bluuebunny/crossref_metadata_2025 huggingface dataset:
URBANISTINIO PLANAVIMO DEFORMACIJOS
Authors: Juškevičius Pranciškus , Gaučė Kristina
Published: March 2011

As deformations in urbanism is a massive phenomenon, the aim of the paper authors is to point out crucial deformations, experienced in municipal territory planning, which mutilate the meaning of comprehensive planning. Any deviations (distortions) from anything that is normal, logical, systematic, objective and reasoned economically, socially, etc. are understood as urban planning deformations and factors encouraging these deformations are the main object of this paper. These deformations affect the implementation success of comprehensive planning solutions and in general have an influence on the quality of urban planning. The quality of planning should be the most important concern, but the evaluation of planning quality is complicated, that’s why the authors suggest an idea of comparative evaluation and reasoned principles which should change deformations in existing planning system and in this way modernize it.

Santrauka

Urbanistinės deformacijos yra masinis reiškinys. Straipsnio autorių tikslas – remiantis teorine ir praktine miestų bei rajonų, savivaldybių teritorijų planavimo patirtimi parodyti esmines deformacijas, kurios iškraipo b e n d r o j o planavimo esmę ir nuo kurių priklauso jo sprendinių įgyvendinimo sėkmė bei apskritai urbanistinio (teritorinio) planavimo vertė. Šiame straipsnyje urbanistinio planavimo deformacijos suprantamos kaip bet kokie nukrypimai (iškreipimai) nuo to, kas normalu, logiška, sistemiška, objektyvu ir pagrįsta ekonomiškai, socialiai bei kitais aspektais, o juos (nukrypimus) veikiančių veiksnių visuma ir yra šio straipsnio objektas. Planavimo kokybė turėtų būti svarbiausias rūpestis, tačiau jos įvertinimas yra sudėtingas, todėl šiame straipsnyje autoriai siūlo santykinio vertinimo idėją bei argumentuotus principus, kurie turėtų pakeisti pačios dabar veikiančios planavimo sistemos deformacijas ir tai ją modernizuotų.
Les avatars de la loi belge de défense sociale : le changement dans la continuité
Authors: van de Kerchove Michel
Published: March 2011

Reflet par excellence d’une politique criminelle de défense sociale, la loi belge du 9 avril 1930 de défense sociale à l’égard des anormaux et des délinquants d’habitude a fait l’objet de plusieurs modifications, dont les plus récentes datent de 2007. Si ces modifications aboutissent généralement à une extension des catégories de personnes ou de comportements visées, ainsi qu’à changer les rapports d’équilibre entre les instances médicales et judiciaires, elles n’affectent pas fondamentalement la nature et les objectifs des mesures instituées, consacrant ainsi des changements, sans doute non négligeables, mais dans une continuité incontestable.
L'internement de sûreté en Allemagne : une mesure de défense sociale à la dérive
Authors: Pin Xavier
Published: March 2011

L’internement de sûreté ou Sicherungsverwahrung est une mesure de défense sociale, introduite en Allemagne par la loi du 23 novembre 1933 sur les criminels d’habitude. Elle puise sa source autant dans le positivisme italien, que dans les écrits de Stooß ou de Von Liszt de la fin du XIX e siècle. Dévoyée sous le troisième Reich, elle fut maintenue après guerre puis encadrée dans les années 1970 et revigorée à la fin des années 1990. Depuis, son domaine n’a eu de cesse de s’élargir en raison d’une série de lois d’application rétroactive, qui peuvent se réclamer du « droit pénal de l’ennemi ». Le présent article montre que cet emballement législatif participe de dérives à la fois idéologiques et juridiques, auxquelles la Cour européenne des droits de l’Homme est venue mettre un frein, dans un arrêt « M. c. Allemagne » du 17 décembre 2009.
La défense sociale en Belgique, entre soin et sécurité.
Authors: Cartuyvels Yves , Champetier Brice , Wyvekens Anne
Published: March 2011

En application de la loi de défense sociale en Belgique, l’auteur d’un fait qualifié infraction considéré comme irresponsable fait l’objet d’une mesure d’internement, soit dans une annexe psychiatrique rattachée à une prison, soit dans un établissement de défense sociale prévu à cet effet, soit encore dans un hôpital psychiatrique. La mesure d’internement est décrite comme une mesure de sécurité et de soin. Dans les faits, tant en annexe psychiatrique de prison qu’en établissement de défense sociale, la place faite au soin reste problématique : le manque de moyens est chronique et le recours à la médication systématique dans des lieux d’internement souvent surpeuplés. La scission entre les fonctions de soin et d’expertise, intervenue dans certains lieux d’internement, constitue à cet égard un enjeu important.
Usages et abus du risque dans la justice pénale britannique
Authors: Raynor Peter
Published: March 2011

Tenter de mesurer et de contrôler le risque est devenu une préoccupation centrale de la justice pénale. Les auteurs critiques ont souligné combien pratiquer l’évaluation du risque peut entrer en contradiction avec le principe de proportionnalité et ont également avancé que son utilisation peut accroître le niveau général de punitivité et d’inégalité sociale. Quant aux promoteurs et aux partisans de l’évaluation du risque, ils mettent en lumière ses avantages, par exemple le socle qu’elle offre aux mesures de réhabilitation. Cet article discute le développement de l’évaluation du risque dans les pratiques de la justice pénale britannique et avance que ses conséquences, tant positives que négatives, ont été les effets, non seulement des pratiques elles-mêmes, mais également des politiques au service desquelles elles ont été déployées.
Surveiller et punir à l'âge actuariel
Authors: Harcourt Bernard E.
Published: March 2011

