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1.
ACS Photonics ; 9(8): 2683-2690, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35996365

RESUMO

Inorganic van der Waals bonded semiconductors such as transition metal dichalcogenides are the subject of intense research due to their electronic and optical properties which are promising for next-generation optoelectronic devices. In this context, understanding the carrier dynamics, as well as charge and energy transfer at the interface between metallic contacts and semiconductors, is crucial and yet quite unexplored. Here, we present an experimental study to measure the effect of mutual interaction between thermionically injected and directly excited carriers on the exciton formation dynamics in bulk WS2. By employing a pump-push-probe scheme, where a pump pulse induces thermionic injection of electrons from a gold substrate into the conduction band of the semiconductor, and another delayed push pulse that excites direct transitions in the WS2, we can isolate the two processes experimentally and thus correlate the mutual interaction with its effect on the ultrafast dynamics in WS2. The fast decay time constants extracted from the experiments show a decrease with an increasing ratio between the injected and directly excited charge carriers, thus disclosing the impact of thermionic electron injection on the exciton formation dynamics. Our findings might offer a new vibrant direction for the integration of photonics and electronics, especially in active and photodetection devices, and, more in general, in upcoming all-optical nanotechnologies.

2.
Biomed Pharmacother ; 151: 113155, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35598371

RESUMO

It is widely reported that the overexpression of the C-C Motif Chemokine Receptor 2 (CCR2) has negative implications in neuroinflammatory diseases such as traumatic brain injury (TBI), although promising drugs to tackle this have been less forthcoming. As of 2016, only 2 drugs specifically targeting this receptor have made their way to market, with unsuccessful outcome unfortunately, suggesting that the search for more specific and precise ligands is utterly necessary. In this paper we hypothesized that by targeting Glu291, Met295, Trp98, Leu45 and Val189 amino acids, essential in the binding of CCR2 with C-C Motif Chemokine Ligand 2 (CCL2), the endogenous substrate, mitigates its activity in TBI. We used a pharmacophore model to screen for suitable ligands that may bind to CCR2, which returned 871 ligands. Docking and molecular dynamics results uncovered that two ligands (A102) and (A435) contained several of those important residues and showed a stability and compactness when in complex with CCR2, with these results confirmed by MMGBSA calculations with A102 recording a better interaction compared to A435. Finally, a PPI network was built to explore downstream signaling being regulated by both ligands in TBI, showing amyloid precursor protein (APP) as a key target and neuroactive-ligand receptor interaction (1.80E-27) the top functional annotated category. In conclusion, for the first time we report novel ligands A102 and A435 targeting CCR2 as a potential new pharmacological approach to target inflammation post-TBI.


Assuntos
Lesões Encefálicas Traumáticas , Receptores CCR2 , Lesões Encefálicas Traumáticas/tratamento farmacológico , Quimiocina CCL2/metabolismo , Humanos , Inflamação , Ligantes , Receptores CCR2/metabolismo , Transdução de Sinais
3.
J Phys Chem A ; 126(8): 1336-1344, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35179905

RESUMO

TLD1433 is the first ruthenium (Ru)-based photodynamic therapy (PDT) agent to advance to clinical trials and is currently in a phase II study for treating nonmuscle bladder cancer with PDT. Herein, we present a photophysical study of TLD1433 and its derivative TLD1633 using complex, biologically relevant solvents to elucidate the excited-state properties that are key for biological activity. The complexes incorporate an imidazo [4,5-f][1,10]phenanthroline (IP) ligand appended to α-ter- or quaterthiophene, respectively, where TLD1433 = [Ru(4,4'-dmb)2(IP-3T)]Cl2 and TLD1633 = [Ru(4,4'-dmb)2(IP-4T)]Cl2 (4,4'-dmb = 4,4'-dimethyl-2,2'-bipyridine; 3T = α-terthiophene; 4T = α-quaterthiophene). Time-resolved transient absorption experiments demonstrate that the excited-state dynamics of the complexes change upon interaction with biological macromolecules (e.g., DNA). In this case, the accessibility of the lowest-energy triplet intraligand charge-transfer (3ILCT) state (T1) is increased at the expense of a higher-lying 3ILCT state. We attribute this behavior to the increased rigidity of the ligand framework upon binding to DNA, which prolongs the lifetime of the T1 state. This lowest-lying state is primarily responsible for O2 sensitization and hence photoinduced cytotoxicity. Therefore, to gain a realistic picture of the excited-state kinetics that underlie the photoinduced function of the complexes, it is necessary to interrogate their photophysical dynamics in the presence of biological targets once they are known.


