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1.
Phys Rev Lett ; 123(13): 133201, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31697513

RESUMO

In a seminal article, Fano predicts that absorption of light occurs preferably with increase of angular momentum. We generalize Fano's propensity rule to laser-assisted photoionization, consisting of absorption of an extreme-ultraviolet photon followed by absorption or emission of an infrared photon. The predicted asymmetry between absorption and emission leads to incomplete quantum interference in attosecond photoelectron interferometry. It explains both the angular dependence of the photoionization time delays and the delay dependence of the photoelectron angular distributions. Our theory is verified by experimental results in Ar in the 20-40 eV range.

2.
Phys Chem Chem Phys ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31436275

RESUMO

Momenta of ions from diiodomethane molecules after multiple ionization by soft-X-ray free-electron-laser pulses are measured. Correlations between the ion momenta are extracted by covariance methods formulated for the use in multiparticle momentum-resolved ion time-of-flight spectroscopy. Femtosecond dynamics of the dissociating multiply charged diiodomethane cations is discussed and interpreted by using simulations based on a classical Coulomb explosion model including charge evolution.

3.
Nat Commun ; 10(1): 2186, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31097703

RESUMO

The increasing availability of X-ray free-electron lasers (XFELs) has catalyzed the development of single-object structural determination and of structural dynamics tracking in real-time. Disentangling the molecular-level reactions triggered by the interaction with an XFEL pulse is a fundamental step towards developing such applications. Here we report real-time observations of XFEL-induced electronic decay via short-lived transient electronic states in the diiodomethane molecule, using a femtosecond near-infrared probe laser. We determine the lifetimes of the transient states populated during the XFEL-induced Auger cascades and find that multiply charged iodine ions are issued from short-lived (∼20 fs) transient states, whereas the singly charged ones originate from significantly longer-lived states (∼100 fs). We identify the mechanisms behind these different time scales: contrary to the short-lived transient states which relax by molecular Auger decay, the long-lived ones decay by an interatomic Coulombic decay between two iodine atoms, during the molecular fragmentation.

4.
Proc Natl Acad Sci U S A ; 116(11): 4779-4787, 2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30824594

RESUMO

The shortest light pulses produced to date are of the order of a few tens of attoseconds, with central frequencies in the extreme UV range and bandwidths exceeding tens of electronvolts. They are often produced as a train of pulses separated by half the driving laser period, leading in the frequency domain to a spectrum of high, odd-order harmonics. As light pulses become shorter and more spectrally wide, the widely used approximation consisting of writing the optical waveform as a product of temporal and spatial amplitudes does not apply anymore. Here, we investigate the interplay of temporal and spatial properties of attosecond pulses. We show that the divergence and focus position of the generated harmonics often strongly depend on their frequency, leading to strong chromatic aberrations of the broadband attosecond pulses. Our argument uses a simple analytical model based on Gaussian optics, numerical propagation calculations, and experimental harmonic divergence measurements. This effect needs to be considered for future applications requiring high-quality focusing while retaining the broadband/ultrashort characteristics of the radiation.

5.
Opt Express ; 27(3): 2656-2670, 2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30732300

RESUMO

We perform wavefront measurements of high-order harmonics using an extreme-ultraviolet (XUV) Hartmann sensor and study how their spatial properties vary with different generation parameters, such as pressure in the nonlinear medium, fundamental pulse energy and duration as well as beam size. In some conditions, excellent wavefront quality (up to λ/11) was obtained. The high throughput of the intense XUV beamline at the Lund Laser Centre allows us to perform single-shot measurements of both the full harmonic beam generated in argon and individual harmonics selected by multilayer mirrors. We theoretically analyze the relationship between the spatial properties of the fundamental and those of the generated high-order harmonics, thus gaining insight into the fundamental mechanisms involved in high-order harmonic generation (HHG).

6.
Nature ; 565(7738): 251-254, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30602787

RESUMO

Mammalian gene expression is inherently stochastic1,2, and results in discrete bursts of RNA molecules that are synthesized from each allele3-7. Although transcription is known to be regulated by promoters and enhancers, it is unclear how cis-regulatory sequences encode transcriptional burst kinetics. Characterization of transcriptional bursting, including the burst size and frequency, has mainly relied on live-cell4,6,8 or single-molecule RNA fluorescence in situ hybridization3,5,8,9 recordings of selected loci. Here we determine transcriptome-wide burst frequencies and sizes for endogenous mouse and human genes using allele-sensitive single-cell RNA sequencing. We show that core promoter elements affect burst size and uncover synergistic effects between TATA and initiator elements, which were masked at mean expression levels. Notably, we provide transcriptome-wide evidence that enhancers control burst frequencies, and demonstrate that cell-type-specific gene expression is primarily shaped by changes in burst frequencies. Together, our data show that burst frequency is primarily encoded in enhancers and burst size in core promoters, and that allelic single-cell RNA sequencing is a powerful model for investigating transcriptional kinetics.


