1,091 research outputs found
Engaging Empirical Dynamic Modeling to Detect Intrusions in Cyber-Physical Systems
Modern cyber-physical systems require effective intrusion detection systems to ensure adequate critical infrastructure protection. Developing an intrusion detection capability requires an understanding of the behavior of a cyber-physical system and causality of its components. Such an understanding enables the characterization of normal behavior and the identification and reporting of anomalous behavior. This chapter explores a relatively new time series analysis technique, empirical dynamic modeling, that can contribute to system understanding. Specifically, it examines if the technique can adequately describe causality in cyber-physical systems and provides insights into it serving as a foundation for intrusion detection
Anatomical and molecular properties of long descending propriospinal neurons in mice
Long descending propriospinal neurons (LDPNs) are interneurons that form direct connections between cervical and lumbar spinal circuits. LDPNs are involved in interlimb coordination and are important mediators of functional recovery after spinal cord injury (SCI). Much of what we know about LDPNs comes from a range of species, however, the increased use of transgenic mouse lines to better define neuronal populations calls for a more complete characterisation of LDPNs in mice. In this study, we examined the cell body location, inhibitory neurotransmitter phenotype, developmental provenance, morphology and synaptic inputs of mouse LDPNs throughout the cervical and upper thoracic spinal cord. LDPNs were retrogradely labelled from the lumbar spinal cord to map cell body locations throughout the cervical and upper thoracic segments. Ipsilateral LDPNs were distributed throughout the dorsal, intermediate and ventral grey matter as well as the lateral spinal nucleus and lateral cervical nucleus. In contrast, contralateral LDPNs were more densely concentrated in the ventromedial grey matter. Retrograde labelling in GlyT2GFP and GAD67GFP mice showed the majority of inhibitory LDPNs project either ipsilaterally or adjacent to the midline. Additionally, we used several transgenic mouse lines to define the developmental provenance of LDPNs and found that V2b positive neurons form a subset of ipsilaterally projecting LDPNs. Finally, a population of Neurobiotin (NB) labelled LDPNs were assessed in detail to examine morphology and plot the spatial distribution of contacts from a variety of neurochemically distinct axon terminals. These results provide important baseline data in mice for future work on their role in locomotion and recovery from SCI
Pathogenic Variants in Fucokinase Cause a Congenital Disorder of Glycosylation
FUK encodes fucokinase, the only enzyme capable of converting L-fucose to fucose-1-phosphate, which will ultimately be used for synthesizing GDP-fucose, the donor substrate for all fucosyltransferases. Although it is essential for fucose salvage, this pathway is thought to make only a minor contribution to the total amount of GDP-fucose. A second pathway, the major de novo pathway, involves conversion of GDP-mannose to GDP-fucose. Here we describe two unrelated individuals who have pathogenic variants in FUK and who presented with severe developmental delays, encephalopathy, intractable seizures, and hypotonia. The first individual was compound heterozygous for c.667T>C (p.Ser223Pro) and c.2047C>T (p.Arg683Cys), and the second individual was homozygous for c.2980A>C (p.Lys994Gln). Skin fibroblasts from the first individual confirmed the variants as loss of function and showed significant decreases in total GDP-[3H] fucose and [3H] fucose-1-phosphate. There was also a decrease in the incorporation of [5,6-3H]-fucose into fucosylated glycoproteins. Lys994 has previously been shown to be an important site for ubiquitin conjugation. Here, we show that loss-of-function variants in FUK cause a congenital glycosylation disorder characterized by a defective fucose-salvage pathway
Rhizobial peptidase HrrP cleaves host-encoded signaling peptides and mediates symbiotic compatibility
Legume–rhizobium pairs are often observed that produce symbiotic root nodules but fail to fix nitrogen. Using the Sinorhizobium meliloti and Medicago truncatula symbiotic system, we previously described several naturally occurring accessory plasmids capable of disrupting the late stages of nodule development while enhancing bacterial proliferation within the nodule. We report here that host range restriction peptidase (hrrP), a gene found on one of these plasmids, is capable of conferring both these properties. hrrP encodes an M16A family metallopeptidase whose catalytic activity is required for these symbiotic effects. The ability of hrrP to suppress nitrogen fixation is conditioned upon the genotypes of both the host plant and the hrrP-expressing rhizobial strain, suggesting its involvement in symbiotic communication. Purified HrrP protein is capable of degrading a range of nodule-specific cysteine-rich (NCR) peptides encoded by M. truncatula. NCR peptides are crucial signals used by M. truncatula for inducing and maintaining rhizobial differentiation within nodules, as demonstrated in the accompanying article [Horváth B, et al. (2015) Proc Natl Acad Sci USA, 10.1073/pnas.1500777112]. The expression pattern of hrrP and its effects on rhizobial morphology are consistent with the NCR peptide cleavage model. This work points to a symbiotic dialogue involving a complex ensemble of host-derived signaling peptides and bacterial modifier enzymes capable of adjusting signal strength, sometimes with exploitative outcomes.National Institutes of Health (U.S.) (GM31010
Solvent inhibition in the liquid-phase catalytic oxidation of 1,4-butanediol: understanding the catalyst behaviour from NMR relaxation time measurements