Assuntos
Fotoquimioterapia , Rutênio , Ligantes , Fenantrolinas/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Rutênio/química , Rutênio/farmacologia
4.
J Phys Chem B ; 125(41): 11498-11511, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34617757

RESUMO

Cu(I) 4H-imidazolato complexes are excellent photosensitizers with broad and intense light absorption properties, based on an earth-abundant metal, and hold great promise as photosensitizers in artificial photosynthesis and for accumulation of redox equivalents. In this study, the excited-state relaxation dynamics of three novel heteroleptic Cu(I) 4H-imidazolato complexes with phenyl, tolyl, and mesityl side groups are systematically investigated by femtosecond and nanosecond time-resolved transient absorption spectroscopy and theoretical methods, complemented by steady-state absorption spectroscopy and (spectro)electrochemistry. After photoexcitation into the metal-to-ligand charge transfer (MLCT) and intraligand charge transfer absorption band, fast (0.6-1 ps) intersystem crossing occurs into the triplet MLCT manifold. The triplet-state population relaxes via the geometrical planarization of the N-aryl rings on the Cu(I) 4H-imidazolato complexes. Depending on the initial Franck-Condon state, the remaining small singlet state population relaxes into two geometrically distinct minima geometries with similar energy, S1/2,relax and S3/4,relax. Subsequent ground-state recovery from S1/2,relax and internal conversion from S3/4,relax to S1/2,relax take place on a 100 ps time scale. The internal conversion can be understood as hole transfer from a dyz-orbital to a dxz-orbital, which is accompanied with the structural reorganization of the coordination environment. Generally, the photophysical processes are determined by the steric hindrance of the side groups on the ligands. And the excited singlet-state pathways are dependent on the excitation wavelength.


Assuntos
Compostos Organometálicos , Ligantes , Fármacos Fotossensibilizantes , Teoria Quântica , Análise Espectral
5.
ChemPhotoChem ; 5(5): 421-425, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34337147

RESUMO

TLD1433 is the first Ru(II) complex to be tested as a photodynamic therapy agent in a clinical trial. In this contribution we study TLD1433 in the context of structurally-related Ru(II)-imidozo[4,5-f][1,10]phenanthroline (ip) complexes appended with thiophene rings to decipher the unique photophysical properties which are associated with increasing oligothiophene chain length. Substitution of the ip ligand with ter- or quaterthiophene changes the nature of the long-lived triplet state from metal-to-ligand charge-transfer to 3ππ* character. The addition of the third thiophene thus presents a critical juncture which not only determines the photophysics of the complex but most importantly its capacity for 1O2 generation and hence the potential of the complex to be used as a photocytotoxic agent. ENTRY FOR THE TABLE OF CONTENTS: A low-lying triplet intraligand state (3IL) determines the properties of the long-lived excited states in a series of Ru(II) complexes. The 3IL state can be accessed by increasing the length of an oligothiophene chain. The 3IL state is extremely efficient at generating 1O2 and thus enhances the potency of the complexes as PDT agents.

6.
J Phys Chem A ; 125(32): 6985-6994, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34370485

RESUMO

We explore the photophysical properties of a family of Ru(II) complexes, Ru-ip-nT, designed as photosensitizers (PSs) for photodynamic therapy (PDT). The complexes incorporate a 1H-imidazo[4,5-f][1,10]-phenanthroline (ip) ligand appended to one or more thiophene rings. One of the complexes studied herein, Ru-ip-3T (known as TLD1433), is currently in phase II human clinical trials for treating bladder cancer by PDT. The potent photocytotoxicity of Ru-ip-3T is attributed to a long-lived intraligand charge-transfer triplet state. The accessibility of this state changes upon varying the length (n) of the oligothiophene substituent. In this paper, we highlight the impact of n on the ultrafast photoinduced dynamics in Ru-ip-nT, leading to the formation of the function-determining long-lived state. Femtosecond time-resolved transient absorption combined with resonance Raman data was used to map the excited-state relaxation processes from the Franck-Condon point of absorption to the formation of the lowest-energy triplet excited state, which is a triplet metal-to-ligand charge-transfer excited state for Ru-ip-0T-1T and an oligothienyl-localized triplet intraligand charge-transfer excited state for Ru-ip-2T-4T. We establish the structure-activity relationships with regard to changes in the excited-state dynamics as a function of thiophene chain length, which alters the photophysics of the complexes and presumably impacts the photocytotoxicity of these PSs.

