bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the Ross Procedure a Suitable Choice for Aortic Valve Replacement in Children With Rheumatic Aortic Valve Disease?
Authors: Alsoufi Bahaaldin , Manlhiot Cedric , Fadel Bahaa , Al-Fayyadh Majid , McCrindle Brian W. , Alwadai Abdullah , Al-Halees Zohair
Published: January 2012

Background: Ross procedure is the aortic valve replacement of choice in children. Nonetheless, late autograft reoperation for dilatation and/or regurgitation is concerning. We examine whether Ross procedure is suitable in children with rheumatic fever. Methods: Medical records of 104 children with rheumatic fever who underwent Ross procedure were reviewed (1991-2004). Competing risks methodology determined time-related prevalence and associated factors for two mutually exclusive end states: autograft reoperation and death prior to subsequent reoperation. Results: Mean age was 13.8 ± 2.7, 83 (80%) were males. Hemodynamic dysfunction was primarily regurgitation (n = 92, 88%) and stenosis/mixed (n = 12, 12%). Competing risks analysis showed that in ten years after the Ross procedure, 1% of patients died, 32% underwent autograft reoperation, and 67% were alive and free from reoperation. Ten-year freedom from aortic regurgitation greater than or equal to moderate was 63%. Ten-year freedom from autograft reoperation was 65% for regurgitation versus 90% for stenosis/mixed disease. Risk factors for autograft reoperation were earlier surgery year (PE: 0.26 ± 0.06 per year; P < .001), additional surgery (PE: 0.82 ± 0.39, P = .04), no annular stabilization (PE: 1.21 ± 0.61, P = .05). Ten-year freedom from homograft replacement was 83%. Risk factors were fresh homografts (PE: 1.36 ± 0.71; P = .06) and aortic homografts (PE: 1.15 ± 0.59; P = .05). Ten-year freedom from any cardiac reoperation was 53%. Concomitant cardiac surgery was risk factor (PE: 1.37 ± 0.47; P = .004). Conclusions: Ross procedure in children with rheumatic fever is associated with excellent survival but results are plagued by aortic regurgitation and frequent autograft reoperation. Risk factors include preoperative regurgitation, concomitant surgery, dilated annulus, and earlier surgery era. Better patient selection in later era has mitigated autograft reoperation risk. Continued, improved candidate selection, along with modifications in autograft implantation and root/sinotubular stabilization techniques, may further decrease late autograft failure.
Ventricular Assist Devices for Mechanical Circulatory Support in Children
Authors: Thiagarajan Ravi R. , Almond Christopher S. , Cooper David S. , Morales David L. S.
Published: January 2012

Ventricular assist devices (VADs) are increasingly used in children to provide mechanical circulatory support as a bridge to cardiac transplantation. In this article, we review information on the current status, outcomes, and future directions for the use of VADs in children.
Surgical Decision Making in Neonatal Ebstein’s Anomaly
Authors: Knott-Craig Christopher J. , Goldberg Steven P. , Ballweg Jean A. , Boston Umar S.
Published: January 2012

Objective: There is currently no consensus of opinion regarding the optimal surgical management of Ebstein’s anomaly (EA) in neonates and young infants. Reported early mortality rates range from 25% to 100%. In this study, we present an algorithm for choosing the best management option for neonates with EA based on analysis of our experience. Patients and Methods: From 1994 to June, 2011, 48 neonates with a diagnosis of EA were managed by the same surgical team. Of these, two died before intervention; the remaining 46 either were managed medically initially (n = 20) or underwent surgical intervention during the neonatal period (n = 26) or early infancy (n = 9). Results: The mean weight was 3.6 ± 1.7 kg (1.9-8.6) and mean follow-up time was 6.3 ± 4.5 years (0.2-16). Of the 20 patients initially managed medically, 11 remain well without intervention and nine required complete repair in infancy, with 100% survival. Of the 26 neonatal operations, 23 (88%) were complete biventricular repairs, 1 Starnes’ palliation, and two Blalock–Taussig shunts (BTSs) ± pulmonary valvotomy. Among those having a two-ventricle repair, anatomic pulmonary atresia (APA) was a risk factor for early mortality (46.1%, 6 of 13) compared with those without pulmonary atresia (EA/no-PA; 10%, 1 of 10), P < .05. Conclusions: Most symptomatic neonates with EA will require early operation. For those with APA and mild tricuspid regurgitation (TR), a modified BTS and reduction atrioplasty may be the best initial option. For those with functional pulmonary atresia and severe TR and pulmonary regurgitation, ligation of the main pulmonary artery and placement of a BTS may provide the best initial palliation. For the rest, either a biventricular repair or a single-ventricle palliation is indicated.
Analysis of Work and Cultural Adjustment of Korean-Chinese and Han-Chinese Workers in Korea under Framework of ERG Theory
Authors: Li Jinxi Michelle
Published: January 2012

