who probably returned from London to The Hague in I638. An analysis of the painting shows how Steenwijck the Younger integrated this monumental self-representation with the painting and its decoration with altarpieces. The artist himself looks out of the painting, stimulating a direct contact with the viewer, who is furthermore encouraged by numerous minute and delicately painted details to look closely at the painting.
The Structure and the Mechanism of Movement of the Gill-Filaments in Teleostei
Authors: Bijtel J. Hubertha
Published: July 2010

It is evident, that the wide apertures between the gills are closed in quiet respiration, during inspiration as well as during expiration, because the filament-tips of the posterior hemibranchia of each gill are in continuous contact with those of the anterior hemibranchia of the next gill. The communication between the inspiratory and the expiratory cavity is kept up by the narrow slits between the lamellae. The skeleton and the ligament apparatus of the filaments are constructed in such a way, that the normal position of abduction of both filament-rows of a gill is maintained in spite of the fact, that in both respiratory phases the pressure in the inspiratory cavity is higher than that in the expiratory cavity. The figures of gills of the Teleostei, which are found in different textbooks, show a wide aperture between the filament-tips of the hemibranchiae of two successive gills. In the living animal this wide communication between the inspiratory and the expiratory cavity does not exist in quiet respiration, but is only seen during the coughing movements. Small fragments of defilement, which are accumulated against the gills, are then removed and are spit out by the mouth (coughing in a forward direction) or appear from under the gill-cover with the respiratory water (coughing in backward direction). During coughing an adduction movement is seen of the filament-tips of the two hemibranchiae of a gill by the contraction of the adductor muscles. The adductor muscles do not act rhythmically. They play no part in the circulation of the blood through the branchial vessels (RIESS 1881, WOSKOBOINIKOFF 1932), nor in the renewal of the respiratory water (ELFRIEDE SCHÖTTLE 1932), but they are of significance for the cleaning of the gills by means of the coughing movements. During coughing the so-called abductor muscles probably prevent a caudal movement of the adducted filament-rows of a gill, by which the branchial apertures could be closed up. It is possible, that they act exclusively during coughing in a forward direction.
Allogeneic stem cell transplantation provides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial
Authors: Dreger Peter , Döhner Hartmut , Ritgen Matthias , Böttcher Sebastian , Busch Raymonde , Dietrich Sascha , Bunjes Donald , Cohen Sandra , Schubert Jörg , Hegenbart Ute , Beelen Dietrich , Zeis Matthias , Stadler Michael , Hasenkamp Justin , Uharek Lutz , Scheid Christof , Humpe Andreas , Zenz Thorsten , Winkler Dirk , Hallek Michael , Kneba Michael , Schmitz Norbert , Stilgenbauer Stephan ,   for the German CLL Study Group
Published: July 2010

The purpose of this prospective multicenter phase 2 trial was to investigate the long-term outcome of reduced-intensity conditioning allogeneic stem cell transplantation (alloSCT) in patients with poor-risk chronic lymphocytic leukemia. Conditioning was fludarabine/ cyclophosphamide-based. Longitudinal quantitative monitoring of minimal residual disease (MRD) was performed centrally by MRD-flow or real-time quantitative polymerase chain reaction. One hundred eligible patients were enrolled, and 90 patients proceeded to alloSCT. With a median follow-up of 46 months (7-102 months), 4-year nonrelapse mortality, event-free survival (EFS) and overall survival (OS) were 23%, 42%, and 65%, respectively. Of 52 patients with MRD monitoring available, 27 (52%) were alive and MRD negative at 12 months after transplant. Four-year EFS of this subset was 89% with all event-free patients except for 2 being MRD negative at the most recent assessment. EFS was similar for all genetic subsets, including 17p deletion (17p−). In multivariate analyses, uncontrolled disease at alloSCT and in vivo T-cell depletion with alemtuzumab, but not 17p−, previous purine analogue refractoriness, or donor source (human leukocyte antigen-identical siblings or unrelated donors) had an adverse impact on EFS and OS. In conclusion, alloSCT for poor-risk chronic lymphocytic leukemia can result in long-term MRD-negative survival in up to one-half of the patients independent of the underlying genomic risk profile. This trial is registered at http://clinicaltrials.gov as NCT00281983.
High-frequency type I/II mutational shifts between diagnosis and relapse are associated with outcome in pediatric AML: implications for personalized medicine
Authors: Bachas Costa , Schuurhuis Gerrit Jan , Hollink Iris H. I. M. , Kwidama Zinia J. , Goemans Bianca F. , Zwaan C. Michel , van den Heuvel-Eibrink Marry M. , de Bont Eveline S. J. M. , Reinhardt Dirk , Creutzig Ursula , de Haas Valerie , Assaraf Yehuda G. , Kaspers Gertjan J. L. , Cloos Jacqueline
Published: July 2010

