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1.
Methods Mol Biol ; 2553: 155-171, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36227543

RESUMO

Synthetic biology aims at engineering new biological systems and functions that can be used to provide new technological solutions to worldwide challenges. Detection and processing of multiple signals are crucial for many synthetic biology applications. A variety of logic circuits operating in living cells have been implemented. One particular class of logic circuits uses site-specific recombinases mediating specific DNA inversion or excision. Recombinase logic offers many interesting features, including single-layer architectures, memory, low metabolic footprint, and portability in many species. Here, we present two automated design strategies for both Boolean and history-dependent recombinase-based logic circuits. One approach is based on the distribution of computation within multicellular consortia, and the other is a single-cell design. Both are complementary and adapted for non-expert users via a web design interface, called CALIN and RECOMBINATOR, for multicellular and single-cell design strategies, respectively. In this book chapter, we are guiding the reader step by step through recombinase logic circuit design, from selecting the design strategy fitting to their final system of interest to obtaining the final design using one of our design web interfaces.


Assuntos
Lógica , Recombinases , DNA , Recombinases/genética , Recombinases/metabolismo , Biologia Sintética/métodos
2.
Science ; 378(6621): 733-740, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36395210

RESUMO

Advances in the theory of semiconductors in the 1930s in addition to the purification of germanium and silicon crystals in the 1940s enabled the point-contact junction transistor in 1947 and initiated the era of semiconductor electronics. Gordon Moore postulated 18 years later that the number of components in an integrated circuit would double every 1 to 2 years with associated reductions in cost per transistor. Transistor density doubling through scaling-the decrease of component sizes-with each new process node continues today, albeit at a slower pace compared with historical rates of scaling. Transistor scaling has resulted in exponential gain in performance and energy efficiency of integrated circuits, which transformed computing from mainframes to personal computers and from mobile computing to cloud computing. Innovations in new materials, transistor structures, and lithographic technologies will enable further scaling. Monolithic 3D integration, design technology co-optimization, alternative switching mechanisms, and cryogenic operation could enable further transistor scaling and improved energy efficiency in the foreseeable future.


Assuntos
Eletrônica , Germânio , Silício , Tecnologia , Lógica
5.
Sensors (Basel) ; 22(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36366129

RESUMO

Software-defined networking (SDN) has gained tremendous growth and can be exploited in different network scenarios, from data centers to wide-area 5G networks. It shifts control logic from the devices to a centralized entity (programmable controller) for efficient traffic monitoring and flow management. A software-based controller enforces rules and policies on the requests sent by forwarding elements; however, it cannot detect anomalous patterns in the network traffic. Due to this, the controller may install the flow rules against the anomalies, reducing the overall network performance. These anomalies may indicate threats to the network and decrease its performance and security. Machine learning (ML) approaches can identify such traffic flow patterns and predict the systems' impending threats. We propose an ML-based service to predict traffic anomalies for software-defined networks in this work. We first create a large dataset for network traffic by modeling a programmable data center with a signature-based intrusion-detection system. The feature vectors are pre-processed and are constructed against each flow request by the forwarding element. Then, we input the feature vector of each request to a machine learning classifier for training to predict anomalies. Finally, we use the holdout cross-validation technique to evaluate the proposed approach. The evaluation results specify that the proposed approach is highly accurate. In contrast to baseline approaches (random prediction and zero rule), the performance improvement of the proposed approach in average accuracy, precision, recall, and f-measure is (54.14%, 65.30%, 81.63%, and 73.70%) and (4.61%, 11.13%, 9.45%, and 10.29%), respectively.


