bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunological and clinical consequences of treating a patient with natalizumab
Authors: Schwab Nicholas , Höhn Karin G , Schneider-Hohendorf Tilman , Metz Imke , Stenner Max-Philipp , Jilek Samantha , Du Pasquier Renaud A , Gold Ralf , Meuth Sven G , Ransohoff Richard M , Brück Wolfgang , Wiendl Heinz 
Published: September 2011

Background: Long-term therapy with natalizumab increases the risk of progressive multifocal leukoencephalopathy (PML). Objectives: We present a patient study through therapy, the diagnosis of PML (after 29 infusions), plasma exchange (PE) and development of immune reconstitution inflammatory syndrome (IRIS). Methods: Routine diagnostics, magnetic resonance imaging (MRI), immunological status (flow cytometry, T-cell migration assays and T-cell repertoire analysis), and brain biopsy with immunohistological analysis. Results: CD49d decreased after 12 months of treatment. At PML diagnosis, CD49d expression and migratory capacity of T cells was low and peripheral T-cell receptor (TCR) complexity showed severe perturbations. The distribution of peripheral monocytes changed from CCR5+ to CCR7+. After PE some changes reverted: CD49d increased and overshot earliest levels, migratory capacities of T cells recovered and peripheral TCR complexity increased. With no clinical, routine laboratory or cerebrospinal fluid (CSF) changes, MRI 2 months after PE demonstrated progressive lesion development. Brain histopathology confirmed the presence of infiltrates indicative of IRIS without clinical signs, immunologically accompanied by CCR7/CCR5 recovery of peripheral monocytes. Conclusion: Natalizumab-associated immunological changes accompanying PML were reversible after PE; IRIS can occur very late, remain asymptomatic and be elusive to CSF analysis. Our study may provide insights into the changes under treatment with natalizumab associated with JC virus control.
Quantitative Reduction Method of Draft in High-Rise Buildings, Using Revolving Doors
Authors: Lee Joonghoon , Hwang Taeyon , Song Doosam , Kim Jeong Tai 
Published: September 2011

Drafts in high-rise buildings caused by the stack effect can cause noise and reduce the performances of ventilation, cooling and heating systems as well as the building’s energy efficiency. Revolving doors are generally used as a method to reduce drafts; however, the effect would only be limited to the main entrance on the lobby floor. Revolving doors have two main advantages; that their opening areas are seldom changed by people passing through the doors, and the doors do not have the pressure-related functional problems. Considering these advantages, this study examined a quantitative draft reduction method using revolving doors in high-rise buildings. This method would contribute to the design process to install revolving doors to buildings and consists of 10 steps with two key steps of selecting the installation locations of revolving doors and to calculate the air leakage area of revolving doors. Verification through simulations showed that, based on this process, the use of revolving doors could reduce the drafts in buildings by a quantified target value. Furthermore, the possibility of problems due to the stack effect in the other walls of buildings would decrease due to the pressure sharing of the additional walls fitted to revolving doors.
Bone marrow dendritic cell progenitors sense pathogens via Toll-like receptors and subsequently migrate to inflamed lymph nodes
Authors: Schmid Michael A. , Takizawa Hitoshi , Baumjohann Dior R. , Saito Yasuyuki , Manz Markus G. 
Published: September 2011

AbstractCommon dendritic cell progenitors (CDPs) in the bone marrow (BM) regenerate dendritic cells (DCs) in lymphoid and nonlymphoid tissues. How the dissemination of progenitor-derived DCs to peripheral tissues is regulated on need remains elusive. Microbes are sensed by pathogen recognition receptors such as Toll-like receptors (TLRs). We found that CDPs in the BM express TLR2, TLR4, and TLR9. On TLR stimulation, CDPs down-regulated CXCR4, the nonredundant chemokine receptor for their BM retention, up-regulated CCR7, and migrated to lymph nodes (LNs). When TLR agonists were injected locally, CDPs preferentially gave rise to DCs in inflamed LNs in expense of noninflamed LNs and the BM, but they did not alter their lineage differentiation and proliferative activity. Consequently, BM DC progenitors can sense TLR agonists and, via regulation of CXCR4 and CCR7, support the replenishment of DCs in reactive LNs. This mechanism likely developed to support DC homeostasis on specific need at sites of inflammation.
The BCR-ABL35INS insertion/truncation mutant is kinase-inactive and does not contribute to tyrosine kinase inhibitor resistance in chronic myeloid leukemia
Authors: O'Hare Thomas , Zabriskie Matthew S. , Eide Christopher A. , Agarwal Anupriya , Adrian Lauren T. , You Huihong , Corbin Amie S. , Yang Fei , Press Richard D. , Rivera Victor M. , Toplin Julie , Wong Stephane , Deininger Michael W. , Druker Brian J. 
Published: September 2011