Although virtually all pediatric patients with acute myeloid leukemia (AML) achieve a complete remission after initial induction therapy, 30%-40% of patients will encounter a relapse and have a dismal prognosis. To prevent relapses, personalized treatment strategies are currently being developed, which target specific molecular aberrations. To determine relevance of established AML type I/II mutations that may serve as therapeutic targets, we assessed frequencies of these mutations and their persistence during disease progression in a large group (n = 69) of paired diagnosis and relapse pediatric AML specimens. In 26 of 42 patients (61%) harboring mutations at either stage of the disease, mutation status changed between diagnosis and relapse, particularly in FLT3, WT1, and RAS genes. Presence or gain of type I/II mutations at relapse was associated with a shorter time to relapse (TTR), whereas absence or loss correlated with longer TTR. Moreover, an adverse outcome was found for patients with activating mutations at relapse, which was statistically significant for FLT3/ITD and WT1 mutations. These findings suggest that mutational shifts affect disease progression. We hence propose that risk stratification, malignant cell detection, and selection of personalized treatment should be based on status of type I/II mutations both at initial diagnosis and during follow-up.
Identification of baboon microRNAs expressed in liver and lymphocytes
Authors: Karere Genesio M , Glenn Jeremy P , VandeBerg John L , Cox Laura A
Published: July 2010

Background

MicroRNAs (miRNAs) are small noncoding RNAs (~22 nucleotides) that regulate gene expression by cleaving mRNAs or inhibiting translation. The baboon is a well-characterized cardiovascular disease model; however, no baboon miRNAs have been identified. Evidence indicates that the baboon and human genomes are highly conserved; based on this conservation, we hypothesized that comparative genomic methods could be used to identify baboon miRNAs.

Methods

We employed an in silico comparative genomics approach and human miRNA arrays to identify baboon expressed miRNAs in liver (n = 6) and lymphocytes (n = 6). Expression profiles for selected miRNAs in multiple tissues were validated by RT-PCR.

Results

We identified in silico 555 putative baboon pre-miRNAs, of which 41% exhibited 100% identity and an additional 58% shared more than 90% sequence identity with human pre-miRNAs. Some of these miRNAs are primate-specific and are clustered in the baboon genome like human miRNA clusters. We detected expression of 494 miRNAs on the microarray and validated expression of selected miRNAs in baboon liver and lymphocytes by RT-PCR. We also observed miRNA expression in additional tissues relevant to dyslipidemia and atherosclerosis. Approximately half of the miRNAs expressed on the array were not predicted in silico suggesting that we have identified novel baboon miRNAs, which could not be predicted using the current draft of the baboon genome.

Conclusion

We identified a subset of baboon miRNAs using a comparative genomic approach, identified additional baboon miRNAs using a human array and showed tissue-specific expression of baboon miRNAs. Our discovery of baboon miRNAs in liver and lymphocytes will provide resources for studies on the roles of miRNAs in dyslipidemia and atherosclerosis, and for translational studies.
Mouse lung contains endothelial progenitors with high capacity to form blood and lymphatic vessels
Authors: Schniedermann Judith , Rennecke Moritz , Buttler Kerstin , Richter Georg , Städtler Anna-Maria , Norgall Susanne , Badar Muhammad , Barleon Bernhard , May Tobias , Wilting Jörg , Weich Herbert A
Published: July 2010

Background

Postnatal endothelial progenitor cells (EPCs) have been successfully isolated from whole bone marrow, blood and the walls of conduit vessels. They can, therefore, be classified into circulating and resident progenitor cells. The differentiation capacity of resident lung endothelial progenitor cells from mouse has not been evaluated.

Results

In an attempt to isolate differentiated mature endothelial cells from mouse lung we found that the lung contains EPCs with a high vasculogenic capacity and capability of de novo vasculogenesis for blood and lymph vessels.

Mouse lung microvascular endothelial cells (MLMVECs) were isolated by selection of CD31+ cells. Whereas the majority of the CD31+ cells did not divide, some scattered cells started to proliferate giving rise to large colonies (> 3000 cells/colony). These highly dividing cells possess the capacity to integrate into various types of vessels including blood and lymph vessels unveiling the existence of local microvascular endothelial progenitor cells (LMEPCs) in adult mouse lung. EPCs could be amplified > passage 30 and still expressed panendothelial markers as well as the progenitor cell antigens, but not antigens for immune cells and hematopoietic stem cells. A high percentage of these cells are also positive for Lyve1, Prox1, podoplanin and VEGFR-3 indicating that a considerabe fraction of the cells are committed to develop lymphatic endothelium. Clonogenic highly proliferating cells from limiting dilution assays were also bipotent. Combined in vitro and in vivo spheroid and matrigel assays revealed that these EPCs exhibit vasculogenic capacity by forming functional blood and lymph vessels.

