3,667 research outputs found
Convergence of simulated annealing by the generalized transition probability
We prove weak ergodicity of the inhomogeneous Markov process generated by the
generalized transition probability of Tsallis and Stariolo under power-law
decay of the temperature. We thus have a mathematical foundation to conjecture
convergence of simulated annealing processes with the generalized transition
probability to the minimum of the cost function. An explicitly solvable example
in one dimension is analyzed in which the generalized transition probability
leads to a fast convergence of the cost function to the optimal value. We also
investigate how far our arguments depend upon the specific form of the
generalized transition probability proposed by Tsallis and Stariolo. It is
shown that a few requirements on analyticity of the transition probability are
sufficient to assure fast convergence in the case of the solvable model in one
dimension.Comment: 11 page
High throughput quantification of N-glycans using one-pot sialic acid modification and matrix assisted laser desorption ionization time of flight mass spectrometry
Appropriate glycosylation of recombinant therapeutic glycoproteins has been emphasized in biopharmaceutical industries because the carbohydrate component can affect safety, efficacy, and consistency of the glycoproteins. Reliable quantification methods are essential to ensure consistency of their products with respect to glycosylation, particularly sialylation. Mass spectrometry (MS) has become a popular tool to analyze glycan profiles and structures, showing high resolution and sensitivity with structure identification ability. However, quantification of sialylated glycans using MS is not as reliable because of the different ionization efficiency between neutral and acidic glycans. We report here that amidation in mild acidic conditions can be used to neutralize acidic N-glycans still attached to the protein. The resulting amidated N-glycans can then released from the protein using PNGase F, and labeled with permanent charges on the reducing end to avoid any modification and the formation of metal adducts during MS analysis. The N-glycan modification, digestion, and desalting steps were performed using a single-pot method that can be done in microcentrifuge tubes or 96-well microfilter plates, enabling high throughput glycan analysis. Using this method we were able to perform quantitative MALDI-TOF MS of a recombinant human glycoprotein to determine changes in fucosylation and changes in sialylation that were in very good agreement with a normal phase HPLC oligosaccharide mapping method
A Transcriptomal Analysis of Bovine Oviductal Epithelial Cells Collected During the Follicular Phase Versus the Luteal Phase of the Estrous Cycle
BACKGROUND: Reproductive success depends on a functional oviduct for gamete storage, maturation, fertilization, and early embryonic development. The ovarian-derived steroids estrogen and progesterone are key regulators of oviductal function. The objective of this study was to investigate luteal and follicular phase-specific oviductal epithelial cell function by using microarray-based transcriptional profiling, to increase our understanding of mRNAs regulating epithelial cell processes, and to identify novel genes and biochemical pathways that may be found to affect fertility in the future.
METHODS: Six normally cycling Angus heifers were assigned to either luteal phase (LP, n = 3) or follicular phase (FP, n = 3) treatment groups. Heifers in the LP group were killed between day 11 and 12 after estrus. Heifers in the FP group were treated with 25 mg PGF2α (Lutalyse, Pfizer, NY) at 8 pm on day 6 after estrus and killed 36 h later. Transcriptional profiling by microarray and confirmation of selected mRNAs by real-time RT-PCR analyses was performed using total RNA from epithelial cells isolated from sections of the ampulla and isthmus collected from LP and FP treatment groups. Differentially expressed genes were subjected to gene ontology classification and bioinformatic pathway analyses.
RESULTS: Statistical one-way ANOVA using Benjamini-hochberg multiple testing correction for false discovery rate (FDR) and pairwise comparison of epithelial cells in the ampulla of FP versus LP groups revealed 972 and 597 transcripts up- and down-regulated, respectively (P \u3c 0.05). Within epithelial cells of the isthmus in FP versus LP groups, 946 and 817 transcripts were up- and down-regulated, respectively (P \u3c 0.05). Up-regulated genes from both ampulla and isthmus were found to be largely involved in cholesterol biosynthesis and cell cycle pathways, while down-regulated genes were found in numerous inflammatory response pathways.