Les méthodes actuarielles pénètrent aujourd’hui la sphère pénale des États-Unis. À la seule exception du profilage racial des Africains-Américains et des Hispaniques, la majeure partie de la population considère que l’adoption des méthodes actuarielles est efficace, rationnelle et rentable. Bernard Harcourt met en question ce consensus naissant en prônant, dans la sphère pénale, l’échantillonnage aléatoire : la randomisation dans le maintien de l’ordre. C’est la seule façon d’obtenir une sphère carcérale qui reflète impartialement et ressemble réellement à la distribution des personnes commettant des délits. Donc, dans le droit pénal et son application, c’est sur la prédiction que les interrogations devraient porter. Dans le premier article, B. Harcourt trace une généalogie des méthodes actuarielles aux États-Unis. Dans le second article, B. Harcourt démontre mathématiquement les effets contre-productifs du profilage et des méthodes actuarielles.
Règle d'or et logique d'équivalence
Authors: Michel Johann
Published: March 2011

Résumé Issue originellement du testament judéo-chrétien, la Règle d'or (« Ne pas faire à autrui ce que l'on ne voudrait pas que l'on nous fasse ») s'est sécularisée dans la culture morale occidentale au point de tenir lieu fréquemment de maxime de nos interactions quotidiennes. L'objectif de cet article consiste à se demander si cette règle peut fonder des principes de morale et de justice. Si l'on se place dans le cadre déontologique d'une philosophie procédurale, la règle d'or est considérée comme un stade inférieure de normativité dans la mesure où il s'agit d'une maxime tirée d'une éthique narrative particulière impropre à s'élever au rang de principes. Si l'on suit au contraire l'herméneutique critique que propose Paul Ricœur, la Règle d'or s'élève au rang de maxime suprême de la normativité présupposée par toute entreprise de fondation procédurale des principes de morale et de justice. La thèse défendue par Johann Michel cherche à montrer que c'est moins la Règle d'or que la logique d'équivalence qui est à même de jouer cette fonction principielle, la première n'étant qu'une expression particulière de la prétention à l'universalité de la seconde.
Continuités et discontinuités du corps chrétien
Authors: de Blic Damien
Published: March 2011

Résumé L'article vise à montrer que les contradictions généralement suscitées par les restes humains sont redoublées dans un contexte dévotionnel catholique par des frontières incertaines entre des usages légitimes et illégitimes de reliques de saints. Il s'appuie sur une enquête ethnographique auprès de différentes formes de vénérations des reliques de sainte Thérèse de Lisieux. Cette enquête montre comment la variété des dispositifs dévotionnels manifeste autant de tensions entre l'inscription de la vénération des reliques dans une tradition rituelle et dogmatique et un encadrement institutionnel visant à écarter les reproches de déviance superstitieuse, sans que ces tensions se résolvent dans définition unique d'un bon usage des reliques.
Du poids relatif des morts
Authors: Detienne Marcel , Esquerre Arnaud
Published: March 2011

Résumé Dans cet entretien, Marcel Detienne explique tout d'abord comment, pour les Grecs de l'Antiquité qui partent fonder des colonies, les morts sont « légers » : ils ne sont pas attachés aux vivants ni à un endroit particulier. Le rapport aux morts mis en place par les historiens en France depuis le 19e siècle jusqu'à Braudel est très différent : il lie ensemble les morts et les vivants dans une communauté nationale, « enracinée » dans un territoire. Pour mieux comprendre la place des morts en France et en Europe aujourd'hui, Marcel Detienne propose, enfin, de travailler en procédant à des comparaisons.
The Food Preference Paradigm: A Review of Autumn–Winter Food Use by North American Dabbling Ducks (1900–2009)
Authors: Callicutt James T. , Hagy Heath M. , Schummer Michael L.
Published: March 2011

Studies describing food use (i.e., diet) of nonbreeding dabbling ducks Anas spp. are essential to understanding physiological needs of and recommending habitat management for these birds. We conducted a review of published autumn and winter food-use studies of dabbling ducks in North America to characterize the current state of knowledge and identify remaining research needs. We initiated our review to determine whether valuations of duck foods and the term “preference” commonly used by researchers and in waterfowl management guides (i.e., the food preference paradigm) were supported by available peer-reviewed literature. We analyzed peer-reviewed literature (1900–2009) on autumn–winter food use of dabbling ducks (n  =  59 studies). Most studies (68%) used methods known to contain substantial bias including data from gizzards and hunter-collected ducks. Only 5% of published articles reliably determined food selection by concurrently measuring food use and availability, and no study determined food use at a scale appropriate for winter home ranges of dabbling ducks. In some habitats commonly managed for waterfowl (e.g., agricultural lands), few if any collections of ducks are available to obtain data on food use. The limited geographic and habitat scope of unbiased food use and selection studies for dabbling ducks during autumn and winter suggests that the food-preference paradigm found in waterfowl management literature is not supported by empirical evidence and that managers must continue to use best judgment in managing foraging habitats for waterfowl. Researchers and conservation planners should aim to reduce uncertainty regarding the value of waterfowl foods by conducting contemporary food-selection studies using unbiased collection and processing methodologies. Further, we suggest future researchers conduct concurrent behavioral observations, habitat use, and food selection studies within winter home ranges of dabbling ducks to aid managers in meeting the nutritional requirements of dabbling ducks during autumn and winter in North America.
Exposure to IL-15 and IL-21 Enables Autoreactive CD8 T Cells To Respond to Weak Antigens and Cause Disease in a Mouse Model of Autoimmune Diabetes
Authors: Ramanathan Sheela , Dubois Stephanie , Chen Xi-Lin , Leblanc Chantal , Ohashi Pamela S. , Ilangumaran Subburaj
Published: March 2011

