Non-volatile, high density, high speed, Micromagnet-Hall effect Random Access Memory (MHRAM)

The micromagnetic Hall effect random access memory (MHRAM) has the potential of replacing ROMs, EPROMs, EEPROMs, and SRAMs because of its ability to achieve non-volatility, radiation hardness, high density, and fast access times, simultaneously. Information is stored magnetically in small magnetic elements (micromagnets), allowing unlimited data retention time, unlimited numbers of rewrite cycles, and inherent radiation hardness and SEU immunity, making the MHRAM suitable for ground based as well as spaceflight applications. The MHRAM device design is not affected by areal property fluctuations in the micromagnet, so high operating margins and high yield can be achieved in large scale integrated circuit (IC) fabrication. The MHRAM has short access times (less than 100 nsec). Write access time is short because on-chip transistors are used to gate current quickly, and magnetization reversal in the micromagnet can occur in a matter of a few nanoseconds. Read access time is short because the high electron mobility sensor (InAs or InSb) produces a large signal voltage in response to the fringing magnetic field from the micromagnet. High storage density is achieved since a unit cell consists only of two transistors and one micromagnet Hall effect element. By comparison, a DRAM unit cell has one transistor and one capacitor, and a SRAM unit cell has six transistors

Fatty acylation of yeast glycoproteins proceeds independently of N-linked glycosylation

AbstractThe relationship between protein glycosylation and fatty acylation of glycoproteins was studied in the wild-type and asparagine-linked glycosylation-deficient mutants (alg1 and alg2) of Saccharomyces cerevisiae. At the non-permissive temperature (37°C), both mutant cells exhibited increased incorporation of [3H]palmitate into five polypeptides based on SDS-PAGE. In contrast, the wild-type yeast cells contained [3H]palmitate-labeled polypeptides of higher molecular weights, which were converted to the bands seen in the mutant cells upon treatment of the cell extract with endoglycosidase H prior to SDS-PAGE. In addition, labeling of the wild-type yeast cells with [3H]palmitate in the presence of tunicamycin revealed the incorporation of [3H]palmitate into the same five bands as found in the alg1 and alg2 mutants at the non-permissive temperature without tunicamycin. These results indicate that fatty acylation of glycoproteins proceeds independently of protein N-glycosylation in yeast cells

ANKYRIN-B AND mTOR COMPLEX 1 IN THE REGULATION OF ELECTRICAL ACTIVITIES IN THE HEART

The mammalian target of rapamycin complex 1 (mTORC1) activity is paramount in the regulation of electrical activities in the brain and the heart. In the brain, the tumor suppressor gene TSC2 encodes the protein product tuberin that interacts with hamartin to form a heterodimer Tuberous Sclerosis Complex (TSC) that regulates mTORC1. When TSC2 is disrupted, mTORC1 activity becomes dysregulated resulting in abnormal electrical activities in the brain manifesting in the form of epileptic seizures. In the heart, mTORC1 activity is triggered by a sustained increase in hemodynamic pressure causing the heart to electrically remodel. A likely candidate serving as the mediator between mTORC1-dependent electrical remodeling in the brain and heart is the adaptor protein ankyrin. In the heart, ankyrin-B targets and maintains the membrane expression of ion channels and transporters that are critical for maintaining calcium ion homeostasis, which underlies normal excitation-contraction coupling. Sustained mTORC1 activity in the heart decreases the expression of ankyrin-B and alters the electrical conductance between the atria and ventricles. These effects are reversed with the administration of the mTORC1 inhibitor rapamycin. In addition, we identified and characterized two functionally and spatially distinct full-length ankyrin-B isoforms – AnkB-188 and AnkB-212. AnkB-188 selectively interacts with the sodium-calcium exchanger (NCX1) increasing its membrane expression, overall current, and targeting to the sarcoplasmic reticulum/transverse-tubule of neonatal cardiomyocytes. Whereas AnkB-212 does not increase NCX1 membrane expression or current, but uniquely localizes to the sarcomeric M-line. Knockdown of either isoform results in abnormal contraction rhythms in vitro, but only the M-line population appears to be regulated by mTORC1. Collectively, the data support the hypothesis that mTORC1 regulates electrical remodeling of the stressed heart by decreasing the expression of the ankyrin-B population at the M-line

Atomic ionization by sterile-to-active neutrino conversion and constraints on dark matter sterile neutrinos with germanium detectors

The transition magnetic moment of a sterile-to-active neutrino conversion gives rise to not only radiative decay of a sterile neutrino, but also its non-standard interaction (NSI) with matter. For sterile neutrinos of keV-mass as dark matter candidates, their decay signals are actively searched for in cosmic X-ray spectra. In this work, we consider the NSI that leads to atomic ionization, which can be detected by direct dark matter experiments. It is found that this inelastic scattering process for a nonrelativistic sterile neutrino has a pronounced enhancement in the differential cross section at energy transfer about half of its mass, manifesting experimentally as peaks in the measurable energy spectra. The enhancement effects gradually smear out as the sterile neutrino becomes relativistic. Using data taken with germanium detectors that have fine energy resolution in keV and sub-keV regimes, constraints on sterile neutrino mass and its transition magnetic moment are derived and compared with those from astrophysical observations

