An Identity Based Key Management Scheme in Wireless Sensor Networks

Pairwise key establishment is one of the fundamental security services in sensor networks which enables sensor nodes in a sensor network to communicate securely with each other using cryptographic techniques. It is not feasible to apply traditional public key management techniques in resource-constrained sensor nodes, and also because the sensor nodes are vulnerable to physical capture. In this paper, we introduce a new scheme called the identity based key pre-distribution using a pseudo random function (IBPRF), which has better trade-off between communication overhead, network connectivity and resilience against node capture compared to the other key pre-distribution schemes. Our scheme can be easily adapted in mobile sensor networks. This scheme supports the addition of new sensor nodes after the initial deployment and also works for any deployment topology. In addition, we propose an improved version of our scheme to support large sensor networks.Comment: 7 pages, Published in Proceedings of 4th Asian International Mobile Computing Conference (AMOC 2006), Kolkata, India, pp. 70-76, January 4-7, 200

Modulation of mitochondrial dynamics, bioenergetics and the innate antiviral immune response in Zika Virus infected Retinal cells

Modulation of mitochondrial dynamics and bioenergetics in Zika Virus infected retinal cells Karim Dirani1, Sneha Singh1, Shailendra Giri2, Ashok Kumar1 1 Department of Ophthalmology, Visual and Anatomical Sciences, and Kresge Eye Institute, Wayne State University School of Medicine, Detroit, MI 2 Department of Neurology, Henry Ford Health Systems, Detroit, MI Purpose: In addition to the powerhouse of the cells and regulation of apoptosis, mitochondria are being increasingly recognized in playing crucial role in modulating innate immune response in viral infections. In this study, we sought to determine the impact of mitochondrial dynamic (fission, fusion, and mitophagy) and bioenergetics status in regulating antiviral innate response to Zika virus (ZIKV) infection. Methods: Human ARPE-19 cells were infected with ZIKV (strain PRVABC59) at MOI of 1. The mitochondria were visualized for fission and fusion process using TOM20 and mitotracker dyes while the mitochondrial membrane potential was measured using JC-1 staining. The temporal expression of key genes/molecules involved in mitochondrial dynamic was assessed by RT-qPCR and Western blot. ARPE-19 cells stably expressing individual ZIKV genes were used to assess the functional role of viral proteins in altering mitochondrial dynamics. The bioenergetics activity of the cells was assessed using Seahorse XF analyzer for monitoring oxygen consumption rate (OCR) and Extracellular acidification rate (ECAR) upon ZIKV infection and with individual viral proteins. Results: All cells tested were permissive to ZIKV infection, as evidenced by a time dependent increase in virion production and immunostaining of viral antigen in the cells. Infected cells exhibited an increase in the expression of antiviral (e.g., IFNs, ISG15, MX1, OAS2) and inflammatory mediators (e.g., CCL5, TNFa). Amongst the molecules regulating the mitochondrial fission and fusion, levels of p-Drp1, mitofusins (MFN1, MFN2), and Opa1 were altered at both mRNA and protein levels. Similarly, molecules regulating mitophagy, PINK1/Parkin -dependent and independent pathways were modulated in ZIKV infected cells. Among individual viral proteins, the non-structural proteins exerted profound effects on mitochondrial dynamic. This correlated with a decrease in OCR response upon ZIKV infection. Interestingly, the pharmacological inhibition of Drp1 reduced ZIKV replication. Conclusion: Collectively, our data indicates that ZIKV virus modulates mitochondrial dynamics and individual ZIKV proteins exert differential effects on bioenergetics and antiviral innate immune response of infected cells. Targeting mitochondrial dynamic may provide new therapeutic avenues for antiviral therapy against ZIKV infection

Mutagenic effects of certain common metal toxicants on mammalian systems

The use of metals for human benefit started more than 6000 years ago. Their harmful effects were noted much later, with the growing consciousness about environmental hazards. The different industrial processes and other adjuncts of industrial revolution have added considerably to the quantities of such metal occurring under natural conditions. An appreciable proportion enters into the formation of aerosols, known to be toxic to living systems. Assessment of the hazards posed by metal effluents and their mode of action are therefore gaining considerable importance as a part of environment protection

