598 research outputs found

    Spoort de OV-studentenkaart met de wensen in de markt?

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    Hoeveel en welke studenten zijn voorstander respectievelijk tegenstander van de OV-studentenkaart en waarom? Dit waren enkele van de vragen die, voorafgaand aan de invoering van de verplichte OV-kaart (januari 1991), zijn onderzocht in voorjaar 1989 bij een steekproef van 931 studerenden aan het MBO, HBO en WO. Als theoretisch kader bij de analyse van deze vragen is gebruik gemaakt van het onderscheid dat Abell maakt in klantengroepen, klantenfuncties en alternatieve techno1ogieĆ«n en van het Fishbein en Ajzen attitudemodel. Het bleek destijds dat de helft van de studerenden de kaart een onaantrekkelijk nieuw produkt vond. Deze tegenstanders haddeneen reis- en vervoersgedrag waardoor zij zeer weinig openbaar vervoerskosten maakten. Dit kwam ofwel omdat men weinig reisde (men woont dicht bij ouders en studieplek), ofwel omdat men wel veel reisde maar dit met eigen vervoer deed (autobezitters en meerijders, motor- of bromfiets). Beide groepen zouden er door de invoering van de kaart, bij ongewijzigd reis- en vervoersgedrag, financieel op achteruit gaan vanwege de korting op de basisbeurs. Compensatie van de financiĆ«1e achteruitgang door bet substitueren van eigen vervoer door openbaarvervoer werd problematisch geacht omdat men de bereikbaarheid van de reisdoelen met openbaar vervoer als slecht beoordeelde. Vergeleken met de tegenstanders reisden de voorstanders reeds veel met openbaar vervoer zodat zij financieel (vrijwel) quitte zouden spelen of er op vooruit zouden gaan. Uit de intenties tot verandering in reisgedrag bleek dat er vooral een toename van het reisgedrag met het openbaar vervoer te verwachten was in de daluren (bezoeken aan familie, vrienden, recreatiedoelene.d.) en niet in de spits. Als belangrijkste conclusie van de resultaten kan genoemd worden dat wanneer een niet-verplichte OV-kaart geĆÆntroduceerd zou zijn tegen een hogere prijs dan de huidige korting op de basisbeurs, dit beter zou hebben gespoord met de wensen in de markt dan de huidige verplichte OV-kaart

    A systematic survey on embodied cognition:11 years of research in childā€“computer interaction

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    Embodied cognition is a concept that has been extensively explored by scholars within the Childā€“Computer Interaction community. However, there is a lack of a synthesis of this research to clarify the field's benefits and drawbacks. This paper presents a survey of articles published between 2010 and 2020 in the Interaction Design and Children (IDC) conference and the International Journal of Childā€“Computer Interaction (IJCCI). We retrieved 158 papers using the keyword ā€embodied cognitionā€ and its derivatives. Further screening narrowed these down to 43. The purpose of this review is to provide an overview of the current landscape of ā€˜embodiedā€™ research by reporting the most common subject areas of application, forms, and modes of embodiment, and the role of children and adults. Our contribution is twofold: we highlight the main trends around these themes within the field, and we provide eight critical areas of future research. By illustrating new challenges and opportunities, we aim to support the growth of this area of research within the CCI community

    Ulocuplumab (BMS-936564 / MDX1338): a fully human anti-CXCR4 antibody induces cell death in chronic lymphocytic leukemia mediated through a reactive oxygen species-dependent pathway.

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    The CXCR4 receptor (Chemokine C-X-C motif receptor 4) is highly expressed in different hematological malignancies including chronic lymphocytic leukemia (CLL). The CXCR4 ligand (CXCL12) stimulates CXCR4 promoting cell survival and proliferation, and may contribute to the tropism of leukemia cells towards lymphoid tissues. Therefore, strategies targeting CXCR4 may constitute an effective therapeutic approach for CLL. To address that question, we studied the effect of Ulocuplumab (BMS-936564), a fully human IgG4 anti-CXCR4 antibody, using a stroma--CLL cells co-culture model. We found that Ulocuplumab (BMS-936564) inhibited CXCL12 mediated CXCR4 activation-migration of CLL cells at nanomolar concentrations. This effect was comparable to AMD3100 (Plerixafor--Mozobil), a small molecule CXCR4 inhibitor. However, Ulocuplumab (BMS-936564) but not AMD3100 induced apoptosis in CLL at nanomolar concentrations in the presence or absence of stromal cell support. This pro-apoptotic effect was independent of CLL high-risk prognostic markers, was associated with production of reactive oxygen species and did not require caspase activation. Overall, these findings are evidence that Ulocuplumab (BMS-936564) has biological activity in CLL, highlight the relevance of the CXCR4-CXCL12 pathway as a therapeutic target in CLL, and provide biological rationale for ongoing clinical trials in CLL and other hematological malignancies

    Carotid artery stenosis in patients with peripheral arterial disease: The SMART study

