699 research outputs found

    Norfloxacin sesquihydrate

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    In the crystal structure of the title compound [systematic name: 1-ethyl-6-fluoro-4-oxo-7-(piperazin-4-ium-1-yl)-1,4-dihydro­quinoline-3-carboxyl­ate sesquihydrate], C16H18FN3O3·1.42H2O, N—H⋯O and O—H⋯O hydrogen bonds assemble the mol­ecules in a two-dimensional layered corrugated sheet structure parallel to the b axis. The water mol­ecules are disordered [occupancies 0.741 (11) and 0.259 (11)]

    Mechanical Ventilation and Clinical Outcomes in Patients with Acute Myocardial Infarction: A Retrospective Observational Study

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    Patients with acute myocardial infarction (AMI) and respiratory impairment may be treated with either invasive or non-invasive mechanical ventilation (MV). However, there has been little testing of non-invasive MV in the setting of AMI. Our objective was to evaluate the incidence and associated clinical outcomes of patients with AMI who were treated with non-invasive or invasive MV

    Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors

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    Funding Information: This research was funded by the Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) grant PTDC/BBB-BMD/4497/2014 (to A.B.), through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), and the Associate Laboratory LS4FUTURE (LA/P/0087/2020). Publisher Copyright: © 2023 by the authors.The Notch signaling ligand JAG1 is overexpressed in various aggressive tumors and is associated with poor clinical prognosis. Hence, therapies targeting oncogenic JAG1 hold great potential for the treatment of certain tumors. Here, we report the identification of specific anti-JAG1 single-chain variable fragments (scFvs), one of them endowing chimeric antigen receptor (CAR) T cells with cytotoxicity against JAG1-positive cells. Anti-JAG1 scFvs were identified from human phage display libraries, reformatted into full-length monoclonal antibodies (Abs), and produced in mammalian cells. The characterization of these Abs identified two specific anti-JAG1 Abs (J1.B5 and J1.F1) with nanomolar affinities. Cloning the respective scFv sequences in our second- and third-generation CAR backbones resulted in six anti-JAG1 CAR constructs, which were screened for JAG1-mediated T-cell activation in Jurkat T cells in coculture assays with JAG1-positive cell lines. Studies in primary T cells demonstrated that one CAR harboring the J1.B5 scFv significantly induced effective T-cell activation in the presence of JAG1-positive, but not in JAG1-knockout, cancer cells, and enabled specific killing of JAG1-positive cells. Thus, this new anti-JAG1 scFv represents a promising candidate for the development of cell therapies against JAG1-positive tumors.publishersversionpublishe

    A Smart Wireless Car Ignition System for Vehicle Security

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    Copyright: © 2017 Haider A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The paper proposes a novel car ignition system to replace the traditional wired technology and enhance vehicle security. This new system uses wireless transmissions to start the engine and hence eliminates the ignition wire behind the dashboard. It also allows the user to set a password of his/her choice to keep the system protected. A theft alarm that goes ‘’ON’’ when an unusual activity is sensed and/or when the wrong password is attempted to unlock the system is integrated in the system. Moreover, important factors such as economic feasibility, adaptability to the new vehicle technologies and customers’ preferences have been taken into consideration in the design of the proposed vehicle security system.Peer reviewedFinal Published versio

    Hypervigilance for fear after basolateral amygdala damage in humans

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    Recent rodent research has shown that the basolateral amygdala (BLA) inhibits unconditioned, or innate, fear. It is, however, unknown whether the BLA acts in similar ways in humans. In a group of five subjects with a rare genetic syndrome, that is, Urbach–Wiethe disease (UWD), we used a combination of structural and functional neuroimaging, and established focal, bilateral BLA damage, while other amygdala sub-regions are functionally intact. We tested the translational hypothesis that these BLA-damaged UWD-subjects are hypervigilant to facial expressions of fear, which are prototypical innate threat cues in humans. Our data indeed repeatedly confirm fear hypervigilance in these UWD subjects. They show hypervigilant responses to unconsciously presented fearful faces in a modified Stroop task. They attend longer to the eyes of dynamically displayed fearful faces in an eye-tracked emotion recognition task, and in that task recognize facial fear significantly better than control subjects. These findings provide the first direct evidence in humans in support of an inhibitory function of the BLA on the brain's threat vigilance system, which has important implications for the understanding of the amygdala's role in the disorders of fear and anxiety

