Review—Organic Materials for Thermoelectric Energy Generation

Organic semiconductor materials have been promising alternatives to their inorganic counterparts in several electronic applications such as solar cells, light emitting diodes, field effect transistors as well as thermoelectric generators. Their low cost, light weight and flexibility make them appealing in future applications such as foldable electronics and wearable circuits using printing techniques. In this report, we present a mini-review on the organic materials that have been used for thermoelectric energy generation

MODELLING THE ELECTRON WITH COSSERAT ELASTICITY

Interactions between a finite number of bodies and the surrounding fluid, in a channel for instance, are investigated theoretically. In the planar model here the bodies or modelled grains are thin solid bodies free to move in a nearly parallel formation within a quasi-inviscid fluid. The investigation involves numerical and analytical studies and comparisons. The three main features that appear are a linear instability about a state of uniform motion, a clashing of the bodies (or of a body with a side wall) within a finite scaled time when nonlinear interaction takes effect, and a continuum-limit description of the body–fluid interaction holding for the case of many bodies

Lack of effect of citalopram on magnetic resonance spectroscopy measures of glutamate and glutamine in frontal cortex of healthy volunteers

Magnetic resonance spectroscopy (MRS) is a non-invasive imaging technique that can provide localised measures of brain chemistry in vivo. We previously found that healthy volunteers receiving the selective serotonin reuptake inhibitor, citalopram, daily for 1 week showed higher levels of a combined measure of glutamate and glutamine (Glx) in occipital cortex than those receiving placebo. The aim of this study was to assess if a similar effect could be detected in the frontal brain region. Twenty-three healthy volunteers randomised to receive either citalopram 20 mg or a placebo capsule daily for 7–10 days were studied and scanned using a 3T Varian INOVA system before and at the end of treatment. Standard short-TE (echo time) PRESS (Point-resolved spectroscopy) (TE = 26 ms) and PRESS-J spectra were acquired from a single 8-cm3 voxel in a frontal region incorporating anterior cingulate cortex. Glutamate and total Glx levels were quantified both relative to creatine and as absolute levels. Relative to placebo, citalopram produced no change in Glx or glutamate alone at the end of the study. Similarly, no effect was seen on other MRS measures studied: myo-inositol, choline, N-acetylaspartate and creatine. These data suggest that the effects of serotonin reuptake to modify cortical glutamatergic MRS measures may be regionally specific. This supports the potential for MRS in assessing neuroanatomically specific serotonin-glutamate interactions in the human brain

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata

The evolution of drug resistance has a profound impact on human health. Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins, which target cell wall biosynthesis and are front-line therapeutics for Candida infections. Here, we provide the first global analysis of mutations accompanying the evolution of fungal drug resistance in a human host utilizing a series of C. glabrata isolates that evolved echinocandin resistance in a patient treated with the echinocandin caspofungin for recurring bloodstream candidemia. Whole genome sequencing identified a mutation in the drug target, FKS2, accompanying a major resistance increase, and 8 additional non-synonymous mutations. The FKS2-T1987C mutation was sufficient for echinocandin resistance, and associated with a fitness cost that was mitigated with further evolution, observed in vitro and in a murine model of systemic candidemia. A CDC6-A511G(K171E) mutation acquired before FKS2-T1987C(S663P), conferred a small resistance increase. Elevated dosage of CDC55, which acquired a C463T(P155S) mutation after FKS2-T1987C(S663P), ameliorated fitness. To discover strategies to abrogate echinocandin resistance, we focused on the molecular chaperone Hsp90 and downstream effector calcineurin. Genetic or pharmacological compromise of Hsp90 or calcineurin function reduced basal tolerance and resistance. Hsp90 and calcineurin were required for caspofungin-dependent FKS2 induction, providing a mechanism governing echinocandin resistance. A mitochondrial respiration-defective petite mutant in the series revealed that the petite phenotype does not confer echinocandin resistance, but renders strains refractory to synergy between echinocandins and Hsp90 or calcineurin inhibitors. The kidneys of mice infected with the petite mutant were sterile, while those infected with the HSP90-repressible strain had reduced fungal burden. We provide the first global view of mutations accompanying the evolution of fungal drug resistance in a human host, implicate the premier compensatory mutation mitigating the cost of echinocandin resistance, and suggest a new mechanism of echinocandin resistance with broad therapeutic potential

