536 research outputs found
Conditions for duality between fluxes and concentrations in biochemical networks
Mathematical and computational modelling of biochemical networks is often
done in terms of either the concentrations of molecular species or the fluxes
of biochemical reactions. When is mathematical modelling from either
perspective equivalent to the other? Mathematical duality translates concepts,
theorems or mathematical structures into other concepts, theorems or
structures, in a one-to-one manner. We present a novel stoichiometric condition
that is necessary and sufficient for duality between unidirectional fluxes and
concentrations. Our numerical experiments, with computational models derived
from a range of genome-scale biochemical networks, suggest that this
flux-concentration duality is a pervasive property of biochemical networks. We
also provide a combinatorial characterisation that is sufficient to ensure
flux-concentration duality. That is, for every two disjoint sets of molecular
species, there is at least one reaction complex that involves species from only
one of the two sets. When unidirectional fluxes and molecular species
concentrations are dual vectors, this implies that the behaviour of the
corresponding biochemical network can be described entirely in terms of either
concentrations or unidirectional fluxes
Acrylamide formation in potato products
End of Project ReportAcrylamide, a substance classified as a potential carcinogen, occurs in heated
starchy foods at concentrations many times in excess of levels permitted in
drinking water. Early surveys indicated that levels of acrylamide in potato
products such as French fries and potato crisps were the highest of the
foodstuffs investigated. The present project addressed this issue by
determining levels of acrylamide precursors (asparagine and reducing sugars)
in raw potatoes and levels of acrylamide in (i) potato products from different
storage regimes, (ii) spot-sampled potatoes purchased from a local
supermarket, (iii) samples that received pre-treatments and were fried at
different temperatures and (iv) French fries reheated in different ovens.A risk
assessment of the estimated acrylamide intake from potato products for
various cohorts of the Irish population was also conducted
Disrupted Superior Collicular Activity May Reveal Cervical Dystonia Disease Pathomechanisms
Cervical dystonia is a common neurological movement disorder characterised by muscle contractions causing abnormal movements and postures affecting the head and neck. The neural networks underpinning this condition are incompletely understood. While animal models suggest a role for the superior colliculus in its pathophysiology, this link has yet to be established in humans. The present experiment was designed to test the hypothesis that disrupted superior collicular processing is evident in affected patients and in relatives harbouring a disease-specific endophenotype (abnormal temporal discrimination). The study participants were 16 cervical dystonia patients, 16 unaffected first-degree relatives with abnormal temporal discrimination, 16 unaffected first-degree relatives with normal temporal discrimination and 16 healthy controls. The response of participantâs superior colliculi to looming stimuli was assessed by functional magnetic resonance imaging. Cervical dystonia patients and relatives with abnormal temporal discrimination demonstrated (i) significantly reduced superior collicular activation for whole brain and region of interest analysis; (ii) a statistically significant negative correlation between temporal discrimination threshold and superior collicular peak values. Our results support the hypothesis that disrupted superior collicular processing is involved in the pathogenesis of cervical dystonia. These findings, which align with animal models of cervical dystonia, shed new light on pathomechanisms in humans
Pevonedistat (MLN4924), a FirstâinâClass NEDD8âactivating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111220/1/bjh13323.pd
Deciphering the genome structure and paleohistory of _Theobroma cacao_
We sequenced and assembled the genome of _Theobroma cacao_, an economically important tropical fruit tree crop that is the source of chocolate. The assembly corresponds to 76% of the estimated genome size and contains almost all previously described genes, with 82% of them anchored on the 10 _T. cacao_ chromosomes. Analysis of this sequence information highlighted specific expansion of some gene families during evolution, for example flavonoid-related genes. It also provides a major source of candidate genes for _T. cacao_ disease resistance and quality improvement. Based on the inferred paleohistory of the T. cacao genome, we propose an evolutionary scenario whereby the ten _T. cacao_ chromosomes were shaped from an ancestor through eleven chromosome fusions. The _T. cacao_ genome can be considered as a simple living relic of higher plant evolution
Thymus transplantation for complete DiGeorge syndrome: European experience
Background: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). Methods: Twelve patients with cDGS were transplanted with allogeneic cultured thymus. Objective: To confirm and extend the results previously obtained in a single centre. Results: Two patients died of pre-existing viral infections without developing thymopoeisis and one late death occurred from autoimmune thrombocytopaenia. One infant suffered septic shock shortly after transplant resulting in graft loss and the need for a second transplant. Evidence of thymopoeisis developed from 5-6 months after transplantation in ten patients. The median (range) of circulating naïve CD4 counts (x10663 /L) were 44(11-440) and 200(5-310) at twelve and twenty-four months post-transplant and T-cell receptor excision circles were 2238 (320-8807) and 4184 (1582 -24596) per106 65 T-cells. Counts did not usually reach normal levels for age but patients were able to clear pre-existing and later acquired infections. At a median of 49 months (22-80), eight have ceased prophylactic antimicrobials and five immunoglobulin replacement. Histological confirmation of thymopoeisis was seen in seven of eleven patients undergoing biopsy of transplanted tissue including five showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator (AIRE) expression was also demonstrated. Autoimmune complications were seen in 7/12 patients. In two, early transient autoimmune haemolysis settled after treatment and did not recur. The other five suffered ongoing autoimmune problems including: thyroiditis (3); haemolysis (1), thrombocytopaenia (4) and neutropenia (1). Conclusions: This study confirms the previous reports that thymus transplantation can reconstitute T cells in cDGS but with frequent autoimmune complications in survivors
BigDL: A Distributed Deep Learning Framework for Big Data
This paper presents BigDL (a distributed deep learning framework for Apache
Spark), which has been used by a variety of users in the industry for building
deep learning applications on production big data platforms. It allows deep
learning applications to run on the Apache Hadoop/Spark cluster so as to
directly process the production data, and as a part of the end-to-end data
analysis pipeline for deployment and management. Unlike existing deep learning
frameworks, BigDL implements distributed, data parallel training directly on
top of the functional compute model (with copy-on-write and coarse-grained
operations) of Spark. We also share real-world experience and "war stories" of
users that have adopted BigDL to address their challenges(i.e., how to easily
build end-to-end data analysis and deep learning pipelines for their production
data).Comment: In ACM Symposium of Cloud Computing conference (SoCC) 201
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