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Solid state quantum emitters are a prime candidate in distributed quantum technologies since they inherently provide a spin-photon interface. An ongoing challenge in the field, however, is the low photon extraction due to the high refractive index of typical host materials. This challenge can be overcome using photonic structures. Here, we report the integration of V2 centers in a cavity-based optical antenna. The structure consists of a silver-coated, 135 nm-thin 4H-SiC membrane functioning as a planar cavity with a broadband resonance yielding a theoretical photon collection enhancement factor of â¼34. The planar geometry allows us to identify over 20 single V2 centers at room temperature with a mean (maximum) count rate enhancement factor of 9 (15). Moreover, we observe 10 V2 centers with a mean absorption line width below 80 MHz at cryogenic temperatures. These results demonstrate a photon collection enhancement that is robust to the lateral emitter position.
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Quantum state readout is a key requirement for a successful qubit platform. In this work, we demonstrate a high-fidelity quantum state readout of a V2 center nuclear spin based on a repetitive readout technique. We demonstrate up to 99.5% readout fidelity and 99% for state preparation. Using this efficient readout, we initialize the nuclear spin by measurement and demonstrate its Rabi and Ramsey nutation. Finally, we use the nuclear spin as a long-lived memory for quantum sensing application of a weakly coupled diatomic nuclear-spin bath.
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Nuclear spins with hyperfine coupling to single electron spins are highly valuable quantum bits. Here we probe and characterize the particularly rich nuclear-spin environment around single silicon vacancy color centers (V2) in 4H-SiC. By using the electron spin-3/2 qudit as a four level sensor, we identify several sets of ^{29}Si and ^{13}C nuclear spins through their hyperfine interaction. We extract the major components of their hyperfine coupling via optical detected nuclear magnetic resonance, and assign them to shells in the crystal via the density function theory simulations. We utilize the ground-state level anticrossing of the electron spin for dynamic nuclear polarization and achieve a nuclear-spin polarization of up to 98±6%. We show that this scheme can be used to detect the nuclear magnetic resonance signal of individual spins and demonstrate their coherent control. Our work provides a detailed set of parameters and first steps for future use of SiC as a multiqubit memory and quantum computing platform.
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BACKGROUND: Currently, a conclusive experience on the uniform implementation and benefits of day hospice structures and interventions is lacking in Germany. The following questions should be clarified: (1) Which structural conditions and interventional measures should be established in day hospices from the point of view of patients, relatives, and specialist staff?; (2) Are the planned structures or interventions feasible and implementable under real conditions and accepted by patients, relatives, and staff?; (3) How can a final implementation and intervention catalog for day hospices be designed?; (4) Is this final catalog of services feasible, reasonable, economical, and effective under everyday conditions in day hospices? METHODS: We planned to perform a multistage investigation, guided by the Medical Research Council Framework for the development and evaluation of complex interventions. In Stage 1, an initial theoretical construct on structures and interventions will be established through an extensive literature and guideline review on day hospices and through qualitative interviews. In a nominal group process, we will create a catalog of offers. In Stage 2, feasibility testing is conducted in a single-day hospice under real-life conditions using quantitative quality indicators and qualitative interviews. Structures and interventions can be adapted here if necessary. In a second nominal group process, a final structure and offer catalog is created, which is then implemented in Stage 3 in the day hospice under investigation and evaluated under real daily conditions through a process and effectiveness test. For this purpose, qualitative and quantitative quality indicators will be used and a comparative cohort of patients who are not cared for in the day hospice - but in the same network structure (oncology-palliative care network Lower Bavaria) - is examined. DISCUSSION: Finally, the initial statements on the reasonable and realizable structures or interventions in day hospices and their benefits in daily real-life conditions as well as possible optimization processes shall be made. TRIAL REGISTRATION: The study was retrospectively registered in the German Clinical Trials Register (DRKS-ID DRKS00031613, registration date April 04, 2023) and the display portal of the Center for Clinical Trials of the University Hospital Regensburg (Z-2022-1734-6, registration date July 01, 2023).
