1,281 research outputs found

    The Elusive Boundaries of Social Work

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    Repeated attempts to conceptualize social work have assumed that social work should and can have a precisely defined domain. One suggestion is to equate social work with personal social services. This article suggests that the uniqueness of social work lies in the very absence of defined boundaries. Implications for social work practice are identified, in particular social work\u27s heavy dependence on resource controllers, and the consequent need of social work education to shift its traditional focus from client-centered interventions to managing non-client interactions

    Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model.

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    Parkinson's disease (PD) is characterized by the presence of α-synuclein aggregates known as Lewy bodies and Lewy neurites, whose formation is linked to disease development. The causal relation between α-synuclein aggregates and PD is not well understood. We generated a new transgenic mouse line (MI2) expressing human, aggregation-prone truncated 1-120 α-synuclein under the control of the tyrosine hydroxylase promoter. MI2 mice exhibit progressive aggregation of α-synuclein in dopaminergic neurons of the substantia nigra pars compacta and their striatal terminals. This is associated with a progressive reduction of striatal dopamine release, reduced striatal innervation and significant nigral dopaminergic nerve cell death starting from 6 and 12 months of age, respectively. In the MI2 mice, alterations in gait impairment can be detected by the DigiGait test from 9 months of age, while gross motor deficit was detected by rotarod test at 20 months of age when 50% of dopaminergic neurons in the substantia nigra pars compacta are lost. These changes were associated with an increase in the number and density of 20-500 nm α-synuclein species as shown by dSTORM. Treatment with the oligomer modulator anle138b, from 9 to 12 months of age, restored striatal dopamine release, prevented dopaminergic cell death and gait impairment. These effects were associated with a reduction of the inner density of large α-synuclein aggregates and an increase in dispersed small α-synuclein species as revealed by dSTORM. The MI2 mouse model recapitulates the progressive dopaminergic deficit observed in PD, showing that early synaptic dysfunction is associated to fine behavioral motor alterations, precedes dopaminergic axonal loss and neuronal death that become associated with a more consistent motor deficit upon reaching a certain threshold. Our data also provide new mechanistic insight for the effect of anle138b's function in vivo supporting that targeting α-synuclein aggregation is a promising therapeutic approach for PD

    The biomechanics of the locust ovipositor valves : a unique digging apparatus

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    The female locust has a unique mechanism for digging in order to deposit its eggs deep in the ground. It utilizes two pairs of sclerotized valves to displace the granular matter, while extending its abdomen as it propagates underground. This ensures optimal conditions for the eggs to incubate, and provides them with protection from predators. Here, two major axes of operation of the digging valves are identified, one in parallel to the propagation direction of the ovipositor, and one perpendicular to it. The direction-dependent biomechanics of the locust major, dorsal digging valves are quantified and analyzed, under forces in the physiological range and beyond, considering hydration level, as well as the females’ age, or sexual maturation state. Our findings reveal that the responses of the valves to compression forces in the specific directions change upon sexual maturation to follow their function, and depend on environmental conditions. Namely, in the physiological force range, the valves are resistant to mechanical failure. In addition, mature females, which lay eggs, have stiffer valves, up to roughly nineteen times the stiffness of the pre-mature locusts. The valves are stiffer in the major working direction, corresponding to soil shuffling and compression, compared to the direction of propagation. Hydration of the valves reduces their stiffness but increases their resilience against failure. These findings provide mechanical and materials guidelines for the design of novel non-drilling excavating tools, including 3D-printed anisotropic materials based on composites.Statement of significance The female locust lay its eggs underground in order to protect them from predators and to provide them with optimal conditions for hatching. In order to dig into the ground, it uses two pairs of valves: The ventral pair is plugged as a wedge, while the dorsal pair performs the digging of the oviposition tunnel. We study the mechanical response of the digging valves, depending on age, hydration level and direction of operation. Our findings show that during the course of roughly two weeks in the life of the adult female, the digging valves become up to nineteen-fold stiffer against failure, in order to fulfill their function as diggers. While hydration reduces the stiffness, it also increases the resilience against failure and renders the valves unbreakable within the estimated physiological force range and beyond. The digging valves are consistently stiffer in the digging direction than in the perpendicular direction, implying on their form-follows-function design.Competing Interest StatementThe authors have declared no competing interest

    In-vivo monitoring for electrical expression of plant living parameters by an impedance lab system

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    We present a complete in-lab system to monitor the plant and its surrounding environment. The plant impedance is directly measured in a continuous manner, while, simultaneously surrounding environment parameters known to affect plant status, are monitored. This is done combining a new in-vivo direct measurement of the plant together with an embedded system using available sensor technology and a designated interface for continuous data acquisition. Furthermore, the next versions this system can be deployed as a field monitoring device, with simple adaptations

    Analysis of in Vivo Plant Stem Impedance Variations in Relation with External Conditions Daily Cycle

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    World population growth and desertification are the most severe issue to agricultural food production. Smart agriculture is a promising solution to ensure food security. The use of sensors to monitor crop production can help farmers improve the yield and reduce water consumption. Here we propose a study where the electrical impedance of green plants' stem is analyzed in vivo, along with environmental conditions. In particular, the variations associated with the daily cycle are highlighted. These analyses lead to the possibility of understanding plant status directly from stem impedance

    Achilles tendon moment arm length is smaller in children with cerebral palsy than in typically developing children