The increased number of foreigners in Korea (now more than one million) urgently calls for understanding, analyzing and interpreting the immigration issues in order to solve the foreign workers' social problems. This paper aims to identify the factors affecting work and cultural adjustment of the foreign workers in Korea and to investigate the differences in adaptation modes of Korean-Chinese and Han-Chinese workers. A total of 23 Korean-Chinese and Han-Chinese workers were randomly selected for interview to select the variables that best represent the research context. The variables, duly sorted by different human needs under ERG theory, were assumed to predict the work and cultural adjustment, and included Work Conditions, Power Distance, Social-Cultural Distance in the Workplace, Legal Status, Duration of Stay, Korean Proficiency, and Social Support. The sample of our respondents was 395 Korean-Chinese and Han-Chinese workers in Korea: 227 Korean-Chinese and 168 Han-Chinese. We used SPSS 12.0 and AMOS 5.0 for statistical analysis. Our study reveals useful results for the development of theories and measurements of international adjustment as well as for organizational and welfare practice. Work conditions, power distance, and social support have a significant effect on work adjustment. Duration of stay (in Korea), Korean language proficiency, and work adjustment have a significant effect on cultural adjustment. Existence needs have a bigger effect on work/cultural adjustment than relatedness needs. The two ethnic groups have significant differences in the paths of poor working conditions with cultural adjustment and of power distance with cultural adjustment. It is necessary to further develop the measurements of work and cultural adjustment in future research.
Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study
Authors: Kanda Junya , Hishizawa Masakatsu , Utsunomiya Atae , Taniguchi Shuichi , Eto Tetsuya , Moriuchi Yukiyoshi , Tanosaki Ryuji , Kawano Fumio , Miyazaki Yasushi , Masuda Masato , Nagafuji Koji , Hara Masamichi , Takanashi Minoko , Kai Shunro , Atsuta Yoshiko , Suzuki Ritsuro , Kawase Takakazu , Matsuo Keitaro , Nagamura-Inoue Tokiko , Kato Shunichi , Sakamaki Hisashi , Morishima Yasuo , Okamura Jun , Ichinohe Tatsuo , Uchiyama Takashi
Published: January 2012

Allogeneic hematopoietic cell transplantation (HCT) is an effective treatment for adult T-cell leukemia (ATL), raising the question about the role of graft-versus-leukemia effect against ATL. In this study, we retrospectively analyzed the effects of acute and chronic graft-versus-host disease (GVHD) on overall survival, disease-associated mortality, and treatment-related mortality among 294 ATL patients who received allogeneic HCT and survived at least 30 days posttransplant with sustained engraftment. Multivariate analyses treating the occurrence of GVHD as a time-varying covariate demonstrated that the development of grade 1-2 acute GVHD was significantly associated with higher overall survival (hazard ratio [HR] for death, 0.65; P = .018) compared with the absence of acute GVHD. Occurrence of either grade 1-2 or grade 3-4 acute GVHD was associated with lower disease-associated mortality compared with the absence of acute GVHD, whereas grade 3-4 acute GVHD was associated with a higher risk for treatment-related mortality (HR, 3.50; P < .001). The development of extensive chronic GVHD was associated with higher treatment-related mortality (HR, 2.75; P = .006) compared with the absence of chronic GVHD. Collectively, these results indicate that the development of mild-to-moderate acute GVHD confers a lower risk of disease progression and a beneficial influence on survival of allografted patients with ATL.
Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML)
Authors: Goodyear Oliver C. , Dennis Mike , Jilani Nadira Y. , Loke Justin , Siddique Shamyla , Ryan Gordon , Nunnick Jane , Khanum Rahela , Raghavan Manoj , Cook Mark , Snowden John A. , Griffiths Mike , Russell Nigel , Yin John , Crawley Charles , Cook Gordon , Vyas Paresh , Moss Paul , Malladi Ram , Craddock Charles F.
Published: January 2012

Strategies that augment a GVL effect without increasing the risk of GVHD are required to improve the outcome after allogeneic stem cell transplantation (SCT). Azacitidine (AZA) up-regulates the expression of tumor Ags on leukemic blasts in vitro and expands the numbers of immunomodulatory T regulatory cells (Tregs) in animal models. Reasoning that AZA might selectively augment a GVL effect, we studied the immunologic sequelae of AZA administration after allogeneic SCT. Twenty-seven patients who had undergone a reduced intensity allogeneic transplantation for acute myeloid leukemia were treated with monthly courses of AZA, and CD8+ T-cell responses to candidate tumor Ags and circulating Tregs were measured. AZA after transplantation was well tolerated, and its administration was associated with a low incidence of GVHD. Administration of AZA increased the number of Tregs within the first 3 months after transplantation compared with a control population (P = .0127). AZA administration also induced a cytotoxic CD8+ T-cell response to several tumor Ags, including melanoma-associated Ag 1, B melanoma antigen 1, and Wilm tumor Ag 1. These data support the further examination of AZA after transplantation as a mechanism of augmenting a GVL effect without a concomitant increase in GVHD. The trial was registered at http://isrctn.org as #ISRCTN36825171.
High-resolution genomic profiling of adult and pediatric core-binding factor acute myeloid leukemia reveals new recurrent genomic alterations
Authors: Kühn Michael W. M. , Radtke Ina , Bullinger Lars , Goorha Salil , Cheng Jinjun , Edelmann Jennifer , Gohlke Juliane , Su Xiaoping , Paschka Peter , Pounds Stanley , Krauter Jürgen , Ganser Arnold , Quessar Asmaa , Ribeiro Raul , Gaidzik Verena I. , Shurtleff Sheila , Krönke Jan , Holzmann Karlheinz , Ma Jing , Schlenk Richard F. , Rubnitz Jeffrey E. , Döhner Konstanze , Döhner Hartmut , Downing James R.
Published: January 2012

