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1.
Sci Adv ; 9(1): eadd3669, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36608119

RESUMO

One of the circuit topologies for the implementation of unipolar integrated circuits (circuits that use either p-channel or n-channel transistors, but not both) is the zero-VGS architecture. Zero-VGS circuits often provide excellent static performance (large small-signal gain and large noise margins), but they suffer from the large signal delay imposed by the load transistor. To address this limitation, we have used electron-beam lithography to fabricate zero-VGS circuits based on organic transistors with channel lengths as small as 120 nm on flexible polymeric substrates. For a supply voltage of 3 V, these circuits have characteristic signal-delay time constants of 14 ns for the low-to-high transition and 560 ns for the high-to-low transition of the circuit's output voltage. These signal delays represent the best dynamic performance reported to date for organic transistor-based zero-VGS circuits. The signal-delay time constant of 14 ns is also the smallest signal delay reported to date for flexible organic transistors.

2.
Sci Rep ; 11(1): 6382, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737629

RESUMO

A critical requirement for the application of organic thin-film transistors (TFTs) in mobile or wearable applications is low-voltage operation, which can be achieved by employing ultrathin, high-capacitance gate dielectrics. One option is a hybrid dielectric composed of a thin film of aluminum oxide and a molecular self-assembled monolayer in which the aluminum oxide is formed by exposure of the surface of the aluminum gate electrode to a radio-frequency-generated oxygen plasma. This work investigates how the properties of such dielectrics are affected by the plasma power and the duration of the plasma exposure. For various combinations of plasma power and duration, the thickness and the capacitance of the dielectrics, the leakage-current density through the dielectrics, and the current-voltage characteristics of organic TFTs in which these dielectrics serve as the gate insulator have been evaluated. The influence of the plasma parameters on the surface properties of the dielectrics, the thin-film morphology of the vacuum-deposited organic-semiconductor films, and the resulting TFT characteristics has also been investigated.

3.
J Mol Biol ; 432(4): 878-896, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31877322

RESUMO

Apicomplexan parasites contain rhoptries, which are specialized secretory organelles that coordinate host cell invasion. During the process of invasion, rhoptries secrete their contents to facilitate interaction with, and entry into, the host cell. Here, we report the crystal structure of the rhoptry protein Armadillo Repeats-Only (ARO) from the human malaria parasite, Plasmodium falciparum (PfARO). The structure of PfARO comprises five tandem Armadillo-like (ARM) repeats, with adjacent ARM repeats stacked in a head-to-tail orientation resulting in PfARO adopting an elongated curved shape. Interestingly, the concave face of PfARO contains two distinct patches of highly conserved residues that appear to play an important role in protein-protein interaction. We functionally characterized the P. falciparum homolog of ARO interacting protein (PfAIP) and demonstrate that it localizes to the rhoptries. We show that conditional mislocalization of PfAIP leads to deficient red blood cell invasion. Guided by the structure, we identified mutations of PfARO that lead to mislocalization of PfAIP. Using proximity-based biotinylation we probe into PfAIP interacting proteins.


Assuntos
Plasmodium falciparum/metabolismo , Plasmodium falciparum/patogenicidade , Proteínas de Protozoários/metabolismo , Sequência de Aminoácidos , Animais , Proteínas do Domínio Armadillo/genética , Proteínas do Domínio Armadillo/metabolismo , Humanos , Malária/fisiopatologia , Dados de Sequência Molecular , Mutagênese/genética , Mutagênese/fisiologia , Mutação , Parasitemia/parasitologia , Filogenia , Plasmodium falciparum/genética , Transporte Proteico/genética , Transporte Proteico/fisiologia , Proteínas de Protozoários/genética
4.
J Mol Med (Berl) ; 97(11): 1547-1555, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31471628

RESUMO

A growing body of evidence indicates the role of melatonin (MT) in the pathogenesis of multiple sclerosis (MS): It modulates immune function, alleviates oxidative stress and it is linked to seasonality of MS relapse. This report addresses the potential clinical relevance of circadian MT rhythms in relapsing-remitting MS (RRMS) patients. The study sample comprised of fifty-five RRMS patients and fifty age- and sex-matched healthy control (HC) subjects. Circadian salivary MT was measured non-invasively at 12 time points over day in participants' home environment. 6-Hydroxy-melatoninsulfate (MT sulfate) concentration in night-time urine was assessed as an estimate for nocturnal MT. Ratings for neurological disability, health-related quality of life (HrQoL), fatigue, depressive symptoms and sleep patterns were additionally obtained. There was no evidence for an overall disturbed MT rhythm in RRMS patients. However, lower MT levels within the first hour after awakening were associated with longer disease duration. MT levels only correlated moderately with neurological disability. Sleep disruptions were more common in patients than in controls and were associated with lower nocturnal MT sulfate levels. MT also correlated moderately with fatigue and HrQoL. We did not find evidence for a generally disturbed circadian MT rhythm in RRMS patients but longer disease duration was associated with significantly lower MT levels. Moreover, MT correlated with a series of clinical features. The exact nature of this relationship remains unclear and future studies are needed in order to determine whether MT could serve as a potential therapeutic target in MS. KEY MESSAGES: Melatonin acts as a free radical scavenger and modulates immune function. In multiple sclerosis, low melatonin levels were associated with acute exacerbations. Melatonin levels are not generally disturbed in multiple sclerosis patients. But lower levels are associated with disease duration and clinical aspects. Salivary melatonin after awakening might serve as a good measure of melatonin.


