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Collinear laser spectroscopy is performed on the nickel isotopes ^{58-68,70}Ni, using a time-resolved photon counting system. From the measured isotope shifts, nuclear charge radii R_{c} are extracted and compared to theoretical results. Three ab initio approaches all employ, among others, the chiral interaction NNLO_{sat}, which allows an assessment of their accuracy. We find agreement with experiment in differential radii δ⟨r_{c}^{2}⟩ for all employed ab initio methods and interactions, while the absolute radii are consistent with data only for NNLO_{sat}. Within nuclear density functional theory, the Skyrme functional SV-min matches experiment more closely than the Fayans functional Fy(Δr,HFB).
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STUDY QUESTION: Can a targeted whole exome sequencing (WES) on a cohort of women showing a primary ovarian insufficiency (POI) phenotype at a young age, combined with a study of copy number variations, identify variants in candidate genes confirming their deleterious effect on ovarian function? SUMMARY ANSWER: This integrated approach has proved effective in identifying novel candidate genes unveiling mechanisms involved in POI pathogenesis. WHAT IS KNOWN ALREADY: POI, a condition occurring in 1% of women under 40 years of age, affects women's fertility leading to a premature loss of ovarian reserve. The genetic causes of POI are highly heterogeneous and several determinants contributing to its prominent oligogenic inheritance pattern still need to be elucidated. STUDY DESIGN, SIZE, DURATION: WES screening for pathogenic variants of 41 Italian women with non-syndromic primary and early secondary amenorrhoea occurring before age 25 was replicated on another 60 POI patients, including 35 French and 25 American women, to reveal statistically significant shared variants. PARTICIPANTS/MATERIALS, SETTING, METHODS: The Italian POI patients' DNA were processed by targeted WES including 542 RefSeq genes expressed or functioning during distinct reproductive or ovarian processes (e.g. DNA repair, meiosis, oocyte maturation, folliculogenesis and menopause). Extremely rare variants were filtered and selected by means of a Fisher Exact test using several publicly available datasets. A case-control Burden test was applied to highlight the most significant genes using two ad-hoc control female cohorts. To support the obtained data, the identified genes were screened on a novel cohort of 60 Caucasian POI patients and the same case-control analysis was carried out. Comparative analysis of the human identified genes was performed on mouse and Drosophila melanogaster by analysing the orthologous genes in their ovarian phenotype, and two of the selected genes were fruit fly modelled to explore their role in fertility. MAIN RESULTS AND THE ROLE OF CHANCE: The filtering steps applied to search for extremely rare pathogenic variants in the Italian cohort revealed 64 validated single-nucleotide variants/Indels in 59 genes in 30 out of 41 screened women. Burden test analysis highlighted 13 ovarian genes as being the most enriched and significant. To validate these findings, filtering steps and Burden analysis on the second cohort of Caucasian patients yielded 11 significantly enriched genes. Among them, AFP, DMRT3, MOV10, FYN and MYC were significant in both patient cohorts and hence were considered strong candidates for POI. Mouse and Drosophila comparative analysis evaluated a conserved role through the evolution of several candidates, and functional studies using a Drosophila model, when applicable, supported the conserved role of the MOV10 armitage and DMRT3 dmrt93B orthologues in female fertility. LARGE SCALE DATA: The datasets for the Italian cohort generated during the current study are publicly available at ClinVar database (http://www.ncbi.nlm.nih.gov/clinvar/): accession numbers SCV001364312 to SCV001364375. LIMITATIONS, REASONS FOR CAUTION: This is a targeted WES analysis hunting variants in candidate genes previously identified by different genomic approaches. For most of the investigated sporadic cases, we could not track the parental inheritance, due to unavailability of the parents' DNA samples; in addition, we might have overlooked additional rare variants in novel candidate POI genes extracted from the exome data. On the contrary, we might have considered some inherited variants whose clinical significance is uncertain and might not be causative for the patients' phenotype. Additionally, as regards the Drosophila model, it will be extremely important in the future to have more mutants or RNAi strains available for each candidate gene in order to validate their role in POI pathogenesis. WIDER IMPLICATIONS OF THE FINDINGS: The genomic, statistical, comparative and functional approaches integrated in our study convincingly support the extremely heterogeneous oligogenic nature of POI, and confirm the maintenance across the evolution of some key genes safeguarding fertility and successful reproduction. Two principal classes of genes were identified: (i) genes primarily involved in meiosis, namely in synaptonemal complex formation, asymmetric division and oocyte maturation and (ii) genes safeguarding cell maintenance (piRNA and DNA repair pathways). STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Italian Ministry of Health grants 'Ricerca Corrente' (08C621_2016 and 08C924_2019) provided to IRCCS Istituto Auxologico Italiano, and by 'Piano Sostegno alla Ricerca' (PSR2020_FINELLI_LINEA_B) provided by the University of Milan; M.P.B. was supported by Telethon-Italy (grant number GG14181). There are no conflicts of interest.