    Using Stars, Not Just ‘Reading’ Them:The roles and functions of film stars in mother-daughter relations

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    This article explores the various and important ways in which film stars can function within mother-daughter relations over the life-cycle of their relationship. Drawing on detailed qualitative material from an interdisciplinary audience study of mothers’ and daughters’ shared relations to film stars, it demonstrates how a significant shift can be identified with regard to the kinds of roles that stars play in dyadic relations as a daughter experiences various developmental and transitional phases to adulthood. Necessitating an alternative approach to those previously employed within Star and Celebrity Studies, the article takes a significant new perspective on the study of audiences for stars from the work of art anthropologist Alfred Gell (1998) and proposes a move away from semiotic, ‘textualist’ readings of stars towards an ‘action’-centred exploration of the ways in which films stars are used and function in social interactions over the life-cycle of personal relationships

    Molecular Evolution of HIV-1 CRF01_AE Env in Thai Patients

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    BACKGROUND: The envelope glycoproteins (Env), gp120 and gp41, are the most variable proteins of human immunodeficiency virus type 1 (HIV-1), and are the major targets of humoral immune responses against HIV-1. A circulating recombinant form of HIV-1, CRF01_AE, is prevalent throughout Southeast Asia; however, only limited information regarding the immunological characteristics of CRF01_AE Env is currently available. In this study, we attempted to examine the evolutionary pattern of CRF01_AE Env under the selection pressure of host immune responses. METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood samples were collected periodically over 3 years from 15 HIV-1-infected individuals residing in northern Thailand, and amplified env genes from the samples were subjected to computational analysis. The V5 region of gp120 showed highest variability in several samples over 3 years, whereas the V1/V2 and/or V4 regions of gp120 also showed high variability in many samples. In addition, the N-terminal part of the C3 region of gp120 showed highest amino acid diversity among the conserved regions of gp120. Chronological changes in the numbers of amino acid residues in gp120 variable regions and potential N-linked glycosylation (PNLG) sites are involved in increasing the variability of Env gp120. Furthermore, the C3 region contained several amino acid residues potentially under positive selection, and APOBEC3 family protein-mediated G to A mutations were frequently detected in such residues. CONCLUSIONS/SIGNIFICANCE: Several factors, including amino acid substitutions particularly in gp120 C3 and V5 regions as well as changes in the number of PNLG sites and in the length of gp120 variable regions, were revealed to be involved in the molecular evolution of CRF01_AE Env. In addition, a similar tendency was observed between CRF01_AE and subtype C Env with regard to the amino acid variation of gp120 V3 and C3 regions. These results may provide important information for understanding the immunological characteristics of CRF01_AE Env

    Competing Neural Responses for Auditory and Visual Decisions

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    Why is it hard to divide attention between dissimilar activities, such as reading and listening to a conversation? We used functional magnetic resonance imaging (fMRI) to study interference between simple auditory and visual decisions, independently of motor competition. Overlapping activity for auditory and visual tasks performed in isolation was found in lateral prefrontal regions, middle temporal cortex and parietal cortex. When the visual stimulus occurred during the processing of the tone, its activation in prefrontal and middle temporal cortex was suppressed. Additionally, reduced activity was seen in modality-specific visual cortex. These results paralleled impaired awareness of the visual event. Even without competing motor responses, a simple auditory decision interferes with visual processing on different neural levels, including prefrontal cortex, middle temporal cortex and visual regions
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