RESUMO
Antibody discovery by phage display consists of two phases, i.e., the binding phase and the amplification phase. Ideally, the selection process is dominated by the former, and all the retrieved clones are amplified equally during the latter. In reality, the amplification efficiency of antibody fragments varies widely among different sequences and, after a few rounds of phage display panning, the output repertoire often includes rapidly amplified sequences with low or no binding activity, significantly diminishing the efficiency of antibody isolation. In this work, a novel synthetic single-chain variable fragment (scFv) library with complementarity-determining region (CDR) diversities aimed at improved amplification efficiency was designed and constructed. A previously reported synthetic scFv library with low, non-combinatorial CDR diversities was panned against protein A superantigen, and the library repertoires before and after the panning were analyzed by next generation sequencing. The enrichment or depletion patterns of CDR sequences after panning served as the basis for the design of the new library. Especially for CDR-H3 with a higher and more random diversity, a machine learning method was applied to predict potential fast-amplified sequences among a simulated sequence repertoire. In a direct comparison with the previous generation library, the new library performed better against a panel of antigens in terms of the number of binders isolated, the number of unique sequences, and/or the speed of binder enrichment. Our results suggest that the amplification-centric design of sequence diversity is a valid strategy for the construction of highly functional phage display antibody libraries.
Assuntos
Regiões Determinantes de Complementaridade , Anticorpos de Cadeia Única , Regiões Determinantes de Complementaridade/genética , Sequenciamento de Nucleotídeos em Larga Escala , Biblioteca de Peptídeos , Anticorpos de Cadeia Única/genéticaRESUMO
Objective/Background: In the present study, we compared differences in brain activity during the Stroop task between patients with chronic insomnia disorder (CID) and good sleepers (GS). Furthermore, we evaluated changes in Stroop task-related brain activity after cognitive-behavioral therapy for insomnia (CBT-I). Participants/Methods: The final analysis included 21 patients with CID and 25 GS. All participants underwent functional magnetic resonance imaging (fMRI) while performing the color-word Stroop task. CBT-I, consisting of 5 sessions, was administered to 14 patients with CID in the absence of medication. After CBT-I, fMRI was repeated in the patients with CID while performing the same task. Sleep-related questionnaires and sleep variables from a sleep diary were also obtained before and after CBT-I. Results: No significant differences in behavioral performance in the Stroop task or task-related brain activation were observed between the CID and GS groups. No changes in behavioral performance or brain activity were found after CBT-I. However, clinical improvement in the Insomnia Severity Index (ISI) score was significantly associated with changes in the Stroop task-related regional blood oxygen level-dependent signals in the left supramarginal gyrus. Conclusions: Our findings suggest that cognitive impairment in patients with CID was not detectable by the Stroop task or Stroop task-related brain activation on fMRI. Moreover, there was no altered brain activity during the Stroop task after CBT-I. However, the ISI score reflected changes in the neural correlates of cognitive processes in patients with CID after CBT-I.
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Terapia Cognitivo-Comportamental/métodos , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Teste de Stroop/normas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do TratamentoRESUMO
PURPOSE/BACKGROUND: The aim of this study was to evaluate the effects of quetiapine XR and lithium on actigraphy-measured circadian parameters in patients with bipolar II depression. METHODS/PROCEDURES: This was an 8-week, open-label, prospective, randomized comparative study. The assessments included the 17-item Hamilton Depression Rating Scale score and actigraphic measures concerning the previous 7 days, collected at each visit (weeks 0 [baseline], 1, 2, 4, 6, and 8); the actigraphic data were analyzed with a cosinor analysis. FINDINGS/RESULTS: Medication, time, and the interaction between medication and time were significantly associated with acrophase for the entire group (Ps = 0.003, 0.020, and 0.042, respectively). More specifically, acrophase was significantly delayed at weeks 1 and 6 (Ps = 0.004 and 0.039, respectively) in the quetiapine XR group. The F statistics significantly increased over time for the entire group (P < 0.001), and there was a significant increase in F statistics on weeks 4 and 6 in the quetiapine XR group (Ps = 0.016 and 0.020, respectively) and on weeks 4 and 8 in the lithium group (Ps = 0.001 and 0.016, respectively). In addition, scores on the 17-item Hamilton Depression Rating Scale were significantly associated with the F statistics during 8 weeks for the entire group (P = 0.008). IMPLICATIONS/CONCLUSIONS: Both quetiapine XR and lithium affected several circadian parameters, including peak activity time and robustness of circadian rhythm, but exerted different effects on acrophase in patients with bipolar II depression. In particular, clinical depressive symptoms were associated with robustness of circadian rhythm during the course of the 8-week treatment.