Assuntos
Genes/genética , Genômica , Transcrição Genética/genética , Alelos , Animais , Elementos Facilitadores Genéticos/genética , Fibroblastos/metabolismo , Humanos , Cinética , Masculino , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Especificidade de Órgãos/genética , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Análise de Sequência de RNA , Deleção de Sequência , Análise de Célula Única , Processos Estocásticos , TATA Box/genética , Transcriptoma/genética
7.
J Chem Phys ; 149(20): 204313, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30501230

RESUMO

The photodissociation dynamics of CH3I and CH2ClI at 272 nm were investigated by time-resolved Coulomb explosion imaging, with an intense non-resonant 815 nm probe pulse. Fragment ion momenta over a wide m/z range were recorded simultaneously by coupling a velocity map imaging spectrometer with a pixel imaging mass spectrometry camera. For both molecules, delay-dependent pump-probe features were assigned to ultraviolet-induced carbon-iodine bond cleavage followed by Coulomb explosion. Multi-mass imaging also allowed the sequential cleavage of both carbon-halogen bonds in CH2ClI to be investigated. Furthermore, delay-dependent relative fragment momenta of a pair of ions were directly determined using recoil-frame covariance analysis. These results are complementary to conventional velocity map imaging experiments and demonstrate the application of time-resolved Coulomb explosion imaging to photoinduced real-time molecular motion.

8.
BMC Cancer ; 18(1): 789, 2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30081937

RESUMO

BACKGROUND: Individual patients differ in their psychological response when receiving a cancer diagnosis, in this case breast cancer. Given the same disease burden, some patients master the situation well, while others experience a great deal of stress, depression and lowered quality of life. Patients with high psychological resilience are likely to experience fewer stress reactions and better adapt to and manage the life threat and the demanding treatment that follows the diagnosis. If this phenomenon of mastering difficult situations is reflected also in biomolecular processes is not much studied, nor has its capacity for impacting the cancer prognosis been addressed. This project specifically aims, for the first time, to investigate how a breast cancer patient's psychological resilience is coupled to biomolecular parameters using advanced "omics" and, as a secondary aim, whether it relates to prognosis and quality of life one year after diagnosis. METHOD: The study population consists of newly diagnosed breast cancer patients enrolled in the Sweden Cancerome Analysis Network - Breast (SCAN-B) at four hospitals in Sweden. At the time of cancer diagnosis, the patient fills out the standardized method to measure psychological resilience, the "Connor-Davidson Resilience scale" (CD-RISC), the quality of life measure SF-36, as well as providing social and socioeconomic variables. In addition, one blood sample is collected. At the one-year follow-up, the patient will be subjected to the same assessments, and we also collect information regarding smoking, exercise habits, and BMI, as well as patients' trust in the treatment and their satisfaction with the care and treatment. DISCUSSION: This explorative hypothesis-generating project will pave the way for larger validation studies, potentially leading to a standardized method of measuring psychological resilience as an important parameter in cancer care. Revealing the body-mind interaction, in terms of psychological resilience and quality of life, will herald the development of truly personalized psychosocial care and cancer intervention treatment strategies. TRIAL REGISTRATION: This is a retrospectively registered trial at ClinicalTrials.gov, ID: NCT03430492 on February 6, 2018.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/psicologia , Resiliência Psicológica , Adaptação Psicológica , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Efeitos Psicossociais da Doença , Feminino , Perfilação da Expressão Gênica , Genômica/métodos , Humanos , Estudos Multicêntricos como Assunto , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Proteômica , Qualidade de Vida , Inquéritos e Questionários , Suécia , Fatores de Tempo
9.
Cell Death Dis ; 9(7): 736, 2018 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-29970884

RESUMO

The microRNA-34a is a well-studied tumor suppressor microRNA (miRNA) and a direct downstream target of TP53 with roles in several pathways associated with oncogenesis, such as proliferation, cellular growth, and differentiation. Due to its broad tumor suppressive activity, it is not surprising that miR34a expression is altered in a wide variety of solid tumors and hematological malignancies. However, the mechanisms by which miR34a is regulated in these cancers is largely unknown. In this study, we find that a long noncoding RNA transcribed antisense to the miR34a host gene, is critical for miR34a expression and mediation of its cellular functions in multiple types of human cancer. We name this long noncoding RNA lncTAM34a, and characterize its ability to facilitate miR34a expression under different types of cellular stress in both TP53-deficient and wild-type settings.


