9,104 research outputs found
Improving Distributed Gradient Descent Using Reed-Solomon Codes
Today's massively-sized datasets have made it necessary to often perform
computations on them in a distributed manner. In principle, a computational
task is divided into subtasks which are distributed over a cluster operated by
a taskmaster. One issue faced in practice is the delay incurred due to the
presence of slow machines, known as \emph{stragglers}. Several schemes,
including those based on replication, have been proposed in the literature to
mitigate the effects of stragglers and more recently, those inspired by coding
theory have begun to gain traction. In this work, we consider a distributed
gradient descent setting suitable for a wide class of machine learning
problems. We adapt the framework of Tandon et al. (arXiv:1612.03301) and
present a deterministic scheme that, for a prescribed per-machine computational
effort, recovers the gradient from the least number of machines
theoretically permissible, via an decoding algorithm. We also provide
a theoretical delay model which can be used to minimize the expected waiting
time per computation by optimally choosing the parameters of the scheme.
Finally, we supplement our theoretical findings with numerical results that
demonstrate the efficacy of the method and its advantages over competing
schemes
Extrapancreatic actions of incretin-based therapies on bone in diabetes mellitus
Diabetes mellitus is correlated with modifications in bone microarchitectural and
mechanical strength, leading to increased bone fragility. The incretin hormones, with
a classical effect to increase insulin secretion following food ingestion, are now
postulated to have important direct effects on bone. As such, glucose-dependent
insulinotropic polypeptide (GIP) has dual actions on bone cells; enhancing bone�forming activity of osteoblasts and suppressing bone resorption by osteoclasts. The
sister incretin of GIP, glucagon-like peptide-1 (GLP-1), is also suspected to directly
influence bone health in a beneficial manner, although mechanism are less clear at
present. The physiological actions of incretins are attenuated by dipeptidyl peptidase
(DPP-4) activity and it is speculated that introduction of DPP-4 inhibitor may also
positively affect quality of the skeleton. As such, this thesis evaluates the potential
beneficial effects of a DPP-4 resistant GIP analogue, namely [D-Ala2
]GIP, on
osteoblastic-derived, SaOS-2 cells, and also preliminary in vivo studies on the impact
of genetic deficiencies of GIPRs and GLP-1Rs on bone mineral density and content.
Further studies characterised the beneficial effects of incretin-based therapies on
metabolic control, bone microstructure and bone mechanical integrity in animal
models of pharmacologically-, genetically- and environmentally-induced diabetes.
GIP and related stable analogue increased bone-forming biomarkers in SaOS-2 cells
and importantly, [D-Ala2
]GIP was shown to be more potent than native GIP.
Knockout mouse studies revealed that both GIPR and GLP-1R signaling are
important for optimum bone mass. All diabetic mouse models displayed reduced
bone mass, altered bone micromorphology and impairment of bone mechanical
strength, similar to the human situation, confirming their appropriateness. The
incretin-based therapeutics, [D-Ala2
]GIP and Liraglutide, in streptozotocin-diabetic
significantly increased bone matrix properties, indicating recovery of bone strength
at the tissue level. The beneficial effects of administration of [D-Ala2
]GIP�oxyntomodulin on bone health in db/db mice were more prominent as the Oxm
analogue did not only improve bone strength at tissue level, but also at whole-bone
level. These modifications were independent of metabolic status. Twice-daily
Exendin-4 therapy improved glycaemic control and increased work required to resist
bone fracture in high-fat fed mice. It was also established that Sitagliptin had neutral
effects on bone microstructure and mechanical strength in high-fat mice. In summary, these data demonstrate the negative impact of diabetes mellitus on normal
skeleton development and bone quality. Moreover, this thesis highlights the growing
potential of incretin-based therapies for ameliorating bone defects and improving the
increased fragility fracture risk associated with diabete
Extrapancreatic actions of incretin-based therapies on bone in diabetes mellitus
Diabetes mellitus is correlated with modifications in bone microarchitectural and
mechanical strength, leading to increased bone fragility. The incretin hormones, with
a classical effect to increase insulin secretion following food ingestion, are now
postulated to have important direct effects on bone. As such, glucose-dependent
insulinotropic polypeptide (GIP) has dual actions on bone cells; enhancing bone�forming activity of osteoblasts and suppressing bone resorption by osteoclasts. The
sister incretin of GIP, glucagon-like peptide-1 (GLP-1), is also suspected to directly
influence bone health in a beneficial manner, although mechanism are less clear at
present. The physiological actions of incretins are attenuated by dipeptidyl peptidase
(DPP-4) activity and it is speculated that introduction of DPP-4 inhibitor may also
positively affect quality of the skeleton. As such, this thesis evaluates the potential
beneficial effects of a DPP-4 resistant GIP analogue, namely [D-Ala2
]GIP, on
osteoblastic-derived, SaOS-2 cells, and also preliminary in vivo studies on the impact
of genetic deficiencies of GIPRs and GLP-1Rs on bone mineral density and content.
Further studies characterised the beneficial effects of incretin-based therapies on
metabolic control, bone microstructure and bone mechanical integrity in animal
models of pharmacologically-, genetically- and environmentally-induced diabetes.
GIP and related stable analogue increased bone-forming biomarkers in SaOS-2 cells
and importantly, [D-Ala2
]GIP was shown to be more potent than native GIP.
