30,454 research outputs found
Virtual Prototyping for Dynamically Reconfigurable Architectures using Dynamic Generic Mapping
This paper presents a virtual prototyping methodology for Dynamically Reconfigurable (DR) FPGAs. The methodology is based around a library of VHDL image processing components and allows the rapid prototyping and algorithmic development of low-level image processing systems. For the effective modelling of dynamically reconfigurable designs a new technique named, Dynamic Generic Mapping is introduced. This method allows efficient representation of dynamic reconfiguration without needing any additional components to model the reconfiguration process. This gives the designer more flexibility in modelling dynamic configurations than other methodologies. Models created using this technique can then be simulated and targeted to a specific technology using the same code. This technique is demonstrated through the realisation of modules for a motion tracking system targeted to a DR environment, RIFLE-62
Plasma membrane association by N-acylation governs PKG function in Toxoplasma gondii
ABSTRACT
Cyclic GMP (cGMP)-dependent protein kinase (protein kinase G [PKG]) is essential for microneme secretion, motility, invasion, and egress in apicomplexan parasites, However, the separate roles of two isoforms of the kinase that are expressed by some apicomplexans remain uncertain. Despite having identical regulatory and catalytic domains, PKG
I
is plasma membrane associated whereas PKG
II
is cytosolic in
Toxoplasma gondii
. To determine whether these isoforms are functionally distinct or redundant, we developed an auxin-inducible degron (AID) tagging system for conditional protein depletion in
T. gondii
. By combining AID regulation with genome editing strategies, we determined that PKG
I
is necessary and fully sufficient for PKG-dependent cellular processes. Conversely, PKG
II
is functionally insufficient and dispensable in the presence of PKG
I
. The difference in functionality mapped to the first 15 residues of PKG
I
, containing a myristoylated Gly residue at position 2 that is critical for membrane association and PKG function. Collectively, we have identified a novel requirement for cGMP signaling at the plasma membrane and developed a new system for examining essential proteins in
T. gondii
.
IMPORTANCE
Toxoplasma gondii
is an obligate intracellular apicomplexan parasite and important clinical and veterinary pathogen that causes toxoplasmosis. Since apicomplexans can only propagate within host cells, efficient invasion is critically important for their life cycles. Previous studies using chemical genetics demonstrated that cyclic GMP signaling through protein kinase G (PKG)-controlled invasion by apicomplexan parasites. However, these studies did not resolve functional differences between two compartmentalized isoforms of the kinase. Here we developed a conditional protein regulation tool to interrogate PKG isoforms in
T. gondii
. We found that the cytosolic PKG isoform was largely insufficient and dispensable. In contrast, the plasma membrane-associated isoform was necessary and fully sufficient for PKG function. Our studies identify the plasma membrane as a key location for PKG activity and provide a broadly applicable system for examining essential proteins in
T. gondii
.
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Power spectrum and intermittency of the transmitted flux of QSOs Ly-alpha absorption spectra
Using a set of 28 high resolution, high signal to noise ratio (S/N) QSO
Ly-alpha absorption spectra, we investigate the non-Gaussian features of the
transmitted flux fluctuations, and their effect upon the power spectrum of this
field. We find that the spatial distribution of the local power of the
transmitted flux on scales k >= 0.05 s/km is highly spiky or intermittent. The
probability distribution functions (PDFs) of the local power are long-tailed.
The power on small scales is dominated by small probability events, and
consequently, the uncertainty in the power spectrum of the transmitted flux
field is generally large. This uncertainty arises due to the slow convergence
of an intermittent field to a Gaussian limit required by the central limit
theorem (CLT). To reduce this uncertainty, it is common to estimate the error
of the power spectrum by selecting subsamples with an "optimal" size. We show
that this conventional method actually does not calculate the variance of the
original intermittent field but of a Gaussian field. Based on the analysis of
intermittency, we propose an algorithm to calculate the error. It is based on a
bootstrap re-sampling among all independent local power modes. This estimation
doesn't require any extra parameter like the size of the subsamples, and is
sensitive to the intermittency of the fields. This method effectively reduces
the uncertainty in the power spectrum when the number of independent modes
matches the condition of the CLT convergence.Comment: 26 pages (incl. figures). Accepted for publication in MNRA
A Statistical Analysis of the Solar Phenomena Associated with Global EUV Waves
Solar eruptions are the most spectacular events in our solar system and are
associated with many different signatures of energy release including solar
flares, coronal mass ejections, global waves, radio emission and accelerated
particles. Here, we apply the Coronal Pulse Identification and Tracking
Algorithm (CorPITA) to the high cadence synoptic data provided by the Solar
Dynamic Observatory (SDO) to identify and track global waves observed by SDO.
164 of the 362 solar flare events studied (45%) are found to have associated
global waves with no waves found for the remaining 198 (55%). A clear linear
relationship was found between the median initial velocity and the acceleration
of the waves, with faster waves exhibiting a stronger deceleration (consistent
with previous results). No clear relationship was found between global waves
and type II radio bursts, electrons or protons detected in-situ near Earth.
While no relationship was found between the wave properties and the associated
flare size (with waves produced by flares from B to X-class), more than a
quarter of the active regions studied were found to produce more than one wave
event. These results suggest that the presence of a global wave in a solar
eruption is most likely determined by the structure and connectivity of the
erupting active region and the surrounding quiet solar corona rather than by
the amount of free energy available within the active region.Comment: 33 pages, 6 figures, 1 table. Accepted for publication in Solar
Physic
Uncoupling of p97 ATPase activity has a dominant negative effect on protein extraction
p97 is a highly abundant, homohexameric AAA+ ATPase that performs a variety of essential cellular functions. Characterized as a ubiquitin-selective chaperone, p97 recognizes proteins conjugated to K48-linked polyubiquitin chains and promotes their removal from chromatin and other molecular complexes. Changes in p97 expression or activity are associated with the development of cancer and several related neurodegenerative disorders. Although pathogenic p97 mutations cluster in and around p97's ATPase domains, mutant proteins display normal or elevated ATPase activity. Here, we show that one of the most common p97 mutations (R155C) retains ATPase activity, but is functionally defective. p97-R155C can be recruited to ubiquitinated substrates on chromatin, but is unable to promote substrate removal. As a result, p97-R155C acts as a dominant negative, blocking protein extraction by a similar mechanism to that observed when p97's ATPase activity is inhibited or inactivated. However, unlike ATPase-deficient proteins, p97-R155C consumes excess ATP, which can hinder high-energy processes. Together, our results shed new insight into how pathogenic mutations in p97 alter its cellular function, with implications for understanding the etiology and treatment of p97-associated diseases
Double Bottom Line Progress Report: Assessing Social Impact in Double Bottom Line Ventures, Methods Catalog
Outlines methods for social entrepreneurs and their investors to define, measure and communicate social impact and return in early-stage ventures
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