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1.
Appl Opt ; 61(8): 2049-2059, 2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35297897

RESUMO

This paper presents concept, optical design, and the implementation of a novel, to the best of our knowledge, lithographic exposure tool for the fabrication of rotationally symmetric meso- and microscale optical structures using a variable ring-shaped light distribution. Compared to the conventional lithographic technique of direct writing in Cartesian coordinates, which is intrinsically suboptimal for the fabrication of rotationally symmetric optical structures, this approach allows for fast exposure and avoids disturbing stitching effects. The diameter of the exposure ring varies between 1.6 and 6.5 mm, and the ring width measures ∼75µm full width at half-maximum for all diameters. The basic capabilities of the exposure tool are demonstrated by the fabrication of exemplary meso- and microscale structures such as diffractive axicon elements, phase rings, Fresnel zone plates and zone plate arrays.

2.
IEEE Comput Graph Appl ; 41(4): 125-132, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34264822

RESUMO

In recent years, research on immersive environments has experienced a new wave of interest, and immersive analytics has been established as a new research field. Every year, a vast amount of different techniques, applications, and user studies are published that focus on employing immersive environments for visualizing and analyzing data. Nevertheless, immersive analytics is still a relatively unexplored field that needs more basic research in many aspects and is still viewed with skepticism. Rightly so, because in our opinion, many researchers do not fully exploit the possibilities offered by immersive environments and, on the contrary, sometimes even overestimate the power of immersive visualizations. Although a growing body of papers has demonstrated individual advantages of immersive analytics for specific tasks and problems, the general benefit of using immersive environments for effective analytic tasks remains controversial. In this article, we reflect on when and how immersion may be appropriate for the analysis and present four guiding scenarios. We report on our experiences, discuss the landscape of assessment strategies, and point out the directions where we believe immersive visualizations have the greatest potential.

3.
Opt Express ; 28(22): 32499-32516, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33114934

RESUMO

Diffuse reflecting (white) and highly absorbing (black) fused silica based materials are presented, which combine volume modified substrates and surfaces equipped with anti-reflective moth-eye-structures. For diffuse reflection, micrometer sized cavities are created in bulk fused silica during a sol-gel process. In contrast, carbon black particles are added to get the highly absorbing material. The moth-eye-structures are prepared by block copolymer micelle nanolithography (BCML), followed by a reactive-ion-etching (RIE) step. The moth-eye-structures drastically reduce the specular reflectance on both diffuse reflecting and highly absorbing samples across a wide spectral range from 250 nm to 2500 nm and for varying incidence angles. The adjustment of the height of the moth-eye-structures allows us to select the spectral position of the specular reflectance minimum, which measures less than 0.1%. Diffuse Lambertian-like scattering and absorbance appear nearly uniform across the selected spectral range, showing a slight decrease with increasing wavelength.

4.
Sensors (Basel) ; 20(18)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32971822

RESUMO

The technical progress in the last decades makes photo and video recording devices omnipresent. This change has a significant impact, among others, on police work. It is no longer unusual that a myriad of digital data accumulates after a criminal act, which must be reviewed by criminal investigators to collect evidence or solve the crime. This paper presents the VICTORIA Interactive 4D Scene Reconstruction and Analysis Framework ("ISRA-4D" 1.0), an approach for the visual consolidation of heterogeneous video and image data in a 3D reconstruction of the corresponding environment. First, by reconstructing the environment in which the materials were created, a shared spatial context of all available materials is established. Second, all footage is spatially and temporally registered within this 3D reconstruction. Third, a visualization of the hereby created 4D reconstruction (3D scene + time) is provided, which can be analyzed interactively. Additional information on video and image content is also extracted and displayed and can be analyzed with supporting visualizations. The presented approach facilitates the process of filtering, annotating, analyzing, and getting an overview of large amounts of multimedia material. The framework is evaluated using four case studies which demonstrate its broad applicability. Furthermore, the framework allows the user to immerse themselves in the analysis by entering the scenario in virtual reality. This feature is qualitatively evaluated by means of interviews of criminal investigators and outlines potential benefits such as improved spatial understanding and the initiation of new fields of application.