Assuntos
MicroRNAs/metabolismo , RNA Antissenso/fisiologia , Western Blotting , Ciclo Celular/genética , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Imunoprecipitação da Cromatina , Biologia Computacional , Dano ao DNA/genética , Dano ao DNA/fisiologia , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Genes Supressores de Tumor/fisiologia , Humanos , MicroRNAs/genética , Regiões Promotoras Genéticas/genética , RNA Antissenso/genética , Espectrometria de Massas em Tandem
10.
Nat Commun ; 9(1): 955, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29511164

RESUMO

Electron correlation and multielectron effects are fundamental interactions that govern many physical and chemical processes in atomic, molecular and solid state systems. The process of autoionization, induced by resonant excitation of electrons into discrete states present in the spectral continuum of atomic and molecular targets, is mediated by electron correlation. Here we investigate the attosecond photoemission dynamics in argon in the 20-40 eV spectral range, in the vicinity of the 3s-1np autoionizing resonances. We present measurements of the differential photoionization cross section and extract energy and angle-dependent atomic time delays with an attosecond interferometric method. With the support of a theoretical model, we are able to attribute a large part of the measured time delay anisotropy to the presence of autoionizing resonances, which not only distort the phase of the emitted photoelectron wave packet but also introduce an angular dependence.

11.
Nat Methods ; 15(5): 339-342, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29553578

RESUMO

As methods for measuring spatial gene expression at single-cell resolution become available, there is a need for computational analysis strategies. We present trendsceek, a method based on marked point processes that identifies genes with statistically significant spatial expression trends. trendsceek finds these genes in spatial transcriptomic and sequential fluorescence in situ hybridization data, and also reveals significant gene expression gradients and hot spots in low-dimensional projections of dissociated single-cell RNA-seq data.


Assuntos
Regulação da Expressão Gênica/fisiologia , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Animais , Hipocampo/fisiologia , Camundongos , Transporte Proteico , RNA/genética , Transcriptoma
12.
J Eat Disord ; 6: 5, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29588853

RESUMO

Background: The developmental study of subtypes of disordered eating (DE) during adolescence may be relevant to understand the development of eating disorders. The purpose of the present study was to identify subgroups with different profiles of DE in a community sample of adolescent girls aged 13-15 years, and to study the stability of these profiles and subgroups over a one-year interval in order to find patterns that may need to be addressed in further research and prevention. Methods: Cluster analysis according to the LICUR procedure was performed on five aspects of DE, and the structural and individual stability of these clusters was analysed. The clusters were compared with regard to BMI, body esteem, deliberate self-harm, and other kinds of psychological difficulties. Results: The analysis revealed six clusters (Multiple eating problems including purging, Multiple eating problems without purging, Social eating problems, Weight concerns, Fear of not being able to stop eating, and No eating problems) all of which had structurally stable profiles and five of which showed stability at the individual level. The more pronounced DE clusters (Multiple eating problems including/without purging) were consistently associated with higher levels of psychological difficulties and lower levels of body esteem. Furthermore, girls that reported purging reported engaging in self-harm to a larger extent. Conclusions: Subgroups of 13-15 year old girls show stable patterns of disordered eating that are associated with higher rates of psychological impairment and lower body esteem. The subgroup of girls who engage in purging also engage in more deliberate self-harm.

13.
Struct Dyn ; 5(1): 014301, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29430482

RESUMO

We explore time-resolved Coulomb explosion induced by intense, extreme ultraviolet (XUV) femtosecond pulses from a free-electron laser as a method to image photo-induced molecular dynamics in two molecules, iodomethane and 2,6-difluoroiodobenzene. At an excitation wavelength of 267 nm, the dominant reaction pathway in both molecules is neutral dissociation via cleavage of the carbon-iodine bond. This allows investigating the influence of the molecular environment on the absorption of an intense, femtosecond XUV pulse and the subsequent Coulomb explosion process. We find that the XUV probe pulse induces local inner-shell ionization of atomic iodine in dissociating iodomethane, in contrast to non-selective ionization of all photofragments in difluoroiodobenzene. The results reveal evidence of electron transfer from methyl and phenyl moieties to a multiply charged iodine ion. In addition, indications for ultrafast charge rearrangement on the phenyl radical are found, suggesting that time-resolved Coulomb explosion imaging is sensitive to the localization of charge in extended molecules.

