Mechanistic and computational studies of ferroin, simple organic acids, and bromine oxides : elucidating the complex electrochemical dance in an oscillating reaction

Before the year 1950, many chemists in their 'right mind' held the archaic belief that all chemical reactions proceed strictly from reactants to products, though some could be coaxed into reverse. What we now know colloquially as a potential energy surface was only visualized in more than two dimensions by the greatest thinkers at the time. The Belousov-Zhabotinsky (BZ) reaction is perhaps the most well-known of the 'chemical oscillators' and a prime example of a phenomenon that simply cannot be demystified given a two-dimensional data set. Though simulations of the BZ reaction produce reasonable results, to this day, not one published model has been capable of completely describing the chemistry that occurs. Some sort of halidehalogen-oxide cycle drives almost, if not, all known inorganic chemical oscillators, including those that proceed naturally in Earth's atmosphere. Catalytic indicators like cerium and ferroin, when added to the reaction mixtures, provide intuitive views of the chemical environment that we cannot normally see while moderately altering the reaction dynamics. Researchers worldwide have invested countless man-hours into producing different sets of data, from which the ultimate goal of describing this type of oscillating chemical reaction in detail will eventually be realized. In this study, we examine both basic and obscure chemical processes that proceed in a BZ mixture with a focus on those prepared in a continuously stirred tank reactor (CSTR), ideally in order to pave a new path for researchers that choose to fixate on this phenomenon in the future and help complete the already daunting collections of reactions that have been devised to describe the peculiar chemistry that occurs. Most everyone that has studied the BZ reaction in the past knows that it is perhaps the single most influential process in the modern era of knowledge regarding non-linear chemical dynamics. Since we opt for an entire laboratory in silico, this study will primarily examine physical and electronic mechanisms at the single- 2 molecule scale

A degenerate operator in non divergence form

In this paper we consider a fourth order operator in nondivergence form $Au:= au""$, where $a: [0,1] \rightarrow \mathcal R_+$ is a function that degenerates somewhere in the interval. We prove that the operator generates an analytic semigroup, under suitable assumptions on the function $a$. We extend these results to a general operator $A_nu := au^{(2n)}$

Cytochrome c Oxidase Deficiency: Study of Aberrant Phenotypes and their Connection to Secondary Functions of Assembly Factors

Mitochondria are double membrane-bound organelles present in all eukaryotic organisms and are involved in myriad cellular pathways. Cytochrome c oxidase (COX) is a mitochondrial inner membrane protein complex that is an essential component of the electron transport chain. The assembly of this multi-subunit protein complex is aided by the activities of proteins referred to as COX assembly factors. Mutations in COX assembly factors result in assembly failure and therefore cause COX deficiencies, which are associated with human diseases, such as Leigh syndrome. In this study, we used the model organism Saccharomyces cerevisiae to characterize phenotypes resulting from the loss of any one of a subset of COX assembly factors in cells grown to stationary phase. The vast majority of studies that involve yeast mitochondria have been performed in cells at late exponential phase/early diauxic shift, while the behaviours of mitochondrial mutants at stationary phase are still largely unexplored. Analyses of cellular functions such as growth, viability and budding index led us to uncover phenotypic differences among the COX assembly mutant strains that were further investigated as a first step towards identifying potential secondary functions of these proteins. Analysis of the cell cycle in a wild-type, respiratory competent strain and in COX assembly mutants led to the novel finding that strains unable to synthesize proteins involved in COX copper metalation, namely Cox17, Sco1 and Cox11, are characterized by a cell cycle progression defect. The same strains also displayed higher sensitivity to hydroxyurea, which is known to increase oxidative stress levels in yeast, leading us to propose that yeast strains defective for these proteins are subject to higher oxidative stress levels than mutants defective for COX assembly factors involved in other assembly pathways. The results of this study represent a major step forward in the phenotypic differentiation of COX deficiencies that arise from the loss of different assembly factors and may be relevant for future studies of human neurodegenerative disorders resulting from faulty COX assembly