5.
J Opt Soc Am A Opt Image Sci Vis ; 37(8): 1369-1380, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32749271

RESUMO

The majority of spectrometers use reflective dispersion gratings with a metal-coated blazed grating profile for spectral decomposition. They achieve high diffraction efficiency at the design wavelength, which decays considerably in the adjacent longer and shorter wavelength ranges. We introduce a structured metal double-blazed grating with a high diffraction efficiency for a broadband spectral range, consisting of a sawtooth-like structured metal surface filled with a first dielectric transparent material. The planarized upper surface is covered with a second blazed profile of a different transparent material. We present a systematical theoretical analysis of the diffraction efficiency in reflection geometry, based on a scalar approach involving fundamental dispersion parameters such as Abbe numbers and relative partial dispersions of the materials. We find material combinations reducing the profile heights down to 1-2 µm.

6.
Brain Sci ; 10(8)2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32784990

RESUMO

The progress of technology has increased research on neuropsychological emotion and attention with virtual reality (VR). However, direct comparisons between conventional two-dimensional (2D) and VR stimulations are lacking. Thus, the present study compared electroencephalography (EEG) correlates of explicit task and implicit emotional attention between 2D and VR stimulation. Participants (n = 16) viewed angry and neutral faces with equal size and distance in both 2D and VR, while they were asked to count one of the two facial expressions. For the main effects of emotion (angry vs. neutral) and task (target vs. nontarget), established event related potentials (ERP), namely the late positive potential (LPP) and the target P300, were replicated. VR stimulation compared to 2D led to overall bigger ERPs but did not interact with emotion or task effects. In the frequency domain, alpha/beta-activity was larger in VR compared to 2D stimulation already in the baseline period. Of note, while alpha/beta event related desynchronization (ERD) for emotion and task conditions were seen in both VR and 2D stimulation, these effects were significantly stronger in VR than in 2D. These results suggest that enhanced immersion with the stimulus materials enabled by VR technology can potentiate induced brain oscillation effects to implicit emotion and explicit task effects.

7.
Appl Opt ; 59(5): 1338-1346, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32225391

RESUMO

Echelle inspired cross-grating spectrometers offer the potential to bridge the gap between classical high-end echelle spectrometers and curved-grating single-element instruments. In particular, the cross-grating approach offers the possibility to simultaneously achieve a high spectral resolution and a wide accessible spectral range in compact dimensions and without moving parts. We report on the complete realization and implementation details of an all-reflective cross-grating spectrometer based on a modified Czerny-Turner configuration including a folded beam path and a toric-convex mirror for aberration compensation. The applicability of the cross-grating spectrometer is demonstrated by test measurements including the recording of the spectra of different plant leaves. For the cross-grating spectrometer, with an accessible wavelength range between 330 and 1100 nm, a spectral resolution of 0.6 nm at 589 nm was achieved.

8.
Adipocyte ; 9(1): 197-205, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32272867

RESUMO

Objectives: Adipogenesis is the differentiation process generating mature adipocytes from undifferentiated mesenchymal stem cells. The differentiation can be inhibited by androgens, although knowledge about intracellular effectors of this inhibition is scarce. Recently, androgen-regulated microRNAs were detected as interesting candidates in this context. In this study, we analyse the role of miR-130a and miR-301 in the adipogenesis of human SGBS preadipocytes and whether they are prone to androgen regulation. Materials and Methods: microRNA expression during adipogenic differentiation with or without androgen stimulation was measured by qPCR. Putative target genes of miR-130a and miR-301 were identified by target database search and validated in luciferase reporter assays. Results: miR-130a and miR-301 are both significantly downregulated on day 3 and day 5 of adipogenic differentiation in comparison to day 0. Under androgen stimulation, a significant upregulation of miR-130a was detected after 7 days of adipogenesis lasting to day 14, while miR-301 did not change significantly until day 14. Luciferase reporter assays revealed the androgen receptor (AR), adiponectin (ADIPOQ) and tumour necrosis factor alpha (TNFα) as miR-130a target genes. Conclusions: miR-130a is an androgen-regulated microRNA that is downregulated during the early phase of adipogenesis and exerts its functions by regulating AR and ADIPOQ translation. These data may help to identify new signalling pathways associated with the androgen-mediated inhibition of adipogenesis.