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Cuidados Paliativos na Terminalidade da Vida , Hospitais para Doentes Terminais , Humanos , Cuidados Paliativos , Pesquisa Qualitativa , AlemanhaRESUMO
Optically addressable spin defects in silicon carbide (SiC) are an emerging platform for quantum information processing compatible with nanofabrication processes and device control used by the semiconductor industry. System scalability towards large-scale quantum networks demands integration into nanophotonic structures with efficient spin-photon interfaces. However, degradation of the spin-optical coherence after integration in nanophotonic structures has hindered the potential of most colour centre platforms. Here, we demonstrate the implantation of silicon vacancy centres (VSi) in SiC without deterioration of their intrinsic spin-optical properties. In particular, we show nearly lifetime-limited photon emission and high spin-coherence times for single defects implanted in bulk as well as in nanophotonic waveguides created by reactive ion etching. Furthermore, we take advantage of the high spin-optical coherences of VSi centres in waveguides to demonstrate controlled operations on nearby nuclear spin qubits, which is a crucial step towards fault-tolerant quantum information distribution based on cavity quantum electrodynamics.
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Compostos Inorgânicos de Carbono , Compostos de Silício , Compostos Inorgânicos de Carbono/química , Cor , Fótons , Compostos de Silício/químicaRESUMO
OBJECTIVES: Early tumor shrinkage (ETS) quantifies the objective response at the first assessment during systemic treatment. In metastatic colorectal cancer (mCRC), ETS gains relevance as an early available surrogate for patient survival. The aim of this study was to increase the predictive accuracy of ETS by using semi-automated volumetry instead of standard diametric measurements. METHODS: Diametric and volumetric ETS were retrospectively calculated in 253 mCRC patients who received 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) combined with either cetuximab or bevacizumab. The association of diametric and volumetric ETS with overall survival (OS) and progression-free survival (PFS) was compared. RESULTS: Continuous diametric and volumetric ETS predicted survival similarly regarding concordance indices (p > .05). In receiver operating characteristics, a volumetric threshold of 45% optimally identified short-term survivors. For patients with volumetric ETS ≥ 45% (vs < 45%), median OS was longer (32.5 vs 19.0 months, p < .001) and the risk of death reduced for the first and second year (hazard ratio [HR] = 0.25, p < .001, and HR = 0.39, p < .001). Patients with ETS ≥ 45% had a reduced risk of progressive disease only for the first 6 months (HR = 0.26, p < .001). These survival times and risks were comparable to those of diametric ETS ≥ 20% (vs < 20%). CONCLUSIONS: The accuracy of ETS in predicting survival was not increased by volumetric instead of diametric measurements. Continuous diametric and volumetric ETS similarly predicted survival, regardless of whether patients received cetuximab or bevacizumab. A volumetric ETS threshold of 45% and a diametric ETS threshold of 20% equally identified short-term survivors. KEY POINTS: ⢠ETS based on volumetric measurements did not predict survival more accurately than ETS based on standard diametric measurements. ⢠Continuous diametric and volumetric ETS predicted survival similarly in patients receiving FOLFIRI with cetuximab or bevacizumab. ⢠A volumetric ETS threshold of 45% and a diametric ETS threshold of 20% equally identified short-term survivors.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Fluoruracila/uso terapêutico , Estudos RetrospectivosRESUMO
With the growth of protein structure data, the analysis of molecular interactions between ligands and their target molecules is gaining importance. PLIP, the protein-ligand interaction profiler, detects and visualises these interactions and provides data in formats suitable for further processing. PLIP has proven very successful in applications ranging from the characterisation of docking experiments to the assessment of novel ligand-protein complexes. Besides ligand-protein interactions, interactions with DNA and RNA play a vital role in many applications, such as drugs targeting DNA or RNA-binding proteins. To date, over 7% of all 3D structures in the Protein Data Bank include DNA or RNA. Therefore, we extended PLIP to encompass these important molecules. We demonstrate the power of this extension with examples of a cancer drug binding to a DNA target, and an RNA-protein complex central to a neurological disease. PLIP is available online at https://plip-tool.biotec.tu-dresden.de and as open source code. So far, the engine has served over a million queries and the source code has been downloaded several thousand times.
