Fatty acid cycling mechanism and mitochondrial uncoupling proteins

AbstractWe hypothesize that fatty acid-induced uncoupling serves in bioenergetic systems to set the optimum efficiency and tune the degree of coupling of oxidative phosphorylation. Uncoupling results from fatty acid cycling, enabled by several phylogenetically specialized proteins and, to a lesser extent, by other mitochondrial carriers. It is suggested that the regulated uncoupling in mammalian mitochondria is provided by uncoupling proteins UCP-1, UCP-2 and UCP-3, whereas in plant mitochondria by PUMP and StUCP, all belonging to the gene family of mitochondrial carriers. UCP-1, and hypotheticaly UCP-3, serve mostly to provide nonshivering thermogenesis in brown adipose tissue and skeletal muscle, respectively. Fatty acid cycling was documented for UCP-1, PUMP and ADP/ATP carrier, and is predicted also for UCP-2 and UCP-3. UCP-1 mediates a purine nucleotide-sensitive uniport of monovalent unipolar anions, including anionic fatty acids. The return of protonated fatty acid leads to H+ uniport and uncoupling. UCP-2 is probably involved in the regulation of body weight and energy balance, in fever, and defense against generation of reactive oxygen species. PUMP has been discovered in potato tubers and immunologically detected in fruits and corn, whereas StUCP has been cloned and sequenced from a potato gene library. PUMP is supposed to act in the termination of synthetic processes in mature fruits and during the climacteric respiratory rise

Models for Minimax Stochastic Linear Optimization Problems with Risk Aversion

We propose a semidefinite optimization (SDP) model for the class of minimax two-stage stochastic linear optimization problems with risk aversion. The distribution of second-stage random variables belongs to a set of multivariate distributions with known first and second moments. For the minimax stochastic problem with random objective, we provide a tight SDP formulation. The problem with random right-hand side is NP-hard in general. In a special case, the problem can be solved in polynomial time. Explicit constructions of the worst-case distributions are provided. Applications in a production-transportation problem and a single facility minimax distance problem are provided to demonstrate our approach. In our experiments, the performance of minimax solutions is close to that of data-driven solutions under the multivariate normal distribution and better under extremal distributions. The minimax solutions thus guarantee to hedge against these worst possible distributions and provide a natural distribution to stress test stochastic optimization problems under distributional ambiguity.Singapore-MIT Alliance for Research and TechnologyNational University of Singapore. Dept. of Mathematic

Assessment of endometrial and ovarian characteristics using three dimensional power Doppler ultrasound to predict response in frozen embryo transfer cycles

<p>Abstract</p> <p>Objective</p> <p>To evaluate whether endometrial or ovarian parameters as measured using 3D power Doppler ultrasound would predict the outcome in frozen embryo transfer (FET) cycles.</p> <p>Methods</p> <p>Thirty women with no known gynecological pathology undergoing FET were recruited. The FET was carried out in the natural menstrual cycle 3-4 days after the first positive LH test result. Blood samples for hormonal analysis were collected, and three-dimensional (3D) ultrasonographic examination was performed on the day of the FET and repeated with analysis of the total hCG one week later.</p> <p>Results</p> <p>The demographic, clinical, and embryological characteristics were similar between the pregnant (15/30) and nonpregnant groups (15/30). There were no differences between the groups in endometrial/subendometrial thickness, volume, or vascularization index (VI). The endometrial triple-line pattern was more often present in the pregnant group on the day of the FET (93.3% vs. 40.0%, 95% CI 25.5-81.2%). No differences in the ovaries were observed on the day of the FET. At the second visit, the triple-line pattern was still more often present in those patients who had conceived (91.7% vs. 42.9%, 95% CI 18.5-79.1%), and their corpus luteum was more active as judged by the rise in 17-hydroxyprogesterone and estradiol levels. No differences were observed in the dominant ovarian vasculature.</p> <p>Conclusions</p> <p>According to our results, measurement of power Doppler indices using 3D ultrasound on the day of the FET does not provide any additional information concerning the outcome of the cycle. The existence of the triple-line pattern on the day of the FET seems to be a prognostic sign of a prosperous outcome after FET. The dominant ovary in the pregnant group seems to be already activated one week after the FET.</p