Assuntos
Algoritmos , Software , Aprendizado de Máquina , Lógica
6.
Sci Rep ; 12(1): 19431, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371447

RESUMO

Inferring reliable brain-behavior associations requires synthesizing evidence from thousands of functional neuroimaging studies through meta-analysis. However, existing meta-analysis tools are limited to investigating simple neuroscience concepts and expressing a restricted range of questions. Here, we expand the scope of neuroimaging meta-analysis by designing NeuroLang: a domain-specific language to express and test hypotheses using probabilistic first-order logic programming. By leveraging formalisms found at the crossroads of artificial intelligence and knowledge representation, NeuroLang provides the expressivity to address a larger repertoire of hypotheses in a meta-analysis, while seamlessly modeling the uncertainty inherent to neuroimaging data. We demonstrate the language's capabilities in conducting comprehensive neuroimaging meta-analysis through use-case examples that address questions of structure-function associations. Specifically, we infer the specific functional roles of three canonical brain networks, support the role of the visual word-form area in visuospatial attention, and investigate the heterogeneous organization of the frontoparietal control network.


Assuntos
Inteligência Artificial , Neuroimagem Funcional , Neuroimagem/métodos , Encéfalo/diagnóstico por imagem , Lógica
7.
Anal Chem ; 94(45): 15839-15846, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36318504

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated) system has been widely explored for the detection of disease-related nucleic acids. Nevertheless, the simultaneous detection of multiple nucleic acids within one assay using the CRISPR-Cas system is still challenging. In this study, we develop an AND logic-gate-based CRISPR-Cas12a biosensing platform to achieve the sensitive colorimetric detection of dual miRNAs. Specifically, the DNA probe was designed to recognize the binary input of miRNAs and to output trigger DNA, which activated the CRISPR-Cas12a system to cut single-stranded DNA (ssDNA). The ssDNA on magnetic beads (MBs) was cleaved by the activated CRISPR-Cas12a, causing the separation of glucose oxidase (GOx) from MB and the subsequent generation of a colorimetric signal. The color change induced by 1 pM of target miRNAs can be directly distinguished by the naked eye and the instrumental limit of detection reaches 36.4 fM. The overexpressed miR-205 and miR-944 in the real human serum can be detected, allowing us to differentiate between lung cancer patients and healthy people. Furthermore, the developed strategy achieves simultaneous detection of dual miRNAs using CRISPR-Cas12a with one kind of crRNA, avoiding sophisticated nucleic acid amplifications and the use of bulky instruments. The current method can broaden the CRISPR-Cas12a-based applications for multiple biomarkers detection and precise disease diagnosis.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Humanos , Sistemas CRISPR-Cas/genética , Colorimetria , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , DNA de Cadeia Simples , Lógica , Técnicas Biossensoriais/métodos
8.
Soc Sci Med ; 314: 115494, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36334494

RESUMO

Taking an institutional logics perspective, this study investigates how "internet-informed" patients manage tensions between the logic of personal choice and the logic of medical professionalism as they navigate treatment decisions and the patient-doctor relationship. Based on 44 semi-structured interviews with members of an online health community for people with diabetes, this study finds that patients exercise a great deal of agency in evaluating healthcare options not only by activating the logic of personal choice but also by appropriating the logic of medical professionalism. Furthermore, patients are strategic in deciding what community advice to share with their doctor or nurse depending on the healthcare professionals' reaction to the logic of personal choice. In contrast to many previous studies that emphasise patient consumerism fuelled by information on the Internet, this study provides a more nuanced picture of patient-doctor relationship engendered by patients' participation in online health communities.


Assuntos
Relações Médico-Paciente , Médicos , Humanos , Participação do Paciente , Internet , Lógica
9.
Hist Philos Life Sci ; 44(4): 65, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36417009