Assuntos
Antimaníacos/farmacologia , Antipsicóticos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Ritmo Circadiano/efeitos dos fármacos , Compostos de Lítio/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Fumarato de Quetiapina/farmacologia , Actigrafia , Adulto , Antimaníacos/administração & dosagem , Antipsicóticos/administração & dosagem , Transtorno Bipolar/fisiopatologia , Feminino , Humanos , Compostos de Lítio/administração & dosagem , Masculino , Pessoa de Meia-Idade , Fumarato de Quetiapina/administração & dosagem , Adulto JovemRESUMO
In this paper, the newly developed 3D-constructed AlScN piezoelectric MEMS mirror is presented. This paper describes the structure and driving mechanism of the proposed mirror device, covering its driving characteristics in both quasi-static and resonant scan modes. Particularly, this paper deals with various achievable scan patterns including 1D line scan and 2D area scan capabilities and driving methods to realize each scanning strategy. Bidirectional quasi-static actuation along horizontal, vertical, and diagonal scanning directions was experimentally characterized and even under a low voltage level of ±20 V, a total optical scan angle of 10.4° was achieved. In addition, 1D line scanning methods using both resonant and non-resonant frequencies were included and a total optical scan angle of 14° was obtained with 100 mVpp under out-of-phase actuation condition. Furthermore, 2D scan patterns including Lissajous, circular and spiral, and raster scans were realized. Diverse scan patterns were realized with the presented AlScN-based MEMS mirror device even under a low level of applied voltage. Further experiments using high voltage up to ±120 V to achieve an enhanced quasi-static scan angle of more than 20° are ongoing to ensure repeatability. This multi-functional MEMS mirror possesses the potential to implement multiple scanning strategies suitable for various application purposes.
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We investigated the process and outcome of spiritually integrated psychotherapies (SIPs) with 34 Catholic therapists and 359 clients in Asia, Africa, Europe, and Latin America using a practice-based evidence design. The three most frequently used spiritual interventions across all therapists were: "encouraging personal prayer," "affirming trusting God," and "encouraging listening to the heart," but "discussing hope" was also one of the top three in Asia and Africa, "self-control" in Asia, "spiritual confrontation" and "self-disclosure" in Latin America, and "listening to spiritual issues" in Europe. In addition, using growth curve analyses, we found a significant decrease in both spiritual and nonspiritual distress over the course of SIPs; the levels of spiritual and nonspiritual concerns were highly correlated (but distinct) at any given time point. Also, the nonspiritual outcomes at one session significantly predicted the subsequent session's spiritual outcomes, but not the other way around. Finally, a moderate number of spiritual interventions were associated with a faster decline in nonspiritual distress than was a low number, although we found mixed results regarding whether a high number of spiritual interventions was associated with a faster decline of clients' nonspiritual distress than a moderate number. Results suggest that therapists should attend to spiritual concerns in psychotherapy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Comparação Transcultural , Psicoterapia , África , Ásia , Humanos , América Latina , Psicoterapia/métodosRESUMO
This study aimed to identify differences between physiological age-related and Alzheimer's disease (AD)-related alterations in sleep and rest-activity rhythm. All participants (n = 280; 20-90 years) underwent clinical assessments, [11C] Pittsburgh compound B-positron emission tomography, and actigraphic monitoring. In cognitively normal adults without cerebral amyloid-ß, older age was associated with earlier timing of circadian phase and robust rest-activity rhythm, but sleep quantity and quality were mostly unaffected by age. While preclinical AD was associated with earlier circadian timing, clinical AD exhibited later timing of daily rhythm and increased sleep duration. In conclusion, our findings suggest that older age itself leads to a more regular daily activity rhythm, but does not affect sleep duration. While preclinical AD made the effects of age-related phase advance more prominent, clinical AD was related to later circadian timing and increased sleep duration.