Conclusion

The lung contains large numbers of EPCs that display commitment for both types of vessels, suggesting that lung blood and lymphatic endothelial cells are derived from a single progenitor cell.
Modeling secondary level of HIV contact tracing: its impact on HIV intervention in Cuba
Authors: Hsieh Ying-Hen , Wang Yun-Shih , de Arazoza Hector , Lounes Rachid
Published: July 2010

Background

Universal HIV testing/treatment program has currently been suggested and debated as a useful strategy for elimination of HIV epidemic in Africa, although not without practical issues regarding the costs and feasibility of a fully implemented program.

Methods

A mathematical model is proposed which considers two levels of detection of HIV-infectives through contact tracing of known infectives in addition to detections through other means such as random screening. Simulations based on Cuban contact tracing data were performed to ascertain the potential impact of the different levels of contact tracing.

Results

Simulation studies illustrate that: (1) contact tracing is an important intervention measure which, while less effective than random screening, is perhaps less costly and hence ideal for large-scale intervention programs in developing countries with less resources; (2) the secondary level of contact tracing could significantly change the basic disease transmission dynamics, depending on the parameter values; (3) the prevalence of the epidemic at the time of implementation of contact tracing program might be a crucial factor in determining whether the measure will be effective in preventing disease infections and its eventual eradication.

Conclusions

Our results indicate that contact tracing for detection of HIV infectives could be suitably used to remedy inadequacies in a universal HIV testing program when designing timely and effective intervention measures.
Modeling the Aneuploidy Control of Cancer
Authors: Li Yao , Berg Arthur , Wu Louie R , Wang Zhong , Chen Gang , Wu Rongling
Published: July 2010

Background

Aneuploidy has long been recognized to be associated with cancer. A growing body of evidence suggests that tumorigenesis, the formation of new tumors, can be attributed to some extent to errors occurring at the mitotic checkpoint, a major cell cycle control mechanism that acts to prevent chromosome missegregation. However, so far no statistical model has been available quantify the role aneuploidy plays in determining cancer.

Methods

We develop a statistical model for testing the association between aneuploidy loci and cancer risk in a genome-wide association study. The model incorporates quantitative genetic principles into a mixture-model framework in which various genetic effects, including additive, dominant, imprinting, and their interactions, are estimated by implementing the EM algorithm.

Results

Under the new model, a series of hypotheses tests are formulated to explain the pattern of the genetic control of cancer through aneuploid loci. Simulation studies were performed to investigate the statistical behavior of the model.

Conclusions

The model will provide a tool for estimating the effects of genetic loci on aneuploidy abnormality in genome-wide studies of cancer cells.
The tumor suppressor gene KCTD11
REN
is regulated by Sp1 and methylation and its expression is reduced in tumors
Authors: Mancarelli M Michela , Zazzeroni Francesca , Ciccocioppo Lucia , Capece Daria , Po Agnese , Murgo Simona , Di Camillo Raffaello , Rinaldi Christian , Ferretti Elisabetta , Gulino Alberto , Alesse Edoardo
Published: July 2010

A hallmark of several human cancers is loss of heterozygosity (LOH) of chromosome 17p13. The same chromosomal region is also frequently hypermethylated in cancer. Although loss of 17p13 has been often associated with p53 genetic alteration or Hypermethylated in Cancer 1 (HIC1) gene hypermethylation, other tumor suppressor genes (TSGs) located in this region have critical roles in tumorigenesis. A novel TSG mapping on human chromosome 17p13.2 is KCTD11

REN
(KCTD11). We have recently demonstrated that KCTD11 expression is frequently lost in human medulloblastoma (MB), in part by LOH and in part by uncharacterized epigenetic events. Using a panel of human 177 tumor samples and their normal matching samples representing 18 different types of cancer, we show here that the down-regulation of KCTD11 protein level is a specific and a diffusely common event in tumorigenesis. Additionally, in order to characterize the regulatory regions in KCTD11 promoter, we identified a CpG island and several Sp1 binding sites on this promoter, and demonstrated that Sp1 transcription factor and DNA methylation contribute, at least in part, to regulate KCTD11 expression. Our findings identify KCTD11 as a widely down-regulated gene in human cancers, and provide a basis to understand how its expression might be deregulated in tumor cells.
Voluntary exercise increases cholesterol efflux but not macrophage reverse cholesterol transport in vivo in mice
Authors: Meissner Maxi , Nijstad Niels , Kuipers Folkert , Tietge Uwe JF
Published: July 2010