Abstract
Chronic myeloid leukemia is effectively treated with imatinib, but reactivation of BCR-ABL frequently occurs through acquisition of kinase domain mutations. The additional approved ABL tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib, along with investigational TKIs such as ponatinib (AP24534) and DCC-2036, support the possibility that mutation-mediated resistance in chronic myeloid leukemia can be fully controlled; however, the molecular events underlying resistance in patients lacking BCR-ABL point mutations are largely unknown. We previously reported on an insertion/truncation mutant, BCR-ABL35INS, in which structural integrity of the kinase domain is compromised and all ABL sequence beyond the kinase domain is eliminated. Although we speculated that BCR-ABL35INS is kinase-inactive, recent reports propose this mutant contributes to ABL TKI resistance. We present cell-based and biochemical evidence establishing that BCR-ABL35INS is kinase-inactive and does not contribute to TKI resistance, and we find that detection of BCR-ABL35INS does not consistently track with or explain resistance in clinical samples from chronic myeloid leukemia patients.
The role of the annexin A2 heterotetramer in vascular fibrinolysis
Authors: Madureira Patricia A. , Surette Alexi P. , Phipps Kyle D. , Taboski Michael A. S. , Miller Victoria A. , Waisman David M. 
Published: September 2011

AbstractThe vascular endothelial cells line the inner surface of blood vessels and function to maintain blood fluidity by producing the protease plasmin that removes blood clots from the vasculature, a process called fibrinolysis. Plasminogen receptors play a central role in the regulation of plasmin activity. The protein complex annexin A2 heterotetramer (AIIt) is an important plasminogen receptor at the surface of the endothelial cell. AIIt is composed of 2 molecules of annexin A2 (ANXA2) bound together by a dimer of the protein S100A10. Recent work performed by our laboratory allowed us to clarify the specific roles played by ANXA2 and S100A10 subunits within the AIIt complex, which has been the subject of debate for many years. The ANXA2 subunit of AIIt functions to stabilize and anchor S100A10 to the plasma membrane, whereas the S100A10 subunit initiates the fibrinolytic cascade by colocalizing with the urokinase type plasminogen activator and receptor complex and also providing a common binding site for both tissue-type plasminogen activator and plasminogen via its C-terminal lysine residue. The AIIt mediated colocalization of the plasminogen activators with plasminogen results in the rapid and localized generation of plasmin to the endothelial cell surface, thereby regulating fibrinolysis.
Mast cell modulation of the vascular and lymphatic endothelium
Authors: Kunder Christian A. , St John Ashley L. , Abraham Soman N. 
Published: September 2011

AbstractMast cells (MCs) promote a wide range of localized and systemic inflammatory responses. Their involvement in immediate as well as chronic inflammatory reactions at both local and distal sites points to an extraordinarily powerful immunoregulatory capacity with spatial and temporal versatility. MCs are preferentially found in close proximity to both vascular and lymphatic vessels. On activation, they undergo a biphasic secretory response involving the rapid release of prestored vasoactive mediators followed by de novo synthesized products. Many actions of MCs are related to their capacity to regulate vascular flow and permeability and to the recruitment of various inflammatory cells from the vasculature into inflammatory sites. These mediators often work in an additive fashion and achieve their inflammatory effects locally by directly acting on the vascular and lymphatic endothelia, but they also can affect distal sites. Along these lines, the lymphatic and endothelial vasculatures of the host act as a conduit for the dissemination of MC signals during inflammation. The central role of the MC-endothelial cell axis to immune homeostasis is emphasized by the fact that some of the most effective current treatments for inflammatory disorders are directed at interfering with this interaction.
The Pocket Erodometer Test: Development and Preliminary Results
Authors: Briaud J.-L. , Bernhardt M. , Leclair M. 
Published: September 2011