Catalytic reaction studies and Nuclear Magnetic Resonance (NMR) relaxation time measurements have been compared to study the influence of competitive adsorption of reactant and solvent on catalytic conversion. The reaction chosen is the aerobic catalytic oxidation of 1,4-butanediol in methanol over different supported-metal catalysts. From the NMR T1/T2 ratio, where T1 is the longitudinal and T2 the transverse spin relaxation time, the relative affinity of reactant and solvent for different catalytic surfaces is determined. The catalysts with the lowest activity show a preferential surface affinity for the solvent compared to the reactant. Conversely, the catalyst with the highest activity shows a preferential surface affinity for the reactant compared to the solvent. Significantly, Ru/SiO2, which is totally inactive for the oxidation of 1,4-butanediol, exhibited a lower T1/T2 ratio (surface affinity) for 1,4-butanediol (reactant) than for a “weakly-interacting” alkane, indicating a very poor surface affinity for the diol functionality. The results provide direct evidence of the importance of the adsorbate-adsorbent interactions on catalyst activity in liquid-phase oxidations and indicate that the competitive adsorption of the solvent plays an important role in these reactions. This work demonstrates that NMR relaxation time analysis is a powerful method for comparing adsorption of liquids in porous catalysts, providing valuable information on the affinity of different chemical species for a catalyst surface. Moreover, the results demonstrate that NMR relaxation time measurements can be used not only to guide selection of solvent for use with a specific catalyst, but also selection of the catalyst itself. The results suggest that this method may be used to predict catalyst behaviour, enabling improved design and optimisation of heterogeneous catalytic processes
Biallelic variants in COX4I1 associated with a novel phenotype resembling Leigh syndrome with developmental regression, intellectual disability, and seizures
Autosomal recessive COX4I1 deficiency has been previously reported in a single individual with a homozygous pathogenic variant in COX4I1, who presented with short stature, poor weight gain, dysmorphic features, and features of Fanconi anemia. COX4I1 encodes subunit 4, isoform 1 of cytochrome c oxidase. Cytochrome c oxidase is a respiratory chain enzyme that plays an important role in mitochondrial electron transport and reduces molecular oxygen to water leading to the formation of ATP. Defective production of cytochrome c oxidase leads to a variable phenotypic spectrum ranging from isolated myopathy to Leigh syndrome. Here, we describe two siblings, born to consanguineous parents, who presented with encephalopathy, developmental regression, hypotonia, pathognomonic brain imaging findings resembling Leigh‐syndrome, and a novel homozygous variant on COX4I1, expanding the known clinical phenotype associated with pathogenic variants in COX4I1
Astrometry with the Keck-Interferometer: the ASTRA project and its science
The sensitivity and astrometry upgrade ASTRA of the Keck Interferometer is
introduced. After a brief overview of the underlying interferometric
principles, the technology and concepts of the upgrade are presented. The
interferometric dual-field technology of ASTRA will provide the KI with the
means to observe two objects simultaneously, and measure the distance between
them with a precision eventually better than 100 uas. This astrometric
functionality of ASTRA will add a unique observing tool to fields of
astrophysical research as diverse as exo-planetary kinematics, binary
astrometry, and the investigation of stars accelerated by the massive black
hole in the center of the Milky Way as discussed in this contribution.Comment: 22 pages, 10 figures (low resolution), contribution to the
summerschool "Astrometry and Imaging with the Very Large Telescope
Interferometer", 2 - 13 June, 2008, Keszthely, Hungary, corrected authorlis
A modified BlÄzka–type respirometer for the study of swimming metabolism in fishes having deep, laterally compressed bodies or unusual locomotor modes
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73888/1/j.1095-8649.2000.tb00890.x.pd
Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure
Mitochondrial dysfunction and metabolic remodelling are pivotal in the development of cardiomyopathy. Here, we show that myocardial COUP-TFII overexpression causes heart failure in mice, suggesting a causal effect of elevated COUP-TFII levels on development of dilated cardiomyopathy. COUP-TFII represses genes critical for mitochondrial electron transport chain enzyme activity, oxidative stress detoxification and mitochondrial dynamics, resulting in increased levels of reactive oxygen species and lower rates of oxygen consumption in mitochondria. COUP-TFII also suppresses the metabolic regulator PGC-1 network and decreases the expression of key glucose and lipid utilization genes, leading to a reduction in both glucose and oleate oxidation in the hearts. These data suggest that COUP-TFII affects mitochondrial function, impairs metabolic remodelling and has a key role in dilated cardiomyopathy. Last, COUP-TFII haploinsufficiency attenuates the progression of cardiac dilation and improves survival in a calcineurin transgenic mouse model, indicating that COUP-TFII may serve as a therapeutic target for the treatment of dilated cardiomyopathy
The Covariant Entropy Bound, Brane Cosmology, and the Null Energy Condition
In discussions of Bousso's Covariant Entropy Bound, the Null Energy Condition
is always assumed, as a sufficient {\em but not necessary} condition which
helps to ensure that the entropy on any lightsheet shall necessarily be finite.
The spectacular failure of the Strong Energy Condition in cosmology has,
however, led many astrophysicists and cosmologists to consider models of dark
energy which violate {\em all} of the energy conditions, and indeed the current
data do not completely rule out such models. The NEC also has a questionable
status in brane cosmology: it is probably necessary to violate the NEC in the
bulk in order to obtain a "self-tuning" theory of the cosmological constant. In
order to investigate these proposals, we modify the Karch-Randall model by
introducing NEC-violating matter into in such a way that the brane
cosmological constant relaxes to zero. The entropy on lightsheets remains
finite. However, we still find that the spacetime is fundamentally incompatible
with the Covariant Entropy Bound machinery, in the sense that it fails the
Bousso-Randall consistency condition. We argue that holography probably forbids
all {\em cosmological} violations of the NEC, and that holography is in fact
the fundamental physical principle underlying the cosmological version of the
NEC.Comment: 21 pages, 3 figures, version 2:corrected and greatly improved
discussion of the Bousso-Randall consistency check, references added;
version3: more references added, JHEP versio
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