Quantitation of mitochondrial dynamics by photolabeling of individual organelles shows that mitochondrial fusion is blocked during the Bax activation phase of apoptosis

A dynamic balance of organelle fusion and fission regulates mitochondrial morphology. During apoptosis this balance is altered, leading to an extensive fragmentation of the mitochondria. Here, we describe a novel assay of mitochondrial dynamics based on confocal imaging of cells expressing a mitochondrial matrix–targeted photoactivable green fluorescent protein that enables detection and quantification of organelle fusion in living cells. Using this assay, we visualize and quantitate mitochondrial fusion rates in healthy and apoptotic cells. During apoptosis, mitochondrial fusion is blocked independently of caspase activation. The block in mitochondrial fusion occurs within the same time range as Bax coalescence on the mitochondria and outer mitochondrial membrane permeabilization, and it may be a consequence of Bax/Bak activation during apoptosis

Potential Risks Inherent in Robotic Process Automation

Robotic process automation (RPA) uses automation technologies to perform tasks typically performed by humans. Although such technology has been instrumental in expediting business operations and lowering costs, it has also created several risks that warrant scrutiny. When discussing the drawbacks of automation, many will point to the number of jobs lost to the influx of automation. However, there are technology risks that organizations must consider such as fraud and cybersecurity. Fraudsters may utilize RPA to commit more novel and subtle technological and cyber security fraud. Organizations may implement internal control measures to prevent or mitigate such schemes, segregation of duties, and change management. RPA has many benefits, but the effective use of such technology will ultimately come down to how businesses adapt to risks in such an ever-changing business environment

A Multidisciplinary Primary Care Team Consultation In a Socio-economically Deprived Community: An Exploratory Randomised Controlled Trial

Background: Psychosocial problems in socioeconomically deprived communities are not always amenable to traditional medical approaches. Mothers living in these areas are a particularly vulnerable group. The objective of this study was to evaluate the effectiveness of a lengthened multi-disciplinary team consultation in primary care in reducing anxiety and depression in mothers.Methods: This was a prospective randomised controlled trial of a multidisciplinary team consultation against normal care. 94 mothers were recruited from three general practices from an area of extreme socio-economic deprivation. Mothers randomised into the intervention group attended a multidisciplinary consultation with up to four case-specific health care professionals. Consultations addressed medical, psychological and social problems and lasted up to one hour. Conventional primary care continued to be available to the intervention families. Control group families received normal primary care services. The outcomes measured were anxiety and depression as using the Hospital Anxiety and Depression Scale (HADS), health status using SF36v2, and quality of life using the abbreviated Schedule for the Evaluation of Individual Quality of Life (SEIQoL-DW) at baseline, 6 months and 12 months.Results: Ordered logistic regression was used to analyse the data. There was no significant difference found between intervention and control groups after 6 months and 12 months in all of the measured outcomes.Conclusions: The new lengthened multi-disciplinary team consultation did not have any impact on the mental health, general health, and quality of life of mothers after 6 and 12 months. Other methods of primary health care delivery in socio-economically deprived communities need to be evaluated

Reduced glycogen availability is associated with increased AMPKα2 activity, nuclear AMPKα2 protein abundance, and GLUT4 mRNA expression in contracting human skeletal muscle

Glycogen availability can influence glucose transporter 4 (GLUT4) expression in skeletal muscle through unknown mechanisms. The multisubstrate enzyme AMP-activated protein kinase (AMPK) has also been shown to play an important role in the regulation of GLUT4 expression in skeletal muscle. During contraction, AMPK [alpha]2 translocates to the nucleus and the activity of this AMPK isoform is enhanced when skeletal muscle glycogen is low. In this study, we investigated if decreased pre-exercise muscle glycogen levels and increased AMPK [alpha]2 activity reduced the association of AMPK with glycogen and increased AMPK [alpha]2 translocation to the nucleus and GLUT4 mRNA expression following exercise. Seven males performed 60 min of exercise at ~70% [VO.sub.2] peak on 2 occasions: either with normal (control) or low (LG) carbohydrate pre-exercise muscle glycogen content. Muscle samples were obtained by needle biopsy before and after exercise. Low muscle glycogen was associated with elevated AMPK [alpha]2 activity and acetyl-CoA carboxylase [beta] phosphorylation, increased translocation of AMPK [alpha]2 to the nucleus, and increased GLUT4 mRNA. Transfection of primary human myotubes with a constitutively active AMPK adenovirus also stimulated GLUT4 mRNA, providing direct evidence of a role of AMPK in regulating GLUT4 expression. We suggest that increased activation of AMPK [alpha]2 under conditions of low muscle glycogen enhances AMPK [alpha]2 nuclear translocation and increases GLUT4 mRNA expression in response to exercise in human skeletal muscle. <br /

Preliminary Results from an Experimental Assessment of a Natural Laminar Flow Design Method