Abstract
Over the last 20 years, several tools have been developed in an effort to quantify the erodibility of a soil; however, they all require a significant amount of time for set up and sample preparation. The pocket erodometer test (PET) is a simple test which can be performed in a few seconds with an inexpensive, compact, and very light instrument. The pocket erodometer is a regulated mini jet impulse generating device. The jet is aimed horizontally at the vertical face of the sample. The depth of the hole in the surface of the sample created by 20 impulses of water is recorded. The hole depth is compared to an erosion chart to determine the erodibility category of the soil. This erosion category allows the engineer to make preliminary decisions in erosion related work. This paper describes the development of the pocket erodometer idea and the PET test procedure as well as the erosion chart. PET results are presented for various soils and compared to previous EFA test results. These parallel tests are used to introduce the values in the erosion chart and easily obtain the erosion category for the soil. The advantages and disadvantages of this very simple tool and its place as a preliminary erosion estimator are also discussed.
Measurement of Total Soil Suction Using Filter Paper: Investigation of Common Filter Papers, Alternative Media, and Corresponding Confidence
Authors: Randy Rainwater N. , McDowell Lori A. , Drumm Eric C. 
Published: September 2011

Abstract
The small range of moisture contents measured with typical filter paper media in test method ASTM D5298 Measurement of Soil Potential (Suction) Using Filter Paper, require that the mass of the paper be measured to 0.0001 g. The accuracy and resolution of several readily available filter papers was investigated, along with investigating a polymer material as a possible alternative media. The importance of calibrating the filter paper was supported by the study, and suggested that because the slope of the calibration curve varies from paper to paper, the filter papers with the capability of measuring a broad range of water contents (low slope of the water content suction calibration curve) provide increased measurement resolution. The polymer media strips were found to have a much greater range of the moisture content than any of the filter papers, providing even greater resolution in the prediction of suction. The polymer strips performed just as well as the filter papers and showed repeatability in the measured suction values. The primary limitation in using polymer material is the lack of mass production of the material in a form suitable for suction measurements.
On The Shear Behavior of Ballast-Geosynthetic Interfaces
Authors: Indraratna Buddhima , Karimullah Hussaini Sd. K. , Vinod J. S. 
Published: September 2011

Abstract
Large-scale direct shear tests were performed to explore the behavior of rail ballast-geogrid interfaces and establish the role of geogrid aperture size on the interface shear strength. Fresh latite ballast with an average particle size (D50) of 35 mm, and seven geogrids with equivalent aperture sizes ranging from 20.8 to 88 mm were used for this current study. The laboratory experimental results confirm that the interface shear strength is influenced by the geogrid aperture size. The interface efficiency factor (α), defined as the ratio of the shear strength of the interface to the internal shear strength of the ballast varies from 0.8 to 1.16, and the ballast-geosynthetic interface friction angles vary from 52 to 67°. Moreover, a criterion to determine the minimum and maximum aperture sizes required to generate the beneficial effects of the geogrid has been identified in this study.
Laboratory Simulation of the Stresses Within Inclined Stopes
Authors: Hung Ting Ching , Sivakugan Nagaratnam , Kumar Shukla Sanjay 
Published: September 2011

Abstract
In the process of mining for earth resources, large underground voids called stopes are created that are later backfilled. For stability analysis of the backfilled stopes, it is necessary to understand the stress developments within the stope while the filling is in progress. Due to an arching effect, a substantial fraction of the fill weight is carried by the stope walls, depending on the physical characteristics of the walls. This paper describes the development of a laboratory model that simulates mine backfilling in an inclined stope and enables determination of the average vertical stress at any depth within the fill. The experimental results are validated against numerical models and stresses determined from an analytical expression. The effect of arching is the least when the stope is inclined at about 80° to the horizontal, giving highest vertical stresses at any depth. This fact is not captured in both the mathematical and numerical models developed in the past and the ones discussed herein. The model tests show that the lateral earth pressure coefficient is closer to K0 for vertical stopes and Ka for inclined stopes. In the case of walls with dissimilar frictional characteristics, the analytical expression can still be used with an average value of the wall-fill friction angle.
Human TCR Transgenic Bet v 1-Specific Th1 Cells Suppress the Effector Function of Bet v 1-Specific Th2 Cells
Authors: Neunkirchner Alina , Leb-Reichl Victoria M. , Schmetterer Klaus G. , Mutschlechner Sonja , Kueng Hans J. , Haiderer Daniela , Schuch Karina , Wallner Michael , Jahn-Schmid Beatrice , Bohle Barbara , Pickl Winfried F. 
Published: September 2011