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DNA/química , Proteínas de Ligação a RNA/química , RNA/química , Software , Algoritmos , Antineoplásicos/química , Guanosina Trifosfato/química , Ligantes , Conformação de Ácido Nucleico , Fenazinas/química , Conformação Proteica , RNA Polimerase II/química , Elementos de RespostaRESUMO
Body weight loss is frequently regarded as negatively related to outcomes in patients with malignancies. This retrospective analysis of the FIRE-3 study evaluated the evolution of body weight in patients with metastatic colorectal cancer (mCRC). FIRE-3 evaluated first-line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab or bevacizumab in mCRC patients with RAS-WT tumors (ie, wild-type in KRAS and NRAS exons 2-4). The prognostic and predictive relevance of early weight loss (EWL) regarding patient outcomes and treatment side effects were evaluated. Retrospective data on body weight during first 6 months of treatment were evaluated (N = 326). To correlate with efficacy endpoints and treatment side effects, patients were grouped according to clinically significant EWL ≥5% and <5% at Month 3. Age constituted the only significant predictor of EWL following a linear relationship with the corresponding log odds ratio (P = .016). EWL was significantly associated with the incident frequencies of diarrhea, edema, fatigue, nausea and vomiting. Further, a multivariate analysis revealed EWL to be an independent negative prognostic factor for overall survival (32.4 vs 21.1 months; hazard ratio [HR]: 1.64; 95% confidence interval [CI] = 1.13-2.38; P = .0098) and progression-free survival (11.8 vs 9.0 months; HR: 1.72; 95% CI = 1.18-2.5; P = .0048). In conclusion, EWL during systemic treatment against mCRC is significantly associated with patient age. Patients exhibiting EWL had worse survival and higher frequencies of adverse events. Early preventative measures targeted at weight maintenance should be evaluated, especially in elderly patients being at highest risk of EWL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/mortalidade , Neoplasias Hepáticas/mortalidade , Neoplasias Pulmonares/mortalidade , Redução de Peso , Idoso , Bevacizumab/administração & dosagem , Camptotecina/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Irinotecano/administração & dosagem , Leucovorina/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: The evidence on the efficacy of anticancer therapy is limited in older patients with metastatic colorectal cancer (mCRC). This retrospective analysis of phase III FIRE-3 trial assesses the efficacy of FOLFIRI plus either cetuximab or bevacizumab according to the patients' age and sidedness of primary tumour. METHODS: The study endpoints overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared between younger (<65 years) and older (≥65 years) patients, followed by stratification according to primary tumour sidedness. ORR was compared using Fisher´s exact test, OS and PFS were estimated by the Kaplan-Meier method and compared using the log-rank test. Univariate Cox regression analyses assessed hazard ratios and 95% confidence intervals for OS and PFS. RESULTS: Overall, older patients with RAS WT tumours had a significantly shorter OS when compared to younger patients (25.9 months vs 29.3 months, HR 1.29; P = 0.02). Also the proportion of right-sided tumours was significantly greater in older patients (27.1% vs 17.9%; P = 0.029). Secondary resection rates were numerically higher in younger patients (25.4% vs. 17.6%, P = 0.068) than in older patients. This was primarily seen in the Cetuximab arm, where older patients underwent less likely resection (13.1% vs. 26%; P = 0.02). Older patients with left-sided tumours showed only a trend towards greater efficacy of cetuximab (HR 0.86; P = 0.38). In patients with right-sided primary tumours, older patients did not appear to benefit from cetuximab in contrast to younger patients (≥65 years: 16.6 months vs 23.6 months, HR 1.1; P = 0.87; <65 years: 21.9 months vs 16.4 months HR 1.5; P = 0.31). CONCLUSIONS: In FIRE-3, OS was generally shorter in older patients in comparison to younger patients. This could be explained by the overrepresentation of right-sided tumours and a lower secondary resection rate in older patients. The efficacy of targeted therapy was dependent on tumour sidedness in older patients with RAS WT mCRC. CLINICAL TRIAL: FIRE-3 (NCT00433927).
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Camptotecina , Cetuximab , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila , Humanos , Leucovorina , Neoplasias Retais/tratamento farmacológico , Estudos RetrospectivosRESUMO
The creation of antitumor agents with an oral or subcutaneous route of administration has had important positive implications in the development of drugs to treat cancers, but issues such as false drug intake, uncontrolled side effects, and limited supervision may jeopardize the ability of these agents to improve treatment. A potential solution is the recruitment of non-physician healthcare professionals (i.e., nurses and physician assistants) and a special training course for them that focuses on the improvement of patient compliance. We developed and implemented three special professional training modules for non-physician healthcare professionals, which focus on the pharmacological aspects and side effects of oral and subcutaneous antitumor medications in regard to management strategies and communication issues that these non-physician healthcare professionals should address. Subsequently, we administered a questionnaire survey evaluating the course content and the implementation of the course in practice to the training participants to collect data for its implementation. Of 165 questionnaires that were administered, 44 (27%) were answered. The participants rated the course as being highly useful for their daily work. The participants reported a significant improvement in their professional expertise from the course. They emphasized the importance of medical topics and practical content to be included in the course delivery. The course encouraged 75% of the responders to start independent consultations with cancer patients that focused on questions of medication adherence for oral and subcutaneous antitumor medications, as well as the management of their side effects. Based on our results, at least a portion of the non-physician healthcare workforce is highly interested in engaging in active and autonomous co-supervision of patients who are treated with oral and subcutaneous antitumor medications. In addition to the theoretical basics of the treatment modalities, educational courses on oral and subcutaneous antitumor medications for non-physician healthcare professionals should focus on practical training and topics relevant to patient care.