Physical exercise beneficially impacts on the plasma lipoprotein profile as well as on the incidence of cardiovascular events and is therefore recommended in primary and secondary prevention strategies against atherosclerotic cardiovascular disease. However, the underlying mechanisms of the protective effect of exercise remain largely unknown. Therefore, the present study tested the hypothesis that voluntary exercise in mice impacts on cholesterol efflux and in vivo reverse cholesterol transport (RCT). After two weeks of voluntary wheel running (average 10.1 ± 1.4 km/day) plasma triglycerides were lower (p < 0.05), while otherwise lipid and lipoprotein levels did not change. Macrophage cholesterol efflux towards plasma was significantly increased in running (n = 8) compared to sedentary (n = 6) mice (14.93 ± 1.40 vs. 12.33 ± 2.60%, p < 0.05). In addition, fecal excretion of bile acids (3.86 ± 0.50 vs. 2.90 ± 0.51 nmol/d, p = 0.001) and neutral sterols (2.75 ± 0.43 vs. 1.94 ± 0.22 nmol/d, p < 0.01) was significantly higher in running mice. However, RCT from macrophages to feces remained essentially unchanged in running mice compared with sedentary controls (bile acids: 3.2 ± 1.0 vs. 2.9 ± 1.1 % of injected dose, n.s.; neutral sterols: 1.4 ± 0.7 vs. 1.1 ± 0.5 % injected dose, n.s.). Judged by the plasma lathosterol to cholesterol ratio, endogenous cholesterol synthesis was increased in exercising mice (0.15 ± 0.03 vs. 0.11 ± 0.02, p < 0.05), while the hepatic mRNA expression of key transporters for biliary cholesterol (Abcg5/g8, Sr-bI) as well as bile acid (Abcb11) and phospholipd (Abcb4) excretion did not change. These data indicate that the beneficial effects of exercise on cardiovascular health include increased cholesterol efflux, but do not extend to other components of RCT. The increased fecal cholesterol excretion observed in running mice is likely explained by higher endogenous cholesterol synthesis, however, it does not reflect increased RCT in the face of unchanged expression of key transporters for biliary sterol secretion.
Changes in Aβ Non-Nociceptive Primary Sensory Neurons in a Rat Model of Osteoarthritis Pain
Authors: Wu Qi , Henry James L
Published: July 2010

Background:

Pain is a major debilitating factor in osteoarthritis (OA), yet few mechanism-based therapies are available. To address the need to understand underlying mechanisms the aim of the present study was to determine changes in sensory neurons in an animal model of OA pain.

Results:

The model displayed typical osteoarthritis pathology characterized by cartilage degeneration in the knee joint and also manifested knee pathophysiology (edema and increased vasculature permeability of the joint) and altered nociception of the affected limb (hind paw tenderness and knee articulation-evoked reduction in the tail flick latency). Neurons included in this report innervated regions throughout the entire hind limb. Aβ-fiber low threshold mechanoreceptors exhibited a slowing of the dynamics of action potential (AP) genesis, including wider AP duration and slower maximum rising rate, and muscle spindle neurons were the most affected subgroup. Only minor AP configuration changes were observed in either C- or Aδ-fiber nociceptors.

Conclusion:

Thus, at one month after induction of the OA model Aβ-fiber low threshold mechanoreceptors but not C- or Aδ-fiber nociceptors had undergone changes in electrophysiological properties. If these changes reflect a change in functional role of these neurons in primary afferent sensory processing, then Aβ-fiber non-nociceptive primary sensory neurons may be involved in the pathogenesis of OA pain. Further, it is important to point out that the patterns of the changes we observed are consistent with observations in models of peripheral neuropathy but not models of peripheral inflammation.
Curcumin mediated suppression of nuclear factor-κB promotes chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment
Authors: Buhrmann Constanze , Mobasheri Ali , Matis Ulrike , Shakibaei Mehdi
Published: July 2010

Introduction

Osteoarthritis (OA) and rheumatoid arthritis (RA) are characterised by joint inflammation and cartilage degradation. Although mesenchymal stem cell (MSC)-like progenitors are resident in the superficial zone of articular cartilage, damaged tissue does not possess the capacity for regeneration. The high levels of pro-inflammatory cytokines present in OA/RA joints may impede the chondrogenic differentiation of these progenitors. Interleukin (IL)-1β activates the transcription factor nuclear factor-κB (NF-κB), which in turn activates proteins involved in matrix degradation, inflammation and apoptosis. Curcumin is a phytochemical capable of inhibiting IL-1β-induced activation of NF-κB and expression of apoptotic and pro-inflammatory genes in chondrocytes. Therefore, the aim of the present study was to evaluate the influence of curcumin on IL-1β-induced NF-κB signalling pathway in MSCs during chondrogenic differentiation.

Methods

MSCs were either cultured in a ratio of 1:1 with primary chondrocytes in high-density culture or cultured alone in monolayer with/without curcumin and/or IL-1β.

Results

We demonstrate that although curcumin alone does not have chondrogenic effects on MSCs, it inhibits IL-1β-induced activation of NF-κB, activation of caspase-3 and cyclooxygenase-2 in MSCs time and concentration dependently, as it does in chondrocytes. In IL-1β stimulated co-cultures, four-hour pre-treatment with curcumin significantly enhanced the production of collagen type II, cartilage specific proteoglycans (CSPGs), β1-integrin, as well as activating MAPKinase signaling and suppressing caspase-3 and cyclooxygenase-2.