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    When studying muscle and whole-body function in children with cerebral palsy (CP), knowledge about both internal and external moment arms is essential since they determine the mechanical advantage of a muscle over an external force. Here we asked if Achilles tendon moment arm (MAAT) length is different in children with CP and age-matched typically developing (TD) children, and if MAAT can be predicted from anthropometric measurements. Sixteen children with CP (age: 10y 7 m ± 3y, 7 hemiplegia, 12 diplegia, GMFCS level: I (11) and II (8)) and twenty TD children (age: 10y 6 m ± 3y) participated in this case-control study. MAAT was calculated at 20° plantarflexion by differentiating calcaneus displacement with respect to ankle angle. Seven anthropometric variables were measured and related to MAAT. We found normalized MAAT to be 15% (∼7 mm) smaller in children with CP compared to TD children (p = 0.003). MAAT could be predicted by all anthropometric measurements with tibia length explaining 79% and 72% of variance in children with CP and TD children, respectively. Our findings have important implications for clinical decision making since MAAT influences the mechanical advantage about the ankle, which contributes to movement function and is manipulated surgically

    A Theory of Organization-EHR Affordance Actualization

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    While organizations implement information technology (IT) to effect change, current theories of IT-associated organizational change pay insufficient attention to the change goals, the role of IT in organizational change, and the multilevel nature of change processes. We take a fresh look at IT-associated organizational change using grounded theory methods. Our longitudinal study of an electronic health record (EHR) system implementation in a multi-site medical group found user behaviors that did not fit well with existing theories. Instead, we found that they fit better with the concept of affordances from ecological psychology. In developing our affordance-based theory of IT-associated organizational change from our field data, we discovered three gaps in the affordance literature; namely, the lack of theory for (1) the process of actualizing an affordance’s potential, (2) affordances in an organizational context, and (3) bundles of interrelated affordances. This paper extends the theory of affordances to handle these three gaps and, in doing so, develops a mid-range theory for EHR-associated organizational change in a healthcare organization. While the resulting theory is specific to EHR implementations, it offers a template for other mid-range affordance-actualization theories and a more general affordance-actualization lens. Our affordance-actualization lens considers the materiality of the IT artifact, the non-deterministic process by which IT leads to organizational effects, the multilevel nature of IT-associated change processes, and the intentionality of managers and users as agents of change, and thus addresses important criteria for theories of IT effects in organizations. The paper also provides practical guidance for implementing EHR systems and other organizational systems

    Continuous wave amplified spontaneous emission in phase-stable lead halide perovskites

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    Sustained stimulated emission under continuous-wave (CW) excitation is a prerequisite for new semiconductor materials being developed for laser gain media. Although hybrid organic-inorganic lead-halide perovskites have attracted much attention as optical gain media, the demonstration of room-temperature CW lasing has still not been realized. Here, we present a critical step towards this goal by demonstrating CW amplified spontaneous emission (ASE) in a phase-stable perovskite at temperatures up to 120 K. The phase-stable perovskite maintains its room-temperature phase while undergoing cryogenic cooling and can potentially support CW lasing also at higher temperatures. We find the threshold level for CW ASE to be 387 W cm-2 at 80 K. These results indicate that easily-fabricated single-phase perovskite thin films can sustain CW stimulated emission, potential at higher temperatures as well, by further optimization of the material quality in order to extend the carrier lifetimes

    Nanoparticles presenting clusters of CD4 expose a universal vulnerability of HIV-1 by mimicking target cells

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    CD4-based decoy approaches against HIV-1 are attractive options for long-term viral control, but initial designs, including soluble CD4 (sCD4) and CD4-Ig, were ineffective. To evaluate a therapeutic that more accurately mimics HIV-1 target cells compared with monomeric sCD4 and dimeric CD4-Ig, we generated virus-like nanoparticles that present clusters of membrane-associated CD4 (CD4-VLPs) to permit high-avidity binding of trimeric HIV-1 envelope spikes. In neutralization assays, CD4-VLPs were >12,000-fold more potent than sCD4 and CD4-Ig and >100-fold more potent than the broadly neutralizing antibody (bNAb) 3BNC117, with >12,000-fold improvements against strains poorly neutralized by 3BNC117. CD4-VLPs also neutralized patient-derived viral isolates that were resistant to 3BNC117 and other bNAbs. Intraperitoneal injections of CD4-CCR5-VLP produced only subneutralizing plasma concentrations in HIV-1–infected humanized mice but elicited CD4-binding site mutations that reduced viral fitness. All mutant viruses showed reduced sensitivity to sCD4 and CD4-Ig but remained sensitive to neutralization by CD4-VLPs in vitro. In vitro evolution studies demonstrated that CD4-VLPs effectively controlled HIV-1 replication at neutralizing concentrations, and viral escape was not observed. Moreover, CD4-VLPs potently neutralized viral swarms that were completely resistant to CD4-Ig, suggesting that escape pathways that confer resistance against conventional CD4-based inhibitors are ineffective against CD4-VLPs. These findings suggest that therapeutics that mimic HIV-1 target cells could prevent viral escape by exposing a universal vulnerability of HIV-1: the requirement to bind CD4 on a target cell. We propose that therapeutic and delivery strategies that ensure durable bioavailability need to be developed to translate this concept into a clinically feasible functional cure therapy
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