7.
BMC Public Health ; 21(1): 468, 2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685418

RESUMO

BACKGROUND: Leaders in small and medium-sized enterprises (SMEs) are exposed to increased stress as a result of a range of challenges. Moreover, they rarely have the opportunity to participate in stress management trainings. Therefore, KMU-GO (ger: Kleine und mittlere Unternehmen - Gesundheitsoffensive; en: small and medium-sized enterprises - health campaign) aims at conducting and evaluating such a stress management training. The focus of evaluation does not only lie on the effects on leaders participating but also on their employees. METHODS: The study is planned as a 2 × 3 mixed design with two groups (intervention and waiting control group) as a between factor and point in time (at baseline, 6 and 12 months later) as a within factor. We aim at collecting data from N = 200 leaders. Based on the results of a preceding assessment, an already successfully implemented stress management training was adapted to SME needs and now serves as the framework of this intervention. The stress management training comprises one and a half days and is followed by two booster sessions (each 180 min) about 3 and 6 months after the training. The main focus of this intervention lies on specifying leaders stress reactivity while at the same time investigating its effects on employees' mental health. Further dependent variables are leaders´ depression and anxiety scores, effort-reward imbalance, sick days and psychophysiological measures of heart rate variability, hair cortisol, and salivary alpha-amylase. Cost-effectiveness analyses will be conducted from a societal and employers' point of view. DISCUSSION: Stress management is a highly relevant issue for leaders in SMEs. By providing an adequate occupational stress management training, we expect to improve leaders´ and also employees` mental health, thereby preventing economic losses for SMEs and the national economy. However, collecting data from employees about the success of a stress management training of their leader is a highly sensitive topic. It requires a carefully planned proceeding ensuring for example a high degree of transparency, anonymity, and providing team incentives. TRIAL REGISTRATION: The KMU-GO trial is registered at the German Clinical Trial Register (DRKS): DRKS00023457 (05.11.2020).


Assuntos
Serviços de Saúde do Trabalhador , Saúde Ocupacional , Análise Custo-Benefício , Humanos , Saúde Mental , Ensaios Clínicos Controlados Aleatórios como Assunto , Licença Médica
8.
Opt Lett ; 45(17): 4714-4717, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32870839

RESUMO

The nonlinear transformation of fluctuations by frequency broadening is found to produce strong anti-correlations in the spectral output. This effect is investigated by dispersive Fourier transform measurements. We exploit the anti-correlations in order to cancel the intensity noise in a subsequent sum-frequency mixing step. This principle allows for the generation of tunable visible pulses by cascaded nonlinear mixing whilst maintaining the same intensity noise performance as the input pulses. In addition, we demonstrate that the power fluctuations occurring in the process of passive stabilization of the carrier-envelope phase locking via difference frequency generation may be cancelled by an analogous strategy.

9.
Chemistry ; 26(65): 14844-14851, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-32761643

RESUMO

This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy)2 (IP-4T)](PF6 )2 with bpy=2,2'-bipyridine and IP-4T=2-{5'-[3',4'-diethyl-(2,2'-bithien-5-yl)]-3,4-diethyl-2,2'-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1, comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited-state relaxation is a long-lived 3 ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited-state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for a possible photodrug.

10.
Eur J Psychotraumatol ; 11(1): 1753939, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32537097

RESUMO

Background: Caregivers play a key role in the success of trauma-focused cognitive behavioural therapy (TF-CBT). Yet, the effect of their alliance on treatment outcomes besides the other parties in treatment has hardly been studied. Objective: This study examined the working alliance (WA) of therapists, patients and caregivers in TF-CBT and its contribution on treatment outcome over time. Methods: N = 76 children and adolescents (mean age = 12.66 years, range 7-17, M/F ratio: .43) participated in the TF-CBT arm of a randomized controlled trial. The WA was assessed with the Working Alliance Inventory Short Version (WAI-S) at two measurement points, while symptom level of posttraumatic stress symptoms (PTSS) was assessed with the Clinician-Administered PTSD Scale for Children and Adolescents (CAPS-CA). Paired sample t-tests, intraclass correlations (ICC), and mixed-effects regression models for longitudinal data were performed. Results: The alliance rating was high across all informants, with caregivers achieving the highest rating. The average level of cross-informant agreement on the alliance was low between therapists and caregivers (ICC = .26) and moderate between therapists and patients (ICC =.65). A significant contribution of an alliance improvement to the reduction of PTSS over time was found in each of the two tested models: therapists with patients model (b = .682) and therapists with caregivers model (b = .807). However, these effects were not detected with all four perspectives in one comprehensive model. Conclusion: In summary, the potential of caregivers' views should receive more attention in the therapeutic process of trauma-focused therapy.


