bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with intravenous melphalan and dexamethasone is not able to overcome the poor prognosis of patients with newly diagnosed systemic light chain amyloidosis and severe cardiac involvement
Authors: Dietrich Sascha , Schönland Stefan O. , Benner Axel , Bochtler Tilmann , Kristen Arnt V. , Beimler Jörg , Hund Ernst , Zorn Markus , Goldschmidt Hartmut , Ho Antony D. , Hegenbart Ute 
Published: April 2010

Abstract
Treatment with oral melphalan and dexamethasone (M-Dex) was reported to be effective and feasible in patients with systemic light chain amyloidosis (AL) not eligible for high-dose melphalan. We report on 61 patients with advanced AL who were treated with intravenous M-Dex as first-line therapy. Estimated median overall survival (OS) was 17.5 months. Seventeen patients (28%) died within 3 months, mostly of disease-related complications. In addition, nonhematologic toxicity of Common Terminology Criteria grade 3 or 4 was observed in 20 patients, whereas hematologic toxicity was low. Twenty-seven patients (44%) had hematologic response, including complete in 7 patients (11%) and partial remission in 20 patients (33%). Organ response was observed in 15 patients (25%). The amount of the involved free light chains in serum and Karnofsky Index at diagnosis significantly influenced OS. Plasma levels of the cardiac biomarkers before start of treatment and their increase after the third M-Dex cycle also were strong negative predictors of OS. These parameters might help to identify patients who will not benefit from M-Dex chemotherapy.
Cognitive function in COPD
Authors: Dodd J. W. , Getov S. V. , Jones P. W. 
Published: April 2010

In order to characterise the overall clinical picture of chronic obstructive pulmonary disease (COPD) a better understanding of all relevant comorbidities is required. It is increasingly recognised that COPD is a multi-component disease, but little attention has been paid to its effects on cognitive function.Cognitive dysfunction is associated with increased mortality and disability; however, it remains poorly understood in COPD. This review examines mechanisms of injury and dysfunction to the brain and considers the methods used to evaluate cognition, and assembles evidence concerning the nature and level of cognitive impairment in COPD.Our main findings are: 1) there may be a pattern of cognitive dysfunction specific to COPD; 2) cognitive function is only mildly impaired in patients without hypoxaemia; 3) the incidence of cognitive dysfunction is higher in hypoxaemia; 4) hypoxaemia, hypercapnia, smoking and comorbidities (such as vascular disease) are unlikely to account for all of the cognitive dysfunction seen in COPD; 5) there is weak or no association between cognitive function and mood, fatigue or health status; 6) cognitive dysfunction may be associated with increased mortality and disability; and 7) there is limited evidence for a significant effect of treatment on cognitive function.
Differential effects of Paclitaxel on dendritic cell function
Authors: John Justin , Ismail Mohammed , Riley Catherine , Askham Jonathan , Morgan Richard , Melcher Alan , Pandha Hardev 
Published: April 2010

AbstractBackgroundThe potential utility of dendritic cells (DC) as cancer vaccines has been established in early trials in human cancers. The concomitant administration of cytotoxic agents and DC vaccines has been previously avoided due to potential immune suppression by chemotherapeutics. Recent studies show that common chemotherapy agents positively influence adaptive and innate anti-tumour immune responses.ResultsWe investigated the effects of paclitaxel on human DC biologyin vitro. DCs appear to sustain a significant level of resistance to paclitaxel and maintain normal viability at concentrations of up to 100 μmol. In some cases this resistance against paclitaxel is significantly better than the level seen in tumour cell lines. Paclitaxel exposure led to a dose dependent increase in HLA class II expression equivalent to exposure to lipopolysaccharide (LPS), and a corresponding increase in proliferation of allogeneic T cells at the clinically relevant doses of paclitaxel. Increase in HLA-Class II expression induced by paclitaxel was not blocked by anti TLR-4 antibody. However, paclitaxel exposure reduced the endocytic capacity of DC but reduced the expression of key pro-inflammatory cytokines such as IL-12 and TNFα. Key morphological changes occurred when immature DC were cultured with 100 μmol paclitaxel. They became small rounded cells with stable microtubules, whereas there were little effects on LPS-matured DC.ConclusionsThe effect of paclitaxel on human monocyte derived DC is complex, but in the clinical context of patients receiving preloaded and matured DC vaccines, its immunostimulatory potential and resistance to direct cytotoxicity by paclitaxel would indicate potential advantages to co-administration with vaccines.
Virulence-related Mycobacterium avium subsp hominissuis MAV_2928 gene is associated with vacuole remodeling in macrophages
Authors: Jha Samradhni S , Danelishvili Lia , Wagner Dirk , Maser Jörg , Li Yong-jun , Moric Ivana , Vogt Steven , Yamazaki Yoshitaka , Lai Barry , Bermudez Luiz E 
Published: April 2010