Assuntos
Adipócitos/metabolismo , Adipogenia , Androgênios/metabolismo , MicroRNAs/metabolismo , Células Cultivadas , Humanos , MicroRNAs/genética
9.
Opt Express ; 27(24): 34655-34664, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31878652

RESUMO

We present a hybrid antireflective coating (ARC) providing a complete continuous graded refractive index (GRIN) transition from a high-index substrate down to ambient air. The ARC comprises a first GRIN layer of dense silicon-oxy-nitride with a varying, height adjusted material composition. Secondly, a layer of quasi-periodic nanopillars imitating AR-"moth-eye structure" is added to the dense GRIN layer. Demonstrated on a high index glass with a refractive index of ne=1.73 the hybrid GRIN-ARC is applicable to a broad material selection and allows to eliminate any step-like transition up to a refractive index of the substrate of ∼2.0. The ARC offers antireflective properties for large incidence angles and over an extremely broad spectrum ranging from 400 nm up to 2.5 µm. Compared to the sole substrate, the hybrid GRIN-ARC results in an increase of transmittance of more than 10% in the maximum, and more than 6% in the peripheral regions of the spectrum.

10.
J Opt Soc Am A Opt Image Sci Vis ; 36(3): 345-352, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30874187

RESUMO

The concept of a new compact echelle-inspired cross-grating spectrometer is introduced, and a specific optical design is presented. The new concept aims to achieve simultaneously a high spectral resolution, a wide accessible spectral range, and compact dimensions. The essential system novelty concerns the combination of different aspects: the implementation of a crossed grating comprising both the main dispersion and order separation, a folded reflective beam path, which enables a reduction of the system volume, and the introduction of a form-adjustable mirror for aberration compensation. The exemplary optical design offers a spectral bandwidth ranging from 330-1100 nm with spectral resolution better than 1.4 nm in the fourth and 0.4 nm in the 11th order. The optical setup covers a volume of 110 mm×110 mm×30 mm.

11.
Appl Opt ; 57(25): 7109-7116, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30182968

RESUMO

The concept and the implementation of a compact and simplified echelle spectrometer are presented, and the working principle is demonstrated by first experimental measurements. The crucial element of the setup is a cross-grating, combining an echelle grating utilizing several higher diffraction orders (5th up to 11th) and a superposed perpendicular-oriented cross-dispersing grating. Two alternative manufacturing approaches for the cross-grating are presented and discussed. The first approach combines Talbot lithography for the deep echelle grating and interference lithography for the cross-dispersing structure. As a second approach, direct laser-beam writing was applied. The compact echelle spectrometer covers a spectral range from 380 to 700 nm and offers a spectral resolution of ∼2 nm.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30130221