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Insuficiência Ovariana Primária , Animais , Variações do Número de Cópias de DNA , Drosophila , Drosophila melanogaster , Feminino , Humanos , Camundongos , Insuficiência Ovariana Primária/genética , RNA Helicases , Fatores de Transcrição/genética , Sequenciamento do ExomaRESUMO
We present the first ab initio calculations for open-shell nuclei past the tin isotopic line, focusing on Xe isotopes as well as doubly magic Sn isotopes. We show that, even for moderately hard interactions, it is possible to obtain meaningful predictions and that the NNLO_{sat} chiral interaction predicts radii and charge density distributions close to the experiment. We then make a new prediction for ^{100}Sn. This paves the way for ab initio studies of exotic charge density distributions at the limit of the present ab initio mass domain, where experimental data is becoming available. The present study closes the gap between the largest isotopes reachable by ab initio methods and the smallest exotic nuclei accessible to electron scattering experiments.
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The quantum radiation pressure and the quantum shot noise in laser-interferometric gravitational wave detectors constitute a macroscopic manifestation of the Heisenberg inequality. If quantum shot noise can be easily observed, the observation of quantum radiation pressure noise has been elusive, so far, due to the technical noise competing with quantum effects. Here, we discuss the evidence of quantum radiation pressure noise in the Advanced Virgo gravitational wave detector. In our experiment, we inject squeezed vacuum states of light into the interferometer in order to manipulate the quantum backaction on the 42 kg mirrors and observe the corresponding quantum noise driven displacement at frequencies between 30 and 70 Hz. The experimental data, obtained in various interferometer configurations, is tested against the Advanced Virgo detector quantum noise model which confirmed the measured magnitude of quantum radiation pressure noise.
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We derive ab initio optical potentials from self-consistent Green's function theory and compute the elastic scattering of neutrons off oxygen and calcium isotopes. The comparison with scattering data is satisfactory at low scattering energies. The method is benchmarked against the no-core shell model with continuum calculations, showing that virtual excitations of the target are crucial to predict proper fragmentation and absorption at higher energies. This is a significant step toward deriving optical potentials for medium mass nuclei and complex many-body systems in general.
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Exclusive cross sections and momentum distributions have been measured for quasifree one-neutron knockout reactions from a ^{54}Ca beam striking on a liquid hydrogen target at â¼200 MeV/u. A significantly larger cross section to the p_{3/2} state compared to the f_{5/2} state observed in the excitation of ^{53}Ca provides direct evidence for the nature of the N=34 shell closure. This finding corroborates the arising of a new shell closure in neutron-rich calcium isotopes. The distorted-wave impulse approximation reaction formalism with shell model calculations using the effective GXPF1Bs interaction and ab initio calculations concur our experimental findings. Obtained transverse and parallel momentum distributions demonstrate the sensitivity of quasifree one-neutron knockout in inverse kinematics on a thick liquid hydrogen target with the reaction vertex reconstructed to final state spin-parity assignments.
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Current interferometric gravitational-wave detectors are limited by quantum noise over a wide range of their measurement bandwidth. One method to overcome the quantum limit is the injection of squeezed vacuum states of light into the interferometer's dark port. Here, we report on the successful application of this quantum technology to improve the shot noise limited sensitivity of the Advanced Virgo gravitational-wave detector. A sensitivity enhancement of up to 3.2±0.1 dB beyond the shot noise limit is achieved. This nonclassical improvement corresponds to a 5%-8% increase of the binary neutron star horizon. The squeezing injection was fully automated and over the first 5 months of the third joint LIGO-Virgo observation run O3 squeezing was applied for more than 99% of the science time. During this period several gravitational-wave candidates have been recorded.