AbstractBackgroundMycobacterium aviumsubsphominissuis(previouslyMycobacterium aviumsubspavium) is an environmental organism associated with opportunistic infections in humans.Mycobacterium hominissuisinfects and replicates within mononuclear phagocytes. Previous study characterized an attenuated mutant in which the PPE gene (MAV_2928) homologous to Rv1787 was inactivated. This mutant, in contrast to the wild-type bacterium, was shown both to have impaired the ability to replicate within macrophages and to have prevented phagosome/lysosome fusion.ResultsMAV_2928 gene is primarily upregulated upon phagocytosis. The transcriptional profile of macrophages infected with the wild-type bacterium and the mutant were examined using DNA microarray, which showed that the two bacteria interact uniquely with mononuclear phagocytes. Based on the results, it was hypothesized that the phagosome environment and vacuole membrane of the wild-type bacterium might differ from the mutant. Wild-type bacterium phagosomes expressed a number of proteins different from those infected with the mutant. Proteins on the phagosomes were confirmed by fluorescence microscopy and Western blot. The environment in the phagosome of macrophages infected with the mutant differed from the environment of vacuoles withM. hominissuiswild-type in the concentration of zinc, manganese, calcium and potassium.ConclusionThe results suggest that the MAV_2928 gene/operon might participate in the establishment of bacterial intracellular environment in macrophages.
Salt tolerance in Solanum pennellii: antioxidant response and related QTL
Authors: Frary Anne , Göl Deniz , Keleş Davut , Ökmen Bilal , Pınar Hasan , Şığva Hasan Ö , Yemenicioğlu Ahmet , Doğanlar Sami 
Published: April 2010

AbstractBackgroundExcessive soil salinity is an important problem for agriculture, however, salt tolerance is a complex trait that is not easily bred into plants. Exposure of cultivated tomato to salt stress has been reported to result in increased antioxidant content and activity. Salt tolerance of the related wild species,Solanum pennellii, has also been associated with similar changes in antioxidants. In this work,S. lycopersicumM82,S. pennelliiLA716 and aS. pennelliiintrogression line (IL) population were evaluated for growth and their levels of antioxidant activity (total water-soluble antioxidant activity), major antioxidant compounds (phenolic and flavonoid contents) and antioxidant enzyme activities (superoxide dismutase, catalase, ascorbate peroxidase and peroxidase) under both control and salt stress (150 mM NaCl) conditions. These data were then used to identify quantitative trait loci (QTL) responsible for controlling the antioxidant parameters under both stress and nonstress conditions.ResultsUnder control conditions, cultivated tomato had higher levels of all antioxidants (except superoxide dismutase) thanS. pennellii. However, under salt stress, the wild species showed greater induction of all antioxidants except peroxidase. The ILs showed diverse responses to salinity and proved very useful for the identification of QTL. Thus, 125 loci for antioxidant content under control and salt conditions were detected. Eleven of the total antioxidant activity and phenolic content QTL matched loci identified in an independent study using the same population, thereby reinforcing the validity of the loci. In addition, the growth responses of the ILs were evaluated to identify lines with favorable growth and antioxidant profiles.ConclusionsPlants have a complex antioxidant response when placed under salt stress. Some loci control antioxidant content under all conditions while others are responsible for antioxidant content only under saline or nonsaline conditions. The localization of QTL for these traits and the identification of lines with specific antioxidant and growth responses may be useful for breeding potentially salt tolerant tomato cultivars having higher antioxidant levels under nonstress and salt stress conditions.
Specificity and functionality of microRNA inhibitors
Authors: Robertson Barbara , Dalby Andrew B , Karpilow Jon , Khvorova Anastasia , Leake Devin , Vermeulen Annaleen 
Published: April 2010