To identify cooperating lesions in core-binding factor acute myeloid leukemia, we performed single-nucleotide polymorphism-array analysis on 300 diagnostic and 41 relapse adult and pediatric leukemia samples. We identified a mean of 1.28 copy number alterations per case at diagnosis in both patient populations. Recurrent minimally deleted regions (MDRs) were identified at 7q36.1 (7.7%), 9q21.32 (5%), 11p13 (2.3%), and 17q11.2 (2%). Approximately one-half of the 7q deletions were detectable only by single-nucleotide polymorphism-array analysis because of their limited size. Sequence analysis of MLL3, contained within the 7q36.1 MDR, in 46 diagnostic samples revealed one truncating mutation in a leukemia lacking a 7q deletion. Recurrent focal gains were identified at 8q24.21 (4.7%) and 11q25 (1.7%), both containing a single noncoding RNA. Recurrent regions of copy-neutral loss-of-heterozygosity were identified at 1p (1%), 4q (0.7%), and 19p (0.7%), with known mutated cancer genes present in the minimally altered region of 1p (NRAS) and 4q (TET2). Analysis of relapse samples identified recurrent MDRs at 3q13.31 (12.2%), 5q (4.9%), and 17p (4.9%), with the 3q13.31 region containing only LSAMP, a putative tumor suppressor. Determining the role of these lesions in leukemogenesis and drug resistance should provide important insights into core-binding factor acute myeloid leukemia.
MicroRNA-650 expression is influenced by immunoglobulin gene rearrangement and affects the biology of chronic lymphocytic leukemia
Authors: Mraz Marek , Dolezalova Dasa , Plevova Karla , Stano Kozubik Katerina , Mayerova Veronika , Cerna Katerina , Musilova Katerina , Tichy Boris , Pavlova Sarka , Borsky Marek , Verner Jan , Doubek Michael , Brychtova Yvona , Trbusek Martin , Hampl Ales , Mayer Jiri , Pospisilova Sarka
Published: January 2012

MicroRNAs (miRNAs) play a key role in chronic lymphocytic leukemia as well as in normal B cells. Notably, miRNA gene encoding miR-650 and its homologs overlap with several variable (V) subgenes coding for lambda immunoglobulin (IgLλ). Recent studies describe the role of miR-650 in solid tumors, but its role in chronic lymphocytic leukemia (CLL) has not yet been studied. Our experiments demonstrate that miR-650 expression is regulated by coupled expression with its host gene for IgLλ. This coupling provides a unique yet unobserved mechanism for microRNA gene regulation. We determine that higher expression of miR-650 is associated with a favorable CLL prognosis and influences the proliferation capacity of B cells. We also establish that in B cells, miR-650 targets proteins important in cell proliferation and survival: cyclin dependent kinase 1 (CDK1), inhibitor of growth 4 (ING4), and early B-cell factor 3 (EBF3). This study underscores the importance of miR-650 in CLL biology and normal B-cell physiology.
Does a shift in host plants trigger speciation in the Alpine leaf beetle Oreina speciosissima(Coleoptera, Chrysomelidae)?
Authors: Borer Matthias , van Noort Tom , Arrigo Nils , Buerki Sven , Alvarez Nadir
Published: January 2012

Background

Within the Coleoptera, the largest order in the animal kingdom, the exclusively herbivorous Chrysomelidae are recognized as one of the most species rich beetle families. The evolutionary processes that have fueled radiation into the more than thirty-five thousand currently recognized leaf beetle species remain partly unresolved. The prominent role of leaf beetles in the insect world, their omnipresence across all terrestrial biomes and their economic importance as common agricultural pest organisms make this family particularly interesting for studying the mechanisms that drive diversification. Here we specifically focus on two ecotypes of the alpine leaf beetleOreina speciosissima(Scop.), which have been shown to exhibit morphological differences in male genitalia roughly corresponding to the subspeciesOreina speciosissima sensu strictoandOreina speciosissima troglodytes. In general the two ecotypes segregate along an elevation gradient and by host plants:Oreina speciosissima sensu strictocolonizes high forb vegetation at low altitude andOreina speciosissima troglodytesis found in stone run vegetation at higher elevations. Both host plants and leaf beetles have a patchy geographical distribution. Through use of gene sequencing and genome fingerprinting (AFLP) we analyzed the genetic structure and habitat use ofOreina speciosissimapopulations from the Swiss Alps to examine whether the two ecotypes have a genetic basis. By investigating a wide range of altitudes and focusing on the structuring effect of habitat types, we aim to provide answers regarding the factors that drive adaptive radiation in this phytophagous leaf beetle.

Results

While little phylogenetic resolution was observed based on the sequencing of four DNA regions, the topology and clustering resulting from AFLP genotyping grouped specimens according to their habitat, mostly defined by plant associations. A few specimens with intermediate morphologies clustered with one of the two ecotypes or formed separate clusters consistent with habitat differences. These results were discussed in an ecological speciation framework.

Conclusions

The question of whether this case of ecological differentiation occurred in sympatry or allopatry remains open. Still, the observed pattern points towards ongoing divergence between the two ecotypes which is likely driven by a recent shift in host plant use.
Host cell and expression engineering for development of an E. coli ketoreductase catalyst: Enhancement of formate dehydrogenase activity for regeneration of NADH
Authors: Mädje Katharina , Schmölzer Katharina , Nidetzky Bernd , Kratzer Regina
Published: January 2012

Background

Enzymatic NADH or NADPH-dependent reduction is a widely applied approach for the synthesis of optically active organic compounds. The overall biocatalytic conversion usually involves in situ regeneration of the expensive NAD(P)H. Oxidation of formate to carbon dioxide, catalyzed by formate dehydrogenase (EC 1.2.1.2; FDH), presents an almost ideal process solution for coenzyme regeneration that has been well established for NADH. Because isolated FDH is relatively unstable under a range of process conditions, whole cells often constitute the preferred form of the biocatalyst, combining the advantage of enzyme protection in the cellular environment with ease of enzyme production. However, the most prominent FDH used in biotransformations, the enzyme from the yeast Candida boidinii, is usually expressed in limiting amounts of activity in the prime host for whole cell biocatalysis, Escherichia coli. We therefore performed expression engineering with the aim of enhancing FDH activity in an E. coli ketoreductase catalyst. The benefit resulting from improved NADH regeneration capacity is demonstrated in two transformations of technological relevance: xylose conversion into xylitol, and synthesis of (S)-1-(2-chlorophenyl)ethanol from o-chloroacetophenone.

