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Hybrid mesoporous silica nanoparticles (MSNs) modified with polymer polyethylene glycol (PEG) through the biodegradable disulfide bonds were prepared to achieve ‘on demand’ drug ...release. In this system, PEG chains were chosen as the representative gatekeepers that can block drugs within the mesopores of MSNs. After the addition of glutathione (GSH), the gatekeepers were removed from the pore outlets of MSNs, followed by the release of encapsulated drugs. In this research, the effects of grafting density of gatekeepers on the drug release and biocompatibility of silica carriers were also investigated. First, PEG modified MSNs were prepared by the condensation reaction between the carboxyl groups of MSN and the hydroxyl of PEG. The structure of the resultant MSN-SS-PEG was characterized by transmission electron microscopy (TEM), nitrogen adsorption/desorption isotherms analysis and Fourier transform infrared spectroscopy (FTIR). Rhodamine B (RhB) as the model drug was loaded into MSNs. The in vitro assay results indicated that RhB was released rapidly after the addition of 10mM GSH; M1-SS-PEG had the best capping efficiency compared with M0.5 and M1.5 groups. Moreover, hemolysis assay, serum protein adsorption and cell viability test indicated that with the increase of PEG grafting density, the biocompatibility of silica carriers increased.
The role of mentors for talented students varies according to developmental level and domain. Domains differ as to when they begin, peak, and end. Therefore, mentoring at the beginning of a talent ...trajectory may take place in middle school for a science student and in elementary school for a violinist. In the later stages of talent development, mentors are more likely to select their protégés than to be organizationally matched with mentees. As mentees gain the requisite skills and knowledge, mentors place more emphasis on modeling and coaching for psychosocial skills and insider knowledge (access to networks of information, attitudes, and behaviors rewarded by gatekeepers) that allow their mentees to stand out and, if necessary, endure pushback derived from proposing creative ideas or performances that challenge the status quo. The conclusions reported here are derived from studies of mentoring talented students, with an emphasis on identifying similarities across domains, and recognition that mentors’ provision of insider knowledge is particularly important for low‐income children and youth.
This paper offers a conceptualization of mentoring for talented children, youth, and young adults as they transition from novices to experts. The conclusions reported here are derived from studies of mentoring talented students, with an emphasis on identifying similarities across domains. The authors argue for the role of psychosocial skill training and provision of insider knowledge as increasingly important contributions made by mentors to their mentees.
Lack of identification and referral of children and adolescents with mental health problems contributes to the treatment gap in low- and middle-income countries, and especially in humanitarian ...settings. The Community Case Detection Tool (CCDT) is developed to improve community-based detection and increase help-seeking among children and adolescents in need of mental health care. The CCDT uses brief, easily understood pictorial vignettes that represent common symptoms of childhood internalizing and externalizing problems. The tool is developed for gatekeepers to support proactive detection of children in need of mental health care and to subsequently encourage help-seeking. This study evaluates the accuracy of the CCDT in detecting children and adolescents aged 6–18 years with significant mental health care needs in a conflict-affected setting: the occupied Palestinian territory.
Teachers and community workers were trained to use the CCDT. Children detected using the tool were invited for a structured clinical interview with a psychologist using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version, as well as the Strengths and Difficulties Questionnaire, to test the accuracy of CCDT-based detection.
Our sample consists of 52 children positively detected as matching with one of the vignettes. Approximately three of four detected children were indicated for psychological treatment based on the clinical interview (positive predictive value = .769), and 64.6% returned ‘borderline’ or ‘abnormal’ total difficulty scores on the Strengths and Difficulties Questionnaire.
The CCDT offers a promising low-cost solution to mitigate underdetection of mental health problems in challenging settings.