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Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R^{3}B/LAND setup with incident beam energies in the range of 300-450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type ^{A}O(p,2p)^{A-1}N have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.
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A precision mass investigation of the neutron-rich titanium isotopes ^{51-55}Ti was performed at TRIUMF's Ion Trap for Atomic and Nuclear science (TITAN). The range of the measurements covers the N=32 shell closure, and the overall uncertainties of the ^{52-55}Ti mass values were significantly reduced. Our results conclusively establish the existence of the weak shell effect at N=32, narrowing down the abrupt onset of this shell closure. Our data were compared with state-of-the-art ab initio shell model calculations which, despite very successfully describing where the N=32 shell gap is strong, overpredict its strength and extent in titanium and heavier isotones. These measurements also represent the first scientific results of TITAN using the newly commissioned multiple-reflection time-of-flight mass spectrometer, substantiated by independent measurements from TITAN's Penning trap mass spectrometer.
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BACKGROUND: Oral leukoplakia (OL) is the most typical potentially malignant disorder of the oral mucosa. We aimed to evaluate the clinical outcome of oral leukoplakia treated with several types of lasers and with the use of quantic molecular resonance (QMR) lancet, in terms of recurrence rate. MATERIAL AND METHODS: Eighty-seven previously untreated OL (52 occurring in females and 35 in males, mean age of 59.4 ± 13.9 years) were consecutively submitted to surgical treatment at University Hospital of Parma, Italy, and Hospital de Valongo, Portugal, (1999 to 2012). Interventions were subclassified into 5 groups according to the instrument used for the surgical removal of OL (cold blade - 17; Nd:YAG 1064nm laser - 14; Er:YAG 2940nm laser - 33; CO2 10600nm laser - 15; and QMR scalpel - 8). The mean follow-up period after treatment was 21.6 months (range 1-151 months). The outcome of treatment was scored through the same clinical protocol in the two participating units. Statistical analysis were carried by univariate analysis using chi-square test (or Pearson's test when appropriate). RESULTS: Recurrences were observed in 24 cases of OL (27.6%). Malignant transformation occurred in one patient (1.1%) after a period of 35 months. Statistical comparison of the 5 surgical treatment modalities showed no differences in clinical outcomes nor in the recurrence rate of OL. However, when Er:YAG laser group was compared with traditional scalpel, a significantly better outcome in cases treated with Er:YAG laser (P = 0.015) was highlighted. CONCLUSIONS: Our results suggests that Er:YAG laser could be a promising option for the treatment of OL.
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Leucoplasia Oral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Terapia a Laser , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Bucais/métodos , Recidiva , Estudos RetrospectivosRESUMO
We present a systematic study of both nuclear radii and binding energies in (even) oxygen isotopes from the valley of stability to the neutron drip line. Both charge and matter radii are compared to state-of-the-art ab initio calculations along with binding energy systematics. Experimental matter radii are obtained through a complete evaluation of the available elastic proton scattering data of oxygen isotopes. We show that, in spite of a good reproduction of binding energies, ab initio calculations with conventional nuclear interactions derived within chiral effective field theory fail to provide a realistic description of charge and matter radii. A novel version of two- and three-nucleon forces leads to considerable improvement of the simultaneous description of the three observables for stable isotopes but shows deficiencies for the most neutron-rich systems. Thus, crucial challenges related to the development of nuclear interactions remain.
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The recently confirmed neutron-shell closure at N=32 has been investigated for the first time below the magic proton number Z=20 with mass measurements of the exotic isotopes (52,53)K, the latter being the shortest-lived nuclide investigated at the online mass spectrometer ISOLTRAP. The resulting two-neutron separation energies reveal a 3 MeV shell gap at N=32, slightly lower than for 52Ca, highlighting the doubly magic nature of this nuclide. Skyrme-Hartree-Fock-Bogoliubov and ab initio Gorkov-Green function calculations are challenged by the new measurements but reproduce qualitatively the observed shell effect.