Results

As compared to individual expression of C. boidinii FDH in E. coli BL21 (DE3) that gave an intracellular enzyme activity of 400 units/gCDW, co-expression of the FDH with the ketoreductase (Candida tenuis xylose reductase; XR) resulted in a substantial decline in FDH activity. The remaining FDH activity of only 85 U/gCDW was strongly limiting the overall catalytic activity of the whole cell system. Combined effects from increase in FDH gene copy number, supply of rare tRNAs in a Rosetta strain of E. coli, dampened expression of the ketoreductase, and induction at low temperature (18°C) brought up the FDH activity threefold to a level of 250 U/gCDW while reducing the XR activity by just 19% (1140 U/gCDW). The E. coli whole-cell catalyst optimized for intracellular FDH activity showed improved performance in the synthesis of (S)-1-(2-chlorophenyl)ethanol, reflected in a substantial, up to 5-fold enhancement of productivity (0.37 g/gCDW) and yield (95% based on 100 mM ketone used) as compared to the reference catalyst. For xylitol production, the benefit of enhanced FDH expression was observed on productivity only after elimination of the mass transfer resistance caused by the cell membrane.

Conclusions

Expression engineering of C. boidinii FDH is an important strategy to optimize E. coli whole-cell reductase catalysts that employ intracellular formate oxidation for regeneration of NADH. Increased FDH-activity was reflected by higher reduction yields of D-xylose and o-chloroacetophenone conversions provided that mass transfer limitations were overcome.
Evaluation of human enterovirus 71 and coxsackievirus A16 specific immunoglobulin M antibodies for diagnosis of hand-foot-and-mouth disease
Authors: Yu Nan , Guo Min , He Si-Jie , Pan Yu-Xian , Chen Xin-Xin , Ding Xi-Xia , Hao Wei , Wang Ya-Di , Ge Sheng-Xiang , Xia Ning-Shao , Che Xiao-Yan
Published: January 2012

Background

Hand-foot-and-mouth disease (HFMD) is caused mainly by the human enterovirus type 71 (HEV71) and the Coxsackievirus A group type 16 (CVA16). Large outbreaks of disease have occurred frequently in the Asia-Pacific region. Reliable methods are needed for diagnosis of HFMD in childen. IgM-capture ELISA, with its notable advantages of convenience and low cost, provides a potentially frontline assay. We aimed to evaluate the newly developed IgM-capture ELISAs for HEV71 and CVA16 in the diagnosis of HFMD, and to measure the kinetics of IgM over the course of HEV71 or CVA16 infections.

Results

We mapped, for the first time, the kinetics of IgM in HEV71 and CVA16 infection. HEV71- and CVA16-IgM were both detectable in some patients on day 1 of illness, and in 100% of patients by day 5 (HEV71) and day 8 (CVA16) respectively; both IgMs persisted for several weeks. The IgM detection rates were 90.2% (138 of 153 sera) and 68.0% (66 of 97 sera) for HEV71 and CVA16 infections, respectively, during the first 7 days of diseases. During the first 90 days after onset these values were 93.6% (233 of 249 sera) and 72.8% (91 of 125 sera) for HEV71 and CVA16 infections, respectively. Some cross-reactivity was observed between HEV71- and CVA16-IgM ELISAs. HEV71-IgM was positive in 38 of 122 (31.1%) CVA16 infections, 14 of 49 (28.6%) other enteroviral infections and 2 of 105 (1.9%) for other respiratory virus infected sera. Similarly, CVA16-IgM was apparently positive in 58 of 211 (27.5%) HEV71 infections, 16 of 48 (33.3%) other enterovirus infections and 3 of 105 (2.9%) other respiratory virus infected sera. Nevertheless, the ELISA yielded the higher OD450value of main antibody than that of cross-reaction antibody, successfully identifying the enteroviral infection in 96.6% (HEV71) and 91.7% (CVA16) cases. When blood and rectal swabs were collected on the same day, the data showed that the agreement between IgM-capture ELISA and real-time RT-PCR in HEV71 was high (Kappa value = 0.729) while CVA16 somewhat lower (Kappa value = 0.300).

Conclusions

HEV71- and CVA16-IgM ELISAs can be deployed successfully as a convenient and cost-effective diagnostic tool for HFMD in clinical laboratories.
Differential Regulation of Glucose Transporters Mediated by CRH Receptor Type 1 and Type 2 in Human Placental Trophoblasts
Authors: Gao Lu , Lv Chunmei , Xu Chen , Li Yuan , Cui Xiaorui , Gu Hang , Ni Xin
Published: January 2012

