Testing the Tester: Lessons Learned During the Testing of a State-of-the-Art Commercial 14nm Processor Under Proton Irradiation

Testing of an Intel 14nm desktop processor was conducted under proton irradiation. We share lessons learned, demonstrating that complex devices beget further complex challenges requiring practical and theoretical investigative expertise to solve

Preliminary Radiation Testing of a State-of-the-Art Commercial 14nm CMOS Processor/System-on-a-Chip

Hardness assurance test results of Intel state-of-the-art 14nm Broadwell U-series processor / System-on-a-Chip (SoC) for total ionizing dose (TID) are presented, along with exploratory results from trials at a medical proton facility. Test method builds upon previous efforts [1] by utilizing commercial laptop motherboards and software stress applications as opposed to more traditional automated test equipment (ATE)

Hardness Assurance for Total Dose and Dose Rate Testing of a State-of-the-Art Off-Shore 32 nm SOI CMOS Processor

No abstract availabl

Synergy Between Proline-Rich Antimicrobial Peptides and Small Molecule Antibiotics Against Selected Gram-Negative Pathogens in vitro and in vivo

As monotherapy, modified proline-rich antimicrobial peptides (PrAMPs) protect animals from experimental bacteremia in a dose-dependent manner. We evaluated the in vitro synergy of a modified PrAMP, A3-APO, a dimer, previously shown to inhibit the 70 kDa bacterial heat shock protein DnaK, with imipenem or colistin against two antibiotic-resistant pathogens; a carbapenemase-expressing Klebsiella pneumoniae strain K97/09 and Acinetobacter baumannii (ATCC BAA-1605). Combining antimicrobials resulted in synergy for PrAMP/colistin combination against both K. pneumoniae and A. baumannii (ΣFIC = 0.08 both) and additive activity for the A3-APO/imipenem combination against K. pneumoniae (ΣFIC = 0.53). Chex1-Arg20, (designated as ARV-1502 in preclinical development), the single chain PrAMP monomer of A3-APO, showed synergy with meropenem against a carbapenem-resistant uropathogenic Escherichia coli strain (ΣFIC = 0.38). In a murine bacteremia model using K97/09, A3-APO at 1 mg/kg demonstrated improved survival when co-administered with standard (10 mg/kg) or subtherapeutic (1 mg/kg) doses of colistin at 36 h (p < 0.05). Surprisingly, the survival benefit of A3-APO was augmented when the A3-APO dose was decreased by 50% to 0.5 mg/kg (p < 0.02) in conjunction with a subtherapeutic colistin dose (1 mg/kg). ARV-1502, as monotherapy demonstrated prolonged (>24 h) activity in a mouse Escherichia coli infection assay. Co-treatment with ARV-1502 and subtherapeutic doses of ceftazidime (150 mg/kg) was studied in a mouse model of melioidosis. ARV-1502 provided a 50% improvement in long-term (62 days) survival, but only at the lowest of 3 administered doses; survival advantage was demonstrated at 2.5 mg/kg but not at 5 or 10 mg/kg. The mortality benefit of combination therapies was not routinely accompanied by a parallel decline in blood or tissue bacterial counts in surviving animals, suggesting that the anti-infective activity of the host defense peptides (HDP) is broader than simply bacterial eradication. In fact, the hormetic effect observed in either animal models suggest that low dose HDP treatment may change the dominant mode of action in experimental bacteremia

Ouabain-induced perturbations in intracellular ionic homeostasis regulate death receptor-mediated apoptosis

Apoptosis is defined by specific morphological and biochemical characteristics including cell shrinkage (termed apoptotic volume decrease), a process that results from the regulation of ion channels and plasma membrane transporter activity. The Na(+)-K(+)-ATPase is the predominant pump that controls cell volume and plasma membrane potential in cells and alterations in its function have been suggested to be associated with apoptosis. We report here that the Na(+)-K(+)-ATPase inhibitor ouabain, potentiates apoptosis in the human lymphoma Jurkat cells exposed to Fas ligand (FasL) or Tumor necrosis factor--related apoptosis-inducing ligand (TRAIL) but not other apoptotic agents such as H(2)O(2), thapsigargin or UV-C implicating a role for the Na(+)-K(+)-ATPase in death receptor-induced apoptosis. Interestingly, ouabain also potentiated perturbations in cell Ca(2+) homeostasis only in conjunction with the apoptotic inducer FasL but not TRAIL. Ouabain did not affect alterations in the intracellular Ca(2+) levels in response to H(2)O(2), thapsigargin or UV-C. FasL-induced alterations in Ca(2+) were not abolished in Ca(2+)-free medium but incubation of cells with BAPTA-AM inhibited both Ca(2+) perturbations and the ouabain-induced potentiation of FasL-induced apoptosis. Our data suggest that the impairment of the Na(+)-K(+)-ATPase activity during apoptosis is linked to perturbations in cell Ca(2+) homeostasis that modulate apoptosis induced by the activation of Fas by FasL

Coronal Heating as Determined by the Solar Flare Frequency Distribution Obtained by Aggregating Case Studies

Flare frequency distributions represent a key approach to addressing one of the largest problems in solar and stellar physics: determining the mechanism that counter-intuitively heats coronae to temperatures that are orders of magnitude hotter than the corresponding photospheres. It is widely accepted that the magnetic field is responsible for the heating, but there are two competing mechanisms that could explain it: nanoflares or Alfv\'en waves. To date, neither can be directly observed. Nanoflares are, by definition, extremely small, but their aggregate energy release could represent a substantial heating mechanism, presuming they are sufficiently abundant. One way to test this presumption is via the flare frequency distribution, which describes how often flares of various energies occur. If the slope of the power law fitting the flare frequency distribution is above a critical threshold, $\alpha=2$ as established in prior literature, then there should be a sufficient abundance of nanoflares to explain coronal heating. We performed $>$600 case studies of solar flares, made possible by an unprecedented number of data analysts via three semesters of an undergraduate physics laboratory course. This allowed us to include two crucial, but nontrivial, analysis methods: pre-flare baseline subtraction and computation of the flare energy, which requires determining flare start and stop times. We aggregated the results of these analyses into a statistical study to determine that $\alpha = 1.63 \pm 0.03$. This is below the critical threshold, suggesting that Alfv\'en waves are an important driver of coronal heating.Comment: 1,002 authors, 14 pages, 4 figures, 3 tables, published by The Astrophysical Journal on 2023-05-09, volume 948, page 7