RESUMO

What sets someone on a life trajectory? This question is at the heart of studies of 21st-century neurosciences that build on scientific models developed over the last 150 years that attempt to link psychopathology risk and human development. Historically, this research has documented persistent effects of singular, negative life experiences on people's subsequent development. More recently, studies have documented neuromolecular effects of early life adversity on life trajectories, resulting in models that frame lives as disproportionately affected by early negative experiences. This view is dominant, despite little evidence of the stability of the presumably early-developed molecular traits and their potential effects on phenotypes. We argue that in the context of gaps in knowledge and the need for scientists to reason across molecular and phenotypic scales, as well as time spans that can extend beyond an individual's life, specific interpretative frameworks shape the ways in which individual scientific findings are assessed. In the process, scientific reasoning oscillates between understandings of cellular homeostasis and organisms' homeorhesis, or life trajectory. Biologist and historian François Jacob described this framework as the "attitude" that researchers bring to bear on their "objects" of study. Through an analysis of, first, historical and contemporary scientific literature and then ethnographic research with neuroscientists, we consider how early life trauma came to be associated with specific psychological and neurobiological effects grounded in understandings of life trajectories. We conclude with a consideration of the conceptual, ontological, and ethical implications of interpreting life trajectories as the result of the persistence of long-embodied biological traits, persistent life environments, or both.


Assuntos
Conhecimento , Neurobiologia , Humanos , Antropologia Cultural , Princípios Morais , Lógica
10.
Int J Chron Obstruct Pulmon Dis ; 17: 2757-2788, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36317184

RESUMO

Purpose: This review aimed to summarize empirical evidence about pharmacist-led interventions for chronic obstructive pulmonary disease (COPD) patients in hospital settings and to identify the components of a logic model (including input, interventions, output, outcome and contextual factors) to inform the development of hospital pharmacist's role in COPD management. Methods: A systematic review of literature retrieved from four English databases (PubMed, Web of Science, Scopus, ScienceDirect) and one Chinese database (CNKI) were conducted to identify eligible studies published from inception to March 2022. Studies concerning pharmacist and COPD were identified to screen for randomized controlled studies that focused on pharmacist interventions for COPD at the hospital setting. Results: Twenty-nine studies were included in this review. The components of interventions identified were categorized according to the six service domains in the International Pharmaceutical Federation's Basel Statements, and mainly concerned prescribing, preparation, administration and monitoring but not procurement and training. Extended interventions were also identified including life guidance, psychological counseling, and respiratory function exercise. The most common outputs reported were improvement in medication adherence, rational drug use, level of knowledge, and inhalation technique. The clinical outcomes (symptomatic control, lung function, rates of hospital readmission, length of hospital stay, and adverse drug adverse reactions), humanistic outcomes (quality of life and patient satisfaction), and economic outcomes (drug costs, hospitalization costs, antibiotic costs, and direct costs) were reported only in some studies. The contextual factors mainly included geographical factors, education level of patients, socio-economic factors, and no-smoking policy. Conclusion: The evidence for hospital pharmacists' interventions in improving COPD patients' outcome is growing. However, considering the challenges of COPD management, hospital pharmacists should further leverage the advantages of cross-sector and multi-disciplinary collaboration in order to provide more comprehensive support to better address the needs of their patients.


Assuntos
Farmacêuticos , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Hospitais , Lógica
11.
Anal Chim Acta ; 1234: 340516, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36328728

RESUMO

Stimuli responsive sensors QI 1 and QI 2 were rationally developed which exhibited diverse features of mutable mechanofluorochromism, reversible photochromism, solvatochromism, aggregation induced emission enhancement (AIEE), and metal ion sensing. After observing the exceptional structural property relationship, sensors were applied for reversible colorimetric and fluorometric determination of Ni2+ with low detection limits of 12 and 17 nM, respectively. Fluorescence emission enhancement based Ni2+ sensing was induced by chelation enhanced fluorescence (CHEF) mechanism. CHEF is triggered by the inhibition of excited state intramolecular proton transfer (ESIPT) and -C=N isomerization. The proposed Ni2+ sensing mechanism was investigated through 1H NMR, FT-IR titration, theoretical studies, and Jobs plots. Further, the developed sensors successfully demonstrated the selective acid-base induced absorption/emission switching through reversible ring-opening/closing and keto-enol tautomerization, evidenced by 1H NMR titration experiments. Additionally, the sensitivity of the sensor QI 1 towards Ni2+ was effectively mimicked in live MCF-7 cells and industrial effluents. Furthermore, monitoring of Ni2+ ions was also accessed through inexpensive and portable sensors' coated fluorescent films. Finally, an INHIBIT logic gate was fabricated imputing Ni2+ and EDTA as input signals to electronically scrutinize the targeted Ni2+.