RESUMO

While many VA workflows make use of machine-learned models to support analytical tasks, VA workflows have become increasingly important in understanding and improving Machine Learning (ML) processes. In this paper, we propose an ontology (VIS4ML) for a subarea of VA, namely "VA-assisted ML". The purpose of VIS4ML is to describe and understand existing VA workflows used in ML as well as to detect gaps in ML processes and the potential of introducing advanced VA techniques to such processes. Ontologies have been widely used to map out the scope of a topic in biology, medicine, and many other disciplines. We adopt the scholarly methodologies for constructing VIS4ML, including the specification, conceptualization, formalization, implementation, and validation of ontologies. In particular, we reinterpret the traditional VA pipeline to encompass model-development workflows. We introduce necessary definitions, rules, syntaxes, and visual notations for formulating VIS4ML and make use of semantic web technologies for implementing it in the Web Ontology Language (OWL). VIS4ML captures the high-level knowledge about previous workflows where VA is used to assist in ML. It is consistent with the established VA concepts and will continue to evolve along with the future developments in VA and ML. While this ontology is an effort for building the theoretical foundation of VA, it can be used by practitioners in real-world applications to optimize model-development workflows by systematically examining the potential benefits that can be brought about by either machine or human capabilities. Meanwhile, VIS4ML is intended to be extensible and will continue to be updated to reflect future advancements in using VA for building high-quality data-analytical models or for building such models rapidly.

13.
Front Microbiol ; 9: 211, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29487589

RESUMO

A wide variety of endogenous retroviral sequences has been demonstrated in the human genome so far, divided into several different families according to the sequence homology to viral strains. While increased expression of human endogenous retrovirus (HERV) elements has already been linked to unfavorable prognosis in hepatocellular carcinoma, breast cancer, and ovarian carcinoma yet less is known about the impact of the expression of different HERV elements on sarcomagenesis in general as well as the outcome of soft tissue sarcoma (STS) patients. Therefore, in this study the association between expression of HERV-K and HERV-F and the clinicopathological characteristics in a cohort of STSs as well as the patients' prognosis was evaluated. HERV-K and HERV-F expression was assessed by quantitative real-time PCR in 120 patient specimens. HERV-K and HERV-F expression was significantly correlated (rS = 0.5; p = 6.4 × 10-9; Spearman's rank bivariate correlation). Also, tumor diameter exhibited a significant negative association to HERV-K and HERV-F expression. Levels of several hypoxia-related RNAs like HIF-1α and miR-210 showed a significant positive correlation with both HERV-K and HERV-F expression. Although in survival analyses no impact of HERV expression on disease-specific survival could be detected, patients with elevated HERV-K expression had a significantly shorter relapse-free survival (p = 0.014, log-rank analysis). In conclusion, we provide evidence for the first time that the increased expression of HERV-K in tumors is associated with STS patients' prognosis.

14.
IEEE Trans Vis Comput Graph ; 24(1): 120-130, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28866559

RESUMO

Clustering is a core building block for data analysis, aiming to extract otherwise hidden structures and relations from raw datasets, such as particular groups that can be effectively related, compared, and interpreted. A plethora of visual-interactive cluster analysis techniques has been proposed to date, however, arriving at useful clusterings often requires several rounds of user interactions to fine-tune the data preprocessing and algorithms. We present a multi-stage Visual Analytics (VA) approach for iterative cluster refinement together with an implementation (SOMFlow) that uses Self-Organizing Maps (SOM) to analyze time series data. It supports exploration by offering the analyst a visual platform to analyze intermediate results, adapt the underlying computations, iteratively partition the data, and to reflect previous analytical activities. The history of previous decisions is explicitly visualized within a flow graph, allowing to compare earlier cluster refinements and to explore relations. We further leverage quality and interestingness measures to guide the analyst in the discovery of useful patterns, relations, and data partitions. We conducted two pair analytics experiments together with a subject matter expert in speech intonation research to demonstrate that the approach is effective for interactive data analysis, supporting enhanced understanding of clustering results as well as the interactive process itself.

15.
Adv Sci (Weinh) ; 4(3): 1600362, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28331790

RESUMO

Buildings represent more than 40% of Europe's energy demands and about one third of its CO2 emissions. Energy efficient buildings and, in particular, building skins have therefore been among the key priorities of international research agendas. Here, glass-glass fluidic devices are presented for large-area integration with adaptive façades and smart windows. These devices enable harnessing and dedicated control of various liquids for added functionality in the building envelope. Combining a microstructured glass pane, a thin cover sheet with tailored mechanical performance, and a liquid for heat storage and transport, a flat-panel laminate is generated with thickness adapted to a single glass sheet in conventional windows. Such multimaterial devices can be integrated with state-of-the-art window glazings or façades to harvest and distribute thermal as well as solar energy by wrapping buildings into a fluidic layer. High visual transparency is achieved through adjusting the optical properties of the employed liquid. Also secondary functionality, such as chromatic windows, polychromatism, or adaptive energy uptake can be generated on part of the liquid.