Abstract

Background
Micro(mi)RNAs regulate gene expression through translational attenuation and messenger (m)RNA degradation, and are associated with differentiation, homeostasis and disease. Natural miRNA target recognition is determined primarily by perfect complementarity in a seed region (nucleotide positions 2 to 7) with additional interactions contributing in a sequence- and target-specific manner. Synthetic miRNA target analogs, which are fully complementary, chemically modified oligonucleotides, have been used successfully to inhibit miRNA function.

Results
In this paper, we present a first systematic study to evaluate the effect of mismatches in the target site on synthetic inhibitor activity. Panels of miRNA inhibitors containing two-nucleotide mismatches across the target site were tested against three miRNAs (miR-21, miR-22 and miR-122). The results showed that the function of inhibitors vary as mismatch positions in the inhibitors change.

Conclusions
The data indicate that features important for natural miRNA target recognition (such as seed region complementarity) are also important for inhibitor functionality. In addition, base pairing at a second, more 3' region appears to be equally important in determining the efficacy of synthetic inhibitors. Considering the importance of these inhibitor regions and the expression of closely related miRNA sequences will enable researchers to interpret results more accurately in future experiments.
The association between subchondral bone cysts and tibial cartilage volume and risk of joint replacement in people with knee osteoarthritis: a longitudinal study
Authors: Tanamas Stephanie K , Wluka Anita E , Pelletier Jean-Pierre , Martel-Pelletier Johanne , Abram François , Wang Yuanyuan , Cicuttini Flavia M 
Published: April 2010

Abstract
Introduction
To examine the natural history of subchondral bone cysts and to determine whether knee cartilage loss and risk of joint replacement is higher in knees with cysts, compared with those with bone marrow lesions (BMLs) only or those with neither BMLs nor cysts.

Methods
The symptomatic knee in 132 subjects with knee osteoarthritis (OA) was imaged by using magnetic resonance imaging at baseline and 2 years later. Tibial cartilage volume, subchondral bone cysts, and BMLs were measured by using validated methods. Knee arthroplasty over a 4-year period was ascertained.

Results
Bone cysts were present in 47.7% of subjects, 98.1% of whom also had BMLs. Over a 2-year period, 23.9% of subjects had cysts progress, 13.0% developed new cysts, and 11.4% had cysts regress. Bone cysts at baseline were associated with lower medial and lateral tibial cartilage volume compared with those with BMLs only or those with neither (P for trend 0.004 and <0.001, respectively). Annual medial cartilage volume loss was greatest in those with bone cysts compared with those with BMLs only or those with neither (9.3%, 6.3%, and 2.6%, respectively; P for trend, <0.001). As the severity of bone abnormality in the medial compartment increased from no BMLs or cysts present, to BMLs only, to subchondral bone cysts present, the risk of knee replacement was increased (odds ratio, 1.99; 95% confidence interval (CI), 1.01 to 3.90; P = 0.05).

Conclusions
When cysts are present, cartilage loss and risk of knee replacement are higher than if only BMLs are present, suggesting that cysts identify those most likely to benefit from prevention of disease progression. As cysts can regress, they may also provide therapeutic targets in knee OA.
Conserved developmental transcriptomes in evolutionarily divergent species
Authors: Parikh Anup , Miranda Edward Roshan , Katoh-Kurasawa Mariko , Fuller Danny , Rot Gregor , Zagar Lan , Curk Tomaz , Sucgang Richard , Chen Rui , Zupan Blaz , Loomis William F , Kuspa Adam , Shaulsky Gad 
Published: April 2010

Abstract
Background
Evolutionarily divergent organisms often share developmental anatomies despite vast differences between their genome sequences. The social amoebae Dictyostelium discoideum and Dictyostelium purpureum have similar developmental morphologies although their genomes are as divergent as those of man and jawed fish.