Autoreactive CD8+ T lymphocytes play a key role in the pathogenesis of several autoimmune diseases. It is not yet well understood how autoreactive CD8+ T cells, which express TCRs with low reactivity toward self-Ags, gain the ability to respond to autoantigens to cause disease. Previously, we have shown that prior stimulation of CD8+ T cells with synergistic combinations of cytokines produced by the innate immune response, such as IL-21 and IL-15, induces Ag-independent proliferation. Such “cytokine-primed” CD8 T cells displayed increased responsiveness to limiting quantities of the cognate Ag. In this paper, we report that prior stimulation with IL-15 and IL-21 also enables CD8+ T cells to respond to weakly agonistic TCR ligands, resulting in proliferation, cytokine secretion, and cytolytic activity. Using a transgenic mouse model of autoimmune diabetes, we show that cytokine-primed autoreactive CD8+ T cells induce disease following stimulation by weak TCR ligands, but their diabetogenic potential is dependent on continuous availability of IL-15 in vivo. These findings suggest that inflammatory cytokines could facilitate the triggering of autoreactive CD8+ T cells by weak autoantigens, and this mechanism may have important implications for autoimmune diseases associated with microbial infections and chronic inflammation.
Lipopolysaccharide Signaling without a Nucleus: Kinase Cascades Stimulate Platelet Shedding of Proinflammatory IL-1β–Rich Microparticles
Authors: Brown G. Thomas , McIntyre Thomas M.
Published: March 2011

Platelets contain unspliced heteronuclear IL-1β RNA, which is rapidly spliced and translated upon activation. LPS is a superior agonist for this atypical platelet response, but how LPS induces proinflammatory cytokine production in anucleate cells lacking NF-κB is unknown. Platelets express functional TLR4, and stimulation by LPS induced rapid splicing, translation, and secretion of mature IL-1β after caspase-1 processing. LPS stimulated microparticle shedding, and secreted IL-1β was exclusively present in these particles. Microparticles from LPS-stimulated platelets induced VCAM-1 production by cultured human endothelial cells, and blockade of endothelial IL-1β receptor with IL-1 receptor antagonist completely suppressed endothelial activation. Splicing was posttranscriptional as the SR kinase inhibitor TG003 blocked IL-1β RNA production by platelets, but not by monocytes, and was dependent on exogenous CD14—a property of platelets. We used a combination of small-molecule inhibitors, cell-penetrating chimeric peptide inhibitors, and gene-targeted animals to show splicing required MyD88 and TIRAP, and IRAK1/4, Akt, and JNK phosphorylation and activation. Traf6 couples MyD88 to the Akt pathway and, remarkably, a Traf6 interacting peptide–antennapedia chimera was more effective than LPS in stimulating IL-1β splicing. The Traf6 chimera did not, however, stimulate microparticle shedding, nor was IL-1β released. We conclude LPS-induced kinase cascades are sufficient to alter cellular responses, that three signals emanate from platelet TLR4, and that Akt and JNK activation are sufficient to initiate posttranscriptional splicing while another event couples microparticle shedding to TLR4 activation. Platelets contribute to the inflammatory response to LPS through production of microparticles that promote endothelial cell activation.
Enhanced Sensitivity to IL-2 Signaling Regulates the Clinical Responsiveness of IL-12–Primed CD8+ T Cells in a Melanoma Model
Authors: Lisiero Dominique N. , Soto Horacio , Liau Linda M. , Prins Robert M.
Published: March 2011

The optimal expansion, trafficking, and function of adoptively transferred CD8+ T cells are parameters that currently limit the effectiveness of antitumor immunity to established tumors. In this study, we addressed the mechanisms by which priming of self tumor-associated Ag-specific CD8+ T cells influenced antitumor functionality in the presence of the inflammatory cytokine IL-12. In vitro priming of mouse tumor-specific CD8+ T cells in the presence of IL-12 induced a diverse and rapid antitumor effector activity while still promoting the generation of memory cells. Importantly, IL-12–primed effector T cells dramatically reduced the growth of well-established s.c. tumors and significantly increased survival to highly immune resistant, established intracranial tumors. Control of tumor growth by CD8+ T cells was dependent on IL-12–mediated upregulation of the high-affinity IL-2R (CD25) and a subsequent increase in the sensitivity to IL-2 stimulation. Finally, IL-12–primed human PBMCs generated tumor-specific T cells both phenotypically and functionally similar to IL-12–primed mouse tumor-specific T cells. These results highlight the ability of IL-12 to obviate the strict requirement for administering high levels of IL-2 during adoptive cell transfer-mediated antitumor responses. Furthermore, acquisition of a potent effector phenotype independent of cytokine support suggests that IL-12 could be added to adoptive cell transfer clinical strategies in cancer patients.
IFN-α Production by Plasmacytoid Dendritic Cells Stimulated with RNA-Containing Immune Complexes Is Promoted by NK Cells via MIP-1β and LFA-1
Authors: Hagberg Niklas , Berggren Olof , Leonard Dag , Weber Gert , Bryceson Yenan T. , Alm Gunnar V. , Eloranta Maija-Leena , Rönnblom Lars
Published: March 2011