CONCLUSIONS: Microarray-based transcriptional profiling revealed phase of the cycle-dependent changes in the expression of mRNA within the epithelium of the oviducts\u27 ampulla and isthmus
High throughput quantification of N-glycans using one-pot sialic acid modification and matrix assisted laser desorption ionization time of flight mass spectrometry
Appropriate glycosylation of recombinant therapeutic glycoproteins has been emphasized in biopharmaceutical industries because the carbohydrate component can affect safety, efficacy, and consistency of the glycoproteins. Reliable quantification methods are essential to ensure consistency of their products with respect to glycosylation, particularly sialylation. Mass spectrometry (MS) has become a popular tool to analyze glycan profiles and structures, showing high resolution and sensitivity with structure identification ability. However, quantification of sialylated glycans using MS is not as reliable because of the different ionization efficiency between neutral and acidic glycans. We report here that amidation in mild acidic conditions can be used to neutralize acidic N-glycans still attached to the protein. The resulting amidated N-glycans can then released from the protein using PNGase F, and labeled with permanent charges on the reducing end to avoid any modification and the formation of metal adducts during MS analysis. The N-glycan modification, digestion, and desalting steps were performed using a single-pot method that can be done in microcentrifuge tubes or 96-well microfilter plates, enabling high throughput glycan analysis. Using this method we were able to perform quantitative MALDI-TOF MS of a recombinant human glycoprotein to determine changes in fucosylation and changes in sialylation that were in very good agreement with a normal phase HPLC oligosaccharide mapping method
Tricarballylic ester formation during biosynthesis of fumonisin mycotoxins in \u3ci\u3eFusarium verticillioides\u3c/i\u3e
Fumonisins are agriculturally important mycotoxins produced by the maize pathogen Fusarium verticillioides. The chemical structure of fumonisins contains two tricarballylic esters, which are rare structural moieties and important for toxicity. The mechanism for the tricarballylic ester formation is not well understood. FUM7 gene of F. verticillioides was predicted to encode a dehydrogenase/reductase, and when it was deleted, the mutant produced tetradehydro fumonisins (DH4–FB). MS and NMR analysis of DH4–FB1 indicated that the esters consist of aconitate with a 3′-alkene function, rather than a 2′-alkene function. Interestingly, the purified DH4–FB1 eventually yielded three chromatographic peaks in HPLC. However, MS revealed that the metabolites of the three peaks all had the same mass as the initial single-peak DH4–FB1. The results suggest that DH4–FB1 can undergo spontaneous isomerization, probably including both cis–trans stereoisomerization and 3′- to 2′-ene regioisomerization. In addition, when FUM7 was expressed in Escherichia coli and the resulting enzyme, Fum7p, was incubated with DH4–FB, no fumonisin with typical tricarballylic esters was formed. Instead, new fumonisin analogs that probably contained isocitrate and/or oxalosuccinate esters were formed, which reveals new insight into fumonisin biosynthesis. Together, the data provided both genetic and biochemical evidence for the mechanism of tricarballylic ester formation in fumonisin biosynthesis
Methotrexate area under the curve is an important outcome predictor in patients with primary CNS lymphoma: A pharmacokinetic–pharmacodynamic analysis from the IELSG no. 20 trial
This analysis was initiated to define the predictive value of the area under the curve of high-dose methotrexate (AUC(HD-MTX)) in patients with primary central nervous system lymphoma (PCNSL).; We included 55 patients with PCNSL and available pharmacokinetic (PK) data from the International Extranodal Lymphoma Study Group (IELSG) no. 20 trial, randomised to HD-MTX (n=30) or HD-MTX and high-dose cytarabine (HD-AraC) (n=25). Individual AUC(HD-MTX) from population PK analysis was tested on drug toxicity and clinical outcome using multivariate logistic regression analysis and Cox hazards modelling.; AUC(HD-MTX), the IELSG score and treatment group were significant predictors for treatment response (complete or partial) in the adjusted model. The AUC(HD-MTX) did not predict toxicity, with the exception of liver toxicity and neutropaenia. A high AUC(HD-MTX) was associated with better event-free survival (EFS) (P=0.01) and overall survival (OAS) (P=0.02). Both the AUC(HD-MTX) and the IELSG score were significant predictors of EFS and OAS in the adjusted model, with a hazard ratio of 0.82 and 0.73, respectively, per 100 micromol l(-1) h(-1) increase in AUC(HD-MTX).; Individualised dosing of HD-MTX might have the potential to improve clinical outcome in patients with PCNSL, even when administered concurrently with HD-AraC. In the future, this could be carried out by using first-cycle PK modelling with determination of potential dose adaptations for later cycles using Bayesian analysis
Transport and superconducting properties of Fe-based superconductors: SmFeAs(O1-x Fx) versus Fe1+y (Te1-x, Sex)
We present transport and superconducting properties - namely resistivity,
magnetoresistivity, Hall effect, Seebeck effect, thermal conductivity, upper
critical field - of two different families of Fe-based superconductors, which
can be viewed in many respects as end members: SmFeAs(O1-xFx) with the largest
Tc and the largest anisotropy and Fe1+y(Te1-x,Sex), with the largest Hc2, the
lowest Tc and the lowest anisotropy. In the case of the SmFeAs(O1-xFx) series,
we find that a single band description allows to extract an approximated
estimation of band parameters such as carrier density and mobility from
experimental data, although the behaviour of Seebeck effect as a function of
doping demonstrates that a multiband description would be more appropriate. On
the contrary, experimental data of the Fe1+y(Te1-x,Sex) series exhibit a
strongly compensated behaviour, which can be described only within a multiband
model. In the Fe1+y(Te1-x,Sex) series, the role of the excess Fe, tuned by Se
stoichiometry, is found to be twofold: it dopes electrons in the system and it
introduces localized magnetic moments, responsible for Kondo like scattering
and likely pair-breaking of Cooper pairs. Hence, excess Fe plays a crucial role
also in determining superconducting properties such as the Tc and the upper
critical field Bc2. The huge Bc2 values of the Fe1+y(Te1-x,Sex) samples are
described by a dirty limit law, opposed to the clean limit behaviour of the
SmFeAs(O1-xFx) samples. Hence, magnetic scattering by excess Fe seems to drive
the system in the dirty regime, but its detrimental pairbreaking role seems not
to be as severe as predicted by theory. This issue has yet to be clarified,
addressing the more fundamental issue of the interplay between magnetism and
superconductivity
Excited States in 52Fe and the Origin of the Yrast Trap at I=12+
Excited states in 52Fe have been determined up to spin 10\hbar in the
reaction 28Si + 28Si at 115 MeV by using \gamma-ray spectroscopy methods at the
GASP array. The excitation energy of the yrast 10+ state has been determined to
be 7.381 MeV, almost 0.5 MeV above the well known \beta+-decaying yrast 12+
state, definitely confirming the nature of its isomeric character. The mean
lifetimes of the states have been measured by using the Doppler Shift
Attenuation method. The experimental data are compared with spherical shell
model calculations in the full pf-shell.Comment: 9 pages, RevTeX, 7 figures include
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