Antecedentes: los cuidadores desempeñan un papel clave en el éxito de la terapia cognitivo-conductual centrada en el trauma (TF-CBT por sus siglas en inglés). Sin embargo, el efecto de su alianza en los resultados del tratamiento, aparte de los otros participantes en el tratamiento, apenas se ha estudiado.Objetivo: Este estudio examinó la alianza de trabajo (WA por sus siglas en inglés) de terapeutas, pacientes y cuidadores en TF-CBT y su contribución en el resultado del tratamiento a lo largo del tiempo.Métodos: N = 76 niños y adolescentes (edad media = 12,66 años, rango 7-17, relación M/F: 0.43) fueron parte del brazo que recibía TF-CBT en un ensayo controlado aleatorio. La WA se evaluó con la versión abreviada del Inventario de la Alianza de Trabajo (WAI-S por sus siglas en inglés) en dos mediciones, mientras que el nivel sintomático de los síntomas de estrés postraumático (PTSS por sus siglas en inglés) fue evaluado con la Escala de TEPT administrada por el profesional clínico para niños y adolescentes (CAPS-CA por sus siglas en inglés). Se realizaron pruebas t de muestras pareadas, correlaciones intraclase (ICC por sus siglas en inglés) y modelos de regresión de efectos mixtos para datos longitudinales.Resultados: La calificación de la alianza fue alta en todos los informantes, con los cuidadores logrando la calificación más elevada. El nivel promedio de acuerdo entre informantes sobre la alianza fue bajo entre terapeutas y cuidadores (ICC = .26, p = .002) y moderado entre terapeutas y pacientes (ICC = .65, p = <.001). Se encontró una contribución significativa de una mejora de la alianza a la reducción de PTSS a lo largo del tiempo en cada uno de los dos modelos probados: modelo de terapeutas con pacientes (b = ­.682; p = .039) y modelo de terapeutas con cuidadores (b = ­.807; p <.001). Sin embargo, estos efectos no se detectaron con las cuatro perspectivas en un modelo integral.Conclusión: en resumen, el potencial de las opiniones de los cuidadores debería recibir más atención en el proceso terapéutico de la terapia centrada en el trauma.

11.
Nat Struct Mol Biol ; 25(9): 823-832, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30177756

RESUMO

Nuclear actin (N-actin) and actin-related proteins (Arps) are critical components of several chromatin modulating complexes, including the chromatin remodeler INO80, but their function is largely elusive. Here, we report the crystal structure of the 180-kDa Arp8 module of Saccharomyces cerevisiae INO80 and establish its role in recognition of extranucleosomal linker DNA. Arp8 engages N-actin in a manner distinct from that of other actin-fold proteins and thereby specifies recruitment of the Arp4-N-actin heterodimer to a segmented scaffold of the helicase-SANT-associated (HSA) domain of Ino80. The helical HSA domain spans over 120 Å and provides an extended binding platform for extranucleosomal entry DNA that is required for nucleosome sliding and genome-wide nucleosome positioning. Together with the recent cryo-electron microscopy structure of INO80Core-nucleosome complex, our findings suggest an allosteric mechanism by which INO80 senses 40-bp linker DNA to conduct highly processive chromatin remodeling.