Mean ergodic composition operators on generalized Fock spaces

[EN] Every bounded composition operator C psi defined by an analytic symbol psi on the complex plane when acting on generalized Fock spaces F phi p,1 <= p <=infinity and p=0, is power bounded. Mean ergodic and uniformly mean ergodic bounded composition operators on these spaces are characterized in terms of the symbol. The behaviour for p=0 and p=infinity differs. The set of periodic points of these operators is also determined.The research of the first author is supported by ISP project, Addis Ababa University, Ethiopia. The research of the third author was partially supported by the research projects MTM2016-76647-P and GV Prometeo 2017/102 (Spain).Seyoum, W.; Mengestie, T.; Bonet Solves, JA. (2019). Mean ergodic composition operators on generalized Fock spaces. Revista de la Real Academia de Ciencias Exactas Físicas y Naturales Serie A Matemáticas. 114(1):1-11. https://doi.org/10.1007/s13398-019-00738-wS1111141Albanese, A.A., Bonet, J., Ricker, W.J.: Mean ergodic operators in Fréchet spaces. Anal. Acad. Sci. Fenn. Math. 34, 401–436 (2009)Beltrán-Meneu, M.J., Gómez-Collado, M.C., Jordá, E., Jornet, D.: Mean ergodic composition operators on Banach spaces of holomorphic functions. J. Funct. Anal. 270, 4369–4385 (2016)Bierstedt, K.D., Summers, W.H.: Biduals of weighted Banach spaces of analytic functions. J. Austr. Math. Soc. Ser. A 54, 70–79 (1993)Blasco, O.: Boundedness of Volterra operators on spaces of entire functions. Ann. Acad. Sci. Fenn. Math. 43, 89–107 (2018)Bonet, J., Domański, P.: A note on mean ergodic composition operators on spaces of holomorphic functions. Rev. R. Acad. Cienc. Exactas Fís. Nat. Ser. A Mat. RACSAM 105, 389–396 (2011)Bonet, J., Mangino, E.: Associated weights for spaces of $$p$$-integrable entire functions. Quaestiones Math. (2019). https://doi.org/10.2989/16073606.2019.1605420Bonet, J., Ricker, W.J.: Mean ergodicity of multiplication operators in weighted spaces of holomorphic functions. Arch. Math. 92, 428–437 (2009)Carswell, B.J., MacCluer, B.D., Schuster, A.: Composition operators on the Fock space. Acta Sci. Math. (Szeged) 69, 871–887 (2003)Constantin, O., Peláez, J.Á.: Integral operators, embedding theorems and a Littlewood-Paley formula on weighted Fock spaces. J. Geom. Anal. 26, 1109–1154 (2015)Cowen, C., MacCluer, B.: Composition Operators on Spaces of Analytic Functions. CRC Press, Boca Raton (1995)Dunford, N.: Spectral theory I convergence to projections. Trans. Am. Math. Soc. 54, 185–217 (1943)Guo, K., Izuchi, K.: Composition operators on Fock type space. Acta Sci. Math. (Szeged) 74, 807–828 (2008)Krengel, U.: Ergodic Theorems. Walter de Gruyter, Berlin (1985)Lotz, H.P.: Tauberian theorems for operators on $$L^1$$ and similar spaces. In: Bierstedt, K.D., Fuchssteiner, B. (eds.) Functional Analysis: Surveys and Recent Results III, pp. 117–133. North Holland, Amsterdam (1984)Lotz, H.P.: Uniform convergence of operators on $$L^{\infty }$$ and similar spaces. Math. Z. 190, 207–220 (1985)Lusky, W.: On the isomophism classes of weighted spaces of harmonic and holomorphic functions. Studia Math. 175, 19–45 (2006)Mengestie, T., Ueki, S.: Integral, differential and multiplication operators on weighted Fock spaces. Complex Anal. Oper. Theory. 13, 935–958 (2019)Mengestie, T., Seyoum, W.: Topological and dynamical properties of composition operators. Complex Anal. Oper. Theory (2018) (to appear)Mengestie, T., Seyoum, W.: Spectral properties of composition operators on Fock-Type spaces. Quaest. Math. (2019). https://doi.org/10.2989/16073606.2019.1692092Shapiro, J.H.: Composition Operators and Classical Function Theory. Springer, New York (1993)Wolf, E.: Power bounded composition operator. Comp. Method Funct. Theory 12, 105–117 (2012)Yosida, K.: Functional Analysis. Springer, Berlin (1978)Yosida, K., Kakutani, S.: Operator-theoretical treatment of Markoff’s Process and Mean Ergodic Theorem. Ann. Math. 42, 188–228 (1941

Childhood loneliness as a predictor of adolescent depressive symptoms: an 8-year longitudinal study