Glucose transport across the placenta is mediated by glucose transporters (GLUT), which is critical for normal development and survival of the fetus. Regulatory mechanisms of GLUT in placenta have not been elucidated. Placental CRH has been implicated to play a key role in the control of fetal growth and development. We hypothesized that CRH, produced locally in placenta, could act to modulate GLUT in placenta. To investigate this, we obtained human placentas from uncomplicated term pregnancies and isolated and cultured trophoblast cells. GLUT1 and GLUT3 expressions in placenta were determined, and effects of CRH on GLUT1 and GLUT3 were examined. GLUT1 and GLUT3 were identified in placental villous syncytiotrophoblasts and the endothelium of vessels. Treatment of cultured placental trophoblasts with CRH resulted in an increase in GLUT1 expression while a decrease in GLUT3 expression in a dose-dependent manner. Cells treated with either CRH antibody or nonselective CRH receptor (CRH-R) antagonist astressin showed a decrease in GLUT1 and an increase in GLUT3 expression. CRH-R1 antagonist antalarmin decreased GLUT1 expression while increased GLUT3 expression. CRH-R2 antagonist astressin2b increased the expression of both GLUT1 and GLUT3. Knockdown of CRH-R1 decreased GLUT1 expression while increased GLUT3 expression. CRH-R2 knockdown caused an increase in both GLUT1 and GLUT3 expression. Our data suggest that, in placenta, CRH produced locally regulates GLUT1 and GLUT3 expression, CRHR1 and CRHR2-mediated differential regulation of GLUT1 and GLUT3 expression. Placental CRH may regulate the growth of fetus and placenta by modulating the expression of GLUT in placenta during pregnancy.
Conversion of TSH Heterodimer to a Single Polypeptide Chain Increases Bioactivity and Longevity
Authors: Azzam Naiel , Bar-Shalom Rinat , Fares Fuad
Published: January 2012

TSH is a dimeric glycoprotein hormone composed of a common α-subunit noncovalently linked to a hormone-specific β-subunit. Previously, the TSH heterodimer was successfully converted to an active single-chain hormone by genetically fusing α and β genes with [TSHβ- carboxyl-terminal peptide (CTP)-α] or without (TSHβ-α) the CTP of human chorionic gonadotropin β-subunit as a linker. In the present study, TSH variants were expressed in Chinese hamster ovarian cells. The results indicated that TSHβ-α single chain has the highest binding affinity to TSH receptor and the highest in vitro bioactivity. With regard to the in vivo bioactivity, all TSH variants increased the levels of T4 in circulation after 2 and 4 h of treatment. However, the level of T4 after treatment with TSH-wild type was significantly decreased after 6 and 8 h, compared with the levels after treatment with the other TSH variants. TSHβ-α and TSHβ-CTP-α single chains exhibited almost the same bioactivity after 8 h of treatment. Evaluating the half-life of TSH variants, TSHβ-CTP-α single chain revealed the longest half-life in circulation, whereas TSH-wild type exhibited the shortest serum half-life. These findings indicate that TSH single-chain variants with or without CTP as a linker may display conformational structures that increase binding affinity and serum half-life, thereby, suggesting novel attitudes for engineering and constructing superagonists of TSH, which may be used for treating different conditions of defected thyroid gland activity. Other prominent potential clinical use of these variants is in a diagnostic test for metastasis and recurrence of thyroid cancer.
Introduction: Warburg's Library and Its Legacy
Authors: Grafton Anthony , Hamburger Jeffrey F. , Mack Peter , Baxandall Michael , Sears Elizabeth , Didi-Huberman Georges , Ginzburg Carlo , Koerner Joseph Leo , Wood Christopher S. , Kraye Jill , Steinberg Michael P. , van Eck Caroline , Anderson Christy , Kaufmann Thomas DaCosta , Crossley Paul , Stafford Barbara Maria
Published: January 2012

In this introduction to a Common Knowledge special issue on the Warburg Institute, the authors argue that the Institute remains today — as it has been, in different forms, for almost a century — one of Europe's central institutions for the study of cultural history. At once a rich and uniquely organized library, a center for doctoral and postdoctoral research, and a teaching faculty, the Institute was first envisioned by Aby Warburg, a pioneering historian of art and culture from a wealthy Jewish family in Hamburg. Warburg rejected the traditional view that the classical tradition was a simple, purely rational Greek creation, inherited by modern Europe. He argued that it was as much Mesopotamian as Greek in origin, as at home in the Islamic as in the European world, and as often irrational as rational in its content — and on the basis of this rich vision he devised brilliant new interpretations of medieval and Renaissance symbols and ideas. Warburg's chosen associate Fritz Saxl put his creation on a firm institutional base, first in Hamburg and then, after a narrow escape from the Nazi regime, in London. For all the changes the Institute has undergone over the decades since then, it continues to ask the questions that Warburg was the first to raise and to build on the methods that he created.
WRITING RITUALS
Authors: Koerner Joseph Leo
Published: January 2012

This essay finds its departure point in a title page that Aby Warburg (1866 – 1929) drafted for his lecture on the Pueblo Indians. Through the labyrinthine thought pathways evidenced by this much-amended and overwritten typescript, it explores the relation between reason and mania in Warburg's thought specifically and in humanistic scholarship more generally. Composed in 1923 while Warburg was committed to the Bellevue mental sanatorium in Kreuzlingen, Switzerland, the title page, and the lecture that it attempts to name, belong to their author's profound and influential meditations on the defensive function of rituals and symbols. More practically, the lecture was intended, by its successful drafting and delivery before an audience of inmates, doctors, and professional colleagues, to prove Warburg's sanity and secure his release. Through an investigation of the outbreak and symptoms of Warburg's psychosis, which uncannily prefigure real historical terrors, this article represents the lecture as (in Warburg's words) a powerful “seismograph” of the European soul. Placing us at Warburg's writing desk at the pivotal moment of the author's cure-by-writing, the title page also illuminates the legacy of Warburg's Library, today at the core of the Warburg Institute in London, since the crisis that the page documents — larger than Warburg's personal one — still lies at the heart of humanistic scholarship as it attempts to grasp the essence of what it means to be human.
WAR WORK
Authors: Anderson Christy
Published: January 2012

