Recent advances in sensing the inter-biomolecular interactions at the nanoscale – A comprehensive review of AFM-based force spectroscopy

Biomolecular interactions underpin most processes inside the cell. Hence, a precise and quantitative understanding of molecular association and dissociation events is crucial, not only from a fundamental perspective, but also for the rational design of biomolecular platforms for state-of-the-art biomedical and industrial applications. In this context, atomic force microscopy (AFM) appears as an invaluable experimental technique, allowing the measurement of the mechanical strength of biomolecular complexes to provide a quantitative characterization of their interaction properties from a single molecule perspective. In the present review, the most recent methodological advances in this field are presented with special focus on bioconjugation, immobilization and AFM tip functionalization, dynamic force spectroscopy measurements, molecular recognition imaging and theoretical modeling. We expect this work to significantly aid in grasping the principles of AFM-based force spectroscopy (AFM-FS) technique and provide the necessary tools to acquaint the type of data that can be achieved from this type of experiments. Furthermore, a critical assessment is done with other nanotechnology techniques to better visualize the future prospects of AFM-FS

A Receptor of the Immunoglobulin Superfamily Regulates Adaptive Thermogenesis

Exquisite regulation of energy homeostasis protects from nutrient deprivation but causes metabolic dysfunction upon nutrient excess. In human and murine adipose tissue, the accumulation of ligands of the receptor for advanced glycation end products (RAGE) accompanies obesity, implicating this receptor in energy metabolism. Here, we demonstrate that mice bearing global- or adipocyte-specific deletion of Ager, the gene encoding RAGE, display superior metabolic recovery after fasting, a cold challenge, or high-fat feeding. The RAGE-dependent mechanisms were traced to suppression of protein kinase A (PKA)-mediated phosphorylation of its key targets, hormone-sensitive lipase and p38 mitogen-activated protein kinase, upon beta-adrenergic receptor stimulation-processes that dampen the expression and activity of uncoupling protein 1 (UCP1) and thermogenic programs. This work identifies the innate role of RAGE as a key node in the immunometabolic networks that control responses to nutrient supply and cold challenges, and it unveils opportunities to harness energy expenditure in environmental and metabolic stress

Program Corporate Social Responsibility Dalam Perspektif Indeks Kepuasan Publik Di Riau

Program Corporate Social Reponsibility (CSR) merupakan salah satu kebutuhan dan di Indonesia merupakan suatu kewajiban dan ditetapkan melalui Undang-Undang Nomor 40 Tahun 2007 tentang Perseroan Terbatas. Dimana pada pasal 74 menjelaskan bahwa tanggung jawab sosial merupakan suatu kegiatan yang diwajibkan dan dilaksanakan berdasarkan pada kepatutan dan kewajaran sesuai dengan peraturan pemerintahan. Pelaksanaan tanggung jawab sosial dikenal dengan istilah CSR oleh Perusahaan merupakan suatu bentuk komitmen Perusahaan untuk membangun kualitas kehidupan yang lebih baik bersama stakeholders terkait, terutama masyarakat disekitar Perusahaan tersebut berada. Karena peran CSR ternyata saat ini semakin penting bagi masyarakat di sekitar Perusahaan dalam upaya menyeimbangkan pembangunan, baik ekonomi, sosial dan lingkungan. Penelitian ini dilaksanakan secara komprehensif mengenai implementasi dan prioritas program CSR di PT. Pertamina (Persero) RU II Dumai dan PT. Cevron Pasific Indonesia (CPI) di Tapung, Minas dan Rumbai Provinsi Riau. Metode penelitian dilakukan dengan metode campuran (mixed methods) yaitu mengkombinasikan pendekatan kuantitatif dan pendekatan kualitatif. Pengumpulan data dilakukan dengan penyebaran angket, in-dept interview dan observasi terhadap multistakeholders. Hasil penelitian yang ditemukan implementasi program CSR oleh PT. Pertamina (Persero) RU II Dumai dan PT. Cevron Pasific Indonesia (CPI) di Provinsi Riau masih berjalan dengan kurang baik. Sedangkan prioritas program CSR yang dibutuhkan berdasarkan indeks kepuasan publik di PT. Pertamina (Persero) RU II Dumai dan PT. Cevron Pasific Indonesia (CPI) di Tapung, Minas dan Rumbai Provinsi Riau adalah program yang berbasis pemberdayaan ekonomi masyarakat.Kata Kunci: pemberdayaan, program Corporate Social Reponsibility, indeks kepuasan publik. Corporate Social Reponsibility program (CSR) is seen as an urgent thing on social development. Its supported by regulation that stated in Act No. 40 year 2007 about Limited Company. In the article number 74 stated that social responsibility is one among activities that should be conducted by the companies. The companies should have committed for surround people quality of life, in terms of social and economic perspective. The sample of this research covers the implementation of the priority programmes and corporate social responsibility (CSR) PT. Pertamina (Persero) RU II Dumai and PT. Cevron Pacific Indonesia (CPI) at Tapung, Minas and Rumbai Riau Province. Data has been collected by questionnaire, in-depth interview and observation. Results of the study found implementation of programs of corporate social responsibility by PT. Pertamina (Persero) RU II Dumai and PT Cevron Pacific Indonesia (CPI) in Riau Province is still inadequate. The CSR program of the sample have been emphasized on social-economy empowerment