Assuntos
Colorimetria , Lógica , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier
12.
Front Public Health ; 10: 811876, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330104

RESUMO

The elderly population in China is expected to exceed 300 million and enter the stage of moderate aging during the 14th Five-Year plan period from 2021 to 2025. From the sustainable development perspective of elderly care enterprises, the supply of elderly care services would be unsustainable if enterprises suffer long-term losses. In the latter pursuit of high profits, the burden on consumers will increase. Equity financing of these enterprises is the key to achieving high-quality transformation and development by considering economic and social benefits. This study considers 20 well-known China-based elderly care enterprises as the research object. It uses a fuzzy set to explore system logic, operation mode, management performance, and attitude of elderly care enterprises toward investment through the qualitative comparative analysis method. The causal relationship between them is clarified-because, before the endowment enterprise equity financing intention of China, it is important to explore the effective path of equity financing of endowment enterprises. In the past, this helped Chinese elderly care enterprises actively cope with the trend of population aging, meet the needs of diversified and multi-level elderly care services, establish a sustainable development mode, and achieve high-quality transformation and development. The results show that (1) the operating performance of elderly care enterprises under the mode of public construction and private operation is poor; (2) elderly care enterprises driven by public welfare logic are more likely to achieve higher business performance, and (3) elderly care enterprises driven by business logic are more willing to introduce investment when they have made profits.


Assuntos
Financiamento de Capital , Intenção , Humanos , Idoso , China , Envelhecimento , Lógica
13.
Sci Rep ; 12(1): 18156, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36307465

RESUMO

Boolean networks have been widely used to model gene networks. However, such models are coarse-grained to an extent that they abstract away molecular specificities of gene regulation. Alternatively, bipartite Boolean network models of gene regulation explicitly distinguish genes from transcription factors (TFs). In such bipartite models, multiple TFs may simultaneously contribute to gene regulation by forming heteromeric complexes, thus giving rise to composition structures. Since bipartite Boolean models are relatively recent, an empirical investigation of their biological plausibility is lacking. Here, we estimate the prevalence of composition structures arising through heteromeric complexes. Moreover, we present an additional mechanism where composition structures may arise as a result of multiple TFs binding to cis-regulatory regions and provide empirical support for this mechanism. Next, we compare the restriction in BFs imposed by composition structures and by biologically meaningful properties. We find that though composition structures can severely restrict the number of Boolean functions (BFs) driving a gene, the two types of minimally complex BFs, namely nested canalyzing functions (NCFs) and read-once functions (RoFs), are comparatively more restrictive. Finally, we find that composition structures are highly enriched in real networks, but this enrichment most likely comes from NCFs and RoFs.


Assuntos
Regulação da Expressão Gênica , Modelos Genéticos , Redes Reguladoras de Genes , Lógica
14.
Philos Trans R Soc Lond B Biol Sci ; 377(1866): 20210334, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36314149

RESUMO

The ability to entertain and reflect on possibilities is a crucial component of human reasoning. However, the origin of this reasoning-whether it is language-based or not-is highly debated. We contribute to this debate by investigating the relation between language and thought in the domain of possibility from a developmental perspective. Our investigation focuses on disjunctive syllogism, a specific type of possibility reasoning that has been explored extensively in the developmental literature and has clear linguistic correlates. Seeking links between conceptual and linguistic representations, we review evidence on how children reason by the disjunctive syllogism and how they acquire logical and modal language. We sketch a proposal for how language and thought interact during development. This article is part of the theme issue 'Thinking about possibilities: mechanisms, ontogeny, functions and phylogeny'.