In 1941 Fritz Saxl and Rudolf Wittkower of the Warburg Institute organized an exhibition on English Art and the Mediterranean. The photographic exhibition showed the long history of artistic and cultural ties between English art and the classical tradition, employing Aby Warburg's method. The project was an attempt by Saxl, as director, to show the relevance of the Warburg Institute's work in England, the new home of the Library since 1933. Kenneth Clark, director of the National Gallery, actively promoted the work of the Institute, including by supporting the naturalization process for many of the Warburg scholars. The popular belief in the cultural ties between England and Italy fed into the positive reception for the exhibition and into acceptance of the work of the Warburg Institute. The exhibition was published in a large format catalog in 1948, further adding to the popularity of the exhibition with a diverse British public. Although the motivation for the exhibition emerged from political conditions and institutional circumstance, it had a lasting effect on the history of the study of English art and architecture. Wittkower and others turned to research on the classical tradition in English art, even though the method had limited relevance beyond the “neoclassical” period.
Contagious Adverse Selection
Authors: Morris Stephen , Shin Hyun Song
Published: January 2012

We illustrate the corrosive effect of even small amounts of adverse selection in an asset market and show how it can lead to the total breakdown of trade. The problem is the failure of “market confidence,” defined as approximate common knowledge of an upper bound on expected losses. Small probability events can unravel market confidence. We discuss the role of contagious adverse selection and the problem of “toxic assets” in the recent financial crisis. (JEL D82, G01, G12, G14)
Effects of Fiscal Stimulus in Structural Models
Authors: Coenen Günter , Erceg Christopher J , Freedman Charles , Furceri Davide , Kumhof Michael , Lalonde René , Laxton Douglas , Lindé Jesper , Mourougane Annabelle , Muir Dirk , Mursula Susanna , de Resende Carlos , Roberts John , Roeger Werner , Snudden Stephen , Trabandt Mathias , in't Veld Jan
Published: January 2012

The paper subjects seven structural DSGE models, all used heavily by policymaking institutions, to discretionary fiscal stimulus shocks using seven different fiscal instruments, and compares the results to those of two prominent academic DSGE models. There is considerable agreement across models on both the absolute and relative sizes of different types of fiscal multipliers. The size of many multipliers is large, particularly for spending and targeted transfers. Fiscal policy is most effective if it has moderate persistence and if monetary policy is accommodative. Permanently higher spending or deficits imply significantly lower initial multipliers.(JEL E12, E13, E52, E62)
Alcoholic liver disease and the potential role of plasminogen activator inhibitor-1 and fibrin metabolism
Authors: Beier Juliane I , Arteel Gavin E
Published: January 2012

Plasminogen activator inhibitor-1 (PAI-1) is a major player in fibrinolysis due to its classical role of inhibiting plasminogen activators. Although increased fibrinolysis is common in alcoholic cirrhosis, decreased fibrinolysis (driven mostly by elevated levels of PAI-1) is common during the development of alcoholic liver disease (ALD). However, whether or not PAI-1 plays a causal role in the development of early ALD was unclear. Recent studies in experimental models have suggested that PAI-1 may contribute to the development of early (steatosis), intermediate (steatohepatitis) and late (fibrosis) stages of ALD. For example, fatty liver owing to both acute and chronic ethanol was blunted by the genetic inhibition of PAI-1. This effect of targeting PAI-1 appears to be mediated, at least in part, by an increase in very low-density lipoprotein (VLDL) synthesis in the genetic absence of this acute phase protein. Results from a two-hit model employing ethanol and lipopolysaccharide administration suggest that PAI-1 plays a critical role in hepatic inflammation, most likely due to its ability to cause fibrin accumulation, which subsequently sensitizes the liver to ensuing damaging insults. Lastly, the role of PAI-1 in hepatic fibrosis is less clear and appears that PAI-1 may serve a dual role in this pathological change, both protective (enhancing regeneration) and damaging (blocking matrix degradation). In summary, results from these studies suggest that PAI-1 may play multiple roles in the various stages of ALD, both protective and damaging. The latter effect is mediated by its influence on steatosis (i.e. decreasing VLDL synthesis), inflammation (i.e. impairing fibrinolysis) and fibrosis (i.e. blunting matrix degradation), whereas the former is mediated by maintaining hepatocyte division after an injury.
Fragile X Mental Retardation 1 (FMR1) Intron 1 Methylation in Blood Predicts Verbal Cognitive Impairment in Female Carriers of Expanded FMR1 Alleles: Evidence from a Pilot Study
Authors: Godler David E , Slater Howard R , Bui Quang M , Storey Elsdon , Ono Michele Y , Gehling Freya , Inaba Yoshimi , Francis David , Hopper John L , Kinsella Glynda , Amor David J , Hagerman Randi J , Loesch Danuta Z
Published: January 2012

BACKGROUND

Cognitive status in females with mutations in the FMR1 (fragile X mental retardation 1) gene is highly variable. A biomarker would be of value for predicting which individuals were liable to develop cognitive impairment and could benefit from early intervention. A detailed analysis of CpG sites bridging exon 1 and intron 1 of FMR1, known as fragile X–related epigenetic element 2 (FREE2), suggests that a simple blood test could identify these individuals.

METHODS

Study participants included 74 control females (<40 CGG repeats), 62 premutation (PM) females (55–200 CGG repeats), and 18 full-mutation (FM) females assessed with Wechsler intelligence quotient (IQ) tests. We used MALDI-TOF mass spectrometry to determine the methylation status of FREE2 CpG sites that best identified low-functioning (IQ <70) FM females (>200 CGG repeats), compared the results with those for Southern blot FMR1 activation ratios, and related these assessments to the level of production of the FMR1 protein product in blood.