Conclusions

Curcumin treatment may help establish a microenvironment in which the effects of pro-inflammatory cytokines are antagonized, thus facilitating chondrogenesis of MSC-like progenitor cells in vivo. This strategy may support the regeneration of articular cartilage.
Molecular Signature of Mineralocorticoid Receptor Signaling in Cardiomyocytes: From Cultured Cells to Mouse Heart
Authors: Latouche Celine , Sainte-Marie Yannis , Steenman Marja , Castro Chaves Paulo , Naray-Fejes-Toth Aniko , Fejes-Toth Geza , Farman Nicolette , Jaisser Frederic
Published: July 2010

Excess mineralocorticoid signaling is deleterious for cardiovascular functions, as demonstrated by the beneficial effects of mineralocorticoid receptor (MR) antagonism on morbidity and mortality in patients with heart failure. However, the understanding of signaling pathways after MR activation in the heart remains limited. We performed transcriptomic analyses in the heart of double-transgenic mice with conditional, cardiomyocyte-specific, overexpression of the MR (MRcardio mice) or the glucocorticoid receptor (GR; GRcardio mice). Some of the genes induced in MRcardio mice were selected for comparative evaluation (real time PCR) in vivo in the heart of mice and ex vivo in the MR-expressing cardiomyocyte H9C2 cell line after aldosterone or corticosterone treatment. We demonstrate that chronic MR overexpression in the heart results in a limited number of induced (n = 24) and repressed (n = 22) genes compared with their control littermates. These genes are specifically modulated by MR because there is limited overlap (three induced, four repressed) with the genes that are regulated in the heart of GRcardio mice (compared with control mice: 70 induced, 73 repressed). Interestingly, some MR-induced genes that are up-regulated in vivo in mice are also induced by 24-h aldosterone treatment in H9C2 cells, such as plasminogen activator inhibitor 1 and Serpina-3 (α1-antichymotrypsin). The signaling pathways that are affected by long-term activation of MR may be of particular interest to design novel therapeutic targets in cardiac diseases.
Research Resource: Gonadotropin-Releasing Hormone Receptor-Mediated Signaling Network in LβT2 Cells: A Pathway-Based Web-Accessible Knowledgebase
Authors: Fink Marc Y. , Pincas Hanna , Choi Soon Gang , Nudelman German , Sealfon Stuart C.
Published: July 2010

The GnRH receptor (GnRHR), expressed at the cell surface of the anterior pituitary gonadotrope, is critical for normal secretion of gonadotropins LH and FSH, pubertal development, and reproduction. The signaling network downstream of the GnRHR and the molecular bases of the regulation of gonadotropin expression have been the subject of intense research. The murine LβT2 cell line represents a mature gonadotrope and therefore is an important model for the study of GnRHR-signaling pathways and modulation of the gonadotrope cell by physiological regulators. In order to facilitate access to the information contained in this complex and evolving literature, we have developed a pathway-based knowledgebase that is web hosted. At present, using 106 relevant primary publications, we curated a comprehensive knowledgebase of the GnRHR signaling in the LβT2 cell in the form of a process diagram. Positive and negative controls of gonadotropin gene expression, which included GnRH itself, hypothalamic factors, gonadal steroids and peptides, as well as other hormones, were illustrated. The knowledgebase contains 187 entities and 206 reactions. It was assembled using CellDesigner software, which provides an annotated graphic representation of interactions, stored in Systems Biology Mark-up Language. We then utilized Biological Pathway Publisher, a software suite previously developed in our laboratory, to host the knowledgebase in a web-accessible format as a public resource. In addition, the network entities were linked to a public wiki, providing a forum for discussion, updating, and error correction. The GnRHR-signaling network is openly accessible at http://tsb.mssm.edu/pathwayPublisher/GnRHR_Pathway/GnRHR_Pathway_ index.html.
Looking Inside the Black Box: Using Intervention Mapping to Describe the Development of the Automated Smoking Cessation Intervention ‘Happy Ending’
Authors: Brendryen Håvar , Kraft Pål , Schaalma Herman
Published: July 2010

The digital therapy intervention for smoking cessation, ‘Happy Ending’, has been shown to be efficacious in two previous randomised controlled trials. The aim of the current article is to disentangle the rationale of the intervention and describe its development. For this purpose, Intervention Mapping is used as a descriptive tool. The intervention is fully automated and delivered by means of the Internet and mobile phones. It is based on self-regulation theory, social cognitive theory, cognitive–behaviour therapy, motivational interviewing and relapse prevention. The ordering of the content is based on a reasoned chronology, modelled according to psychological processes that people experience at certain time points in a process of therapy-supported self-regulation. The design of the intervention is innovative in that it combines four media channels (SMS, IVR, e-mail, and web), and in the combination of just-in-time therapy and a tunnelling strategy based on the natural chronology of quitting. The two forms of just-in-time therapy are a craving helpline (mainly targeting negative affect), and the provision of relapse therapy based on a daily assessment of the target behaviour. The present article meets the recent calls for more thorough descriptions of interventions, and may inform systematic reviews and the development of interventions.
Can mammalian mothers influence the sex of their offspring peri-conceptually?
Authors: Grant Valerie J , Chamley Lawrence W
Published: July 2010