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Pessoal de Saúde , Neoplasias , Atenção à Saúde , Pessoal de Saúde/educação , Humanos , Neoplasias/tratamento farmacológico , Encaminhamento e Consulta , Inquéritos e QuestionáriosRESUMO
Secondary resection of metastases is recommended in metastatic colorectal cancer (mCRC). Data describing changes in mutational profiles of corresponding primary tumor and metastatic tissue after conversion treatment are limited. Next generation sequencing was performed in formalin-fixed mCRC samples from patients of the FIRE-3 trial (FOLFIRI plus cetuximab or bevacizumab) before treatment start (baseline) and after secondary resection of metastases (post baseline). Changes of mutational profiles and tumor mutational burden (TMB) were assessed within a post-hoc analysis. Median overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were compared between treatment arms. Paired tumor samples were obtained from 25 patients (19 RAS wild-type, 6 RAS mutant by pyrosequencing). ORR (92.0% vs 58.0%) and OS (60.8 vs 35.4 months, hazard ratio = 0.39 [95% CI 0.14-1.12], P = .08) were higher for patients receiving cetuximab. After conversion therapy, 56 alterations (42 in the cetuximab and 14 in the bevacizumab arm) were newly observed in 18 patients (9 each treated with cetuximab or bevacizumab). Gains (n = 21) and losses (n = 21) of alterations occurred during cetuximab-based treatment, while mainly gains of alterations occurred during bevacizumab (n = 10). Three of nine patients treated with cetuximab that presented a change of mutational profiles, developed resistance to cetuximab. Mutational profiles were largely comparable before and after treatment with anti-VEGF or anti-EGFR directed monoclonal antibodies after secondary resection. Mutations associated with resistance to anti-EGFR antibodies were observed in only one-third of patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Mutação , Adulto , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/genética , Camptotecina/uso terapêutico , Neoplasias Colorretais/secundário , Neoplasias Colorretais/cirurgia , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes. METHODS: The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC. Further testing identified 400 patients with extended RAS wild-type disease; of these, 352 (88%) who received ≥3 cycles of therapy and had ≥1 post-baseline scan were evaluable for response and constituted the per-protocol population (169 cetuximab and 183 bevacizumab). Patients received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) with either weekly cetuximab or biweekly bevacizumab given on day 1 of each 14-day cycle until response, progression or toxicity occurred. The primary endpoint was the objective response rate (ORR) in the per-protocol population. Secondary endpoints included overall survival (OS) and progression-free survival (PFS). The effect of primary tumour location was evaluated. RESULTS: Median OS in the RAS wild-type population was 31 vs 26 months in the cetuximab and bevacizumab groups, respectively (HR 0.76, P = 0.012). In the per-protocol population, outcomes favoured cetuximab for ORR (77% vs 65%, P = 0.014) and median OS (33 vs 26 months, HR 0.75, P = 0.011), while PFS was comparable between groups. The advantage of cetuximab over bevacizumab occurred only in patients with left-sided primary tumours. CONCLUSIONS: FOLFIRI plus cetuximab resulted in a significantly higher ORR and longer OS compared to FOLFIRI plus bevacizumab among patients with left-sided tumours. The superior response associated with cetuximab may particularly benefit patients with symptomatic tumours or borderline-resectable metastases. CLINICALTRIALS. GOV IDENTIFIER: NCT00433927.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Camptotecina/uso terapêutico , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Esquema de Medicação , Fluoruracila/uso terapêutico , Genes ras , Humanos , Análise de Intenção de Tratamento , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Pessoa de Meia-Idade , Intervalo Livre de ProgressãoRESUMO
The Onko-Nexus ("Caretaker-Project"), sponsored by the Bavarian Ministry for Health and Nursing, is dedicated to improving the outpatient/hospitalized care interface issue for patients with highly complex malignant diseases requiring inpatient care in a university hospital. A total of 26 patients were recruited during the 3-year period of the project. The patients were managed and supported by 2 "Caretakers" (physician assistants), one from the outpatient unit and one working in the wards. Additionally, the university hospital provided a special consultation hour in an oncological private practice close to patient's home. After completion of the project, 9 patients and the 2 "Caretakers" were interviewed via guided qualitative interviews. The main benefits for the patients were intensive support, avoiding long journeys and the close contact between hospital and private practice. The project had a clear positive effect on the patients' quality of life.