RESULTS

A methylation analysis of intron 1 CpG sites 10–12 showed the highest diagnostic sensitivity (100%) and specificity (98%) of all the molecular measures tested for detecting females with a standardized verbal IQ of <70 among the study participants. In the group consisting of only FM females, methylation of these sites was significantly correlated with full-scale IQ, verbal IQ, and performance IQ. Several verbal subtest scores showed strong correlation with the methylation of these sites (P = 1.2 × 10−5) after adjustment for multiple measures.

CONCLUSIONS

The data suggest that hypermethylation of the FMR1 intron 1 sites in blood is predictive of cognitive impairment in FM females, with implications for improved fragile X syndrome diagnostics in young children and screening of the newborn population.
l-DOPA Impairs Proteasome Activity in Parkinsonism through D1Dopamine Receptor
Authors: Berthet Amandine , Bezard Erwan , Porras Gregory , Fasano Stefania , Barroso-Chinea Pedro , Dehay Benjamin , Martinez Audrey , Thiolat Marie-Laure , Nosten-Bertrand Marika , Giros Bruno , Baufreton Jérôme , Li Qin , Bloch Bertrand , Martin-Negrier Marie-Laure
Published: January 2012

Aberrant membrane localization of dopamine D1receptor (D1R) is associated withl-DOPA-induced dyskinesia (LID), a major complication ofl-DOPA treatment in Parkinson's disease (PD). Since the proteasome plays a central role in modulating neuronal response through regulation of neurotransmitter receptor intraneuronal fate, we hypothesized that the ubiquitine-proteasome proteolytic pathway could be impaired in LID. Those LIDs are actually associated with a striatum-specific decrease in proteasome catalytic activity and accumulation of polyubiquitinated proteins in experimental rodent and monkey parkinsonism. We then demonstrated that such decreased proteasome catalytic activity (1) results from D1R activation and (2) feed-back the D1R abnormal trafficking, i.e., its exaggerated cell surface abundance. We further showed that the genetic invalidation of the E3 ubiquitin-protein ligase parkin PD gene leads to exaggerated abnormal involuntary movements compared with wild-type mice. We thus established in an unprecedented series of experimental models that impairment of the ubiquitine-proteasome system at specific nodes (E3 ligase parkin, polyubiquitination, proteasome catalytic activity) leads to the same phenomenon, i.e., aberrant behavioral response to dopamine replacement therapy in PD, highlighting the intimate interplay between dopamine receptor and proteasome activity in a nondegenerative context.
Predicting Conceptual Processing Capacity from Spontaneous Neuronal Activity of the Left Middle Temporal Gyrus
Authors: Wei Tao , Liang Xia , He Yong , Zang Yufeng , Han Zaizhu , Caramazza Alfonso , Bi Yanchao
Published: January 2012

Conceptual processing is a crucial brain function for humans. Past research using neuropsychological and task-based functional brain-imaging paradigms indicates that widely distributed brain regions are related to conceptual processing. Here, we explore the potential contribution of intrinsic or spontaneous brain activity to conceptual processing by examining whether resting-state functional magnetic resonance imaging (rs-fMRI) signals can account for individual differences in the conceptual processing efficiencies of healthy individuals. We acquired rs-fMRI and behavioral data on object conceptual processing tasks. We found that the regional amplitude of spontaneous low-frequency fluctuations in the blood oxygen level-dependent signal in the left (posterior) middle temporal gyrus (LMTG) was highly correlated with participants' semantic processing efficiency. Furthermore, the strength of the functional connectivity between the LMTG and a series of brain regions—the left inferior frontal gyrus, bilateral anterior temporal lobe, bilateral medial temporal lobe, posterior cingulate gyrus, and ventromedial and dorsomedial prefrontal cortices—also significantly predicted conceptual behavior. The regional amplitude of low-frequency fluctuations and functionally relevant connectivity strengths of LMTG together accounted for 74% of individual variance in object conceptual performance. This semantic network, with the LMTG as its core component, largely overlaps with the regions reported in previous conceptual/semantic task-based fMRI studies. We conclude that the intrinsic or spontaneous activity of the human brain reflects the processing efficiency of the semantic system.
Improved Outcome after Peripheral Nerve Injury in Mice with Increased Levels of Endogenous Omega-3 Polyunsaturated Fatty Acids
Authors: Gladman Stacy J. , Huang Wenlong , Lim Siew-Na , Dyall Simon C. , Boddy Sophie , Kang Jing X. , Knight Martin M. , Priestley John V. , Michael-Titus Adina T.
Published: January 2012

Functional recovery after a peripheral nerve injury (PNI) is often poor. There is a need for therapies that protect neurons against injury and enhance regeneration. Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to have therapeutic potential in a variety of neurological disorders, including acute traumatic injury. The objective of this study was to assess the neuroprotective and pro-regenerative potential of ω-3 PUFAs in PNI. We investigated this in mice that express thefat-1gene encoding for ω-3 fatty acid desaturase, which leads to an increase in endogenous ω-3 PUFAs and a concomitant decrease in ω-6 PUFAs. Dorsal root ganglion (DRG) neurons from wild-type orfat-1mice were subjected to a mechanical strain or hypoxic injury, and cell death was assessed using ethidium homodimer-1 labeling. Thefat-1background appears to confer robust neuroprotection against both injuries. We then examined the early functional and morphological changes in wild-type andfat-1mice after a sciatic nerve crush. An accelerated functional recovery 7 d after injury was seen infat-1mice when assessed using von Frey filaments and the sciatic nerve functional index. These observations were also mapped to changes in injury-related markers. The injury-induced expression of ATF-3 was decreased in the DRG offat-1mice, whereas the axons detected 6 mm distal to the crush were increased.Fat-1animals also had some protection against muscle atrophy after injury. In conclusion, bothin vitroandin vivoexperiments support the idea that a higher endogenous ω-3 PUFA could lead to beneficial effects after a PNI.
Genetic Analysis of DSCAM's Role as a Netrin-1 Receptor in Vertebrates
Authors: Palmesino Elena , Haddick Patrick C. G. , Tessier-Lavigne Marc , Kania Artur
Published: January 2012

