16 research outputs found
Q# as a Quantum Algorithmic Language
Q# is a standalone domain-specific programming language from Microsoft for
writing and running quantum programs. Like most industrial languages, it was
designed without a formal specification, which can naturally lead to ambiguity
in its interpretation. We aim to provide a formal language definition for Q#,
placing the language on a solid mathematical foundation and enabling further
evolution of its design and type system. This paper presents -Q#, an
idealized version of Q# that illustrates how we may view Q# as a quantum Algol
(algorithmic language). We show the safety properties enforced by
-Q#'s type system and present its equational semantics based on a
fully complete algebraic theory by Staton.Comment: In Proceedings QPL 2022, arXiv:2311.0837
CIViCdb 2022: Evolution of an open-access cancer variant interpretation knowledgebase
CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC\u27s functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new Evidence Types (Predisposing, Oncogenic and Functional). The growing CIViC knowledgebase has over 300 contributors and distributes clinically-relevant cancer variant data currently representing \u3e3200 variants in \u3e470 genes from \u3e3100 publications
Differential Effects of Short Term Feeding of a Soy Protein Isolate Diet and Estrogen Treatment on Bone in the Pre-Pubertal Rat
BACKGROUND: Previous reports suggest that beneficial effects of soy on bone quality are due to the estrogenic actions of isoflavone phytochemicals associated with the protein. However, mechanistic studies comparing the effects of soy diet and estrogens on bone, particularly in rapidly growing animals are lacking. METHODOLOGY AND PRINCIPAL FINDINGS: We studied the effects of short term feeding of soy protein isolate (SPI) on bone in comparison to the effects of 17β-estradiol (E2) in pre-pubertal rats. Female rats were weaned to one of 4 treatments: 1) a control casein-based diet (CAS); 2) CAS with subcutaneous E2 (10 µg/kg/d) (CAS+E2); 3) a SPI-containing diet (SPI); or 4) SPI with subcutaneous E2 (SPI) or SPI with 10 µg/kg/d E2 (SPI+E2) for 14 days beginning on postnatal day 20. SPI increased while E2 decreased bone turnover compared to CAS. In contrast, both treatments decreased serum sclerostin levels. Microarray analysis of RNA isolated from bone revealed 652 genes regulated by SPI, 491 genes regulated by E2, and 266 genes regulated by both SPI diet and E2 compared to CAS. The expression of caveolin-1, a protein localized in the cell membrane, was down-regulated (p<0.05) in rats fed SPI, but not by E2 compared to rats fed casein. Down-regulation of caveolin-1 by SPI was associated with increased BMP2, Smad and Runx2 expression in bone and osteoblasts (p<0.05). CONCLUSIONS/SIGNIFICANCE: These results suggest SPI and E2 have different effects on bone turnover prior to puberty. Approximately half of the genes are regulated in the same direction by E2 or SPI, but in combination, SPI blocks the estrogen effects and returns the profile towards control levels. In addition, there are E2 specific and SPI-specific gene changes related to regulation of bone formation
Maternal Obesity during Gestation Impairs Fatty Acid Oxidation and Mitochondrial SIRT3 Expression in Rat Offspring at Weaning
In utero exposure to maternal obesity increases the offspring's risk of obesity in later life. We have also previously reported that offspring of obese rat dams develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature in the liver at postnatal day (PND)21. In the current study, we examined systemic and hepatic adaptations in male Sprague-Dawley offspring from lean and obese dams at PND21. Indirect calorimetry revealed decreases in energy expenditure (p<0.001) and increases in RER values (p<0.001), which were further exacerbated by high fat diet (45% kcals from fat) consumption indicating an impaired ability to utilize fatty acids in offspring of obese dams as analyzed by PRCF. Mitochondrial function is known to be associated with fatty acid oxidation (FAO) in the liver. Several markers of hepatic mitochondrial function were reduced in offspring of obese dams. These included SIRT3 mRNA (p = 0.012) and mitochondrial