Several systemic autoimmune diseases display a prominent IFN signature. This is caused by a continuous IFN-α production by plasmacytoid dendritic cells (pDCs), which are activated by immune complexes (ICs) containing nucleic acid. The IFN-α production by pDCs stimulated with RNA-containing IC (RNA-IC) consisting of anti-RNP autoantibodies and U1 small nuclear ribonucleoprotein particles was recently shown to be inhibited by monocytes, but enhanced by NK cells. The inhibitory effect of monocytes was mediated by TNF-α, PGE2, and reactive oxygen species, but the mechanisms for the NK cell-mediated increase in IFN-α production remained unclear. In this study, we investigated the mechanisms whereby NK cells increase the RNA-IC–induced IFN-α production by pDCs. Furthermore, NK cells from patients with systemic lupus erythematosus (SLE) were evaluated for their capacity to promote IFN-α production. We found that CD56dim NK cells could increase IFN-α production >1000-fold after RNA-IC activation, whereas CD56bright NK cells required costimulation by IL-12 and IL-18 to promote IFN-α production. NK cells produced MIP-1α, MIP-1β, RANTES, IFN-γ, and TNF-α via RNA-IC–mediated FcγRIIIA activation. The IFN-α production in pDCs was promoted by NK cells via MIP-1β secretion and LFA-mediated cell–cell contact. Moreover, NK cells from SLE patients displayed a reduced capacity to promote the RNA-IC–induced IFN-α production, which could be restored by exogenous IL-12 and IL-18. Thus, different molecular mechanisms can mediate the NK cell-dependent increase in IFN-α production by RNA-IC–stimulated pDCs, and our study suggests that the possibility to therapeutically target the NK–pDC axis in IFN-α–driven autoimmune diseases such as SLE should be investigated.
Attenuated Bordetella pertussis Vaccine Candidate BPZE1 Promotes Human Dendritic Cell CCL21-Induced Migration and Drives a Th1/Th17 Response
Authors: Fedele Giorgio , Bianco Manuela , Debrie Anne-Sophie , Locht Camille , Ausiello Clara Maria
Published: March 2011

New vaccines against pertussis are needed to evoke full protection and long-lasting immunological memory starting from the first administration in neonates—the major target of the life-threatening pertussis infection. A novel live attenuated Bordetella pertussis vaccine strain, BPZE1, has been developed by eliminating or detoxifying three important B. pertussis virulence factors: pertussis toxin, dermonecrotic toxin, and tracheal cytotoxin. We used a human preclinical ex vivo model based on monocyte-derived dendritic cells (MDDCs) to evaluate BPZE1 immunogenicity. We studied the effects of BPZE1 on MDDC functions, focusing on the impact of Bordetella-primed dendritic cells in the regulation of Th and suppressor T cells (Ts). BPZE1 is able to activate human MDDCs and to promote the production of a broad spectrum of proinflammatory and regulatory cytokines. Moreover, conversely to its parental wild-type counterpart BPSM, BPZE1-primed MDDCs very efficiently migrate in vitro in response to the lymphatic chemokine CCL21, due to the inactivation of pertussis toxin enzymatic activity. BPZE1-primed MDDCs drove a mixed Th1/Th17 polarization and also induced functional Ts. Experiments performed in a Transwell system showed that cell contact rather than the production of soluble factors was required for suppression activity. Overall, our findings support the potential of BPZE1 as a novel live attenuated pertussis vaccine, as BPZE1-challenged dendritic cells might migrate from the site of infection to the lymph nodes, prime Th cells, mount an adaptive immune response, and orchestrate Th1/Th17 and Ts responses.
The Role of ChemR23 in the Induction and Resolution of Cigarette Smoke-Induced Inflammation
Authors: Demoor Tine , Bracke Ken R. , Dupont Lisa L. , Plantinga Maud , Bondue Benjamin , Roy Marie-Odile , Lannoy Vincent , Lambrecht Bart N. , Brusselle Guy G. , Joos Guy F.
Published: March 2011

Chronic obstructive pulmonary disease is mainly triggered by cigarette smoke (CS) and progresses even after smoking cessation. CS induces an exaggerated influx of inflammatory cells to the bronchoalveolar space and lung parenchyma, likely resulting from a complex interplay between chemoattractants and their respective receptors. In a murine CS model of chronic obstructive pulmonary disease, we studied the importance of chemokine-like receptor ChemR23 for the induction and resolution of inflammation in CS-exposed lungs. Subacute and chronic CS exposure increased protein levels of the ChemR23 ligand and chemoattractant, chemerin, in bronchoalveolar lavage (BAL) fluid of wild-type (WT) mice. Moreover, the proinflammatory chemokines CXCL1, CCL2, and CCL20 were increased in the airways of CS-exposed WT mice, accompanied by a massive accumulation of inflammatory neutrophils and monocytes, CD11bhiCD103− and CD11bloCD103+ dendritic cells (DCs), and CD4+ and CD8+ T cells. The lung parenchyma of WT mice was infiltrated with inflammatory neutrophils, CD11bhiCD103− DCs, and activated CD4+ T cells after CS exposure. CS-induced inflammation was severely attenuated in BAL fluid and lungs of ChemR23 knockout mice with regard to the induction of inflammatory chemokines and the recruitment of inflammatory cells. Neutrophils and CD8+ T cells persisted in the airways of WT mice, as did the airway-derived conventional DCs in the mediastinal lymph nodes, for at least 14 d after smoking cessation. In the BAL fluid of CS-exposed ChemR23 knockout mice, there was a remarkable delayed accumulation of T cells 14 d after the final exposure. Our data support a role for ChemR23 in directing innate and adaptive immune cells to CS-exposed lungs.
Correlation between the Type of BCR-ABL Transcripts and Blood Cell Counts in Chronic Myeloid Leukemia—A Possible Influence of MDR1 Gene Expression
Authors: Balatzenko Gueorgui , Vundinti Babu Rao , Margarita Guenova
Published: March 2011

