Programmable On-Chip ESD Protection Using Nanocrystal Dots Mechanism and Structures

This paper reports a new nanocrystal quantum-dot (NC-QD)-based tunable on-chip electrostatic discharge (ESD) protection mechanism and structures. Experiments validated the programmable ESD protection concept. Prototype structures achieved an adjustable ESD triggering voltage range of 2.5 V, very fast response to ESD transients of rising time t(r) similar to 100 ps and pulse duration t(d) similar to ns, ESD protection density of 25 mA/mu m in human body model and 400 mA/mu m in charged device model equivalent stressing, and a very low leakage current of I-leak similar to 15 pA. The NC-QD ESD protection concept can potentially be used to design field-programmable on-chip ESD protection circuitry for mixed-signal ICs in nanoscales.Engineering, Electrical & ElectronicNanoscience & NanotechnologyMaterials Science, MultidisciplinaryPhysics, AppliedSCI(E)EI7ARTICLE5884-8891

Plasmodium knowlesi Cytoadhesion Involves SICA Variant Proteins

Plasmodium knowlesiposes a health threat throughout Southeast Asian communities and currently causes most cases of malaria in Malaysia. This zoonotic parasite species has been studied inMacaca mulatta(rhesus monkeys) as a model for severe malarial infections, chronicity, and antigenic variation. The phenomenon ofPlasmodiumantigenic variation was first recognized during rhesus monkey infections.Plasmodium-encoded variant proteins were first discovered in this species and found to be expressed at the surface of infected erythrocytes, and then named the Schizont-Infected Cell Agglutination (SICA) antigens. SICA expression was shown to be spleen dependent, as SICA expression is lost afterP. knowlesiis passaged in splenectomized rhesus. Here we present data from longitudinalP. knowlesiinfections in rhesus with the most comprehensive analysis to date of clinical parameters and infected red blood cell sequestration in the vasculature of tissues from 22 organs. Based on the histopathological analysis of 22 tissue types from 11 rhesus monkeys, we show a comparative distribution of parasitized erythrocytes and the degree of margination of the infected erythrocytes with the endothelium. Interestingly, there was a significantly higher burden of parasites in the gastrointestinal tissues, and extensive margination of the parasites along the endothelium, which may help explain gastrointestinal symptoms frequently reported by patients withP. knowlesimalarial infections. Moreover, this margination was not observed in splenectomized rhesus that were infected with parasites not expressing the SICA proteins. This work provides data that directly supports the view that a subpopulation ofP. knowlesiparasites cytoadheres and sequesters, likelyviaSICA variant antigens acting as ligands. This process is akin to the cytoadhesive function of the related variant antigen proteins, namely Erythrocyte Membrane Protein-1, expressed byPlasmodium falciparum.</jats:p

Clinical recovery of <i>Macaca fascicularis</i> infected with <i>Plasmodium knowlesi</i>

ABSTRACTBackgroundKra monkeys (Macaca fascicularis), a natural host of Plasmodium knowlesi, control parasitaemia caused by this parasite species and escape death without treatment. Knowledge of the disease progression and resilience in kra monkeys will aid the effective use of this species to study mechanisms of resilience to malaria. This longitudinal study aimed to define clinical, physiological and pathological changes in kra monkeys infected with P. knowlesi, which could explain their resilient phenotype.MethodsKra monkeys (n = 15, male, young adults) were infected intravenously with cryopreserved P. knowlesi sporozoites and the resulting parasitaemias were monitored daily. Complete blood counts, reticulocyte counts, blood chemistry and physiological telemetry data (n = 7) were acquired as described prior to infection to establish baseline values and then daily after inoculation for up to 50 days. Bone marrow aspirates, plasma samples, and 22 tissue samples were collected at specific time points to evaluate longitudinal clinical, physiological and pathological effects of P. knowlesi infections.ResultsAs expected, the kra monkeys controlled parasitaemia and remained with low-level, persistent parasitaemias without antimalarial intervention. Unexpectedly, early in the infection, fevers developed, which ultimately returned to baseline, as well as mild to moderate thrombocytopaenia, and moderate to severe anaemia. Mathematical modeling and the reticulocyte production index indicated that the anaemia was largely due to the removal of uninfected erythrocytes and not impaired production of erythrocytes. Mild tissue damage was observed, and tissue parasite load was associated with tissue damage even though parasite accumulation in the tissues was generally low.ConclusionsKra monkeys experimentally infected with P. knowlesi sporozoites presented with multiple clinical signs of malaria that varied in severity among individuals. Overall, the animals shared common mechanisms of resilience characterized by controlling parasitaemia 3-5 days after patency, and controlling fever, coupled with physiological and bone marrow responses to compensate for anaemia. Together, these responses likely minimized tissue damage while supporting the establishment of chronic infections, which may be important for transmission in natural endemic settings. These results provide new foundational insights into malaria pathogenesis and resilience in kra monkeys, which may improve understanding of human infections.</jats:sec