Assuntos
Idioma , Resolução de Problemas , Criança , Humanos , Lógica , Linguística
15.
PLoS Biol ; 20(10): e3001841, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36251652

RESUMO

Sustainable development is often represented as contributing to desirable outcomes across economic, environmental, and social goals, yet policies and interventions attempting to deliver sustainable development often disagree on the order in which these categories of goals should be addressed. In this Essay, we identify and review 5 approaches (called logic models) for sustainable development in ocean systems based on existing policies and interventions and consider the evidence for their contributions to equity-the ultimate goal of sustainable development according to the UN Sustainable Development Goals (SDGs). Two of the 5 logic models prioritize economic growth and lead to social and environmental benefits, 2 prioritize environmental health as a prerequisite for sustainable economic and social benefits, and the final logic model is community driven and prioritizes social dimensions. Looking towards the 2030 maturation of the SDGs, we will need to understand what models are best suited to deliver on equity gains and prevent future inequities in development and how best to operationalize them.


Assuntos
Desenvolvimento Sustentável , Nações Unidas , Saúde Ambiental , Saúde Global , Lógica
16.
Psychiatr Danub ; 34(3): 407-410, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36256974

RESUMO

Brief Strategic Therapy (BST) is a psychosocial treatment for mental disorders based on a unique theory of psychological dysfunction that differs from major psychotherapy approaches in that psychological dysfunction follows non-ordinary logics rather than classic logical principles. BST contends that there are three different kinds of non-ordinary logics that underpin psychological dysfunction: the logic of contradiction, the logic of paradox, and the logic of belief. BST therapeutic strategies are based on these non-ordinary logics processes. Unfortunately, descriptions and case examples of these non-ordinary logics are scattered among a myriad of books so that it is difficult for the clinician to get acquainted with them. Additionally, BST literature has described these non-ordinary logics with a somewhat obscure and metaphorical language that might be difficult for the clinician to grasp. Herein, we condensate descriptions and case examples of the three non-ordinary logics, clarify the phenomenological processes of each of the classes of non-ordinary logics, and highlight research findings from different theoretical orientations that are coherent and consistent with our phenomenological accounts of non-ordinary logics. Based on our clinical observations, non-ordinary logics can be distinguished by three variables: (a) the immediate effect of the dysfunctional attempted solution (DAS), (b) the long-term effect of the DAS, and (c) the most salient mental phenomenon associated with the DAS that maintains a psychological problem. This advancement could foster clinicians' ability to identify non-ordinary logics and their ability to devise appropriate strategies to solve psychological problems.


Assuntos
Idioma , Lógica , Humanos , Transtornos Mentais
17.
Nature ; 610(7932): 496-501, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36261553

RESUMO

Artificial neural networks have revolutionized electronic computing. Similarly, molecular networks with neuromorphic architectures may enable molecular decision-making on a level comparable to gene regulatory networks1,2. Non-enzymatic networks could in principle support neuromorphic architectures, and seminal proofs-of-principle have been reported3,4. However, leakages (that is, the unwanted release of species), as well as issues with sensitivity, speed, preparation and the lack of strong nonlinear responses, make the composition of layers delicate, and molecular classifications equivalent to a multilayer neural network remain elusive (for example, the partitioning of a concentration space into regions that cannot be linearly separated). Here we introduce DNA-encoded enzymatic neurons with tuneable weights and biases, and which are assembled in multilayer architectures to classify nonlinearly separable regions. We first leverage the sharp decision margin of a neuron to compute various majority functions on 10 bits. We then compose neurons into a two-layer network and synthetize a parametric family of rectangular functions on a microRNA input. Finally, we connect neural and logical computations into a hybrid circuit that recursively partitions a concentration plane according to a decision tree in cell-sized droplets. This computational power and extreme miniaturization open avenues to query and manage molecular systems with complex contents, such as liquid biopsies or DNA databases.