Consecuencias económicas de una tecnología de producción robotizada

Observamos que la creciente automatización en los procesos de producción es un fenómeno de interés en la actualidad dado que la humanidad podría estar enfrentando cambios estructurales en varios sentidos. El desarrollo de robots, agentes económicos autónomos capaces de replicar el trabajo de un humano e interactuar con otras máquinas implicará lo que podría ser la entrada a una nueva era. Las consecuencias económicas redefinirán por completo a las sociedades como las conocemos hoy y es importante formalizar lo que sucede ahora para entender hacia dónde vamos. En especial nos interesa estudiar el impacto en términos de consumo per cápita y retribución a los factores. Concluimos que el consumo per cápita va a aumentar notablemente pero que la distribución de la riqueza será más desigual si no hay cambios profundos en materia política, económica y educacional

Consequences of cytochrome c oxidase assembly defects for the yeast stationary phase

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.bbabio.2018.03.011 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/The assembly of cytochrome c oxidase (COX) is essential for a functional mitochondrial respiratory chain, although the consequences of a loss of assembled COX at yeast stationary phase, an excellent model for terminally differentiated cells in humans, remain largely unexamined. In this study, we show that a wild-type respiratory competent yeast strain at stationary phase is characterized by a decreased oxidative capacity, as seen by a reduction in the amount of assembled COX and by a decrease in protein levels of several COX assembly factors. In contrast, loss of assembled COX results in the decreased abundance of many mitochondrial proteins at stationary phase, which is likely due to decreased membrane potential and changes in mitophagy. In addition to an altered mitochondrial proteome, COX assembly mutants display unexpected changes in markers of cellular oxidative stress at stationary phase. Our results suggest that mitochondria may not be a major source of reactive oxygen species at stationary phase in cells lacking an intact respiratory chain.Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant (RGPIN-227415-2012)Undergraduate Research Internship (URI) Program at the University of Waterlo

Hallux rigidus: A cross-sectional study to evaluate clinical parameters

Background: Hallux rigidus (HR) is a common condition with history and physical examination used to help evaluate pathology, grade clinical changes and to inform treatment. Method: A cross-sectional study was undertaken to evaluate the demographics of and clinical parameters encountered in HR. In 110 subjects (180 feet) aged 18–70 years (mean 52 years) a standardized history and physical examination was undertaken. Clinical parameters associated with HR were evaluated. The Foot Health Status Questionnaire (FHSQ) was used to measure health-related quality-of-life dimensions. Results: Seventy (64%) subjects had bilateral HR and 73 (66%)were female. Mean HR onsetwas 44 (14–68 years) years and median HR duration 6 years (1–33 years). A history of 1st MTPJ trauma presented in 22% of subjects; 74% of whom had unilateral HR. Eighty-four (47%) feet had pes planus based on a positive Foot Posture Index. A correlation between pes planus and 1st MTPJ pain was found (r = 0.84, p = 0.05). In 74% of feet, hallux abductus interphalangeus angle (HAI◦) was greater than normal (≤10◦). A correlation between HAI and reduced 1st MTPJ ROM was found (r = 0.92, p = 0.05). Second toe length was the same as the hallux in 111 feet (62%). A correlation between valgus hallucal rotation and 1st MTP joint pain in HR was found (r = .78, p = .05). A positive relationship was found between 2nd toe length and 1st MTPJ pain (p = 0.001 < 0.05). A correlation between hallucal interphalangeal joint (IPJ) hyperextension and 1st MTPJ pain was found (r = 0.78, p = 0.01). A positive relationship was found between lesser MTPJ pain and supination at propulsion (p < 0.001). There was no evidence of Achilles tendon contracture. The FHSQ results concur with clinical findings. Conclusions: HR was associated with female gender, bilateral involvement, older age groups, increased HAI◦, 2nd toe length similar to hallux, hallucal IPJ hyperextension, lesser MTP joint pain, flat foot and certain gait alterations. HR was not associated with Achilles tendon tightness or footwear. The content validity of clinical parameters of HR needs to be established by formal research prior to their inclusion in a classification of H