Results
Here we show that the anatomical similarities are accompanied by extensive transcriptome conservation. Using RNA sequencing we compared the abundance and developmental regulation of all the transcripts in the two species. In both species, most genes are developmentally regulated and the greatest expression changes occur during the transition from unicellularity to multicellularity. The developmental regulation of transcription is highly conserved between orthologs in the two species. In addition to timing of expression, the level of mRNA production is also conserved between orthologs and is consistent with the intuitive notion that transcript abundance correlates with the amount of protein required. Furthermore, the conservation of transcriptomes extends to cell-type specific expression.

Conclusions
These findings suggest that developmental programs are remarkably conserved at the transcriptome level, considering the great evolutionary distance between the genomes. Moreover, this transcriptional conservation may be responsible for the similar developmental anatomies of Dictyostelium discoideum and Dictyostelium purpureum.
A role for STAT3 and cathepsin S in IL-10 down-regulation of IFN-γ-induced MHC class II molecule on primary human blood macrophages
Authors: Chan Lally L Y , Cheung Benny K W , Li James C B , Lau Allan S Y 
Published: April 2010

Abstract
IL-10-STAT3 down-regulation of IFN-γ-induced MHC-II antigen presentation is due to inhibition of cathepsin S and independent of JAK/STAT and NF-κB pathways.
IL-10, a potent anti-inflammatory cytokine, activates its primary mediator STAT3 to exert inhibitory effects on activated immune response. It has been reported that IFN-γ signaling can be suppressed by IL-10, which deactivates macrophages and suppresses cell-mediated antigen presentation. Cathepsin S, a cysteine protease, plays a significant role in the antigen processing. We hypothesize that the IL-10-induced and STAT3-mediated signaling pathway interferes with IFN-γ-induced immune responses in primary human blood macrophages. Here, we investigated whether IL-10 perturbs MHC-II levels via its effect on cathepsin S expression in antigen processing. We showed that the expression of cathepsin S and MHC-II, inducible by IFN-γ, was down-regulated in the presence of IL-10. Additionally, we revealed that the inhibitory effect of IL-10 was demonstrated to be independent of the classical IFN-γ-induced JAK2/STAT1 signaling cascade or the NF-κB pathway. Following STAT3 suppression with specific siRNA, the expression of IFN-γ-induced surface MHC-II antigens and cathepsin S levels was restored, even in the presence of IL-10. Taken together, our results demonstrated that the immunosuppressive effects of IL-10-STAT3 on MHC-II antigen presentation may occur via the inhibition of cathepsin S expression.
Public Remembering, Private Reminiscing: French Military Memoirs and the Revolutionary and Napoleonic Wars
Authors: Dwyer Philip G. 
Published: April 2010

The French Revolution and the Napoleonic Wars resulted in an explosion of personal recollections on a scale never before witnessed, some published in the author's lifetime, many not. These memoirs, and the stories and anecdotes told in them, shaped the images surrounding the wars for generations to come. Given the distance that often separated the writing from the event, the memoirs almost always contained projections, evasions, myths, and outright fantasies. But that is exactly where their value lies. It allows the historian to establish the extent to which those who took part in the wars began to romanticize or indeed contest them and the man most responsible for them—Napoléon—and the degree to which they engaged in the political and cultural debates of the day.
Les guerres révolutionnaires et napoléoniennes déclenchèrent une explosion de remémorations personnelles. Certains textes furent publiés du vivant des auteurs, d'autres après ou jamais. Ces mémoires, et les histoires et anecdotes qu'ils racontent, ont formé et informé l'image des guerres pendant des générations. Etant donné le nombre d'années souvent intervenues entre leur écriture et les événements qu'ils décrivaient, ces mémoires contiennent souvent des projections, des subterfuges, des mythes et mêmes des récits imaginaires. C'est précisément là que réside la valeur de ces textes. Cela nous permet, en tant qu'historiens, d'établir la manière dont ces anciens combattants ont commencé à romancer ou contester les guerres et l'homme qui en était responsable—Napoléon—et jusqu'à quel point ils ont participé aux débats politiques et culturels de leur époque.
French Liberal Governance and the Emancipation of Algeria's Jews
Authors: Shurkin Michael 
Published: April 2010