Although controversial, growing evidence from evolutionary biology suggests that the mammalian mother may have a role in influencing the sex of her offspring. However, there is competing information on the molecular mechanisms by which such influence could be manifested. The new initiatives are based on hypotheses from evolutionary biology: the ‘good condition’ hypothesis, which suggests that post conception, higher levels of maternal glucose may differentially promote the development of male embryos; and the ‘maternal dominance’ hypothesis, which proposes that before conception, higher follicular testosterone may influence the development of the ovum so that it emerges already adapted to receive an X- or a Y-chromosome-bearing spermatozoon. Now, it seems these hypothesised mechanisms could be operating in synchrony, each complementing and reinforcing the other. On the other hand, there are continuing problems in identifying a precise sequence of mechanisms as evidenced from research in sperm-sorting. Research on high-fat diets and the sex ratio in polytocous species may indicate important differences in proximate mechanisms for sex allocation between polytocous and monotocous mammals.
Neonatal Hip Dysplasia: A New Perspective
Authors: Wilkinson A. Graham , Wilkinson Sally
Published: July 2010

This review of neonatal hip dysplasia examines the clinical and ultrasonographic literature that has guided current practice and discusses the controversies involved in detection and treatment of the condition. We present a view that combines clinical and ultrasonographic criteria in a simple and effective treatment decision pathway. Enthusiasm, specialization, and expertise in clinical and ultrasonographic aspects, with clear communication and cooperation between these two disciplines, are necessary to achieve an effective screening program.
Intravenous Immune Globulin: Clinical Applications in the Newborn
Authors: Navarro Mariel , Negre Sergio , Golombek Sergio , Matoses María L. , Vento Máximo
Published: July 2010

Intravenous immune globulin (IVIG) is manufactured from plasma isolated from healthy blood donors and includes mostly immunoglobulin G (IgG). IVIG is approved by the United States Food and Drug Administration (FDA) for use in a variety of diseases in adults and children, although there are no FDA-approved uses of IVIG in newborns. Off-label use of IVIG in newborns includes prophylaxis against infections in low-birthweight infants and treatment of neonatal alloimmune diseases such as hemolytic disease of the newborn (HDN) and neonatal alloimmune thrombocytopenia (NAIT). More recently, IVIG has been used in parvovirus B19 infection, hemochromatosis, and neonatal Kawasaki disease. The mechanism of action of IVIG includes antibody-specific immunity as well as mechanisms triggered via IgG binding to fragment crystallizable (Fc) receptors on phagocytes, natural killer (NK) cells, and reticuloendothelial cells located throughout the body. Adverse effects of IVIG in adults and children are well recognized and include anaphylaxis, thromboembolism, renal failure, and aseptic meningitis. The adverse effects of IVIG in the newborn are less well described but include severe diseases such as necrotizing enterocolitis (NEC). Hence, although IVIG may be indicated as an adjunct for the prevention and treatment of infectious and certain alloimmune-mediated diseases in infants, it should be used with caution in the newborn period.
Biomarkers in lupus nephritis
Authors: Brúgós Boglárka , Zeher Margit
Published: July 2010

A szisztémás lupus erythematosus poliszisztémás autoimmun betegség, egyik legjelentősebb szervi szövődménye a lupus nephritis. A lupus nephritis időbeni, a krónikus szervi érintettség kialakulását megelőző felismerése, a shubok előrejelzése, a korai agresszív kezelés elkezdése és a terápia sikerességének lemérése kívánatos lenne. Ezért a kutatások egy része intenzíven a legmegfelelőbb, aktivitást előre jelző biomarker megtalálására irányul. Jelen összefoglaló célja a hagyományos szerológiai markerek megbeszélésén túl a legújabb, részben még kísérletes, a klinikai gyakorlatban nem használt, de az SLE, illetve lupus nephritis aktivitását jellemző specifikus biomarkerek bemutatása.
Surface Observation of Thin Hydroxyapatite-Coated Implants at 80 Months After Insertion
Authors: Sugiyama Tetsuya , Miake Yasuo , Yajima Yasutomo , Yamamoto Kohji , Sakurai Kaoru
Published: July 2010

We observed surfaces and cross sections of thin hydroxyapatite (HA)-coated implants produced by the thermal decomposition method in a patient attending our clinic who underwent implant removal at 80 months due to fracture of the implants. On the implant surfaces of the removed sample, most of the HA had dissolved, and extensive osseointegration was observed where Ti had closely bonded to bone. This indicated that the HA coated on the implant surfaces had disappeared and osseointegration had been established where Ti directly bonded to the bone. In addition, calcium titanate (CaTiO3) and HA layers formed by the thermal decomposition method showed no desorption. The results clearly indicate the positive clinical potential of thin HA-coating by the thermal decomposition method.
Sensitivity analysis for an unmeasured confounder: a review of two independent methods
Authors: Luiz Ronir Raggio , Cabral Maria Deolinda Borges
Published: July 2010