Assuntos
Computadores Moleculares , Redes Neurais de Computação , Eletrônica , MicroRNAs , DNA , Miniaturização , Lógica
18.
Inorg Chem ; 61(43): 17007-17011, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36264551

RESUMO

Boolean operations with multiple catalysts as output are yet unknown using molecular logic. The issue is solved using a two-component ensemble, composed of a receptor and rotaxane, which acts as a three-input AND gate with a dual catalytic output. Actuation of the ensemble gate by the stoichiometric addition of metal ions (Ag+ and Cd2+) and 2,2,2-trifluoroacetic acid generated in the (1,1,1) truth table state a catalyst duo that synergistically enabled a three-step reaction, furnishing a dihydroisoquinoline as the output of a three-input logic AND gate operation.


Assuntos
Lógica , Catálise , Íons , Prótons , Prata/química
19.
Sci Rep ; 12(1): 15747, 2022 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-36130987

RESUMO

Optical computing is highly desired as a potential strategy for circumventing the performance limitations of semiconductor-based electronic devices and circuits. Optical logic gates are considered as fundamental building blocks for optical computation and they enable logic functions to be performed extremely quickly without the generation of heat and crosstalk. Here, we discuss the design of a multi-functional optical logic gate based on an on-chip diffractive optical neural network that can perform AND, NOT and OR logic operations at the wavelength of 1.55 µm. The wavelength-independent operation of the multi-functional logic gate at seven wavelengths (over a bandwidth of 60 nm) is also studied which paves the way for wavelength division multiplexed parallel computation. This simple, highly-integrable, low-loss, energy-efficient and broadband optical logic gate provides a path for the development of high-speed on-chip nanophotonic processors for future optical computing applications.


Assuntos
Lógica , Redes Neurais de Computação , Eletrônica
20.
Pituitary ; 25(6): 911-926, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36085339

RESUMO

PURPOSE: The efficacy of levoketoconazole for endogenous Cushing's syndrome was demonstrated in a phase 3, open-label study (SONICS). This study (LOGICS) evaluated drug-specificity of cortisol normalization. METHODS: LOGICS was a phase 3, placebo-controlled, randomized-withdrawal study with open-label titration-maintenance (14-19 weeks) followed by double-blind, randomized-withdrawal (~ 8 weeks), and restoration (~ 8 weeks) phases. RESULTS: 79 patients received levoketoconazole during titration-maintenance; 39 patients on a stable dose (~ 4 weeks or more) proceeded to randomization. These and 5 SONICS completers who did not require dose titration were randomized to levoketoconazole (n = 22) or placebo (n = 22). All patients with loss of response (the primary endpoint) met the prespecified criterion of mean urinary free cortisol (mUFC) > 1.5 × upper limit of normal. During randomized-withdrawal, 21 patients withdrawn to placebo (95.5%) lost mUFC response compared with 9 patients continuing levoketoconazole (40.9%); treatment difference: - 54.5% (95% CI - 75.7, - 27.4; P = 0.0002). At the end of randomized-withdrawal, mUFC normalization was observed among 11 (50.0%) patients receiving levoketoconazole and 1 (4.5%) receiving placebo; treatment difference: 45.5% (95% CI 19.2, 67.9; P = 0.0015). Restoration of levoketoconazole reversed loss of cortisol control in most patients who had received placebo. Adverse events were reported in 89% of patients during treatment with levoketoconazole (dose-titration, randomized-withdrawal, and restoration phases combined), most commonly nausea (29%) and hypokalemia (26%). Prespecified adverse events of special interest with levoketoconazole were liver-related (10.7%), QT interval prolongation (10.7%), and adrenal insufficiency (9.5%). CONCLUSIONS: Levoketoconazole reversibly normalized urinary cortisol in patients with Cushing's syndrome. No new risks of levoketoconazole treatment were identified.


Assuntos
Insuficiência Adrenal , Síndrome de Cushing , Humanos , Síndrome de Cushing/tratamento farmacológico , Hidrocortisona/uso terapêutico , Resultado do Tratamento , Lógica
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