Kvalita života pacientů po totální laryngektomii: boj se stigmatizací a sociálním vyloučením pomocí řečové syntézy

V tomto článku se věnujeme problematice potenciální stigmatizace a sociálního vyloučení lidí, kteří mají problémy s mluvením kvůli rakovině v oblasti krku, zejména pak v důsledku ztráty hlasu v souvislosti s prodělanou totální laryngetomií. V článku analyzujeme, jak by mohla být tato potenciální stigmatizace alespoň zmírněna personalizovanou řečovou syntézou. Během výzkumu jsme využili smíšené metody, které se sestávaly z dotazníků cíleným na kvalitu života po totální laryngektomii a hloubkových rozhovorů s lidmi, kteří prodělali totální laryngektomii. Smíšené metody jsme zvolili kvůli větší zobecnitelnosti výsledků a zároveň bohatším datům. Zjistili jsme, že lidé s problémy s hlasem pociťuji depresi kvůli svému zdravotnímu stavu a také úzkost během sociálních interakcí, jelikož si myslí, že je ostatní vnímají jako abnormální, případně přímo zažívají symbolické násilí. Pro překonání těchto pocitů jsou důležité rodinné vazby a udržení zaměstnání. V obou případech může řečová syntéza klíčově pomoci.In this article, we deal with the problem of potential stigmatization and social exclusion of people that have voice/speech problems due to neck cancer, especially those who have lost their voice because of total laryngectomy, and we analyze how this potential stigmatization could be alleviated by personalized speech synthesis. We used a mixed-method approach, consisting of quality of life questionnaires and in-depth semi-structured interviews, in order to provide more generalizable as well as rich information. We found out that people with speech problems feel depressed because of their health status and anxiety during social interactions, as they think that other people perceive them as abnormal, or they directly experience symbolic violence. For overcoming these negative feelings, the crucial factors are family relationships and maintaining employment. In both factors, speech synthesis can help significantly

Distributionally robust optimization and its tractable approximations

10.1287/opre.1090.0795Operations Research584 PART 1902-917OPRE

Uncoupling protein 1 inhibition by purine nucleotides is under the control of the endogenous ubiquinone redox state.

We studied non-esterified fatty acid-induced uncoupling of heterologously expressed rat UCP1 (uncoupling protein 1) in yeast mitochondria, as well as UCP1 in rat BAT (brown adipose tissue) mitochondria. The proton-conductance curves and the relationship between the ubiquinone reduction level and membrane potential were determined in non-phosphorylating BAT and yeast mitochondria. The ADP/O method was applied to determine the ADP phosphorylation rate and the relationship between the ubiquinone reduction level and respiration rate in yeast mitochondria. Our studies of the membranous ubiquinone reduction level in mitochondria demonstrate that activation of UCP1 leads to a purine nucleotide-sensitive decrease in the ubiquinone redox state. Results obtained for non-phosphorylating and phosphorylating mitochondria, as the endogenous ubiquinone redox state was gradually varied by a lowering rate of the ubiquinone-reducing or ubiquinol-oxidizing pathways, indicate that the endogenous ubiquinone redox state has no effect on non-esterified fatty acid-induced UCP1 activity in the absence of GTP, and can only regulate this activity through sensitivity to inhibition by the purine nucleotide. At a given oleic acid concentration, inhibition by GTP diminishes when ubiquinone is reduced sufficiently. The ubiquinone redox state-dependent alleviation of UCP1 inhibition by the purine nucleotide was observed at a high ubiquinone reduction level, when it exceeded 85-88%