Constraints on Astro-unparticle Physics from SN 1987A

SN 1987A observations have been used to place constraints on the interactions between standard model particles and unparticles. In this study we calculate the energy loss from the supernovae core through scalar, pseudo scalar, vector, pseudo vector unparticle emission from nuclear bremsstrahlung for degenerate nuclear matter interacting through one pion exchange. In order to examine the constraints on $d_{\cal U}=1$ we considered the emission of scalar, pseudo scalar, vector, pseudo vector and tensor through the pair annihilation process $e^+e^-\to {\cal U} \gamma$. In addition we have re-examined other pair annihilation processes. The most stringent bounds on the dimensionless coupling constants for $d_{\cal U} =1$ and $\Lambda_{\cal U}= m_Z$ are obtained from nuclear bremsstrahlung process for the pseudo scalar and pseudo-vector couplings $\bigl|\lambda^{\cal P}_{0,1}\bigr|\leq 4\times 10^{-11}$ and for tensor interaction, the best limit on dimensionless coupling is obtained from $e^+ e^-\to {\cal U} \gamma$ and we get $\bigl|\lambda^{\cal T}\bigr| \leq 6\times 10^{-6}$.Comment: 12 pages, 2 postscript figure

Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo

In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ∼10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

5-Aminoimidazole-4-carboxamide ribonucleoside-mediated adenosine monophosphate-activated protein kinase activation induces protective innate responses in bacterial endophthalmitis

The retina is considered to be the most metabolically active tissue in the body. However, the link between energy metabolism and retinal inflammation, as incited by microbial infection such as endophthalmitis, remains unexplored. In this study, using a mouse model of Staphylococcus aureus (SA) endophthalmitis, we demonstrate that the activity (phosphorylation) of 5\u27 adenosine monophosphate-activated protein kinase alpha (AMPKα), a cellular energy sensor and its endogenous substrate; acetyl-CoA carboxylase is down-regulated in the SA-infected retina. Intravitreal administration of an AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), restored AMPKα and acetyl-CoA carboxylase phosphorylation. AICAR treatment reduced both the bacterial burden and intraocular inflammation in SA-infected eyes by inhibiting NF-kB and MAP kinases (p38 and JNK) signalling. The anti-inflammatory effects of AICAR were diminished in eyes pretreated with AMPK inhibitor, Compound C. The bioenergetics (Seahorse) analysis of SA-infected microglia and bone marrow-derived macrophages revealed an increase in glycolysis, which was reinstated by AICAR treatment. AICAR also reduced the expression of SA-induced glycolytic genes, including hexokinase 2 and glucose transporter 1 in microglia, bone marrow-derived macrophages and the mouse retina. Interestingly, AICAR treatment enhanced the bacterial phagocytic and intracellular killing activities of cultured microglia, macrophages and neutrophils. Furthermore, AMPKα1 global knockout mice exhibited increased susceptibility towards SA endophthalmitis, as evidenced by increased inflammatory mediators and bacterial burden and reduced retinal function. Together, these findings provide the first evidence that AMPK activation promotes retinal innate defence in endophthalmitis by modulating energy metabolism and that it can be targeted therapeutically to treat ocular infections

NRC - Dave Sanger Indian Midden

NRC - Dave Sanger Indian Middenhttps://digitalmaine.com/mgs_geologic_field_photos/7281/thumbnail.jp

Neonatal Screening for Congenital Hypothyroidism through Dried Blood Spots: A Cross-sectional Study

Introduction: Congenital Hypothyroidism (CH) is defined as the partial or complete loss of thyroid gland function present at birth. During the first 2-3 years of life, thyroid hormone plays a crucial role in brain development. If a baby is born with a deficiency of thyroid hormone (CH) and is not diagnosed and treated appropriately, it can lead to intellectual disability and growth retardation in the affected child. Aim: To screen newborns for CH using Dried Blood Spot (DBS) sampling. Additionally, the study aimed to compare mean TSH values between two comparison groups based on gender, birth weight, gestational age, and type of delivery. Materials and Methods: This cross-sectional study was conducted at Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India, from November 2021 to October 2022. A total of 250 live-birth newborns delivered either by Spontaneous Vaginal Delivery (SVD) or Lower Segment Caesarean Section (LSCS) were included in the study after obtaining written informed consent from their parents. Blood samples were obtained on DBS cards through heel prick in all newborns. TSH levels were assessed using a neonatal TSH sandwich ELISA kit. The cut-off value of TSH to label as screen positive was set at >20 mIU/L. A two-tailed Independent t-test was performed to compare mean TSH values between the two comparison groups based on gender, birth weight, gestational age, and type of delivery. Results: Out of the 250 babies, 137 (54.8%) were male and 113 (45.2%) were female. The gestational age ranged from a minimum of 29 weeks to a maximum of 41 weeks in both male and female babies. TSH levels in male babies ranged from 0.16 mIU/L to 10.27 mIU/L, with a mean value of 3.98±2.16 mIU/L. TSH levels were below 20 mIU/L in all 250 newborns, indicating negative screening results for CH in all the neonates. Conclusion: The results concluded that the serum levels of TSH obtained through heel prick were not statistically significant in both term and preterm newborns, as well as in Normal Birth Weight (NBW) and Low Birth Weight (LBW) newborns. Furthermore, there was no significant difference based on the type of delivery (SVD/LSCS) or the gender of the newborn (male or female)