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Envelhecimento/fisiologia , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Ritmo Circadiano/fisiologia , Longevidade/fisiologia , Descanso/fisiologia , Sono/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
We introduce the characteristics of the titanium dioxide (TiO(2)) inorganic film deposited by rf magnetron sputtering for liquid crystal display applications. The TiO(2) films demonstrated vertical alignment (VA) of the liquid crystals (LCs) obtained by using ion-beam (IB) bombardment. As observed by using x-ray photoelectron spectroscopy, the chemical structure of the TiO(2) was changed by IB bombardment, altering the Ti-O bonding of the Ti 2p spectra to lower intensity levels. Breaking Ti-O bonding by IB bombardment created pretilt angles between the TiO(2) film and LC molecules. The better voltage-transmittance characteristics of the VA LCDs based on TiO(2) film were measured and compared with the same characteristics of polyimide film.
RESUMO
Electro-optic performance of a liquid-crystal (LC) system is enhanced by TiO(2) nanoparticle dispersed in nematic liquid crystal (NLC). The 2.5 V threshold voltage of LC for device operation is lowered to 0.5 V through TiO(2) nanoparticle mixing up to 2 wt.%. To characterize the shape and size distribution of the nanoparticles, high-resolution transmission electron microscopy is employed. Transmittance spectra for the TiO(2) dispersed LC structure and nondispersed LC structure showed that transparency of the TiO(2) dispersed LC is similar to that of pure liquid LC.
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Central venous catheters are used for various purposes in the operating room. Generally, the use of ultrasound to insert a central venous catheter is rapid and minimally complicated. An advanced venous access (AVA) catheter is used to gain access to the pulmonary artery and facilitate fluid resuscitation through the internal jugular vein. The present report describes a case in which ultrasound was used in a 43-year-old man to avoid complications during insertion of an AVA catheter with a relatively large diameter. The sheath of the catheter was so thin that a dilator was essential to prevent it from folding upon insertion. Despite the use of ultrasound guidance, the AVA catheter sheath became folded within the patient's internal jugular vein. Mechanical complications of central venous catheter insertion are well known, but folding of a large-bore catheter in the internal jugular vein has rarely been reported.
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Cateterismo Venoso Central/métodos , Veias Jugulares/patologia , Veias Jugulares/cirurgia , Cirurgia Assistida por Computador/métodos , Ultrassonografia/métodos , Adulto , Humanos , Veias Jugulares/diagnóstico por imagem , Masculino , PrognósticoRESUMO
Linalool is a natural product present in fruits and aromatic plants with biological activities. Researchers have reported that the inhalation of linalool exerts anti-inflammatory activities. In this study, we examined the therapeutic effects of linalool on airway inflammation and mucus overproduction in mice with allergic asthma. Oral administration of linalool significantly inhibited the levels of eosinophil numbers, Th2 cytokines and immunoglobulin E (IgE) caused by ovalbumin (OVA) exposure. Linalool exerted preventive effects against the influx of inflammatory cells and mucus hypersecretion in the lung tissues. Linalool also dose-dependently decreased the levels of inducible nitric oxide synthase (iNOS) expression and protein kinase B (AKT) activation in the lung tissues. Linalool effectively downregulated the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) caused by OVA exposure. Furthermore, linalool exerted inhibitory effect on OVA-induced airway hyperresponsiveness (AHR). In the in vitro study, the increased secretion of MCP-1 was attenuated with linalool treatment in lipopolysaccharide (LPS)-stimulated H292 airway epithelial cells. In conclusion, linalool effectively exerts a protective role in OVA-induced airway inflammation and mucus hypersecretion, and its protective effects are closely related to the downregulation of inflammatory mediators and MAPKs/NF-κB signaling.