15.
Proc Natl Acad Sci U S A ; 114(37): 9942-9947, 2017 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-28847966

RESUMO

RNA has been found to interact with chromatin and modulate gene transcription. In human cells, little is known about how long noncoding RNAs (lncRNAs) interact with target loci in the context of chromatin. We find here, using the phosphatase and tensin homolog (PTEN) pseudogene as a model system, that antisense lncRNAs interact first with a 5' UTR-containing promoter-spanning transcript, which is then followed by the recruitment of DNA methyltransferase 3a (DNMT3a), ultimately resulting in the transcriptional and epigenetic control of gene expression. Moreover, we find that the lncRNA and promoter-spanning transcript interaction are based on a combination of structural and sequence components of the antisense lncRNA. These observations suggest, on the basis of this one example, that evolutionary pressures may be placed on RNA structure more so than sequence conservation. Collectively, the observations presented here suggest a much more complex and vibrant RNA regulatory world may be operative in the regulation of gene expression.


Assuntos
PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Cromatina/genética , Montagem e Desmontagem da Cromatina , Éxons , Células HEK293 , Humanos , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico , Regiões Promotoras Genéticas/genética , Pseudogenes , Elementos Reguladores de Transcrição/genética , Elementos Reguladores de Transcrição/fisiologia , Análise de Sequência de RNA/métodos , Homologia de Sequência
16.
J Chem Phys ; 147(1): 013933, 2017 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-28688450

RESUMO

Laser-induced adiabatic alignment and mixed-field orientation of 2,6-difluoroiodobenzene (C6H3F2I) molecules are probed by Coulomb explosion imaging following either near-infrared strong-field ionization or extreme-ultraviolet multi-photon inner-shell ionization using free-electron laser pulses. The resulting photoelectrons and fragment ions are captured by a double-sided velocity map imaging spectrometer and projected onto two position-sensitive detectors. The ion side of the spectrometer is equipped with a pixel imaging mass spectrometry camera, a time-stamping pixelated detector that can record the hit positions and arrival times of up to four ions per pixel per acquisition cycle. Thus, the time-of-flight trace and ion momentum distributions for all fragments can be recorded simultaneously. We show that we can obtain a high degree of one-and three-dimensional alignment and mixed-field orientation and compare the Coulomb explosion process induced at both wavelengths.

17.
BMC Psychol ; 5(1): 12, 2017 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-28376909

RESUMO

BACKGROUND: Research on the relationships between adolescent and parental disordered eating (DE) and emotion dysregulation is scarce. Thus, the aim of this study was to explore whether mothers' and fathers' own DE, as measured by SCOFF questionnaire, and emotion dysregulation, as measured by the difficulties in emotion regulation scale (DERS), were associated with their daughters' or sons' DE and emotion dysregulation. Furthermore, the importance of shared family meals and possible parent-related predictors of adolescent DE were explored. METHOD: The total sample comprised 1,265 adolescents (M age = 16.19, SD = 1.21; age range 13.5-19 years, 54.5% female) whose parents had received a self-report questionnaire via mail. Of these, 235 adolescents (18.6% of the total sample) whose parents completed the questionnaire were used in the analyses. Parents' responses were matched and compared with those of their child. RESULTS: Adolescent girls showed greater levels of DE overall than did their parents. Furthermore, DE was associated with emotion dysregulation among both adolescents and parents. Adolescent and parental emotion dysregulation was associated, although there were gender differences in the specifics of this relationship. The frequency of shared dinner meals was the only variable that was associated to DE and emotion dysregulation among adolescents, while parental eating disorder was the only variable that enhanced the probability of adolescent DE. CONCLUSION: The present study contributes to the literature by demonstrating that there are significant associations between parents and their adolescent children in terms of DE, emotion dysregulation, and shared family meals. Future studies should break down these relationships among mothers, fathers, girls, and boys to further clarify the specific associational, and possibly predictive, directions.