Abstract
Pollinosis to birch pollen is a common type I allergy in the Northern Hemisphere. Moreover, birch pollen-allergic individuals sensitized to the major birch pollen allergen Bet v 1 frequently develop allergic reactions to stone fruits, hazelnuts, and certain vegetables due to immunological cross-reactivity. The major T cell epitope Bet v 1142–153 plays an important role in cross-reactivity between the respiratory allergen Bet v 1 and its homologous food allergens. In this study, we cloned and functionally analyzed a human αβ TCR specific for the immunodominant epitope Bet v 1142–153. cDNAs encoding TCR α- and β-chains were amplified from a Bet v 1142–153-specific T cell clone, introduced into Jurkat T cells and peripheral blood T lymphocytes of allergic and nonallergic individuals, and evaluated functionally. The resulting TCR transgenic (TCRtg) T cells responded in an allergen-specific and costimulation-dependent manner to APCs either pulsed with Bet v 1142–153 peptide or coexpressing invariant chain::Bet v 1142–153 fusion proteins. TCRtg T cells responded to Bet v 1-related food and tree pollen allergens that were processed and presented by monocyte-derived dendritic cells. Bet v 1142–153-presenting but not Bet v 14–15-presenting artificial APCs coexpressing membrane-bound IL-12 polarized allergen-specific TCRtg T cells toward a Th1 phenotype, producing high levels of IFN-γ. Coculture of such Th1-polarized T cells with allergen-specific Th2-differentiated T cells significantly suppressed Th2 effector cytokine production. These data suggest that human allergen-specific TCR can transfer the fine specificity of the original T cell clone to heterologous T cells, which in turn can be instructed to modulate the effector function of the disease initiating/perpetuating allergen-specific Th2-differentiated T cells.
Ginger Phenylpropanoids Inhibit IL-1β and Prostanoid Secretion and Disrupt Arachidonate-Phospholipid Remodeling by Targeting Phospholipases A2
Authors: Nievergelt Andreas , Marazzi Janine , Schoop Roland , Altmann Karl-Heinz , Gertsch Jürg 
Published: September 2011

Abstract
The rhizome of ginger (Zingiber officinale) is employed in Asian traditional medicine to treat mild forms of rheumatoid arthritis and fever. We have profiled ginger constituents for robust effects on proinflammatory signaling and cytokine expression in a validated assay using human whole blood. Independent of the stimulus used (LPS, PMA, anti-CD28 Ab, anti-CD3 Ab, and thapsigargin), ginger constituents potently and specifically inhibited IL-1β expression in monocytes/macrophages. Both the calcium-independent phospholipase A2 (iPLA2)-triggered maturation and the cytosolic phospholipase A2 (cPLA2)-dependent secretion of IL-1β from isolated human monocytes were inhibited. In a fluorescence-coupled PLA2 assay, most major ginger phenylpropanoids directly inhibited i/cPLA2 from U937 macrophages, but not hog pancreas secretory phospholipase A2. The effects of the ginger constituents were additive and the potency comparable to the mechanism-based inhibitor bromoenol lactone for iPLA2 and methyl arachidonyl fluorophosphonate for cPLA2, with 10-gingerol/-shogaol being most effective. Furthermore, a ginger extract (2 μg/ml) and 10-shogaol (2 μM) potently inhibited the release of PGE2 and thromboxane B2 (&gt;50%) and partially also leukotriene B4 in LPS-stimulated macrophages. Intriguingly, the total cellular arachidonic acid was increased 2- to 3-fold in U937 cells under all experimental conditions. Our data show that the concurrent inhibition of iPLA2 and prostanoid production causes an accumulation of free intracellular arachidonic acid by disrupting the phospholipid deacylation-reacylation cycle. The inhibition of i/cPLA2, the resulting attenuation of IL-1β secretion, and the simultaneous inhibition of prostanoid production by common ginger phenylpropanoids uncover a new anti-inflammatory molecular mechanism of dietary ginger that may be exploited therapeutically.
Rescue of HIV-1 Broad Neutralizing Antibody-Expressing B Cells in 2F5 VH × VL Knockin Mice Reveals Multiple Tolerance Controls
Authors: Verkoczy Laurent , Chen Yao , Bouton-Verville Hilary , Zhang Jinsong , Diaz Marilyn , Hutchinson Jennifer , Ouyang Ying-Bin , Alam S. Munir , Holl T. Matt , Hwang Kwan-Ki , Kelsoe Garnett , Haynes Barton F. 
Published: September 2011