Assuntos
Monoterpenos Acíclicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Pulmão/metabolismo , Hipersensibilidade Respiratória/tratamento farmacológico , Células Th2/imunologia , Administração Oral , Alérgenos/imunologia , Animais , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina E/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ovalbumina/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologiaRESUMO
OBJECTIVES: To clarify the relationships between sleep-wake cycle and cerebral ß-amyloid (Aß) deposition in cognitively normal (CN) older adults, focusing primarily on the moderating effects of the APOE ε4 allele. METHODS: The present study included 133 CN older adults who participated in the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer's Disease cohort. All participants underwent [11C] Pittsburgh compound B-PET imaging to quantify Aß deposition in the brain and blood sampling for APOE genotyping. Sleep and circadian parameters were measured using actigraphy for 8 consecutive days. RESULTS: The APOE ε4 allele had moderating effects on the associations of sleep latency (SL), mesor, and acrophase with cerebral Aß deposition, and the interactions between APOE ε4 status and SL and between APOE ε4 status and acrophase remained significant after adjusting for multiple comparisons. In APOE ε4 noncarriers, shorter SL, higher mesor, and advanced acrophase were associated with Aß positivity. In contrast, APOE ε4 carriers showed a relationship between delayed acrophase and Aß accumulation that approached but did not reach significance. After the Bonferroni correction, the associations of shorter SL and higher mesor with Aß positivity remained significant for APOE ε4 noncarriers. CONCLUSIONS: Our findings suggest that the APOE ε4 allele may act as a moderator in the relationship between the sleep-wake cycle and Aß accumulation in CN older adults. Thus, APOE ε4 status needs to be considered as a key factor when designing related research or interventions.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4/genética , Encéfalo/metabolismo , Ritmo Circadiano , Sono , Actigrafia , Idoso , Compostos de Anilina , Encéfalo/diagnóstico por imagem , Ritmo Circadiano/genética , Ritmo Circadiano/fisiologia , Feminino , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Compostos Radiofarmacêuticos , Sono/genética , Sono/fisiologia , TiazóisRESUMO
The aim of this study was to investigate the relationships among morningness-eveningness, impulsivity and anger in the general population. A total of 1000 community-dwelling subjects (500 males) aged 20-77 years (mean± SD age: 39.6 ± 11.6 years) completed the morningness-eveningness questionnaire (MEQ), Barratt impulsiveness scale (BIS), Spielberger State-Trait Anger Expression Inventory (STAXI) and Center for Epidemiologic Studies Depression Scale. Moderation and mediation analyses were performed to determine whether the relationship between two variables depended on the third variable, referred to as a moderator, and whether the third variable, known as a mediator, was associated with the other two variables establishing causation. The MEQ scores exhibited significant negative associations with BIS (p < 0.001) and STAXI (p < 0.001) scores, and high scores on the BIS were associated with high scores on the STAXI (p < 0.001). Impulsivity, as measured by the BIS, played a role as a moderator (p < 0.001) in the relationship between MEQ and STAXI, and anger, as measured by the STAXI, acted as moderator (p = 0.030) in the association between MEQ and BIS. However, after controlling for the interaction of the BIS and MEQ, the MEQ scores did not significantly predict STAXI scores (p = 0.070). Additionally, the effect size of the mediating effect of the BIS scores on the relationship between the MEQ and STAXI (percent mediation: 53.2%) was larger than that of the STAXI scores on the association between the MEQ and BIS (percent mediation: 31.8%). The present results demonstrate that morningness-eveningness was closely related with both impulsivity and anger in the general population. Furthermore, these findings suggest that impulsivity may exercise a great influence on the association between morningness-eveningness and anger in two ways: as a moderator by modulating this relationship based on the level of impulsivity and as a mediator by acting as an intermediary factor.
Assuntos
Ira/fisiologia , Ritmo Circadiano/fisiologia , Comportamento Impulsivo/fisiologia , Sono/fisiologia , Adulto , Depressão/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Fatores de TempoRESUMO
A novel polymer-layer-free system for liquid-crystal alignment is demonstrated by various shaped indium tin oxide (ITO) patterns. Liquid crystals are aligned along the ITO line pattern and secondary sputtering lithography can change the shape of the ITO line pattern. Different shapes can control the direction and size of the pretilt angle. This effect eliminates defects and reduces the response time.