Assuntos
Sintomas Afetivos/psicologia , Emoções , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Relações Pais-Filho , Pais/psicologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Refeições/psicologia , Inquéritos e Questionários
18.
J Eat Disord ; 5: 3, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28261478

RESUMO

BACKGROUND: Despite the theoretical links between eating disorders and perfectionism, the definition of perfectionism in practice is complicated. The present study explored descriptions and experiences of perfectionism described by a transdiagnostic sample of patients. METHODS: In-depth, semi-structured interviews were carried out with 15 patients. The interviews were analyzed by Thematic Analysis. A comparison between the patients' scorings on the Eating Disorder Inventory-Perfectionism scale was also performed. RESULTS: Seven themes were found: The origins of perfectionism, Top performance, Order and self-control, A perfect body, Looking good in the eyes of others, A double-edged coping strategy, and A Sisyphean task. The women in this study did not emphasize weight and body as the main perfectionistic strivings. Core descriptions were instead order, self-control and top performances. All of the participants described the awareness of reaching perfectionism as impossible. Scorings of self-oriented perfectionism was significantly higher compared to socially prescribed perfectionism. No differences in the narratives related to perfectionism scores or eating disorder diagnoses were found. CONCLUSIONS: The results showed that psychometric measures do not always capture the patients' definitions of perfectionism, but regarding that perfectionism serves as a means to regulate affects and may lead into an exacerbation of the eating disorder, and the development of obsessive-compulsive symptoms, it is important to investigate the personal definitions of perfectionism.

19.
J Eat Disord ; 4: 28, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27822375

RESUMO

BACKGROUND: Using the person-oriented approach, we determined the relationships between four indicators (restraint and eating, shape, and weight concerns) of disordered eating (DE), as measured by the self-reported Eating Disorders Examination Questionnaire (EDE-Q), to identify typical DE patterns. We then related these patterns to clinical EDE-Q cut-off scores and emotion dysregulation, depression, self-esteem, and two categories of DE behaviors (≥2 or ≤1 "yes" responses on the SCOFF questionnaire). METHOD: Typical patterns of DE were identified in a community sample of 1,265 Swedish adolescents (Mage = 16.19, SD = 1.21; age range 13.5-19 years) using a cluster analysis. Separate analyses were performed for girls (n = 689) and boys (n = 576). RESULTS: The cluster analysis yielded a six-cluster solution for each gender. Four of the six clusters for girls and five for boys showed scores above the clinical cut-off on at least one of the four DE indicators. For girls, the two clusters that scored above the clinical cut-offs on all four DE indicators reported severe psychological problems, including high scores on emotion dysregulation and depression and low scores on self-esteem. In contrast, for boys, although two clusters reported above the clinical cut-off on all four indicators, only the cluster with exceedingly high scores on shape and weight concerns reported high emotion dysregulation and depression, and extremely low self-esteem. Furthermore, significantly more girls and boys in the most problematic DE clusters reported ≥2 "yes" responses on the SCOFF questionnaire (as opposed to ≤1 response), indicating clear signs of DE and severe psychological difficulties. CONCLUSION: We suspect that the various problematic DE patterns will require different paths back to a healthy diet. However, more research is needed to determine the developmental trajectories of these DE patterns and ensure more precise clinical cut-off scores, especially for boys. Comprehensive understanding of DE patterns might be of use to healthcare professionals for detecting DE before it develops into an eating disorder. TRIAL REGISTRATION: Lund, EPN (dnr: 2012/499).

20.
Nat Genet ; 48(11): 1430-1435, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27668657

RESUMO

Cellular heterogeneity can emerge from the expression of only one parental allele. However, it has remained controversial whether, or to what degree, random monoallelic expression of autosomal genes (aRME) is mitotically inherited (clonal) or stochastic (dynamic) in somatic cells, particularly in vivo. Here we used allele-sensitive single-cell RNA-seq on clonal primary mouse fibroblasts and freshly isolated human CD8+ T cells to dissect clonal and dynamic monoallelic expression patterns. Dynamic aRME affected a considerable portion of the cells' transcriptomes, with levels dependent on the cells' transcriptional activity. Notably, clonal aRME was detected, but it was surprisingly scarce (<1% of genes) and mainly affected the most weakly expressed genes. Consequently, the overwhelming majority of aRME occurs transiently within individual cells, and patterns of aRME are thus primarily scattered throughout somatic cell populations rather than, as previously hypothesized, confined to patches of clonally related cells.


Assuntos
Alelos , Linfócitos T CD8-Positivos/metabolismo , Fibroblastos/metabolismo , Perfilação da Expressão Gênica/métodos , Análise de Sequência de RNA , Animais , Células Cultivadas , Células Clonais/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Polimorfismo de Nucleotídeo Único
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