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Pacientes Ambulatoriais , Qualidade de Vida , Alemanha , Hospitalização , Humanos , Encaminhamento e ConsultaRESUMO
BACKGROUND: There is controversy regarding the practical implementation of symptom-focused oncological cancer therapies to hospice residents. In this study, we aim to analyse the use and indication of supportive-oncological cancer therapies in hospices. METHODS: We conducted a retrospective survey of all residents of two hospice centres in the government district of Lower Bavaria, Germany. Hospice 1 (H1) was a member of an oncological-palliative medical network, and hospice 2 (H2) was independently organized. The evaluation period was the first 40 months after the opening of the respective hospice care centre. Demographical and epidemiological data as well as indications and type of supportive-oncological cancer therapies were recorded. A descriptive analysis and statistical tests were performed. RESULTS: Of the 706 residents, 645 had an underlying malignant disease. The average age was 72 years and the mean residence time was 28 days. The most frequent cancer types were gastrointestinal cancers, gynaecological cancers and bronchial carcinomas. Overall 39 residents (33 in H1 and 6 in H2, p < 0.01) received symptom-focused oncological cancer therapy. The average age of these residents was 68 years, and the mean residence time was 55 days. The most common therapeutic indications were dyspnoea and pain. The most common symptom-focused oncological cancer therapies were bisphosphonates, transfusions (erythrocyte- and platelet- concentrates), radiotherapy and anti-proliferative drugs (chemotherapy, anti-hormonal- and targeted- therapies). Patients with therapy lived significantly longer than patients without therapy (p < 0.01). CONCLUSIONS: Symptom-focused oncological cancer therapies can be implemented in hospices; however, their implementation seems to require certain structural and organizational prerequisites as well as careful patient selection. As a palliative medical approach, the focus is to ameliorate the symptoms and not prolong life. Symptom-focused oncology treatment could be a further and important part for the therapy of hospice patients in the future.
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Cuidados Paliativos na Terminalidade da Vida/métodos , Neoplasias/complicações , Exacerbação dos Sintomas , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha , Hospitais para Doentes Terminais/organização & administração , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
Single photon emitters in silicon carbide (SiC) are attracting attention as quantum photonic systems ( Awschalom et al. Nat. Photonics 2018 , 12 , 516 - 527 ; Atatüre et al. Nat. Rev. Mater. 2018 , 3 , 38 - 51 ). However, to achieve scalable devices, it is essential to generate single photon emitters at desired locations on demand. Here we report the controlled creation of single silicon vacancy (VSi) centers in 4H-SiC using laser writing without any postannealing process. Due to the aberration correction in the writing apparatus and the nonannealing process, we generate single VSi centers with yields up to 30%, located within about 80 nm of the desired position in the transverse plane. We also investigated the photophysics of the laser writing VSi centers and concluded that there are about 16 photons involved in the laser writing VSi center process. Our results represent a powerful tool in the fabrication of single VSi centers in SiC for quantum technologies and provide further insights into laser writing defects in dielectric materials.
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Realising a global quantum network requires combining individual strengths of different quantum systems to perform universal tasks, notably using flying and stationary qubits. However, transferring coherently quantum information between different systems is challenging as they usually feature different properties, notably in terms of operation wavelength and wavepacket. To circumvent this problem for quantum photonics systems, we demonstrate a polarisation-preserving quantum frequency conversion device in which telecom wavelength photons are converted to the near infrared, at which a variety of quantum memories operate. Our device is essentially free of noise, which we demonstrate through near perfect single photon state transfer tomography and observation of high-fidelity entanglement after conversion. In addition, our guided-wave setup is robust, compact, and easily adaptable to other wavelengths. This approach therefore represents a major building block towards advantageously connecting quantum information systems based on light and matter.