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    AbstractPurpose: The prevalence of asymptomatic internal carotid artery stenosis (ICAS) in patients with peripheral arterial disease (PAD) and characteristics that are associated with ICAS were studied. Methods: We used data from the first 600 patients enrolled in the Second Manifestations of ARTerial disease (SMART) study, a single-center, prospective cohort study among patients referred with a manifestation of cardiovascular disease, diabetes mellitus, hypertension, or hyperlipidemia. Included in the analysis were 162 patients with PAD or a history of PAD, who were not known to have ICAS at the time of referral and who had no history of cerebrovascular symptoms or previous carotid endarterectomy. ICAS was detected with duplex scanning and defined as a peak systolic velocity more than 150 cm/s (diameter reduction 50% or higher) on at least one side. Cardiovascular risk factors were measured. Logistic regression analysis was performed to investigate associations between these characteristics and ICAS. Results: The prevalence of previously unknown ICAS was 14%. A patient age of 67 years or older, body weight of 68 kg or less, and diastolic blood pressure of 75 mm Hg or lower were independently associated with ICAS. The Prevalence Of Icas In Patients With One Of These Characteristics (38% Of The Patients) Was 8%, In Those With Two Characteristics (21% Of The Patients) Was 32%, And In Those With Three Characteristics (6% Of The Patients) Was 50%. Conclusions: The prevalence of ICAS increases as much as 50% in patients who have PAD and the risk indicators of an age of 67 years or older, a body weight of 68 kg or less, and a diastolic blood pressure of 75 mm Hg or lower, and, therefore, these characteristics may be used as a means of increasing the likelihood of detecting ICAS. (J Vasc Surg 1999;30:519-25.

    Merida virus, a putative novel rhabdovirus discovered in Culex and Ochlerotatus spp. mosquitoes in the Yucatan Peninsula of Mexico.

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    Sequences corresponding to a putative, novel rhabdovirus [designated Merida virus (MERDV)] were initially detected in a pool of Culex quinquefasciatus collected in the Yucatan Peninsula of Mexico. The entire genome was sequenced, revealing 11ā€‰798ā€Šnt and five major ORFs, which encode the nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and RNA-dependent RNA polymerase (L). The deduced amino acid sequences of the N, G and L proteins have no more than 24, 38 and 43ā€‰% identity, respectively, to the corresponding sequences of all other known rhabdoviruses, whereas those of the P and M proteins have no significant identity with any sequences in GenBank and their identity is only suggested based on their genome position. Using specific reverse transcription-PCR assays established from the genome sequence, 27ā€‰571 C. quinquefasciatus which had been sorted in 728 pools were screened to assess the prevalence of MERDV in nature and 25 pools were found positive. The minimal infection rate (calculated as the number of positive mosquito pools per 1000 mosquitoes tested) was 0.9, and similar for both females and males. Screening another 140 pools of 5484 mosquitoes belonging to four other genera identified positive pools of Ochlerotatus spp. mosquitoes, indicating that the host range is not restricted to C. quinquefasciatus. Attempts to isolate MERDV in C6/36 and Vero cells were unsuccessful. In summary, we provide evidence that a previously undescribed rhabdovirus occurs in mosquitoes in Mexico.The authors thank Valeria Bussetti for expert technical assistance. This study was supported by the National Institutes of Health (awards 5R21AI067281, AI057158, 5R21AI067281 and AI088647), the United States Department of Defense and an intramural grant from Iowa State University. AEF is supported by a grant from the Wellcome Trust (award 106207).This is the final version of the article. It first appeared from the Microbiology Society via http://dx.doi.org/10.1099/jgv.0.00042

    Implicit measurement of emotional experience and its dynamics

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    Although many studies revealed that emotions and their dynamics have a profound impact on cognition and behavior, it has proven difficult to unobtrusively measure emotions. In the current study, our objective was to distinguish different experiences elicited by audiovisual stimuli designed to evoke particularly happy, sad, fear and disgust emotions, using electroencephalography

    Targeting the CXCR4 pathway using a novel anti-CXCR4 IgG1 antibody (PF-06747143) in chronic lymphocytic leukemia.

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    BackgroundThe CXCR4-CXCL12 axis plays an important role in the chronic lymphocytic leukemia (CLL)-microenvironment interaction. Overexpression of CXCR4 has been reported in different hematological malignancies including CLL. Binding of the pro-survival chemokine CXCL12 with its cognate receptor CXCR4 induces cell migration. CXCL12/CXCR4 signaling axis promotes cell survival and proliferation and may contribute to the tropism of leukemia cells towards lymphoid tissues and bone marrow. Therefore, we hypothesized that targeting CXCR4 with an IgG1 antibody, PF-06747143, may constitute an effective therapeutic approach for CLL.MethodsPatient-derived primary CLL-B cells were assessed for cytotoxicity in an in vitro model of CLL microenvironment. PF-06747143 was analyzed for cell death induction and for its potential to interfere with the chemokine CXCL12-induced mechanisms, including migration and F-actin polymerization. PF-06747143 in vivo efficacy was determined in a CLL murine xenograft tumor model.ResultsPF-06747143, a novel-humanized IgG1 CXCR4 antagonist antibody, induced cell death of patient-derived primary CLL-B cells, in presence or absence of stromal cells. Moreover, cell death induction by the antibody was independent of CLL high-risk prognostic markers. The cell death mechanism was dependent on CXCR4 expression, required antibody bivalency, involved reactive oxygen species production, and did not require caspase activation, all characteristics reminiscent of programmed cell death (PCD). PF-06747143 also induced potent B-CLL cytotoxicity via Fc-driven antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity activity (CDC). PF-06747143 had significant combinatorial effect with standard of care (SOC) agents in B-CLL treatment, including rituximab, fludarabine (F-ara-A), ibrutinib, and bendamustine. In a CLL xenograft model, PF-06747143 decreased tumor burden and improved survival as a monotherapy, and in combination with bendamustine.ConclusionsWe show evidence that PF-06747143 has biological activity in CLL primary cells, supporting a rationale for evaluation of PF-06747143 for the treatment of CLL patients
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