Down syndrome cell adhesion molecule (DSCAM) has mainly been characterized for its function as an adhesion molecule in axon growth and in self-recognition between dendrites of the same neuron. Recently, it has been shown that DSCAM can bind to Netrin-1 and that downregulation of DSCAM expression by siRNAs in chick and rodent spinal cords leads to impaired growth and turning response of commissural axons to Netrin-1. To investigate the effect of complete genetic ablation of DSCAM on Netrin-1-induced axon guidance, we analyzed spinal commissural neurons inDSCAM-null mice and found that they extend axons that reach and cross the floor plate and express apparently normal levels of the Netrin receptors DCC (deleted in colorectal carcinoma) and Neogenin.In vitro, commissural neurons in dorsal spinal cord explants ofDSCAM-null embryos show normal outgrowth in response to Netrin-1. We therefore conclude that DSCAM is not required for Netrin-induced commissural axon outgrowth and guidance in mice.
Individualization and Electrical Characterization of SiGe Nanowires
Authors: Monasterio M. , Rodríguez A. , Rodríguez T. , Ballesteros C.
Published: January 2012

SiGe nanowires of different Ge atomic fractions up to 15% were grown and ex-situ n-type doped by diffusion from a solid source in contact with the sample. The phenomenon of dielectrophoresis was used to locate single nanowires between pairs of electrodes in order to carry out electrical measurements. The measured resistance of the as-grown nanowires is very high, but it decreases more than three orders of magnitude upon doping, indicating that the doping procedure used has been effective.
Carrier Transport in GaAs Nanowires Using Surface Acoustic Waves
Authors: Hernández-Mínguez A. , Möller M. , Pfüller C. , Breuer S. , Brandt O. , de Lima M. M. , García-Cristóbal A. , Cantarero A. , Geelhaar L. , Riechert H. , Santos P. V.
Published: January 2012

The oscillating piezoelectric field of a surface acoustic wave (SAW) is employed to transport photoexcited electrons and holes in GaAs nanowires (NWs) transferred to a SAW beam line on a LiNbO3 crystal. We show that carriers generated in the NW by a focused light spot can be acoustically transported to a second location, where they recombine emitting short light pulses. The results presented here demonstrate the high-frequency manipulation of carriers in NWs without the use of electrical contacts, which opens new perspectives for applications in opto-electronic devices operating at GHz frequencies.
Atitudes dos enfermeiros face à família: validação da escala Families' Importance in Nursing Care - Nurses Attitudes
Authors: Oliveira Palmira da Conceição M. , Fernandes Henriqueta Ilda V. , Vilar Ana Isabel S. P. , Figueiredo Maria Henriqueta de J. S. , Ferreira Maria Margarida Silva R. S. , Martinho Maria Júlia C. M. , Figueiredo Maria do Céu A. B. , Andrade Luísa Maria da C. , Carvalho José Carlos M. de , Martins Maria Manuela Ferreira P. da S.
Published: January 2012

As atitudes que os enfermeiros adotam em relação à família condicionam o processo de cuidar. Nosso propósito com este estudo foi nesse sentido: dispor de um instrumento que nos permitisse conhecer esta variável. Assim, nossa proposta foi efetuar a adaptação transcultural e avaliar as propriedades psicométricas da versão portuguesa do instrumento Families' Importance in Nursing Care - Nurses Attitudes (FINC-NA), que visa avaliar as atitudes dos enfermeiros acerca da importância de envolver a família nos cuidados de enfermagem. Foi seguido o método preconizado pela literatura. A amostra foi constituída por 136 enfermeiros dos Cuidados de Saúde Primários. Os resultados obtidos nos testes de confiabilidade revelam uma boa consistência interna para o total dos itens (Alpha de Cronbach = 0,87). O estudo psicométrico permite-nos afirmar que a versão em português da FINC-NA, que denominamos A importância das famílias nos cuidados de enfermagem - atitudes dos enfermeiros (IFCE-AE), é um instrumento fidedigno e válido.
O conhecimento do enfermeiro sobre a Sistematização da Assistência de Enfermagem: da teoria à prática
Authors: Silva Elisama Gomes Correia , Oliveira Viviane Carla de , Neves Giselda Bezerra Correia , Guimarães Tânia Maria Rocha
Published: January 2012

O objetivo deste trabalho foi analisar o conhecimento dos enfermeiros sobre a Sistematização da Assistência de Enfermagem (SAE) em um hospital de grande porte em Recife, Pernambuco. Realizou-se um estudo descritivo, exploratório e quantitativo. A população foi composta de 107 enfermeiros assistenciais com amostra de 73 (68%). A coleta de dados foi realizada em junho de 2008, através de um questionário semiestruturado preenchido pelos sujeitos. Verificamos que 50 (69%) não tinham conhecimentos sobre a SAE e especialmente sobre os diagnósticos de enfermagem. Constatamos ausência de formulários na maioria das unidades de internação. Os enfermeiros justificaram diversas razões para não trabalharem com a SAE, dentre elas, a sobrecarga de trabalho e escassez de formulários. Concluímos que existe a necessidade de maiores incentivos institucionais e políticos, de forma a permitir que o enfermeiro exerça a profissão com mais autonomia.