One of the main purposes of epidemiological studies is to estimate causal effects. Causal inference should be addressed by observational and experimental studies. A strong constraint for the interpretation of observational studies is the possible presence of unobserved confounders (hidden biases). An approach for assessing the possible effects of unobserved confounders may be drawn up through the use of a sensitivity analysis that determines how strong the effects of an unmeasured confounder should be to explain an apparent association, and which should be the characteristics of this confounder to exhibit such an effect. The purpose of this paper is to review and integrate two independent sensitivity analysis methods. The two methods are presented to assess the impact of an unmeasured confounder variable: one developed by Greenland under an epidemiological perspective, and the other developed from a statistical standpoint by Rosenbaum. By combining (or merging) epidemiological and statistical issues, this integration became a more complete and direct sensitivity analysis, encouraging its required diffusion and additional applications. As observational studies are more subject to biases and confounding than experimental settings, the consideration of epidemiological and statistical aspects in sensitivity analysis strengthens the causal inference.
Confiabilidade (teste-reteste) da escala sueca do Questionário Demanda-Controle entre Trabalhadores de Restaurantes Industriais do Estado do Rio de Janeiro
Authors: Aguiar Odaleia Barbosa de , Fonseca Maria de Jesus Mendes da , Valente Joaquim Gonçalves
Published: July 2010

OBJETIVO: Este estudo tem o objetivo de verificar a confiabilidade teste-reteste da versão em Português da escala sueca "Demand-Control-Support Questionnaire (DCSQ)" em uma população de trabalhadores com baixa escolaridade. MÉTODO: O questionário foi aplicado em dois momentos para 52 trabalhadores de três restaurantes industriais de uma empresa concessionária do Rio de Janeiro, com intervalos de 7 a 15 dias. Como indicadores de estabilidade foram utilizados o Coeficiente de Correlação Intraclasse (CCIC), a estatística Kappa Ponderado e o gráfico de Bland & Altman. Para avaliação da consistência interna utilizou-se o Coeficiente Alpha de Cronbach. RESULTADOS: O CCIC para as dimensões: demanda psicológica, controle do trabalho e apoio social no trabalho foi de 0,70, 0,68 e 0,80, respectivamente. O Alpha de Cronbach apresentou, no reteste, os seguintes resultados: 0,75, 0,50 e 0,82, para as dimensões anteriormente citadas, na mesma sequência. CONCLUSÕES: Ainda que o resultado da escala controle do trabalho tenha sido considerado baixo para o Alpha de Cronbach, os outros indicadores de confiabilidade apontam para uma boa estabilidade do instrumento, possibilitando sua utilização em estudos de associação entre estresse no trabalho e desfechos relacionados à saúde.
Kailidiscus, a new plesiomorphic edrioasteroid from the basal Middle Cambrian Kaili biota of Guizhou Province, China
Authors: Zhao Yuanlong , Sumrall Colin D. , Parsley Ronald L. , Peng Jin
Published: July 2010

A new genus and species of edrioasteroid grade echinoderm, Kailidiscus chinensis, is described from the Kaili Biota of the basal lower Middle Cambrian Kaili Formation from Guizhou Province, China. This echinoderm has a strong resemblance to isorophid edrioasteroids, bearing a well-developed peripheral rim, long curved ambulacra, and slightly imbricate interambulacral plating at maturity. However, the presence of pore-bearing, double biserial floor plates, tiered cover plates, lack of radially positioned oral frame plates, and unincorporated hydropore/gonopore are unknown in isorophids. Many of these features bear strong resemblance to eocrinoids and helicoplacoids, attesting to the plesiomorphic nature of this taxon. Despite the obvious anatomical differences, specimens of this species preserve a complete ontogeny that resembles that of isorophids. Juveniles show a discoidal theca with straight ambulacra that transitions to an inflated theca with strongly curved ambulacra with maturity.
Prognostic markers of survival after combined mitotane- and platinum-based chemotherapy in metastatic adrenocortical carcinoma
Authors: Malandrino Pasqualino , Al Ghuzlan Abir , Castaing Marine , Young Jacques , Caillou Bernard , Travagli Jean-Paul , Elias Dominique , de Baere Thierry , Dromain Clarisse , Paci Angelo , Chanson Philippe , Schlumberger Martin , Leboulleux Sophie , Baudin Eric
Published: July 2010