The impact of BCR-ABL mRNA type (b3a2 vs. b2a2) on chronic myeloid leukemia (CML) phenotype is still a subject of controversies. We searched for a correlation between the BCR-ABL transcripts type and CML patients’ characteristics, including MDR1 gene expression. Ninety-eight untreated chronic phase CML patients were studied. The type of BCR-ABL fusion transcripts and MDR1 gene expression were determined by reverse transcriptase polymerase chain reaction. B3a2 and b2a2 transcripts were found in 53 [54%] and 44 [45%] patients, respectively. One patient co-expressed b3a2/b2a2 and was excluded from analysis. The only difference in the clinical characteristics between the two groups was the platelets count, that was higher in b3a2(+) patients [791.3 ± 441.3 × 109/L vs. 440.4 ± 283.4 × 109/L in b2a2(+); p = 0.007]. MDR1 over-expression [MDR1(+)] was observed in 48 patients (49.5%), more frequently in older patients >60 years [71% (24/34) vs. 38% (24/63) in younger; p = 0.008], and was associated with a lower white blood cells (WBC) count [105.5 ± 79.8 × 109/L vs. 143.6 ± 96.5 × 109/L in MDR1(–) cases; p = 0.047]. On performing the analysis only within the MDR1(+) group, the b3a2(+) cases were characterized with a significantly higher platelets count [908.7 ± 470.1 × 109/L vs. 472.9 ± 356.1 × 109/L; p = 0.006] and a lower WBC count [85.4 ± 61.2 × 109/L vs. 130 ± 93.9 × 109/L; p = 0.004) compared to b2a2(+) patients. No similar differences were found between b3a2(+) and b2a2(+) groups with normal MDR1 levels. These results indicate that the type of BCR-ABL transcripts correlates with the hematological parameters of CML, however only in the subgroup of patients characterized by MDR1 over-expression.
Usefulness of the Polymerase Chain Reaction Dot-Blot Assay, Used with Ziehl-Neelsen Staining, for the Rapid and Conveni­ent Diagnosis of Pulmonary Tuberculosis in Human Immuno­deficiency Virus-Seropositive and -Seronegative Individuals
Authors: Scherer Luciene Cardoso , Sperhacke Rosa D. , Rossetti Maria L. R. , Ruffino-Netto Antonio , Kritski Afrânio L.
Published: March 2011

There are scarce data regarding the value of molecular tests, when used in parallel with classical tools, for the diagnosis of tuberculosis (TB) under field conditions, especially in regions with a high burden of TB-human immunodeficiency virus (HIV) co-infection. We evaluated the usefulness of the polymerase chain reaction dot-blot assay (PCR) used in parallel with Ziehl-Neelsen staining (ZN) for pulmonary tuberculosis (PTB) diagnosis, in a TB-HIV reference hospital. All sputum samples from 277 patients were tested by ZN, culture, and PCR. Performances were assessed individually, in parallel, for HIV status, history of anti-TB treatment, and in different simulated TB prevalence rates. Overall, the PTB prevalence was 46% (128/277); in HIV-seropositive (HIV+) individuals, PTB prevalence was 54% (40/74); the ZN technique had a lower sensitivity (SE) in the HIV+ group than in the HIV-seronegative (HIV–) group (43% vs. 68%; Fisher test, P<0.05); and the SE of PCR was not affected by HIV status (Fisher test; P=0.46). ZN, in parallel with PCR, presented the following results: i) among all PTB suspects, SE of 90%, specificity (SP) of 84%, likelihood ratio (LR)+ of 5.65 and LR– of 0.12; ii) in HIV– subjects: SE of 92%, LR– of 0.10; iii) in not previously treated cases: SE of 90%, LR– of 0.11; iv) in TB, prevalence rates of 5-20%; negative predictive values (NPV) of 98-99%. ZN used in parallel with PCR showed an improvement in SE, LR–, and NPV, and may offer a novel approach in ruling out PTB cases, especially in not previously treated HIV– individuals, attended in hospitals in developing nations.
Measurement of CO3-610, a Potential Liver Biomarker Derived from Matrix Metalloproteinase-9 Degradation of Collagen Type III, in a Rat Model of Reversible Carbon-Tetrachloride-Induced Fibrosis
Authors: Vassiliadis Efstathios , Vang Larsen Dorthe , Clausen Rikke Elgaard , Veidal Sanne Skovgård , Barascuk Natasha , Larsen Lise , Simonsen Henrik , Silvestre Toni Segovia , Hansen Christina , Overgaard Trine , Leeming Diana Julie , Karsdal Morten A
Published: March 2011

Background and Aim

The current study utilized a carbon tetrachloride (CCl4)-induced liver fibrosis model to measure levels of the MMP9-mediated collagen type III degradation fragment CO3-610 (site of cleavage: KNGETGPQGP), during disease progression and regression, and to investigate a potential prognostic role of the biomarker.

Materials and Methods

72 female Sprague-Dawley rats aged 6 months old were injected with CCl4twice a week over different periods of time to induce varying degrees of liver fibrosis. After 4, 6 and 8 weeks of treatment, administration of CCl4was stopped. The 6- and 8-week treatment groups were left to regress for a further 6 or 12 weeks at which point they were sacrificed and livers removed and sectioned. Liver fibrosis was quantified using Visiopharm software to analyse Sirius red-stained sections. Serum levels of CO3-610 were measured in all animals using an ELISA assay as described by Barascuk et al.1

Results

Quantitative histology revealed total collagen deposition in the liver increased as fibrosis progressed. In animals treated with CCl4for 4 weeks, collagen comprised on average 4.94% of the total tissue in liver sections, while after 6 weeks the mean was 8.25%, and after 8 weeks, 9.11%. During the regression phase, the total collagen deposition gradually decreased to a mean of 6.9% and 5.09% for animals regressing 6 and 12 weeks respectively after 6 weeks treatment, and 6.27% for animals regressed 12 weeks after 8 weeks treatment. CO3-610 values increased progressively in rats treated for 4 weeks (by a mean of 55.0 ng/ml), 6 weeks (mean 61.1 ng/ml) and 8 weeks (mean 70.2 ng/ml). During the regression phase, CO3-610 values rapidly decreased by a mean of 28.9 ng/ml at 6 weeks and 21.6 ng/ml at 12 weeks in animals previously treated for 6 weeks, and by a mean of 19.52 ng/ml in animals treated for 8 weeks and regressed for 12 weeks. CO3-610 levels were statistically significantly correlated with total collagen during disease progression ( r = 0.5701, P < 0.0001). No statistically significant correlation was observed during regression ( r = 0.2081, P = 0.1138).