Abstract
The HIV-1 broadly neutralizing Ab (bnAb) 2F5 has been shown to be poly-/self-reactive in vitro, and we previously demonstrated that targeted expression of its VDJ rearrangement alone was sufficient to trigger a profound B cell developmental blockade in 2F5 VH knockin (KI) mice, consistent with central deletion of 2F5 H chain-expressing B cells. In this study, we generate a strain expressing the entire 2F5 bnAb specificity, 2F5 VH × VL KI mice, and find an even higher degree of tolerance control than observed in the 2F5 VH KI strain. Although B cell development was severely impaired in 2F5 VH × VL KI animals, we demonstrate rescue of their B cells when cultured in IL-7/BAFF. Intriguingly, even under these conditions, most rescued B cell hybridomas produced mAbs that lacked HIV-1 Envelope (Env) reactivity due to editing of the 2F5 L chain, and the majority of rescued B cells retained an anergic phenotype. Thus, when clonal deletion is circumvented, κ editing and anergy are additional safeguards preventing 2F5 VH/VL expression by immature/transitional B cells. Importantly, 7% of rescued B cells retained 2F5 VH/VL expression and secreted Env-specific mAbs with HIV-1–neutralizing activity. This partial rescue was further corroborated in vivo, as reflected by the anergic phenotype of most rescued B cells in 2F5 VH × VL KI × Eμ-Bcl-2 transgenic mice and significant (yet modest) enrichment of Env-specific B cells and serum Igs. The rescued 2F5 mAb-producing B cell clones in this study are the first examples, to our knowledge, of in vivo-derived bone marrow precursors specifying HIV-1 bnAbs and provide a starting point for design of strategies aimed at rescuing such B cells.
MORPHOLOGY AND RHEOLOGY OF NONREACTIVE AND REACTIVE EPDM/PP BLENDS IN TRANSIENT SHEAR FLOW: PLASTICIZED VERSUS NONPLASTICIZED BLENDS
Authors: Shahbikian Shant , Carreau Pierre J. , Heuzey M-C. , Ellul Maria D. , Nadella Hari P. , Cheng John , Shirodkar Pradeep 
Published: September 2011

Abstract
Both nonplasticized and plasticized ethylene-propylene-diene-terpolymer/polypropylene (EPDM/PP) based thermoplastic elastomers (TPEs) were prepared in the presence and absence of a curing system (i.e., reactive vs nonreactive TPEs). The nonlinear viscoelastic behavior and morphology evolution of these blends were investigated through single and multiple start-up transient experiments to find out the effects of composition, plasticizer, and the presence of the curing system in a homogeneous shear flow field. Due to the highly elastic nature of the elastomeric component, the shear rate was set to 0.1 s−1 and in the case of multiple start-up experiments a 10 min rest time was set between consecutive shearing cycles. The specific interfacial area (Q) of the TPEs was analyzed prior and after shearing and subsequently correlated to the corresponding rheological response of these blends. The magnitude and the width of the stress overshoot were correlated to the morphology of the blends, elastomer content, the presence of plasticizer and curing system. The presence of a plasticizer (paraffinic oil) drastically decreased the viscosity and elasticity of both neat polymers and consequently the resulting TPEs; and it further reduced the initial curing rate of the elastomeric component at the early shearing stage of the reactive TPEs. Moreover, the plasticization promoted swelling and coalescence, enlarging the size of the polymeric domains, and decreasing the specific interfacial area. Furthermore, the in situ curing reaction in the reactive TPE blends resulted in less elongated polymeric domains with an irregular and larger interface compared to the nonreactive blends. A phase inverted morphology has also been observed for nonplasticized high elastomer content reactive TPEs sheared for long periods. The obtained experimental morphology data of the nonreactive blends subjected to multiple start-up experiments was fairly well predicted using a phenomenological model proposed by Lee and Park [J. Rheo. 38(5), 1994].