Assuntos
Ritmo Circadiano/fisiologia , Melatonina/metabolismo , Esclerose Múltipla/metabolismo , Esclerose Múltipla/fisiopatologia , Adulto , Feminino , Sequestradores de Radicais Livres/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Glândulas Salivares/metabolismo
5.
Open Vet J ; 8(1): 96-103, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29721438

RESUMO

The angulation of the equine fetlock determines the load of associated tendons and probably their predisposition for injuries. However, it is questionable how the individual toe conformation and tendon properties interact with the dorsal metacarpophalangeal joint angle (DMPJ). Data are needed for a tangible evaluation of the equine limb conformation for more specific orthopaedic treatment. The aim was to evaluate the correlation between the DMPJ, toe conformation and cross-sectional area (CSA) of both flexor tendons; the superficial digital flexor tendon (SDFT) and deep digital flexor tendon (DDFT). Thirty Warmblood horses were available for the study. Lateromedial radiographs of the toe and fetlock and transverse ultrasound images of both flexor tendons were obtained from three zones. The DMPJ, length and angle of the phalanges and CSA SDFT/DDFT were measured. In addition, hoof angle, wither height, age, and sex were documented. Correlations were calculated using Pearson's test. A paired t-test was used to evaluate left-right differences. Length and angle of the proximal and middle phalanx were significantly associated with the DMPJ (r = -0.28 - -0.45, p<0.001-0.04). Neither the angle of the hoof and distal phalanx nor the CSA SDFT/DDFT, showed a noticeable correlation with the DMPJ. Significant left-right differences occurred for the DMPJ (p<0.002) and the angle of the proximal and middle phalanx (p<0.01 - 0.002). A moderate negative correlation was shown between the DMPJ and wither height (r = - 0.31, p=0.04). Results represent only a specific population. The study provides only a static evaluation of a dynamic situation. In a clinical context, it might be useful to focus on the angulation and length of the pastern to evaluate the individual load affecting the DMPJ and its associated structures. These findings might be relevant for orthopaedic treatments and shoeing recommendations.

6.
Vet Rec ; 182(24): 692, 2018 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-29599297

RESUMO

Corrective shoeing is used to change hoof angulation with the intention to influence the angulation of the digital joints to reduce strain on associated tendons. The objective of this study is to examine how gradual changes in hoof angulation affect the dorsal metacarpophalangeal joint (DMPJ) angulation and cross-sectional areas (CSAs) of the deep digital flexor tendon (DDFT) and superficial digital flexor tendon (SDFT) concerning the individual toe conformation. Forelimbs of 30 horses were examined barefoot and equipped with 5°, 10° and 20° toe wedges (TWs) and heel wedges (HWs). Phalangeal angulation and lengths were measured in lateromedial radiographs of the digit. CSAs of both flexor tendons was calculated in sonographic images. Significant effects on the DMPJ and CSA of the DDFT/SDFT were measured with 10° and 20° HWs or 20° TWs. Both flexor tendons showed increasing CSA after heel elevation. Significant interindividual variations occurred. Phalangeal angulation and length influenced the responsivity of the parameters to a changed hoof angulation. Significant impact of corrective shoeing on the DMPJ and flexor tendons is related to a distinct change in hoof orientation and varies with individual toe conformation. Similar response of the DDFT and SDFT to raised and lowered hoof orientation needs further investigation for a more specific application of therapeutic shoeing.


Assuntos
Membro Anterior/anatomia & histologia , Casco e Garras/anatomia & histologia , Articulação Metacarpofalângica/anatomia & histologia , Tendões/anatomia & histologia , Animais , Feminino , Membro Anterior/diagnóstico por imagem , Cavalos , Masculino , Radiografia/veterinária , Sapatos , Ultrassonografia/veterinária
7.
Front Microbiol ; 8: 1922, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29067005