To progress in the stratification of the first-line therapeutic management of metastatic adrenocortical carcinoma (ACC), we searched for prognostic parameters of survival in patients treated with combined mitotane- and cisplatinum-based chemotherapy as first-line. We retrospectively studied prospectively collected parameters from 131 consecutive patients with metastatic ACC (44 with a tissue specimen available) treated at the Gustave Roussy Institute with mitotane- and platinum-based chemotherapy. Fifty-five patients with clinical, pathological, and morphological data available together with treatment characteristics including detailed follow-up were enrolled. Plasma mitotane levels and ERCC1 protein staining were analyzed. Response was analyzed according to RECIST criteria as well as overall survival (OS) from the start of cisplatinum-based chemotherapy. Parameters impacting on OS were evaluated by univariate analysis, and then analyzed by multivariate analysis. Using a landmark method, OS according to response to chemotherapy was analyzed. Objective response to combined mitotane- and cisplatinum-based chemotherapy was 27.3%. Median OS was 1 year. In the univariate analysis, resection of the primary, time since diagnosis, mitotane monotherapy as single first-line treatment, number of affected organs, plasma mitotane above 14 mg/l, and objective response were predictors of survival. In the multivariate analysis, mitotane level ≥14 mg/l and objective response to platinum-based chemotherapy were found to be independent predictors of survival (P=0.03 and <0.001). Our study suggests a prognostic role for mitotane therapy and objective response to platinum-based chemotherapy.
Traffic management in Konya by junction risk factor
Authors: Gundogdu I. B.
Published: July 2010

With the growing population size and number of vehicles, traffic congestion is increasing, particularly in urban areas. Adequate junction management and control are necessary to prevent traffic accidents and jams and to provide optimal traffic flow. In this study, 103 inner city junction points in Konya province in Turkey have been evaluated in terms of their structural data, such as numerical data, intervals and related distances. The aim of the study is to eliminate traffic jams at junctions and to reduce the risk of accidents by regulating components of high-risk junctions in urban areas. Some main sources of traffic congestion have been formularised and termed ‘junction risk factors’ in long-term experiments. The appropriateness of the model was then compared and tested by kernel density estimation and Getis-Ord Gi statistical methods. The superiority of the new model is that the variables of the models are independent and do not affect each other. As a result, besides numerical suggestions, probable maps have been produced for the purpose of future route/junction planning using geographic information systems.
Synthesis of Oxide Particles Using a Polymer-Assisted Spray Pyrolysis Reactor, and a Percolation Explanation of Particle Separation
Authors: Abdullah Mikrajuddin , Khairurrijal Khairurrijal , Nuryadin Bebeh W , Sustini Euis
Published: July 2010

A vertical spray pyrolysis reactor was designed to produce separated/softly agglomerated oxide nanoparticles by dissolving a large amount of high molecular weight polymer into solutions of nitrous or acetic metals. The polymer played a role as a matrix that prevented the tendency of as-grown nuclei to make contacts inside the polymer ball. Decomposition of the polymer ball at the end stage of the reactor released separated nanoparticles. On the first attempt, we produced particles of zinc oxide and compound oxide of CuO/ZnO/Al2O3 at different parameters of synthesis. We found that the size of the particles decreased, as a fraction of the polymer, as the mass increased. We used a percolation theory to explain the particle separation mechanism inside the polymer ball. Separated nanoparticles were obtained if the volume fraction of the particles was far below the percolation threshold.
Urban deciduous tree leaves as biomonitors of trace element (AS, V and Cd) atmospheric pollution in Belgrade, Serbia
Authors: Sucur Katarina , Anicic Mira , Tomasevic Milica , Antanasijevic Davor , Peric-Grujic Aleksandra , Ristic Mirjana
Published: July 2010

Leaves of common deciduous trees: horse chestnut (Aesculus hippocastanum) and linden (Tilia spp.) from three parks within the urban area of Belgrade were studied as biomonitors of trace element (As, V, and Cd) atmospheric pollution. The May-September trace element accumulation in the leaves, and their temporal trends, were assayed in a multi-year period (2002-2006). Significant accumulation in the leaves was evident for As and V, but not so regularly for Cd. Slightly decreasing temporal trends of V and As accumulated in the leaf tissues were observed over the years. During the time span, the concentrations of Cd remained approximately on the same level, except in May 2002 and September 2005, when a rapid increase was observed. The May-September accumulations of As and V were higher in horse chestnut than in linden, although both may be used as biomonitors for these elements, and optionally for Cd in conditions of its high atmospheric loadings.
Influence of the damage level during quenching on thermal shock behavior of low cement castable
Authors: Martinovic S. , Majstorovic J. , Vidojkovic V. , Volkov-Husovic T.
Published: July 2010

In the recent decades, the use of unshaped monolithic refractories has been increasing greatly because of their significant advantages over other shaped refractory bricks of the same class. A low cement high alumina castable was synthetised and sintered at 1300?C in order to investigate thermal and mechanical properties, as well as thermal shock behavior. The water quench test was applied as an experimental method for thermal stability testing. Modification of the water quench test was performed by additional monitoring of the samples behavior during the water quench test such as implementation of image analysis and ultrasonic measurements. The image analysis program was applied on samples in order to measure the level of surface damage before and during the water quench test. Ultrasonic measurements were performed with the aim to measure the Young modulus of elasticity during the testing. Strength deterioration of the samples was calculated by the model based on ultrasonic velocity changes during the water quench test. The influence of monitoring the damage level before and during the quench experiment and its influence on thermal shock behavior will be discussed.