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The origin of the machinery that realizes protein biosynthesis in all organisms is still unclear. One key component of this machinery are aminoacyl tRNA synthetases (aaRS), which ligate tRNAs to amino acids while consuming ATP. Sequence analyses revealed that these enzymes can be divided into two complementary classes. Both classes differ significantly on a sequence and structural level, feature different reaction mechanisms, and occur in diverse oligomerization states. The one unifying aspect of both classes is their function of binding ATP. We identified Backbone Brackets and Arginine Tweezers as most compact ATP binding motifs characteristic for each Class. Geometric analysis shows a structural rearrangement of the Backbone Brackets upon ATP binding, indicating a general mechanism of all Class I structures. Regarding the origin of aaRS, the Rodin-Ohno hypothesis states that the peculiar nature of the two aaRS classes is the result of their primordial forms, called Protozymes, being encoded on opposite strands of the same gene. Backbone Brackets and Arginine Tweezers were traced back to the proposed Protozymes and their more efficient successors, the Urzymes. Both structural motifs can be observed as pairs of residues in contemporary structures and it seems that the time of their addition, indicated by their placement in the ancient aaRS, coincides with the evolutionary trace of Proto- and Urzymes.
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Aminoacil-tRNA Sintetases/classificação , Aminoacil-tRNA Sintetases/metabolismo , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Aminoacil-tRNA Sintetases/genética , Arginina/química , Sequência de Bases , Domínio Catalítico/genética , Códon/genética , Biologia Computacional , Evolução Molecular , Variação Genética , Humanos , Ligantes , Modelos Moleculares , Mutagênese , Conformação Proteica , RNA de Transferência/química , RNA de Transferência/genética , RNA de Transferência/metabolismoRESUMO
In this article, we introduce the "Campbell Paradigm" as a novel variant of Rosenberg and Hovland's (1960) tripartite model of attitudes. The Campbell Paradigm is based on a highly restricted measurement model that speaks of a compensatory relation between a person's latent attitude and the costs that come with any specific behavior. It overcomes the overarching weakness of the original tripartite model (i.e., its relative irrelevance for actual behavior) and offers a parsimonious explanation for behavior. Even though this seems attractive, we also discuss why the paradigm has not gained momentum in the 50 years since it was originally proposed by Donald T. Campbell. To demonstrate the paradigm's suitability even when implemented with an unrefined instrument in a domain where it has not been used previously, we apply the paradigm to a classic data example from attitude research from the 1984 US presidential election to account for the electorate's voting intentions and actual voting behaviors.
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Prospective, longitudinal analyses revealed that over a 12-year period from ages 6 to 18, individuals who grew up with mothers with more proenvironmental attitudes engaged in more proenvironmental behavior as young adults. A similar marginal association was uncovered between mothers' proenvironmental behaviors and the proenvironmental behavior of their young adult offspring. Maternal educational attainment, but not political ideology, was also associated with more proenvironmental behavior as children matured. Moreover, childhood time spent outdoors was positively associated with increased environmentally responsible behavior in young adulthood. Interestingly, one's own childhood proenvironmental behavior and attitude, at least as assessed at age 6, bear little on one's eventual proenvironmental behavior as a young adult. Finally, among this set of childhood factors, maternal education and childhood time spent outdoors were independent predictors of positive changes in environmental behavior from early childhood to young adulthood.
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Comportamento do Adolescente , Atitude , Comportamento Infantil , Meio Ambiente , Mães , Comportamento Social , Adolescente , Criança , Feminino , Seguimentos , Humanos , MasculinoRESUMO
Compliance with a small request (a metaphorical foot-in-the-door) promotes compliance with a subsequent big request. Whereas some explanations expect a drop in the behavioural costs of the big request, others suspect that the effect comes from boosting the underlying attitude. However, evidence for both explanations is equivocal and circumstantial, at best. Drawing on what Kaiser et al. (2010) call the Campbell paradigm, we present an integrative account: Compliance with any request demands a corresponding attitude to counterbalance the costs of the request. In our research, 229 participants were randomly assigned to either a foot-in-the-door (i.e., initially asked to sign a pro-environmental petition) or a control condition. Small-request-compliant participants were more likely than control participants to also comply with the big request and to continue filling out environmental-issues-related questionnaires. However, this foot-in-the-door effect occurred without diminishing behavioural costs or increasing attitude levels. Accordingly, the greater likelihood of small-request-compliant participants to also comply with the big request can be parsimoniously explained by baseline variability in people's attitude levels that manifests in their compliance with the initial request. We conclude that several of the foot-in-the-door effects reported in the literature carry the risk of representing mere pseudo-effects.