Assuntos
Núcleo Celular/metabolismo , Montagem e Desmontagem da Cromatina , DNA Fúngico/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Sequência de Aminoácidos , Proteínas dos Microfilamentos/química , Conformação Proteica , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Homologia de Sequência de Aminoácidos
12.
Nervenarzt ; 89(5): 500-508, 2018 May.
Artigo em Alemão | MEDLINE | ID: mdl-29637233

RESUMO

BACKGROUND: In Germany, informal caregiving becomes an increasingly important issue especially for people with dementia. Spouses often provide nursing care due to the limited daily living skills of people with dementia. This leads to a wide range of caregiver burden and decreased quality of life (QoL). Analyses on the relation between QoL and caregiver burden of older informal caregivers in Germany are rare. OBJECTIVE: The following research questions were assessed: (1) Does caregivers' QoL differ from that of the older general population?; (2) Which sociodemographic, health- and care-related characteristics affect caregivers' QoL? MATERIAL AND METHODS: For this study, two samples (aged 60 years and older) were recruited: informal caregivers (n = 119) and a representative sample of older non-caregivers in the general population (n = 1133). Linear regression analyses were applied to examine the effects of sociodemographic, health and care-related variables on the QoL of older informal caregivers of people with dementia. RESULTS: Older informal caregivers reported a significantly lower QoL compared to older non-caregivers in the general population. Especially the domains autonomy, activities in the past, the present and the future as well as intimacy were negatively associated with caregivers' QoL. CONCLUSION: The results of the study highlighted caregivers' need for assistance. Due to demographic changes, tailored support services should be based on older caregivers' needs.


Assuntos
Cuidadores , Demência , Qualidade de Vida , Idoso , Cuidadores/estatística & dados numéricos , Estudos de Casos e Controles , Alemanha , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários
13.
J Phys Chem A ; 122(6): 1550-1559, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29369626

RESUMO

A ruthenium complex with a half-sandwich geometry ([(p-cymene)Ru(Cl)(curcuminoid)]) was synthesized, characterized, and investigated regarding its ultrafast photophysics. These photophysical investigations of the complex revealed a weak and short-lived emission from the initially populated 1MLCT state and solvent-dependent photoinduced dynamics, where the secondarily populated 3MC state is stabilized by nonpolar solvents. Overall the decay of the 3dd-MC state to the ground state is completed within picoseconds. This short excited-state lifetime is in stark contrast to the typically observed long-lived 3MLCT states with lifetimes of nanoseconds or microseconds in unstrained, octahedral ruthenium complexes but is in good agreement with the findings for distorted octahedral complexes. This is pointing to the half-sandwich geometry as a new and easy approach to study these otherwise often concealed dd states.

14.
Inorg Chem ; 56(21): 12978-12986, 2017 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-29064681

RESUMO

The excited state properties of three heteroleptic copper(I) xantphos 4H-imidazolate complexes are investigated by means of femtosecond and nanosecond time-resolved transient absorption spectroscopy in dichloromethane solution. The subpicosecond spectral changes observed after excitation into the MLCT absorption band are interpreted as intersystem crossing from the singlet to the triplet manifold. This interpretation is corroborated by DFT and TD-DFT results, indicating a comparable molecular geometry in the ground state (and hence the nonrelaxed singlet state) and the excited triplet state. Population of the triplet state is followed by planarization of the N-aryl rings of the 4H-imidazolate ligand on a 10 ps time scale. The planarization strongly depends on the substitution pattern of the N-aryls and correlates with the reduced moment of inertia for the planarization motion. The triplet state subsequently decays to the ground state in about 100 ns. These results demonstrate that the excited state processes of copper(I) complexes depend on the specific ligand(s) and their substitution pattern. Thus, the work presented points to a possibility to design copper(I) complexes with specific photophysical properties.

15.
Water Sci Technol ; 76(5-6): 1474-1489, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28953474

RESUMO

SWINGS was a cooperation project between the European Union and India, aiming at implementing state of the art low-cost technologies for the treatment and reuse of domestic wastewater in rural areas of India. The largest wastewater treatment plant consists of a high-rate anaerobic system, followed by vertical and horizontal subsurface flow constructed wetlands with a treatment area of around 1,900 m2 and a final step consisting of solar-driven anodic oxidation (AO) and ultraviolet (UV) disinfection units allowing direct reuse of the treated water. The implementation and operation of two pilot plants in north (Aligarh Muslim University, AMU) and central India (Indira Gandhi National Tribal University, IGNTU) are shown in this study. The overall performance of AMU pilot plant during the first 7 months of operation showed organic matter removal efficiencies of 87% total suspended solids, 95% 5-day biological oxygen demand (BOD5) and 90% chemical oxygen demand, while Kjeldahl nitrogen removal reached 89%. The UV disinfection unit produces water for irrigation and toilet flushing with pathogenic indicator bacteria well below WHO guidelines. On the other hand, the AO disinfection unit implemented at IGNTU and operated for almost a year has been shown to produce an effluent of sufficient quality to be reused by the local population for agriculture and irrigation.