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We extend the formalism of self-consistent Green's function theory to include three-body interactions and apply it to isotopic chains around oxygen for the first time. The third-order algebraic diagrammatic construction equations for two-body Hamiltonians can be exploited upon defining system-dependent one- and two-body interactions coming from the three-body force, and, correspondingly, dropping interaction-reducible diagrams. The Koltun sum rule for the total binding energy acquires a correction due to the added three-body interaction. This formalism is then applied to study chiral two- and three-nucleon forces evolved to low momentum cutoffs. The binding energies of nitrogen, oxygen, and fluorine isotopes are reproduced with good accuracy and demonstrate the predictive power of this approach. Leading order three-nucleon forces consistently bring results close to the experiment for all neutron rich isotopes considered and reproduce the correct driplines for oxygen and nitrogen. The formalism introduced also allows us to calculate form factors for nucleon transfer on doubly magic systems.
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Single nucleon pickup reactions were performed with a 18.1 MeV/nucleon (14)O beam on a deuterium target. Within the coupled reaction channel framework, the measured cross sections were compared to theoretical predictions and analyzed using both phenomenological and microscopic overlap functions. The missing strength due to correlations does not show significant dependence on the nucleon separation energy asymmetry over a wide range of 37 MeV, in contrast with nucleon removal data analyzed within the sudden-eikonal formalism.
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Atypical odontalgia (AO) is a little known chronic pain condition. It usually presents as pain in a site where a tooth was endodontically treated or extracted, in the absence of clinical or radiographic evidence of tooth pathology. It is a rare clinical challenge for most clinicians, which leads to the patients being referred to several specialists and sometimes undergoing unnecessary surgical procedures. The pain mechanisms involved in AO are far from clear, and numerous potential mechanisms have been suggested. Currently, the most accredited hypothesis is that AO is a neuropathic pain condition caused by deafferentation. The differential diagnosis of AO remains difficult, because it shares symptoms with many others pathologies affecting this area. Patients have difficulties accepting the AO diagnosis and treatment. As a result, they frequently change physicians, and may potentially also receive several invasive treatments, usually resulting in an aggravation of the pain. Although some patients do get complete pain relief following treatment, for most patients the goal should be to achieve adequate pain management. Currently, most management is based on expert opinion and case reports. More research and high quality randomized controlled trials are needed in order to develop evidence-based treatments, currently based on expert opinion or carried over from other neuropathic pain conditions in the orofacial region.
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Odontalgia/fisiopatologia , Adulto , Analgésicos/uso terapêutico , Anestésicos Locais/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Causalgia/tratamento farmacológico , Causalgia/etiologia , Causalgia/fisiopatologia , Criança , Doenças da Polpa Dentária/diagnóstico , Diagnóstico Diferencial , Diagnóstico por Imagem , Feminino , Humanos , Masculino , Modelos Neurológicos , Procedimentos Cirúrgicos Bucais/efeitos adversos , Dor Pós-Operatória/etiologia , Aceitação pelo Paciente de Cuidados de Saúde , Membro Fantasma/tratamento farmacológico , Membro Fantasma/etiologia , Membro Fantasma/fisiopatologia , Exame Físico/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos da Articulação Temporomandibular/diagnóstico , Traumatismos Dentários/complicações , Odontalgia/diagnóstico , Odontalgia/tratamento farmacológico , Odontalgia/etiologia , Odontalgia/psicologia , Procedimentos DesnecessáriosRESUMO
Small molecules that bind to allosteric sites on target proteins to alter protein function are highly sought in drug discovery. High-throughput screening (HTS) assays are needed to facilitate the direct discovery of allosterically active compounds. We have developed technology for high-throughput time-resolved fluorescence lifetime detection of fluorescence resonance energy transfer (FRET), which enables the detection of allosteric modulators by monitoring changes in protein structure. We tested this approach at the industrial scale by adapting an allosteric FRET sensor of cardiac myosin to high-throughput screening (HTS), based on technology provided by Photonic Pharma and the University of Minnesota, and then used the sensor to screen 1.6 million compounds in the HTS facility at Bristol Myers Squibb. The results identified allosteric activators and inhibitors of cardiac myosin that do not compete with ATP binding, demonstrating high potential for FLT-based drug discovery.