Childhood loneliness is characterised by children’s perceived dissatisfaction with aspects of their social relationships. This 8-year prospective study investigates whether loneliness in childhood predicts depressive symptoms in adolescence, controlling for early childhood indicators of emotional problems and a sociometric measure of peer social preference. 296 children were tested in the infant years of primary school (T1 5 years of age), in the upper primary school (T2 9 years of age) and in secondary school (T3 13 years of age). At T1, children completed the loneliness assessment and sociometric interview. Their teachers completed externalisation and internalisation rating scales for each child. At T2, children completed a loneliness assessment, a measure of depressive symptoms, and the sociometric interview. At T3, children completed the depressive symptom assessment. An SEM analysis showed that depressive symptoms in early adolescence (age 13) were predicted by reports of depressive symptoms at age 8, which were themselves predicted by internalisation in the infant school (5 years). The interactive effect of loneliness at 5 and 9, indicative of prolonged loneliness in childhood, also predicted depressive symptoms at age 13. Parent and peer-related loneliness at age 5 and 9, peer acceptance variables, and duration of parent loneliness did not predict depression. Our results suggest that enduring peer-related loneliness during childhood constitutes an interpersonal stressor that predisposes children to adolescent depressive symptoms. Possible mediators are discussed

Ageing of enteric neurons: oxidative stress, neurotrophic factors and antioxidant enzymes

Background: Ageing is associated with gastrointestinal dysfunction, which can have a major impact on quality of life of the elderly. A number of changes in the innervation of the gut during ageing have been reported, including neuronal loss and degenerative changes. Evidence indicates that reactive oxygen species (ROS) are elevated in ageing enteric neurons, but that neurotrophic factors may reduce generation of neuronal ROS. Two such factors, glial cell line derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) have also been found to protect enteric neurons against oxidative stress induced cell death of enteric ganglion cells in vitro. We have investigated the possible roles of neurotrophic factors further, by examining their expression in the gut during ageing, and by analysing their effects on antioxidant enzyme production in cultures of enteric ganglion cells. Results: Analysis of the expression of GDNF and its receptors c-Ret and GFR α − 1 in rat gut by RT-PCR showed that expression continues throughout life and into ageing, in both ad libitum(AL) and calorically-restricted (CR) animals. Levels of expression of GDNF and GFR α − 1 were elevated in 24 month AL animals compared to 24 month CR animals, and to 24 CR and 6 month control animals respectively. The related factor Neurturin and its receptor GFR α − 2 were also expressed throughout life, the levels of the GFR – α-2(b) isoform were reduced in 24 m AL animals. Immunolabelling showed that c-Ret and GFR α − 1 proteins were expressed by myenteric neurons in ageing animals. GDNF, but not NT-3, was found to increase expression of Cu/Zn superoxide dismutase and catalase by cultured enteric ganglion cells. Conclusions: The neurotrophic factors GDNF and neurturin and their receptors continue to be expressed in the ageing gut. Changes in the levels of expression of GDNF , GFR α-1 and GFR α-2(b) isoform occurred in 24 m AL animals. GDNF, but not NT-3, increased the levels of antioxidant enzymes in cultured enteric ganglion cells, indicating a possible mechanism for the reported protective effect of GDNF against menadione-induced neuronal apoptosis in the ageing gut. Together these data suggest that GDNF family members may play a protective role in the gut throughout life, and support the suggestion that dysregulation of neurotrophic factor support could contribute to neuronal ageing in the gut

Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study

OBJECTIVE: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). METHODS: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. RESULTS: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] -9.9 [0.77], p  22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). CONCLUSIONS: DCCR administration to people with PWS was well-tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families

Increased expression of the ubiquitin – proteasome pathway in murine myotubes by proteolysis-inducing factor (PIF) is associated with activation of the transcription factor NF-κB

Proteolysis-inducing factor (PIF), isolated from a cachexia-inducing murine tumour, has been shown to stimulate protein breakdown in C 2C12 myotubes. The effect was attenuated by the specific proteasome inhibitor lactacystin and there was an elevation of proteasome 'chymotrypsin-like' enzyme activity and expression of 205 proteasome α-subunits at concentrations of PIF between 2 and 16 nM. Higher concentrations of PIF had no effect. The action of PIF was attenuated by eicosapentaenoic acid (EPA) (50 μM). At a concentration of 4 nM, PIF induced a transient decrease in IκBα levels after 30 min incubation, while no effect was seen at 20 nM PIF. The level of IκBα, an NF-κB inhibitory protein, returned to normal after 60 min. Depletion of IκBα from the cytosol was not seen in myotubes pretreated with EPA, suggesting that the NF-κB/IκB complex was stabilised. At concentrations between 2 and 8 nM, PIF stimulated an increased nuclear migration of NF-κB, which was not seen in myotubes pretreated with EPA. The PIF-induced increase in chymotrypsin-like enzyme activity was also attenuated by the NF-κB inhibitor peptide SN50, suggesting that NF-κB may be involved in the PIF-induced increase in proteasome expression. The results further suggest that EPA may attenuate protein degradation induced by PIF, at least partly, by preventing NF-κB accumulation in the nucleus. © 2003 Cancer Research UK