Optical Transport Network Design for 5G Fixed Wireless Access

The fifth generation (5G) of mobile technology, 5G is anticipated to be a significant leap in the evolution of mobile communication. 5G will be designed to attain 1000 times higher data volumes, 10 times lower latency, and 100 times more connected devices than its predecessor, 4G. Due to 5Gs ability to sustain high bandwidth per unit area, 5G is considered to be a cost-efficient solution to provide fixed wireless access (FWA) to households on a large scale. FWA is seen as an attractive alternative for fixed broadband access in scenarios where last mile access based on wired technologies is not economically viable. While approaches for enhancing user experience in a 5G FWA environment are investigated in the research community, the problem of providing cost-effective high capacity transport for FWA deployments still remains a major challenge. This is particularly challenging due to diverse transport network architectures and requirements imposed by different 5G deployment models. This paper addresses this problem by formulating a generalized joint-optimization framework to simultaneously plan wireless access and optical transport for 5G FWA networks in order to minimize the deployment cost while meeting various network requirements. We demonstrate the applicability of the proposed framework by applying it to a real scenario with a range of deployment options and where different types of optical x-haul solutions are considered. The results provide a cornerstone for deployment strategies that will be imperative for realizing a future-proof and cost-effective broadband access network

Rethinking of Optical Transport Network Design for 5G/6G Mobile Communication

Driven by the increasing use of emerging smart mobile applications, mobile technology is continuously and rapidly advancing towards the next generation communication systems such as 5G and 6G. However, the transport network, which needs to provide low latency and reliable connectivity between hundreds of thousands of cell sites and the network core, has not advanced at the same pace. This article provides insight into how we can solve the fundamental challenges of implementing cost-optimal transport and 5G and beyond mobile networks simultaneously while satisfying the network and user requirements irrespective of the radio access network\u27s architecture

Sleep Problems Associate With Multimorbidity: A Systematic Review and Meta-analysis

Objectives: To summarize the evidence on the association between sleep problems and multimorbidity.Methods: Six electronic databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, VIP, and Wan fang) were searched to identify observational studies on the association between sleep problems and multimorbidity. A random-effects model was used to estimate the pooled odds ratios (ORs) and 95% confidence intervals for multimorbidity.Results: A total of 17 observational studies of 133,575 participants were included. Sleep problems included abnormal sleep duration, insomnia, snoring, poor sleep quality, obstructive sleep apnea (OSA) and restless legs syndrome (RLS). The pooled ORs (95% CIs) for multimorbidity were 1.49 (1.24–1.80) of short sleep duration, 1.21 (1.11–1.44) of long sleep duration and 2.53 (1.85–3.46) for insomnia. The association of other sleep problems with multimorbidity was narratively summarized due to limited number of comparable studies.Conclusion: Abnormal sleep duration and insomnia are associated with higher odds of multimorbidity, while the evidence on association of snoring, poor sleep quality, obstructive sleep apnea and restless legs syndrome with multimorbidity remains inconclusive. Interventions targeting sleep problems should be delivered for better management of multimorbidity

The effect of ultraviolet C radiation against different N95 respirators inoculated with SARS-CoV-2

OBJECTIVES: There are currently no studies that have examined whether one dosage can be uniformly applied to different respirator types to effectively decontaminate SARS-CoV-2 on N95 filtering facepiece respirators (FFRs). Health care workers have been using this disinfection method during the pandemic. Our objective was to determine the effect of UVC on SARS-CoV-2 inoculated N95 respirators and whether this was respirator material/model type dependent. METHODS: Four different locations (facepiece and strap) on five different N95 FFR models (3M 1860, 8210, 8511, 9211; Moldex 1511) were inoculated with a 10 μL drop of SARS-CoV-2 viral stock (8 × 10 RESULTS: UVC delivered using a dose of 1.5 J/cm(2), to each side, was an effective method of decontamination for the facepieces of 3 M 1860 and Moldex 1511, and for the straps of 3 M 8210 and the Moldex 1511. CONCLUSION: This dose is an appropriate decontamination method to facilitate the reuse of respirators for healthcare personnel when applied to specific models/materials. Also, some straps may require additional disinfection to maximize the safety of frontline workers. Implementation of widespread UVC decontamination methods requires careful consideration of model, material type, design, and fit-testing following irradiation

Molecular Determinants of the Intrinsic Efficacy of the Antipsychotic Aripiprazole

Partial agonists of the dopamine D2 receptor (D2R) have been developed to treat the symptoms of schizophrenia without causing the side effects elicited by antagonists. The receptor-ligand interactions that determine the intrinsic efficacy of such drugs, however, are poorly understood. Aripiprazole has an extended structure comprising a phenylpiperazine primary pharmacophore and a 1,2,3,4-tetrahydroquinolin-2-one secondary pharmacophore. We combined site-directed mutagenesis, analytical pharmacology, ligand fragments and molecular dynamics simulations to identify the D2R-aripiprazole interactions that contribute to affinity and efficacy. We reveal that an interaction between the secondary pharmacophore of aripiprazole and a secondary binding pocket defined by residues at the extracellular portions of transmembrane segments 1, 2 and 7 determine the intrinsic efficacy of aripiprazole. Our findings reveal a hitherto unappreciated mechanism through which to fine-tune the intrinsic efficacy of D2R agonists