Many chaperones favour binding to hydrophobic sequences that are flanked by basic residues while disfavouring acidic residues. However, the origin of this bias in protein quality control remains ...poorly understood. Here, we show that while acidic residues are the most efficient aggregation inhibitors, they are also less compatible with globular protein structure than basic amino acids. As a result, while acidic residues allow for chaperone‐independent control of aggregation, their use is structurally limited. Conversely, we find that, while being more compatible with globular structure, basic residues are not sufficient to autonomously suppress protein aggregation. Using Hsp70, we show that chaperones with a bias towards basic residues are structurally adapted to prioritize aggregating sequences whose structural context forced the use of the less effective basic residues. The hypothesis that emerges from our analysis is that the bias of many chaperones for basic residues results from fundamental thermodynamic and kinetic constraints of globular structure. This also suggests the co‐evolution of basic residues and chaperones allowed for an expansion of structural variety in the protein universe.
Synopsis
Charged gatekeeper residues attenuate short‐stretch‐mediated protein aggregation both kinetically and thermodynamically. An investigation of the aggregation‐breaking characteristics of the charged residues offers novel insight into the molecular basis for aggregation breaking, the structural compatibility of charged residues with the native fold and their interactions with the proteostatic machinery.
Acidic residues are more potent aggregation breakers than basic ones, owing both to their shorter sidechain lengths and the specific characteristics of the charge‐carrying carboxyl moiety.
Acidic residues are less compatible with globular protein structure than positive ones, limiting their use as aggregation gatekeepers.
DnaK, the Escherichia coli Hsp70 ortholog, specifically binds basic residues and compensates for their poorer aggregation‐breaking potential. DnaK recognizes basic residues by the same characteristics that make them poor aggregation breakers, yet more structurally compatible.
These results hint towards a co‐evolution of basic residues and chaperones which allowed for increased structural variety in the protein universe, in line with the pre‐biotic reduced‐alphabet hypothesis.
Stronger aggregation propensities explain why chaperones have evolved to favour hydrophobic sequences flanked by basic residues, despite them being more compatible with globular protein structure than acidic‐residue gatekeeper sequences.
Recent literature has acknowledged the role of CEO social media presence in shaping firm strategic outcomes. We contribute to this literature by invoking the CEO's public recognition on social media ...as an essential part of the CEO social media presence and examining its impact on firm value. Based on the digital gatekeeping theory, we root on public recognition to develop two new measures of CEO celebrity status on social media: CEO social media prominence and tenor. Our empirical analysis reveals that both measures are positively associated with firm value. Moreover, we find that CEO awards from mass media positively moderate the association between CEO social media prominence and firm value. Our empirical analysis reveals that CEO social media prominence positively relates to firm value via advantages from firm sales, reputation, and risk management, while CEO social media tenor improves firm value via reputation enhancement. Collectively, our evidence suggests that CEO social media celebrity status is an important factor that top leaders and firms impound into their firm social media management strategies.
•New measures of CEO social media celebrity status stem from digital gatekeeping theory.•CEO social media celebrity status positively associated with firm value•CEO mass media award positively moderates CEO social media celebrity status and firm value.•CEO social media celebrity status benefits firm sales, reputation, and risk management.
The adoption of the Digital Services Act (DSA) and Digital Markets Act (DMA) has been a great step towards regulating digital space and industry. The two regulations set out a comprehensive and ...long-awaited set of requirements for companies providing intermediary and gatekeeping services. According to some commentators, the new laws will largely redefine the operating conditions for businesses in the digital sector. This article highlights key provisions of the DSA and DMA that may influence the evolution of the digital sector in Europe and shows that the DSA relies heavily on its predecessor, the e-Commerce Directive, and both regulations draw inspiration from other new-age EU secondary legislation, such as the General Data Protection Regulation (GDPR) and industry best practices. The main conclusions of the article are the following: the changes can be considered a significant step forward from a regulatory perspective, but ‘there is nothing new under the sun’. In other words, the regulations do not fundamentally change the liability regime of intermediary service providers, but rather take a necessary step forward to further regulate these businesses. Albeit the DSA and the DMA should be praised for their layered approach on allocating different responsibilities on different size undertakings – unlike the GDPR – as the main ‘targets’ of the regulations are primarily US-based big tech companies. It is still worrying that the DSA could also increase operational costs for European startups, potentially turning them away from the continent, which in turn could produce an innovation-cooling effect in the Union.