Knockout mouse studies revealed that both GIPR and GLP-1R signaling are
important for optimum bone mass. All diabetic mouse models displayed reduced
bone mass, altered bone micromorphology and impairment of bone mechanical
strength, similar to the human situation, confirming their appropriateness. The
incretin-based therapeutics, [D-Ala2
]GIP and Liraglutide, in streptozotocin-diabetic
significantly increased bone matrix properties, indicating recovery of bone strength
at the tissue level. The beneficial effects of administration of [D-Ala2
]GIP�oxyntomodulin on bone health in db/db mice were more prominent as the Oxm
analogue did not only improve bone strength at tissue level, but also at whole-bone
level. These modifications were independent of metabolic status. Twice-daily
Exendin-4 therapy improved glycaemic control and increased work required to resist
bone fracture in high-fat fed mice. It was also established that Sitagliptin had neutral
effects on bone microstructure and mechanical strength in high-fat mice. In summary, these data demonstrate the negative impact of diabetes mellitus on normal
skeleton development and bone quality. Moreover, this thesis highlights the growing
potential of incretin-based therapies for ameliorating bone defects and improving the
increased fragility fracture risk associated with diabete
Carotenoid biosynthesis and overproduction in Corynebacterium glutamicum
Heider S, Peters-Wendisch P, Wendisch VF. Carotenoid biosynthesis and overproduction in Corynebacterium glutamicum. BMC Microbiology. 2012;12(1): 198.Background
Corynebacterium glutamicum contains the glycosylated C50 carotenoid decaprenoxanthin as yellow pigment. Starting from isopentenyl pyrophosphate, which is generated in the non-mevalonate pathway, decaprenoxanthin is synthesized via the intermediates farnesyl pyrophosphate, geranylgeranyl pyrophosphate, lycopene and flavuxanthin.
Results
Here, we showed that the genes of the carotenoid gene cluster crtE-cg0722-crtBIYeYfEb are co-transcribed and characterized defined gene deletion mutants. Gene deletion analysis revealed that crtI, crtEb, and crtYeYf, respectively, code for the only phytoene desaturase, lycopene elongase, and carotenoid C45/C50 epsilon-cyclase, respectively. However, the genome of C. glutamicum also encodes a second carotenoid gene cluster comprising crtB2I2-1/2 shown to be co-transcribed, as well. Ectopic expression of crtB2 could compensate for the lack of phytoene synthase CrtB in C. glutamicum DeltacrtB, thus, C. glutamicum possesses two functional phytoene synthases, namely CrtB and CrtB2. Genetic evidence for a crtI2-1/2 encoded phytoene desaturase could not be obtained since plasmid-borne expression of crtI2-1/2 did not compensate for the lack of phytoene desaturase CrtI in C. glutamicum DeltacrtI. The potential of C. glutamicum to overproduce carotenoids was estimated with lycopene as example. Deletion of the gene crtEb prevented conversion of lycopene to decaprenoxanthin and entailed accumulation of lycopene to 0.03 +/- 0.01 mg/g cell dry weight (CDW). When the genes crtE, crtB and crtI for conversion of geranylgeranyl pyrophosphate to lycopene were overexpressed in C. glutamicum DeltacrtEb intensely red-pigmented cells and an 80 fold increased lycopene content of 2.4 +/- 0.3 mg/g CDW were obtained.
Conclusion
C. glutamicum possesses a certain degree of redundancy in the biosynthesis of the C50 carotenoid decaprenoxanthin as it possesses two functional phytoene synthase genes. Already metabolic engineering of only the terminal reactions leading to lycopene resulted in considerable lycopene production indicating that C. glutamicum may serve as a potential host for carotenoid production
Fast Algebraic Attacks and Decomposition of Symmetric Boolean Functions
Algebraic and fast algebraic attacks are power tools to analyze stream
ciphers. A class of symmetric Boolean functions with maximum algebraic immunity
were found vulnerable to fast algebraic attacks at EUROCRYPT'06. Recently, the
notion of AAR (algebraic attack resistant) functions was introduced as a
unified measure of protection against both classical algebraic and fast
algebraic attacks. In this correspondence, we first give a decomposition of
symmetric Boolean functions, then we show that almost all symmetric Boolean
functions, including these functions with good algebraic immunity, behave badly
against fast algebraic attacks, and we also prove that no symmetric Boolean
functions are AAR functions. Besides, we improve the relations between
algebraic degree and algebraic immunity of symmetric Boolean functions.Comment: 13 pages, submitted to IEEE Transactions on Information Theor
A real-space grid implementation of the Projector Augmented Wave method
A grid-based real-space implementation of the Projector Augmented Wave (PAW)
method of P. E. Blochl [Phys. Rev. B 50, 17953 (1994)] for Density Functional
Theory (DFT) calculations is presented. The use of uniform 3D real-space grids
for representing wave functions, densities and potentials allows for flexible
boundary conditions, efficient multigrid algorithms for solving Poisson and
Kohn-Sham equations, and efficient parallelization using simple real-space
domain-decomposition. We use the PAW method to perform all-electron
calculations in the frozen core approximation, with smooth valence wave
functions that can be represented on relatively coarse grids. We demonstrate
the accuracy of the method by calculating the atomization energies of twenty
small molecules, and the bulk modulus and lattice constants of bulk aluminum.
We show that the approach in terms of computational efficiency is comparable to
standard plane-wave methods, but the memory requirements are higher.Comment: 13 pages, 3 figures, accepted for publication in Physical Review
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