Conclusion

Levels of the MMP-9 generated fragment of collagen type III, CO3-610, correlated with the degree of liver fibrosis in rats during the progression phase, but were not correlated with total collagen levels during regression. CO3-610 seems to be produced only under the CCL4stimulus, and signifies CO3-610 as a potential marker of progression rather than regression. The corresponding steep elevations in levels of CO3-610 total collagen and collagen type III during liver fibrosis progression underline a potential prognostic capacity of the biomarker.
The Emerging Role of Ofatumumab in the Treatment of Chronic Lymphocytic Leukemia
Authors: Nabhan Chadi , Kay Neil E.
Published: March 2011

The treatment of chronic lymphocytic leukemia (CLL) has evolved over the past decade. Our better understanding of disease biology and risk stratification has allowed delivering more effective therapies. In fact, front-line chemoimmunotherapy has demonstrated improvement in overall survival when compared to chemotherapy in randomized studies. Yet, treatment of relapsed CLL remains challenging and few agents are effective in that setting. Ofatumumab (Ofa) is a humanized monoclonal antibody targeted against CD20 with demonstrable activity in rituximab-resistant CLL cell lines. This agent was recently approved for the treatment of relapsed/refractory CLL patients who have failed fludarabine and alemtuzumab. In this review, we provide a historical perspective on approaches to CLL as front-line and in the relapsed setting. We further summarize novel anti-CD20 antibodies with specific emphasis on ofa. We review studies that led to ofatumumab's approval including pre-clinical data, trials using ofa in combination therapies, and adverse events/toxicities reported with this agent.
On the global minimizers of a nonlocal isoperimetric problem in two dimensions
Authors: Sternberg Peter , Topaloglu Ihsan
Published: March 2011

We analyze the minimization of a nonlocal isoperimetric problem (NLIP) posed on the flat 2-torus. After establishing regularity of the free boundary of minimizers, we show that when the parameter controlling the influence of the nonlocality is small, there is an interval of values for the mass constraint such that the global minimizer is exactly lamellar, that is, the free boundary consists of two parallel lines. In other words, in this parameter regime, the global minimizer of the 2d (NLIP) coincides with the global minimizer of the local periodic isoperimetric problem.
Sources of carbonaceous aerosol in the Amazon basin
Authors: Gilardoni S. , Vignati E. , Marmer E. , Cavalli F. , Belis C. , Gianelle V. , Loureiro A. , Artaxo P.
Published: March 2011

Abstract. The quantification of sources of carbonaceous aerosol is important to understand their atmospheric concentrations and regulating processes and to study possible effects on climate and air quality, in addition to develop mitigation strategies. In the framework of the European Integrated Project on Aerosol Cloud Climate Interactions (EUCAARI) fine (Dp < 2.5 μm) and coarse (2.5 μm < Dp <10 μm) aerosol particles were sampled from February to June (wet season) and from August to September (dry season) 2008 in the central Amazon basin. The mass of fine particles averaged 2.4 μg m−3 during the wet season and 4.2 μg m−3 during the dry season. The average coarse aerosol mass concentration during wet and dry periods was 7.9 and 7.6 μg m−3, respectively. The overall chemical composition of fine and coarse mass did not show any seasonality with the largest fraction of fine and coarse aerosol mass explained by organic carbon (OC); the average OC to mass ratio was 0.4 and 0.6 in fine and coarse aerosol modes, respectively. The mass absorbing cross section of soot was determined by comparison of elemental carbon and light absorption coefficient measurements and it was equal to 4.7 m2 g−1 at 637 nm. Carbon aerosol sources were identified by Positive Matrix Factorization (PMF) analysis of thermograms: 44% of fine total carbon mass was assigned to biomass burning, 43% to secondary organic aerosol (SOA), and 13% to volatile species that are difficult to apportion. In the coarse mode, primary biogenic aerosol particles (PBAP) dominated the carbonaceous aerosol mass. The results confirmed the importance of PBAP in forested areas. The source apportionment results were employed to evaluate the ability of global chemistry transport models to simulate carbonaceous aerosol sources in a regional tropical background site. The comparison showed an overestimation of elemental carbon (EC) by the TM5 model during the dry season and OC both during the dry and wet periods. The overestimation was likely due to the overestimation of biomass burning emission inventories and SOA production over tropical areas.
Eddy covariance flux measurements of ammonia by high temperature chemical ionisation mass spectrometry
Authors: Sintermann J. , Spirig C. , Jordan A. , Kuhn U. , Ammann C. , Neftel A.
Published: March 2011