French officials' treatment of Algeria's Jews under three different political regimes (1830–70) demonstrates the extent to which basic liberal practices and values had become part of French governance. French officials consistently treated Jews differently from Muslims and showed the former a solicitude that can best be explained in terms of their identification with liberal governance and arguably even a desire to draw a line in the sand in the altogether illiberal context of a colonial war of conquest. France's treatment of Jews also demonstrates the ambiguities of mid-nineteenth-century liberalism and its capacity to accommodate itself to empire.
Le traitement des juifs d'Algérie par les fonctionnaires de trois régimes politiques différents (la Monarchie de juillet, la Seconde République, le Second Empire) illustre à quel point les pratiques et valeurs libérales s'étaient enracinées dans la manière française de gouverner. Les fonctionnaires privilégiaient les juifs aux musulmans, faisant preuve d'une sollicitude envers les premiers qui ne peut être expliquée que par une internalisation des pratiques et valeurs libérales et même un souci de les défendre dans le contexte non libéral de guerre coloniale et de conquête. Le traitement des juifs par la France relève aussi les ambiguïtés du libéralisme du dix-neuvième siècle et sa capacité de s'accommoder au colonialisme.
Hot Planet, Cold Wars
Authors: Kane Thomas M. 
Published: April 2010

Shared challenges can bring out the best in people, but they can also do the opposite. Global climate change is an archetypal shared challenge for humanity, and although the threat has inspired a substantial amount of international co-operation, efforts to moderate it have already proven divisive. These divisions go beyond economically-driven haggling over who must reduce greenhouse gas emissions by what amount. Attempts to mitigate human civilisation's effects on the climate raise questions of political principle. Moreover, these questions have the specific potential to mobilise certain states and quasi-states against certain other ones, and this has implications for the field of security studies. Thus, climate change threatens to revive ideological dispute among armed, organised economically-developed societies. Although the idea of a world war over carbon remains far-fetched, the parallels with the international politics of the mid–20th century are disturbing. Policymakers would be wise to take the political questions of climate change more seriously than they appear to have done in the past. Scholars may note that disputes over global warming challenge influential models of contemporary global politics. This paper explores the reasons why controversies over climate policy are likely to prove particularly divisive in international politics. The first section discusses the relative ideological consensus that has prevailed among developed societies since the collapse of the Soviet Union. Even pessimistic theorists initially took this consensus for granted. As of 2005, however, this consensus is stretched thin on numerous issues. One of these issues is climate policy. A second section of this paper discusses the stakes in the climate debate, suggesting that this dispute is likely to be a particularly important one. The third section notes that attempts to limit global carbon dioxide emissions raise questions about citizens' relationships to each other and to the state. Historically, such questions have raised issues of principle. These issues have had moral and emotional implications that run far beyond the material issues involved. Many nations, notably the US, have resolved these issues by adopting the political system known as republicanism. A fourth section discusses the concept of a republic and the problems it presents for those who wish to develop an international policy to reduce greenhouse gas emissions. The fifth section notes that a broad, if informal, movement in early 21st century politics directly challenges republicanism. Debates over climate policy have already served to deepen this division. A conclusion sums up the paper's findings and reflects on their implications. Future work in the field of security studies will need to address the potential friction between republican and anti-republican political entities, and this paper highlights one of the forms this friction may take.
Nonlinear Distortion of Traveling Waves in Non-Uniform Gasdynamic Flows
Authors: Tyagi Manav , Sujith R. I. , Vasu Subith 
Published: April 2010

A theory of nonlinear wave propagation in quasi-one-dimensional non-uniform gasdynamic flows is developed in order to explain the effect of flow non-uniformity on nonlinear processes such as shock formation and wave quenching. The methodology used is the tracking of the propagating wave front in a hyperbolic system whose evolution is governed by a first order nonlinear ordinary differential equation (Riccati's equation). The present work is an extension of Whitham's wave front expansion method for uniform flow. The equation can be exactly solved for the first derivative of a flow variable at the wave front as a function of the location of wave front in the base flow. This solution is used to develop the criteria for shock formation of a compressive disturbance and quenching of an expansion wave. The solution shows that shock formation depends upon the history of wave propagation. However, quenching of a wave front is independent of the initial slope. The analysis is applied to two important gasdynamic flows: Rayleigh line flow and Fanno line flow. The analysis is a generalization of the authors' previous work in which shock formation in convergent-divergent nozzles was studied (Tyagi and Sujith 2005).