Assuntos
Conservação dos Recursos Naturais/métodos , Desinfecção , Luz Solar , Águas Residuárias/microbiologia , Purificação da Água/métodos , Áreas Alagadas , Agricultura , Análise da Demanda Biológica de Oxigênio , Índia , Nitrogênio/análise , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Microbiologia da Água , Poluentes Químicos da Água
16.
ACS Chem Biol ; 12(10): 2498-2502, 2017 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-28846366

RESUMO

The class of cyclic lipopeptide natural products consists of compounds with a diverse range of bioactivities. In this study, we elucidated the structure of the cyclic lipopeptide anikasin using X-ray crystallography, analyzed its biosynthetic gene cluster, and investigated its natural role in the interaction between the producer strain Pseudomonas fluorescens HKI0770 and protozoal predators. These results led to the conclusion that anikasin has dual functionality enabling swarming motility and acting as a niche amoebicide, which effectively inhibits the social amoeba Polysphondylium violaceum and protects the producer strain from protozoal grazing.


Assuntos
Amebicidas/farmacologia , Amebozoários/efeitos dos fármacos , Lipopeptídeos/biossíntese , Lipopeptídeos/química , Peptídeos Cíclicos/biossíntese , Peptídeos Cíclicos/química , Pseudomonas fluorescens/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Lipopeptídeos/farmacologia , Modelos Moleculares , Estrutura Molecular , Peptídeos Cíclicos/farmacologia
17.
J Phys Chem A ; 121(30): 5635-5644, 2017 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-28678497

RESUMO

In this study femtosecond and nanosecond time-resolved transient absorption spectroscopy was used to investigate the influence of ionic strength and complexity on the excited state dynamics of a Ru(II)-based metal-organic dyad. The bis-heteroleptic complex [Ru(bpy)2(ippy)]2+ (1), where bpy = 2,2'-bipyridine and ippy = 2-(1-pyrenyl-1H-imidazo[4,5-f][1,10]phenanthroline, is a potent photosensitizer for in vitro photodynamic therapy (PDT) and photodynamic inactivation (PDI) of microorganisms owing to a long-lived triplet excited state derived from a metal-to-ligand charge-transfer (3MLCT) state that is equilibrium with an intraligand (3IL) state. The prolonged lifetime provides ample opportunity for bimolecular quenching of this state by oxygen; thus singlet oxygen (1O2) sensitization is very efficient. In simple aqueous solution, fast cooling within the 3MLCT manifold is followed by energy transfer to an 3IL state, which is facilitated by rotation of a pyrenyl unit about the imidazo-pyrenyl (ip) coannular bond. For solutions of 1 in high ionic strength simulated biological fluid (SBF), a more physiologically relevant solvent that contains a complex mixture of ions at pH 7.4, femtosecond studies revealed an additional excited state, possibly based on an ion-ligand interaction. This new state appearing in high ionic strength SBF was not observable in water, simple buffers, or low ionic strength SBF. These photoinduced dynamics were also affected by the presence of biomolecules such as DNA in simple buffer, whereby relaxation on the picosecond time scale was accelerated from 39 to 18 ps with DNA intercalation by 1. The increased rate of coplanarization of the pyrene and the imidazole units was attributed to DNA-induced conformational restriction of the pyrenyl unit relative to the ip bond. Quantitative changes to excited state decay rates of 1 in solutions of high ionic strength were also observed when probed on the microsecond time scale. Notably, the thermalized excited state decay pathways were altered substantially with DNA intercalation, with access to some states being completely blocked. Experimentally, this manifested in the absence of the slowest microsecond decay channel, which is normally observed for 1 in solution. The quantitative and qualitative observations from this study highlight the importance of employing biologically relevant solvents and potential biomolecule targets when the excited state dynamics and photophysical properties (under cell-free conditions) responsible for the potent photobiological effects are assessed in the context of photodynamic therapy and photodynamic inactivation.


Assuntos
DNA/química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Teoria Quântica , Rutênio/química , Fotoquimioterapia , Oxigênio Singlete/química
18.
Epidemiol Psychiatr Sci ; 26(2): 115-118, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27758726

RESUMO

Politics and policy: It is important to understand why, in the translational continuum from pilot research and randomised controlled efficacy trials to roll-out programmes and routine effectiveness studies, some service innovations are taken up by health service purchasers and providers, while others are not. Why do some innovative interventions or models of care get to the stage of implementation, while others fail to be funded?