16.
Appl Opt ; 55(33): 9370-9377, 2016 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-27869835

RESUMO

This paper presents the conception and implementation of a variable diameter ring-cutting system for a CO2 laser with a working wavelength of 10.6 µm. The laser-cutting system is adapted to an observation zoom microscope for combined use and is applicable for the extraction of small circular areas from polymer films, such as forensic adhesive tapes in a single shot. As an important characteristic for our application, the variable diameter ring-cutting system provides telecentricity in the target area. Ring diameters are continuously tunable between 500 µm and 2 mm. A minimum width of less than 20 µm was found for the ring profile edge. The basic characteristics of the system, including telecentricity, were experimentally evaluated and demonstrated by cutting experiments on different polymer tapes and further exemplary samples.

17.
Mol Cell Endocrinol ; 414: 177-85, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26219823

RESUMO

Late-onset hypogonadism (LOH), defined as a combination of low serum testosterone (T) levels in combination with clinical signs and symptoms of androgen deficiency in ageing men, is nowadays a well-characterized disease. Testosterone therapy in males affected by hypogonadism leads to a significant decrease of fat mass. In humans, the exact molecular mechanism of T effects on inhibition of adipogenesis is still unknown. We hypothesized that specific microRNAs could be regulated by androgens which might cause an inhibition of adipogenic differentiation. To confirm this hypothesis, human mesenchymal stem cells and a preadipocyte cell line were differentiated into mature adipocytes and in parallel treated with testosterone and dihydrotestosterone. The expression level of miR-375 was upregulated during adipogenic differentiation and downregulated after androgen treatment. Furthermore, we could show that after androgen treatment the decreased expression of miR-375 led to increased expression levels of adiponectin receptor 2 (ADIPOR2) compared to untreated adipocytes. Moreover, inhibition of miR-375 also mediated a decreased adipogenic differentiation and increased ADIPOR2 expression levels. In summary, we identified miR-375 as an androgen regulated microRNA, which could play an important role for understanding the mechanism of the increase in visceral fat mass and the associated insulin resistance caused by testosterone deficiency.


Assuntos
Adipogenia/efeitos dos fármacos , Androgênios/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores de Adiponectina/genética , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Di-Hidrotestosterona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Receptores de Adiponectina/metabolismo , Testosterona/farmacologia
18.
J Virol ; 84(23): 12245-54, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20881048

RESUMO

Understanding the lack of disease progression in nonpathogenic simian immunodeficiency virus (SIV) infections is essential for deciphering the immunopathogenesis of human AIDS. Yet, in vivo studies have been hampered by a paucity of infectious molecular clones (IMCs) of SIV suitable to dissect the viral and host factors responsible for the nonpathogenic phenotype. Here, we describe the identification, cloning, and biological analysis of the first transmitted/founder (T/F) virus representing a nonpathogenic SIV infection. Blood was collected at peak viremia from an acutely infected sabaeus monkey (Chlorocebus sabaeus) inoculated intravenously with an African green monkey SIV (SIVagm) strain (Sab92018) that had never been propagated in vitro. To generate IMCs, we first used conventional (bulk) PCR to amplify full-length viral genomes from peripheral blood mononuclear cell (PBMC) DNA. Although this yielded two intact SIVagmSab genomes, biological characterization revealed that both were replication defective. We then performed single-genome amplification (SGA) to generate partially overlapping 5' (n = 10) and 3' (n = 13) half genomes from plasma viral RNA. Analysis of these amplicons revealed clusters of nearly identical viral sequences representing the progeny of T/F viruses. Synthesis of the consensus sequence of one of these generated an IMC (Sab92018ivTF) that produced infectious CCR5-tropic virions and replicated to high titers in Molt-4 clone 8 cells and African green monkey PBMCs. Sab92018ivTF also initiated productive infection in sabaeus monkeys and faithfully recapitulated the replication kinetics and nonpathogenic phenotype of the parental Sab92018 strain. These results thus extend the T/F virus concept to nonpathogenic SIV infections and provide an important new tool to define viral determinants of disease nonprogression.