protein content (p = 0.002), electron transport chain complexes (II, III, and ATPase), and fasting PGC-1α mRNA expression (p<0.001). Moreover, hepatic LCAD, a SIRT3 target, was not only reduced 2-fold (p<0.001) but was also hyperacetylated in offspring of obese dams (p<0.005) suggesting decreased hepatic FAO. In conclusion, exposure to maternal obesity contributes to early perturbations in whole body and liver energy metabolism. Mitochondrial dysfunction may be an underlying event that reduces hepatic fatty acid oxidation and precedes the development of detrimental obesity associated co-morbidities such as insulin resistance and NAFLD
CIViCdb 2022: evolution of an open-access cancer variant interpretation knowledgebase
CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC’s functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new Evidence Types (Predisposing, Oncogenic and Functional). The growing CIViC knowledgebase has over 300 contributors and distributes clinically-relevant cancer variant data currently representing &gt;3200 variants in &gt;470 genes from &gt;3100 publications
Ocular Manifestations of Neuronal Ceroid Lipofuscinoses
Neuronal ceroid lipofuscinoses (NCLs) are a group of rare neurodegenerative storage disorders associated with devastating visual prognosis, with an incidence of 1/1,000,000 in the United States and comparatively higher incidence in European countries. The pathophysiological mechanisms causing NCLs occur due to enzymatic or transmembrane defects in various sub-cellular organelles including lysosomes, endoplasmic reticulum, and cytoplasmic vesicles. NCLs are categorized into different types depending upon the underlying cause i.e., soluble lysosomal enzyme deficiencies or non-enzymatic deficiencies (functions of identified proteins), which are sub-divided based on an axial classification system. In this review, we have evaluated the current evidence in the literature and reported the incidence rates, underlying mechanisms and currently available management protocols for these rare set of neuroophthalmological disorders. Additionally, we also highlighted the potential therapies under development that can expand the treatment of these rare disorders beyond symptomatic relief.Ophthalmic researc
Modulation of Nitrous Oxide (N<sub>2</sub>O) Accumulation by Primary Metabolites in Denitrifying Cultures Adapting to Changes in Environmental C and N
Metabolomics
provides insights into the actual physiology of cells
rather than their mere “potential”, as provided by genomic
and transcriptomic analysis. We investigate the modulation of nitrous
oxide (N<sub>2</sub>O) accumulation by intracellular metabolites in
denitrifying bacteria using metabolomics and genome-based metabolic
network modeling. Profiles of metabolites and their rates of production/consumption
were obtained for denitrifying batch cultures under four conditions:
initial COD:N ratios of 11:1 and 4:1 with and without nitrite spiking
(28 mg-N L<sup>–1</sup>). Only the nitrite-spiked cultures
accumulated N<sub>2</sub>O. The NO<sub>2</sub><sup>–</sup> spiked
cultures with an initial COD:N = 11:1 accumulated 3.3 ± 0.57%
of the total nitrogen added as N<sub>2</sub>O and large pools of tricarboxylic
acid cycle intermediates and amino acids. In comparison, the NO<sub>2</sub><sup>–</sup> spiked cultures with COD:N = 4:1 showed
significantly higher (p = 0.028) N<sub>2</sub>O accumulation (8.5.3
± 0.9% of the total nitrogen added), which was linked to the
depletion of C11–C20 fatty acids. Metabolic modeling analysis
shows that at COD:N of 4:1 the denitrifying cells slowly generate
electron equivalents as FADH<sub>2</sub> through β-oxidation
of saturated fatty acids, while COD:N of 11:1 do it through the TCA
cycle. When combined with NO<sub>2</sub><sup>–</sup> shock,
this prolonged the duration over which insufficient electron equivalents
were available to completely reduce NOx to N<sub>2</sub>, resulting
in increased N<sub>2</sub>O accumulation. Results extend the understanding
of how organic carbon and nitrite loads modulate N<sub>2</sub>O accumulation
in denitrification, which may contribute to further design strategies
to control greenhouse gas emissions from agricultural soils or wastewater
treatment systems