Assuntos
Atenção à Saúde , Fidelidade a Diretrizes , Políticas , Política , Humanos
19.
Environ Technol ; 38(2): 209-219, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27241268

RESUMO

The HIGHWET project combines the hydrolytic up-flow sludge bed (HUSB) anaerobic digester and constructed wetlands (CWs) with forced aeration for decreasing the footprint and improving effluent quality. The HIGHWET plant in A Coruña (NW of Spain) treating municipal wastewater consists of a HUSB and four parallel subsurface horizontal flow (HF) CWs. HF1, HF2 and HF3 units are fitted with forced aeration, while the control HF4 is not aerated. All the HF units are provided with effluent recirculation, but different heights of gravel bed (0.8 m in HF1 and HF2, and 0.5 m in HF3 and HF4) are implemented. Besides, a tobermorite-enriched material was added in the HF2 unit in order to improve phosphorus removal. The HUSB 76-89% of total suspended solids (TSS) and about 40% of chemical oxygen demand (COD) and biological oxygen demand (BOD). Aerated HF units reached above 96% of TSS, COD and BOD at a surface loading rate of 29-47 g BOD5/m2·d. An aeration regime ranging from 5 h on/3 h off to 3 h on/5 h off was found to be adequate to optimize nitrogen removal, which ranged from 53% to 81%. Average removal rates of 3.4 ± 0.4 g total nitrogen (TN)/m2·d and 12.8 ± 3.7 g TN/m3·d were found in the aerated units, being 5.5 and 4.1 times higher than those of the non-aerated system. The tobermorite-enriched HF2 unit showed a distinct higher phosphate (60-67%) and total phosphorus (54%) removal.


Assuntos
Reatores Biológicos , Eliminação de Resíduos Líquidos/métodos , Áreas Alagadas , Compostos de Amônio/análise , Anaerobiose , Análise da Demanda Biológica de Oxigênio , Hidrólise , Nitratos/análise , Nitritos/análise , Nitrogênio/análise , Fosfatos/análise , Fosfatos/química , Fósforo/análise , Fósforo/química , Poaceae , Águas Residuárias/análise , Águas Residuárias/química , Poluentes da Água/análise , Poluentes da Água/química
20.
Epidemiol Psychiatr Sci ; 26(1): 53-60, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-26606884

RESUMO

AIMS: Whether the public stigma associated with mental illness negatively affects an individual, largely depends on whether the person has been labelled 'mentally ill'. For labelled individuals concealing mental illness is a common strategy to cope with mental illness stigma, despite secrecy's potential negative consequences. In addition, initial evidence points to a link between stigma and suicidality, but quantitative data from community samples are lacking. METHODS: Based on previous literature about mental illness stigma and suicidality, as well as about the potential influence of labelling processes and secrecy, a theory-driven model linking perceived mental illness stigma and suicidal ideation by a mediation of secrecy and hopelessness was established. This model was tested separately among labelled and unlabelled persons using data derived from a Swiss cross-sectional population-based study. A large community sample of people with elevated psychiatric symptoms was examined by interviews and self-report, collecting information on perceived stigma, secrecy, hopelessness and suicidal ideation. Participants who had ever used mental health services were considered as labelled 'mentally ill'. A descriptive analysis, stratified logistic regression models and a path analysis testing a three-path mediation effect were conducted. RESULTS: While no significant differences between labelled and unlabelled participants were observed regarding perceived stigma and secrecy, labelled individuals reported significantly higher frequencies of suicidal ideation and feelings of hopelessness. More perceived stigma was associated with suicidal ideation among labelled, but not among unlabelled individuals. In the path analysis, this link was mediated by increased secrecy and hopelessness. CONCLUSIONS: Results from this study indicate that among persons labelled 'mentally ill', mental illness stigma is a contributor to suicidal ideation. One explanation for this association is the relation perceived stigma has with secrecy, which introduces negative emotional consequences. If our findings are replicated, they would suggest that programmes empowering people in treatment for mental illness to cope with anticipated and experienced discrimination as well as interventions to reduce public stigma within society could improve suicide prevention.


Assuntos
Confidencialidade/psicologia , Transtornos Mentais/psicologia , Estigma Social , Ideação Suicida , Adulto , Discriminação Psicológica , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Transtornos Mentais/epidemiologia
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