Deletion of internal twenty-one amino acid residues of Escherichia coli prolipoprotein does not affect the formation of the murein-bound lipoprotein

AbstractMutation pgsA affecting the phosphatidylglycerol phosphate synthesis is lethal for all but certain E. coli strains such as strains deleted for the lpp gene or strains containing unmodifiable prolipoprotein like lppD14. Strain SD312 pgsA3 is tolerant to pgsA mutation, which suggests the lpp alleles in strain SD312 pgsA3 and its parental strain SD12 may be defective. DNA sequence analysis of the lpp genes in Escherichia coli strains SD12 and SD312 pgsA using asymmetric polymerase chain reaction showed that the lpp alleles in these two strains contained a 63 base pair deletion corresponding to the 37th to 57th codons of the wild-type lpp gene. [3H]Palmitate labeling of strains SD12 and SDS312 showed that the mutant lipoprotein in SD12 strain was modified with lipid, while the prolipoprotein in SD312 was not modified. The shortened mature lipoprotein in SD12 and the lipid-modified prolipoprotein in globomycin-treated SD12 were found to be covalently attached to the peptidoglycan, while the unmodified prolipoprotein in SD312 did not form significant amounts of murein-bound lipoprotein

Rotation periods of exoplanet host stars

The stellar rotation periods of ten exoplanet host stars have been determined using newly analysed Ca II H & K flux records from Mount Wilson Observatory and Stromgren b, y photometric measurements from Tennessee State University's automatic photometric telescopes (APTs) at Fairborn Observatory. Five of the rotation periods have not previously been reported, with that of HD 130322 very strongly detected at Prot = 26.1 \pm 3.5 d. The rotation periods of five other stars have been updated using new data. We use the rotation periods to derive the line-of-sight inclinations of the stellar rotation axes, which may be used to probe theories of planet formation and evolution when combined with the planetary orbital inclination found from other methods. Finally, we estimate the masses of fourteen exoplanets under the assumption that the stellar rotation axis is aligned with the orbital axis. We calculate the mass of HD 92788 b (28 MJ) to be within the low-mass brown dwarf regime and suggest that this object warrants further investigation to confirm its true nature.Comment: Accepted for publication in MNRAS. 15 pages, 11 figure

A computational model of induced pluripotent stem-cell derived cardiomyocytes incorporating experimental variability from multiple data sources

KEY POINTS: Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) capture patient-specific genotype-phenotype relationships, as well as cell-to-cell variability of cardiac electrical activity Computational modelling and simulation provide a high throughput approach to reconcile multiple datasets describing physiological variability, and also identify vulnerable parameter regimes We have developed a whole-cell model of iPSC-CMs, composed of single exponential voltage-dependent gating variable rate constants, parameterized to fit experimental iPSC-CM outputs We have utilized experimental data across multiple laboratories to model experimental variability and investigate subcellular phenotypic mechanisms in iPSC-CMs This framework links molecular mechanisms to cellular-level outputs by revealing unique subsets of model parameters linked to known iPSC-CM phenotypes ABSTRACT: There is a profound need to develop a strategy for predicting patient-to-patient vulnerability in the emergence of cardiac arrhythmia. A promising in vitro method to address patient-specific proclivity to cardiac disease utilizes induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). A major strength of this approach is that iPSC-CMs contain donor genetic information and therefore capture patient-specific genotype-phenotype relationships. A cited detriment of iPSC-CMs is the cell-to-cell variability observed in electrical activity. We postulated, however, that cell-to-cell variability may constitute a strength when appropriately utilized in a computational framework to build cell populations that can be employed to identify phenotypic mechanisms and pinpoint key sensitive parameters. Thus, we have exploited variation in experimental data across multiple laboratories to develop a computational framework for investigating subcellular phenotypic mechanisms. We have developed a whole-cell model of iPSC-CMs composed of simple model components comprising ion channel models with single exponential voltage-dependent gating variable rate constants, parameterized to fit experimental iPSC-CM data for all major ionic currents. By optimizing ionic current model parameters to multiple experimental datasets, we incorporate experimentally-observed variability in the ionic currents. The resulting population of cellular models predicts robust inter-subject variability in iPSC-CMs. This approach links molecular mechanisms to known cellular-level iPSC-CM phenotypes, as shown by comparing immature and mature subpopulations of models to analyse the contributing factors underlying each phenotype. In the future, the presented models can be readily expanded to include genetic mutations and pharmacological interventions for studying the mechanisms of rare events, such as arrhythmia triggers.S