RESUMO

Self-transmissible and mobilizable plasmids contribute to the emergence and spread of multidrug-resistant bacteria by enabling the horizontal transfer of acquired antibiotic resistance. The objective of this study was to capture and characterize self-transmissible and mobilizable resistance plasmids from a coastal wetland impacted by urban stormwater runoff and human wastewater during the rainy season. Four plasmids were captured, two self-transmissible and two mobilizable, using both mating and enrichment approaches. Plasmid genomes, sequenced with either Illumina or PacBio platforms, revealed representatives of incompatibility groups IncP-6, IncR, IncN3, and IncF. The plasmids ranged in size from 36 to 144 kb and encoded known resistance genes for most of the major classes of antibiotics used to treat Gram-negative infections (tetracyclines, sulfonamides, ß-lactams, fluoroquinolones, aminoglycosides, and amphenicols). The mobilizable IncP-6 plasmid pLNU-11 was discovered in a strain of Citrobacter freundii enriched from the wetland sediments with tetracycline and nalidixic acid, and encodes a novel AmpC-like ß-lactamase (blaWDC-1), which shares less than 62% amino acid sequence identity with the PDC class of ß-lactamases found in Pseudomonas aeruginosa. Although the IncR plasmid pTRE-1611 was captured by mating wetland bacteria with P. putida KT2440 as recipient, it was found to be mobilizable rather than self-transmissible. Two self-transmissible multidrug-resistance plasmids were also captured: the small (48 kb) IncN3 plasmid pTRE-131 was captured by mating wetland bacteria with Escherichia coli HY842 where it is seemed to be maintained at nearly 240 copies per cell, while the large (144 kb) IncF plasmid pTRE-2011, which was isolated from a cefotaxime-resistant environmental strain of E. coli ST744, exists at just a single copy per cell. Furthermore, pTRE-2011 bears the globally epidemic blaCTX-M-55 extended-spectrum ß-lactamase downstream of ISEcp1. Our results indicate that urban coastal wetlands are reservoirs of diverse self-transmissible and mobilizable plasmids of relevance to human health.

8.
In Vivo ; 27(4): 561-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23812232

RESUMO

BACKGROUND: Lymphoceles account for considerable morbidity rates after kidney transplantation. As yet, there is no therapeutic strategy to prevent the formation of lymphoceles. The lower limb provides a large reservoir for lymphatic tissue. Prophylactic compression therapy limits tissue volume and edema formation and may therefore reduce postoperative lymph flow. PATIENTS AND METHODS AND RESULTS: In a non-randomized prospective study using a historical control group prior to 2006 as comparison from our center (2004-2008: total n=126), we found that lymphoceles are significantly diminished on the ipsilateral lower limb of the operative side when patients wear class II compression stockings (n=69) for four weeks after transplantation compared to patients achieving standard antithrombotic therapy by compression class I stockings (n=57) for thrombosis prophylaxis until full mobilization (33% versus 15%, p-value<0.05). Furthermore, a significantly lower percentage of patients needed surgical treatment of the lymphoceles for obstructive complications after class II compression (4% versus 18%, p-value<0.01). These findings were independent of the recipients' demographics, the duration of the surgical procedure, and the operating surgeon. CONCLUSION: Further studies are needed to demonstrate the usefulness of compressing stockings for the reduction of lymphoceles after kidney transplantation. This approach would not only reduce post-transplantation morbidity, but also provide an easy and cost-effective treatment without side-effects.


Assuntos
Transplante de Rim/efeitos adversos , Linfocele/etiologia , Linfocele/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Meias de Compressão , Adulto , Idoso , Humanos , Incidência , Linfocele/epidemiologia , Linfocele/cirurgia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Doadores de Tecidos , Adulto Jovem
9.
Plant Physiol ; 135(3): 1256-68, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15247386

RESUMO

Tocopherols (vitamin E) are lipophilic antioxidants presumed to play a key role in protecting chloroplast membranes and the photosynthetic apparatus from photooxidative damage. Additional nonantioxidant functions of tocopherols have been proposed after the recent finding that the Suc export defective1 maize (Zea mays) mutant (sxd1) carries a defect in tocopherol cyclase (TC) and thus is devoid of tocopherols. However, the corresponding vitamin E deficient1 Arabidopsis mutant (vte1) lacks a phenotype analogous to sxd1, suggesting differences in tocopherol function between C4 and C3 plants. Therefore, in this study, the potato (Solanum tuberosum) ortholog of SXD1 was isolated and functionally characterized. StSXD1 encoded a protein with high TC activity in vitro, and chloroplastic localization was demonstrated by transient expression of green fluorescent protein-tagged fusion constructs. RNAi-mediated silencing of StSXD1 in transgenic potato plants resulted in the disruption of TC activity and severe tocopherol deficiency similar to the orthologous sxd1 and vte1 mutants. The nearly complete absence of tocopherols caused a characteristic photoassimilate export-defective phenotype comparable to sxd1, which appeared to be a consequence of vascular-specific callose deposition observed in source leaves. CO2 assimilation rates and photosynthetic gene expression were decreased in source leaves in close correlation with excess sugar accumulation, suggesting a carbohydrate-mediated feedback inhibition rather than a direct impact of tocopherol deficiency on photosynthetic capacity. This conclusion is further supported by an increased photosynthetic capacity of young leaves regardless of decreased tocopherol levels. Our data provide evidence that tocopherol deficiency leads to impaired photoassimilate export from source leaves in both monocot and dicot plant species and suggest significant differences among C3 plants in response to tocopherol reduction.


Assuntos
Interferência de RNA/fisiologia , RNA Interferente Pequeno/genética , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Tocoferóis/metabolismo , Cloroplastos/enzimologia , Cloroplastos/genética , Dados de Sequência Molecular , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , RNA de Plantas/genética
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