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Transferência Ressonante de Energia de Fluorescência , Ensaios de Triagem em Larga Escala , Ensaios de Triagem em Larga Escala/métodos , Transferência Ressonante de Energia de Fluorescência/métodos , Miosinas Cardíacas , Descoberta de Drogas/métodosRESUMO
We introduce a new optical vortex coronagraph (OVC) method to determine the angular distance between two sources when the separation is sub-Rayleigh. We have found a direct relationship between the position of the minima and the source angular separation. A priori knowledge about the location of the two sources is not required. The superresolution capabilities of an OVC, equipped with an â = 2 N-step spiral phase plate in its optical path, were investigated numerically. The results of these investigations show that a fraction of the light, increasing with N, from the secondary source can be detected with a sub-Rayleigh resolution of at least 0.1 λ/D.
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Interpretação de Imagem Assistida por Computador/métodos , Modelos Teóricos , Telescópios , Simulação por Computador , Luz , Espalhamento de RadiaçãoRESUMO
The objective was to determine the cross-sectional area of the umbilical cord, its diameter and the diameter of its vessels to establish a reference curve for these parameters during pregnancy, through a prospective cross-sectional study, including 2,310 low-risk pregnancies between 12 and 40 weeks' gestation. Means and standard deviations (SDs), plus the 10th, 50th and 90th percentiles for each measurement were calculated using polynomial regression analysis. Mann-Whitney, Kruskal-Wallis and Wilcoxon tests were used for statistical analysis. These parameters increased significantly with gestational age. The area of the cord also varied significantly with parity. Their new reference curves for low risk pregnancies were calculated using polynomial regression, and an almost linear increase in values was found up to 32 weeks of pregnancy, tending to stabilise from then onwards. The regression equation of the umbilical cord area according to gestational age (GA) was: -1.417 + 0.3026*GA-0.008*GA(2) + 0.000007*GA(3) and the degree of adjustment (R(2)) was 0.89.
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Ultrassonografia Pré-Natal/normas , Cordão Umbilical/diagnóstico por imagem , Adulto , Brasil , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Gravidez , Estudos Prospectivos , Padrões de Referência , Valores de Referência , Análise de Regressão , Artérias Umbilicais/anatomia & histologia , Artérias Umbilicais/diagnóstico por imagem , Cordão Umbilical/anatomia & histologia , Cordão Umbilical/irrigação sanguínea , Veias Umbilicais/anatomia & histologia , Veias Umbilicais/diagnóstico por imagemRESUMO
Abstract: Serious mental illness is associated with a higher risk of violent interpersonal behavior. Characteristic traits denoting a psychopatho-logical picture such as schizophrenia, depression, a borderline, or narcissistic, antisocial, or paranoid personality disorder, are frequently observed in the personality of those who have committed one or more murders. For example, mass murderers are affected by a delusional syndrome with a persecution fixation, that develops in a subject with a paranoid, anacastic personality disorder. An abnormal mental frame-work develops as a consequence of continual experiences interpreted as traumatic. We present a complex case regarding a double murder whose vic-tims were shot by a 50-year-old neighbor, who underwent a psychiatric evaluation for the assessment of criminal responsibility. In the light of the historical reconstruction of his relation sensitive delusional mindset that triggered the final reaction, his life history, the "key event" and the "triggering environment" (constant conflictual and dysfunctional rela-tions with others) led to the violence. The correct understanding of the reported case demands investigation not only of the clinical, diagnostic and psychodiagnostic aspects, but also of the perpetrator-victim/s, their relational context and the situation where the crime evolves, in order to be able to reconstruct the event in a meaningful manner.
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Criminosos , Esquizofrenia , Agressão , Criminosos/psicologia , Homicídio/psicologia , Humanos , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico , Violência/psicologiaRESUMO
ABSTRACT: Childhood traumatic experiences have often been associated with the development of severe psychiatric disorders or, at least, with serious impairment in the victims' developing personality. Emotional abuse and neglect can cause gradual damage to Self-image and to models of self-in-relation to Others. We report a case of a woman who underwent psychiatric evaluations for marriage annulment. The issues were the as-sessment of the outcomes of early psychic trauma and the examination of the remaining individual capacities from a judicial standpoint. The examiners found that the memories of the woman's history of childhood abuse had become integrated into her personality organization. The spheres most strongly influenced were those of psycho-sexual/affective maturation and a dysfunctional bond with religion. Psychodiagnostic evaluation diagnosed a Borderline Personality Disorder. The complexity of the case suggests the need of a multi-dimen-sional analysis by an interdisciplinary team including experts in legal medicine, forensic psychiatry and psychology as well as clinical crimi-nology.