A 5.2% scale semispan model of the new Common Research Model with Natural Laminar Flow (CRM-NLF) was tested in the National Transonic Facility (NTF) at the NASA Langley Research Center. The model was tested at transonic cruise flight conditions with Reynolds numbers based on mean aerodynamic chord ranging from 10 to 30 million. The goal of the test was to experimentally validate a new design method, referred to as Crossflow Attenuated NLF (CATNLF), which shapes airfoils to have pressure distributions that delay transition on wings with high sweep and Reynolds numbers. Additionally, the test aimed to characterize the NTF laminar flow testing capabilities, as well as establish best practices for laminar flow wind tunnel testing. Preliminary results regarding the first goal of validating the new design method are presented in this paper. Experimental data analyzed in this assessment include surface pressure data and transition images. The surface pressure data acquired during the test agree well with computational fluid dynamics (CFD) results. Transition images at a variety of Reynolds numbers and angles of attack are presented and compared to computational transition predictions. The experimental data are used to assess transition due to a turbulent attachment line, as well as crossflow and Tollmien-Schlichting modal instabilities. Preliminary results suggest the CATNLF design method is successful at delaying transition on wings with high sweep. Initial analysis of the transition front images showed transition Reynolds numbers that exceed historic experimental values at similar sweep angles. , section lif

BlindSignedID: Mitigating Denial-of-Service Attacks on Digital Contact Tracing

Due to the recent outbreak of COVID-19, many governments suspended outdoor activities and imposed social distancing policies to prevent the transmission of SARS-CoV-2. These measures have had severe impact on the economy and peoples' daily lives. An alternative to widespread lockdowns is effective contact tracing during an outbreak's early stage. However, mathematical models suggest that epidemic control for SARS-CoV-2 transmission with manual contact tracing is implausible. To reduce the effort of contact tracing, many digital contact tracing projects (e.g., PEPP-PT, DP-3T, TCN, BlueTrace, Google/Apple Exposure Notification, and East/West Coast PACT) are being developed to supplement manual contact tracing. However, digital contact tracing has drawn scrutiny from privacy advocates, since governments or other parties may attempt to use contact tracing protocols for mass surveillance. As a result, many digital contact tracing projects build privacy-preserving mechanisms to limit the amount of privacy-sensitive information leaked by the protocol. In this paper, we examine how these architectures resist certain classes of attacks, specifically DoS attacks, and present BlindSignedIDs, a privacy-preserving digital contact tracing mechanism, which are verifiable ephemeral identifiers to limit the effectiveness of MAC-compliant DoS attacks. In our evaluations, we showed BlindSignedID can effectively deny bogus EphIDs, mitigating DoS attacks on the local storage beyond 90% of stored EphIDs. Our example DoS attacks showed that using 4 attackers can cause the gigabyte level DoS attacks within normal working hours and days.Comment: 10 pages, 6 figure

Dual-targeting anti-angiogenic cyclic peptides as potential drug leads for cancer therapy

Peptide analogues derived from bioactive hormones such as somatostatin or certain growth factors have great potential as angiogenesis inhibitors for cancer applications. In an attempt to combat emerging drug resistance many FDA-approved anti-angiogenesis therapies are co-administered with cytotoxic drugs as a combination therapy to target multiple signaling pathways of cancers. However, cancer therapies often encounter limiting factors such as high toxicities and side effects. Here, we combined two anti-angiogenic epitopes that act on different pathways of angiogenesis into a single non-toxic cyclic peptide framework, namely MCoTI-II (Momordica cochinchinensis trypsin inhibitor-II), and subsequently assessed the anti-angiogenic activity of the novel compound. We hypothesized that the combination of these two epitopes would elicit a synergistic effect by targeting different angiogenesis pathways and result in improved potency, compared to that of a single epitope. This novel approach has resulted in the development of a potent, non-toxic, stable and cyclic analogue with nanomolar potency inhibition in in vitro endothelial cell migration and in vivo chorioallantoic membrane angiogenesis assays. This is the first report to use the MCoTI-II framework to develop a 2-in-1 anti-angiogenic peptide, which has the potential to be used as a form of combination therapy for targeting a wide range of cancers

Correlation potentials and functionals in Hartree-Fock-Kohn-Sham theory

We compute molecular Hartree-Fock-Kohn-Sham correlation potentials from ab initiocoupled-cluster densities via a modified Zhao, Morrison and Parr [Phys. Rev. A, 50, (1994) 2138] scheme involving exact exchange. We examine the potential for several small systems, and observe complex structure. By fitting a functional expansion to our potentials we obtain a closed-shell functional which is an improvement over other pure correlationfunctionals in Hartree-Fock-Kohn-Sham calculations. The leading term in our functional is dependent on the number of electrons. Our results lead us to question the utility of correlation defined within the Hartree-Fock-Kohn-Sham scheme, and to consider alternative partitionings of the exchange-correlation energy