Efficacy of intra-articular hyaluronan (Synvisc®) for the treatment of osteoarthritis affecting the first metatarsophalangeal joint of the foot (hallux limitus): study protocol for a randomised placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis of the first metatarsophalangeal joint (MPJ) of the foot, termed <it>hallux limitus</it>, is common and painful. Numerous non-surgical interventions have been proposed for this disorder, however there is limited evidence for their efficacy. Intra-articular injections of hyaluronan have shown beneficial effects in case-series and clinical trials for the treatment of osteoarthritis of the first metatarsophalangeal joint. However, no study has evaluated the efficacy of this form of treatment using a randomised placebo controlled trial. This article describes the design of a randomised placebo controlled trial to evaluate the efficacy of intra-articular hyaluronan (Synvisc^®) to reduce pain and improve function in people with hallux limitus.</p> <p>Methods</p> <p>One hundred and fifty community-dwelling men and women aged 18 years and over with hallux limitus (who satisfy inclusion and exclusion criteria) will be recruited.</p> <p>Participants will be randomised, using a computer-generated random number sequence, to receive a single intra-articular injection of up to 1 ml hyaluronan (Synvisc^®) or sterile saline (placebo) into the first MPJ. The injections will be performed by an interventional radiologist using fluoroscopy to ensure accurate deposition of the hyaluronan in the joint. Participants will be given the option of a second and final intra-articular injection (of Synvisc^®or sterile saline according to the treatment group they are in) either 1 or 3 months post-treatment if there is no improvement in pain and the participant has not experienced severe adverse effects after the first injection. The primary outcome measures will be the pain and function subscales of the Foot Health Status Questionnaire. The secondary outcome measures will be pain at the first MPJ (during walking and at rest), stiffness at the first MPJ, passive non-weightbearing dorsiflexion of the first MPJ, plantar flexion strength of the toe-flexors of the hallux, global satisfaction with the treatment, health-related quality of life (assessed using the Short-Form-36 version two questionnaire), magnitude of symptom change, use of pain-relieving medication and changes in dynamic plantar pressure distribution (maximum force and peak pressure) during walking. Data will be collected at baseline, then 1, 3 and 6 months post-treatment. Data will be analysed using the intention to treat principle.</p> <p>Discussion</p> <p>This study is the first randomised placebo controlled trial to evaluate the efficacy of intra-articular hyaluronan (Synvisc^®) for the treatment of osteoarthritis of the first MPJ (hallux limitus). The study has been pragmatically designed to ensure that the study findings can be implemented into clinical practice if this form of treatment is found to be an effective treatment strategy.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry: ACTRN12607000654459</p

Electronic Structures and Spin Density Distributions of BrO₂ and (HO)₂BrO Radicals. Mechanisms for Avoidance of Hypervalency and for Spin Delocalization and Spin Polarization

The results are reported of an ab initio study of bromine dioxide BrO2, 1, and of the T-shaped trans- and cis-dihydroxides 2 and 3 of dihydrogen bromate (HO)2BrO. The thermochemistry has been explored of potential synthetic routes to (HO)2BrO involving water addition to BrO2, hydroxyl addition to bromous acid HOBrO, 4, protonation/reduction of bromic acid HOBrO2, 5, via tautomers 6-8 of protonated bromic acid, and by reduction/protonation of bromic acid via radical anion [HOBrO2]−, 9. The potential energy surface analyses were performed at the MP2(full)/6-311G* level (or better) and with the consideration of aqueous solvation at the SMD(MP2(full)/6-311G*) level (or better), and higher-level energies were computed at levels up to QCISD(full,T)/6-311++G(2df,2pd)//MP2. The addition of RO radical to bromous acid or bromite esters and the reduction of protonated bromic acid or protonated bromate esters are promising leads for possible synthetic exploration. Spin density distributions and molecular electrostatic potentials were computed at the QCISD(full)/6-311G*//MP2(full)/6-311G* level to characterize the electronic structures of 1-3. Both radicals employ maximally occupied (pseudo) π-systems to transfer electron density from bromine to the periphery. While the formation of the (3c-5e) π-system suffices to avoid hypervalency in 1, the formation of the (4c-7e) π-system in 2 or 3 still leaves the bromine formally hypervalent and (HO)2BrO requires delocalization of bromine density into σ*-SMOs over the trans O-Br-O moiety. Molecular orbital theory is employed to describe the mechanisms for the avoidance of hypervalency and for spin delocalization and spin polarization. The (4c-7e) π-system in 2 is truly remarkable in that it contains five π-symmetric spin molecular orbitals (SMO) with unique shapes

Isolation and mass spectrometry-based characterization of the proteome of yeast peroxisomes

Sviluppo di un nuovo metodo per la detenzione del contenuto di prostaglandine (PGE2 e 11-BPGE2) in campioni biologici derivati dal saggio enzimatico in PGES