Abstract. A system for fast ammonia (NH3) measurements with chemical ionisation mass spectrometry (CIMS) based on a commercial Proton Transfer Reaction-Mass Spectrometer (PTR-MS) is presented. It uses electron transfer reaction as ionisation pathway and features a drift tube of polyetheretherketone (PEEK) and silica-coated steel. Heating the instrumental inlet and the drift tube to 180 °C enabled an effective time resolution of ~1 s and made it possible to apply the instrument for eddy covariance (EC) measurements. EC fluxes of NH3 were measured over two agricultural fields in Oensingen, Switzerland, following fertilisations with cattle slurry. Air was aspirated close to a sonic anemometer at a flow of 100 STP L min−1 and was directed through a 23 m long 1/2" PFA tube heated to 150 °C to an air-conditioned trailer where the gas was sub-sampled from the large bypass stream. This setup minimised damping of fast NH3 concentration changes between the sampling point and the actual measurement. High-frequency attenuation loss of the NH3 fluxes of 20 to 40% was quantified and corrected for using an empirical ogive method. The instrumental NH3 background signal showed a minor interference with H2O which was characterised in the laboratory. The resulting correction of the NH3 flux after slurry spreading was less than 1‰. The flux detection limit of the EC system was about 5 ng m−2 s−1 while the accuracy of individual flux measurements was estimated 16% for the high-flux regime during these experiments. The NH3 emissions after broad spreading of the slurry showed an initial maximum of 150 μg m−2 s−1 with a fast decline in the following hours.
Greenhouse gas observations from Cabauw Tall Tower (1992–2010)
Authors: Vermeulen A. T. , Hensen A. , Popa M. E. , van den Bulk W. C. M. , Jongejan P. A. C.
Published: March 2011

Abstract. Since 1992 semi-continuous in-situ observations of greenhouse gas concentrations have been performed at the tall tower of Cabauw (4.927° E, 51.971° N, −0.7 m a.s.l.). Through 1992 up to now, the measurement system has been gradually extended and improved in precision, starting with CO2 and CH4 concentrations from 200 m a.g.l. in 1992 to vertical gradients at 4 levels of the gases CO2, CH4, SF6, N2O, H2, CO and gradients at 2 levels for 222Rn. In this paper the measurement systems and measurement results are described for the main greenhouse gases and CO, for the whole period. The automatic measurement system now provides half-hourly concentration gradients with a precision better than or close to the WMO recommendations. The observations at Cabauw show a complex pattern caused by the influence of sources and sinks from a large area around the tower with significant contributions of sources and sinks at distances up to 500–700 km. The concentration footprint area of Cabauw is one the most intensive and complex source areas of greenhouse gases in the world. Despite this, annual mean trends for the most important greenhouse gases, compatible with the values derived using the global network, can be reproduced from the measured concentrations at Cabauw over the entire measurement period, with a measured increase in the period 2000–2009 for CO2 of 1.90 ± 0.1 ppm yr−1, for CH4 of 4.4 ± 0.6 ppb yr−1, for N2O of 0.86 ± 0.04 ppb yr−1, and for SF6 of 0.27 ± 0.01 ppt yr−1; for CO no significant trend could be detected. The influences of strong local sources and sinks are reflected in the amplitude of the mean seasonal cycles observed at Cabauw, that are larger than the mean Northern Hemisphere average; Cabauw mean seasonal amplitude for CO2 is 25–30 ppm (higher value for lower sampling levels). The observed CH4 seasonal amplitude is 50–110 ppb. All gases except N2O show highest concentrations in winter and lower concentrations in summer, N2O observations show two additional concentration maxima in early summer and in autumn. Seasonal cycles of the day-time mean concentrations show that surface concentrations or high elevation concentrations alone do not give a representative value for the boundary layer concentrations, especially in winter time, but that the vertical profile data along the mast can be used to construct a useful boundary layer mean value. The variability at Cabauw in the atmospheric concentrations of CO2 on time scales of minutes to hours is several ppm and is much larger than the precision of the measurements (0.1 ppm). The diurnal and synoptical variability of the concentrations at Cabauw carry information on the sources and sinks in the footprint area of the mast, that will be useful in combination with inverse atmospheric transport model to verify emission estimates and improve ecosystem models. For this purpose a network of tall tower stations like Cabauw forms a very useful addition to the existing global observing network for greenhouse gases.
Climatology of the inter-hemispheric field-aligned current system in the equatorial ionosphere as observed by CHAMP
Authors: Park J. , Lühr H. , Min K. W.
Published: March 2011

Abstract. From geomagnetic field observations of CHAMP during 2001–2009 we extracted characteristic signatures of inter-hemispheric field-aligned currents (IHFACs) in the equatorial ionosphere. The results are in general agreement with previous observations. Nighttime IHFACs are negligibly small. Solstitial IHFACs flow from the summer to winter (from winter to summer) hemisphere at dawn (around noon). Duskside IHFACs flow southbound irrespective of season. We have also found some new IHFAC properties, which may have been predicted by theories, but are not yet given observational support. IHFACs clearly exhibit a longitude dependence, which is modulated by the South Atlantic Anomaly, the offset between geographic and magnetic equators, and tidal waves. IHFACs show little dependence on the solar cycle. We provide a comprehensive assessment of the IHFAC modulation by non-migrating tides.
Effects of changes in carbonate chemistry speciation on Coccolithus braarudii: a discussion of coccolithophorid sensitivities
Authors: Krug S. A. , Schulz K. G. , Riebesell U.
Published: March 2011

Abstract. Ocean acidification and associated shifts in carbonate chemistry speciation induced by increasing levels of atmospheric carbon dioxide (CO2) have the potential to impact marine biota in various ways. The process of biogenic calcification, for instance, is usually shown to be negatively affected. In coccolithophores, an important group of pelagic calcifiers, changes in cellular calcification rates in response to changing ocean carbonate chemistry appear to differ among species. By applying a wider CO2 range we show that a species previously reported insensitive to seawater acidification, Coccolithus braarudii, responds both in terms of calcification and photosynthesis, although at higher levels of CO2. Thus, observed differences between species seem to be related to individual sensitivities while the underlying mechanisms could be the same. On this basis we develop a conceptual model of coccolithophorid calcification and photosynthesis in response to CO2-induced changes in seawater carbonate chemistry speciation.
Anaerobic oxidation of methane: an underappreciated aspect of methane cycling in peatland ecosystems?
Authors: Smemo K. A. , Yavitt J. B.
Published: March 2011