Assuntos
Cercopithecinae , Genoma Viral/genética , Fenótipo , Síndrome de Imunodeficiência Adquirida dos Símios/genética , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/patogenicidade , Animais , Sequência de Bases , Western Blotting , Linfócitos T CD4-Positivos/imunologia , Clonagem Molecular , Análise por Conglomerados , Primers do DNA/genética , Progressão da Doença , Citometria de Fluxo , Dados de Sequência Molecular , Técnicas de Amplificação de Ácido Nucleico , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Síndrome de Imunodeficiência Adquirida dos Símios/fisiopatologia , Vírus da Imunodeficiência Símia/imunologia , Replicação Viral/fisiologia
19.
Virology ; 397(2): 346-57, 2010 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-20003995

RESUMO

Functional studies of HIV-1 envelope glycoproteins (Envs) commonly include the generation of pseudoviruses, which are produced by co-transfection of rev-vpu-env cassettes with an env-deficient provirus. Here, we describe six Env constructs from transmitted/founder HIV-1 that were defective in the pseudotyping assay, although two produced infectious virions when expressed from their cognate proviruses. All of these constructs exhibited an unusual gene arrangement in which the first exon of rev (rev1) and vpu were in the same reading frame without an intervening stop codon. Disruption of the rev1-vpu fusion gene by frameshift mutation, stop codon, or abrogation of the rev initiation codon restored pseudovirion infectivity. Introduction of the fusion gene into wildtype Env cassettes severely compromised their function. The defect was not due to altered env and rev transcription or a dominant negative effect of the expressed fusion protein, but seemed to be caused by inefficient translation at the env initiation codon. Although the rev1-vpu polymorphism affects Env expression only in vitro, it can cause problems in studies requiring Env complementation, such as analyses of co-receptor usage and neutralization properties, since 3% of subtype A, 20% of subtype C and 5% of CRF01_A/E viruses encode the fusion gene. A solution is to eliminate the rev initiation codon when amplifying rev-vpu-env cassettes since this increases Env expression irrespective of the presence of the polymorphism.


Assuntos
HIV-1/genética , HIV-1/patogenicidade , Proteínas do Vírus da Imunodeficiência Humana/genética , Polimorfismo Genético , Proteínas Virais Reguladoras e Acessórias/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/biossíntese , Produtos do Gene rev do Vírus da Imunodeficiência Humana/genética , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular , Proteínas do Vírus da Imunodeficiência Humana/metabolismo , Humanos , Dados de Sequência Molecular , Biossíntese de Proteínas , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Virais Reguladoras e Acessórias/metabolismo , Produtos do Gene rev do Vírus da Imunodeficiência Humana/metabolismo
20.
J Exp Med ; 206(6): 1273-89, 2009 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-19487424

RESUMO

Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes (gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4(+) T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12-20 mo, viruses exhibited concentrated mutations at 17-34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses.


Assuntos
Evolução Molecular , Genoma Viral , Infecções por HIV , HIV-1/genética , HIV-1/imunologia , Fenótipo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Feminino , Infecções por HIV/genética , Infecções por HIV/imunologia , HIV-1/classificação , Humanos , Funções Verossimilhança , Macrófagos/imunologia , Macrófagos/virologia , Masculino , Modelos Teóricos , Mutação , Filogenia , Receptores CCR5/imunologia , Vírion/genética , Replicação Viral/genética , Replicação Viral/imunologia
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