Studied a voice-based information sharing service (VISS) for marginalized and isolated communities of farmers in rural India.
•The VISS was based on IBM’s Spoken Web platform.•Used grounded theory to ...explore how the VISS helped to bridge the information divide among linguistic minorities.•Identified gatekeepers to seed the VISS and, along with members of existing communities of practice, they expanded the VISS.•Benefits resulting from sharing information motivated members to sustain the VISS.
Farming communities in developing countries like India are victims of the information divide. Voice-based information sharing services (VISS) can bridge this divide and help farmers address a range of challenges by exchanging knowledge with their peers. An analysis of in-depth phone interviews with farmers in remote, rural Gujarat, India, reveals four stages for developing a VISS for marginalized communities in developing countries. The four stages are: identify gatekeepers to seed the VISS, expand the VISS by building on existing communities of practice, share information, and incentivize members to sustain the VISS. The VISS in this study is based on IBM’s Spoken Web platform, which enables even illiterate and semi-literate farmers to seek, share, use, and benefit from information using feature mobile phones. Research contributions and practical implications of the study are discussed at the end.
The main objective of this research study is to offer a systematic analysis of the administrative sanctioning regime that applies to large digital platforms. These platforms, often referred to as ...super intermediaries, possess the power to disrupt the delicate balances ad intra and ad extra of markets, even within entire digital ecosystems that have emerged due to advancements in New Information and Communication Technologies. To this end, this paper explores the transformation brought about by the information society from a legal perspective and how, in response to the numerous challenges and questions arising from this new digital reality, it has led to regulations specifically designed to govern such platforms. The two key regulations in this regard are the Digital Services Act and, particularly relevant for this article, the Digital Markets Act. These regulations are instrumental in fostering competitive and equitable markets
El objetivo principal del presente estudio de investigación consiste en ofrecer un análisis sistemático del régimen administrativo sancionador que recae sobre grandes plataformas digitales, en cuanto superintermediadores con poder de alterar los necesarios equilibrios, ad intra y ad extra, de mercados e, incluso, completos ecosistemas digitales surgidos al amparo de las nuevas tecnologías de la información y de la comunicación. Para ello, se ahondará en la transformación que imprime la sociedad de la información desde una perspectiva legal y cómo, para dar respuesta a los múltiples desafíos e interrogantes que propicia esta nueva realidad digital, nace una normativa que regula específicamente este tipo de plataformas: la Digital Services Act y, sobre todo, en lo que aquí interesa, la Digital Markets Act. Estas regulaciones son un instrumento para el fomento de mercados disputables y leales.
Digital mental health (DMH) provides effective methods of overcoming issues of time constraints, accessibility, and availability of mental health care. They can provide a valuable means to deliver ...mental health care in the present pandemic. However, adoption of these methods has been slow. Mental health professional (MHP) concerns at the organizational and policy level that influence this slow adoption need to be examined.
A narrative review was conducted to identify the barriers. Searches using the databases Scopus, Embase, and PubMed were conducted to identify research focused on barriers reported by MHPs to use DMH.
The search resulted in 356 unique citations, and 21 papers met the inclusion and exclusion criteria. Forward and backward sampling resulted in identifying an additional 19 relevant papers.
Unmet needs for information, training, and infrastructure, challenges to the workflow and excessive workloads, and ambiguous policies serve as barriers to DMH use. This article recommends strategies for researchers, organizations, DMH designers, and governmental institutions to ensure efficient utilization of DMH.
Concerted efforts at individual, organizational, and governmental levels are essential to ensure efficient utilization of DMH.
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