Abstract. Despite a large body of literature on microbial anaerobic oxidation of methane (AOM) in marine sediments and saline waters and its importance to the global methane (CH4) cycle, until recently little work has addressed the potential occurrence and importance of AOM in non-marine systems. This is particularly true for peatlands, which represent both a massive sink for atmospheric CO2 and a significant source of atmospheric CH4. Our knowledge of this process in peatlands is inherently limited by the methods used to study CH4 dynamics in soil and sediment and the assumption that there are no anaerobic sinks for CH4 in these systems. Studies suggest that AOM is CH4-limited and difficult to detect in potential CH4 production assays against a background of CH4 production. In situ rates also might be elusive due to background rates of aerobic CH4 oxidation and the difficulty in separating net and gross process rates. Conclusive evidence for the electron acceptor in this process has not been presented. Nitrate and sulfate are both plausible and favorable electron acceptors, as seen in other systems, but there exist theoretical issues related to the availability of these ions in peatlands and only circumstantial evidence suggests that these pathways are important. Iron cycling is important in many wetland systems, but recent evidence does not support the notion of CH4 oxidation via dissimilatory Fe(III) reduction or a CH4 oxidizing archaea in consortium with an Fe(III) reducer. Calculations based on published rates demonstrate that AOM might be a significant and underappreciated constraint on the global CH4 cycle, although much about the process is unknown, in vitro rates may not relate well to in situ rates, and projections based on those rates are fraught with uncertainty. We suggest electron transfer mechanisms, C flow and pathways, and quantifying in situ peatland AOM rates as the highest priority topics for future research.
Climate patterns in north central China during the last 1800 yr and its possible driving force
Authors: Tan L. , Cai Y. , An Z. , Zhang H. , Qin S.
Published: March 2011

Abstract. We synthesized high-resolution precisely-dated stalagmite records and historical document records from north central China to reconstruct a decadal resolution precipitation record during the last 1800 yr (190–1980 AD). Several notable wet intervals were identified: 190s–290s, 560s–850s, 920s–1000s, 1090s–1130s, 1880s–1910s. The most remarkable dry epoch was inferred in 1330s–1860s, and the driest period was in the first half of the 17th century. Other decade droughts were found in the 300s–310s, 340s, 460s, 880s, 1030s, 1070s, 1210s and 1920s. The precipitation variability shows significant positive correlation with the temperature variability, suggesting a warm-humid or cool-dry pattern in north central China over the past 1800 yr. The abnormal warm-dry climate observed in the late 20th century in this region may suggest that the dominant forcing of climate variability changed from natural to anthropogenic. Solar activity may be the dominant natural force that drove the same-phase variations of the temperature and precipitation in north central China on centennial- to decadal-scale.
Uncertainty in climate change impacts on basin-scale freshwater resources – preface to the special issue: the QUEST-GSI methodology and synthesis of results
Authors: Todd M. C. , Taylor R. G. , Osborn T. J. , Kingston D. G. , Arnell N. W. , Gosling S. N.
Published: March 2011

Abstract. This paper presents a preface to this Special Issue on the results of the QUEST-GSI (Global Scale Impacts) project on climate change impacts on catchment scale water resources. A detailed description of the unified methodology, subsequently used in all studies in this issue, is provided. The project method involved running simulations of catchment-scale hydrology using a unified set of past and future climate scenarios, to enable a consistent analysis of the climate impacts around the globe. These scenarios include "policy-relevant" prescribed warming scenarios. This is followed by a synthesis of the key findings. Overall, the studies indicate that in most basins the models project substantial changes to river flow, beyond that observed in the historical record, but that in many cases there is considerable uncertainty in the magnitude and sign of the projected changes. The implications of this for adaptation activities are discussed.
Industrial accidents triggered by natural hazards: an emerging risk issue
Authors: Krausmann E. , Cozzani V. , Salzano E. , Renni E.
Published: March 2011

Abstract. The threat of natural hazards impacting chemical facilities and infrastructures with the subsequent release of hazardous substances has been recognised as an emerging risk which is likely to be exacerbated by the ongoing climate change. Within the European FP7 project iNTeg-Risk, efforts are dedicated to address the problem of Natech accidents by trying to understand their underlying causes and by developing methodologies and tools to assess Natech risk. Special attention is thereby given to the risk of chemical accidents triggered by earthquakes, floods and lightning. This work outlines the ongoing efforts in the development of new concepts and tools for Natech hazard and vulnerability ranking, risk assessment, risk-based design, and emergency planning and early warning.
Probabilistic downscaling of precipitation data in a subtropical mountain area: a two-step approach
Authors: Haas R. , Born K.
Published: March 2011

Abstract. In this study, a two-step probabilistic downscaling approach is introduced and evaluated. The method is exemplarily applied on precipitation observations in the subtropical mountain environment of the High Atlas in Morocco. The challenge is to deal with a complex terrain, heavily skewed precipitation distributions and a sparse amount of data, both spatial and temporal. In the first step of the approach, a transfer function between distributions of large-scale predictors and of local observations is derived. The aim is to forecast cumulative distribution functions with parameters from known data. In order to interpolate between sites, the second step applies multiple linear regression on distribution parameters of observed data using local topographic information. By combining both steps, a prediction at every point of the investigation area is achieved. Both steps and their combination are assessed by cross-validation and by splitting the available dataset into a trainings- and a validation-subset. Due to the estimated quantiles and probabilities of zero daily precipitation, this approach is found to be adequate for application even in areas with difficult topographic circumstances and low data availability.