Detection of molecular transitions with nitrogen-vacancy centers and electron-spin labels

We present a protocol that detects molecular conformational changes with two nitroxide electron-spin labels and a nitrogen-vacancy (NV) center in diamond. More specifically, we demonstrate that the NV can detect energy shifts induced by the coupling between electron-spin labels. The protocol relies on the judicious application of microwave and radiofrequency pulses in a range of parameters that ensures stable nitroxide resonances. Furthermore, we demonstrate that our scheme is optimized by using nitroxides with distinct nitrogen isotopes. We develop a simple theoretical model that we combine with Bayesian inference techniques to demonstrate that our method enables the detection of conformational changes in ambient conditions including strong NV dephasing rates as a consequence of the diamond surface proximity and nitroxide thermalization mechanisms. Finally, we counter-intuitively show that with our method the small residual effect of random molecular tumbling becomes a resource that can be exploited to extract inter-label distances.The authors acknowledge financial support from Spanish Government via PGC2018-095113-B-I00 (MCIU/AEI/FEDER, UE) and, from Basque Government via IT986-16. C.M.-J. acknowledges the predoctoral MICINN grant PRE2019-088519. R.P. acknowledges support from European Union's Horizon 2020 FET-Open project SuperQuLAN (899354). M.B.P. and B.D. acknowledge the ERC Synergy Grants HyperQ (856432), as well as the BMBF project QSens (03ZU1110FF), and Asteriqs (820394). The authors acknowledge support by the state of Baden-Wuerttemberg through bwHPC and the German Research Foundation (DFG) through grant no INST 40/575-1 FUGG (JUSTUS 2 cluster). J.C. acknowledges the Ramon y Cajal (RYC2018-025197-I) research fellowship, the financial support from Spanish Government via EUR2020-112117 and Nanoscale NMR and complex systems (PID2021-126694NB-C21) projects, the EU FET Open Grant Quromorphic (828826), the ELKARTEK project Dispositivos en Tecnologias Cuanticas (KK-2022/00062), and the Basque Government grant IT1470-22

Speeding up quantum perceptron via shortcuts to adiabaticity

The quantum perceptron is a fundamental building block for quantum machine learning. This is a multidisciplinary field that incorporates abilities of quantum computing, such as state superposition and entanglement, to classical machine learning schemes. Motivated by the techniques of shortcuts to adiabaticity, we propose a speed-up quantum perceptron where a control field on the perceptron is inversely engineered leading to a rapid nonlinear response with a sigmoid activation function. This results in faster overall perceptron performance compared to quasi-adiabatic protocols, as well as in enhanced robustness against imperfections in the controls.We acknowledge financial support from Spanish Government via PGC2018-095113-B-I00 (MCIU/AEI/FEDER, UE), Basque Government via IT986-16, as well as from QMiCS (820505) and OpenSuperQ (820363) of the EU Flagship on Quantum Technologies, and the EU FET Open Grant Quromorphic (828826). J. C. acknowledges the Ramón y Cajal program (RYC2018- 025197-I) and the EUR2020-112117 Project of the Spanish MICINN, as well as support from the UPV/EHU through the Grant EHUrOPE. X. C. acknowledges NSFC (12075145), SMSTC (2019SHZDZX01-ZX04, 18010500400 and 18ZR1415500), the Program for Eastern Scholar and the Ramón y Cajal program of the Spanish MICINN (RYC-2017-22482). E. T. acknowledges support from Project PGC2018-094792-B-I00 (MCIU/AEI/FEDER,UE), CSIC Research Platform PTI-001, and CAM/FEDER Project No. S2018/TCS-4342 (QUITEMAD-CM

Expansión Urbana en áreas rurales: normativa territorial y mercado inmobiliario: caso de estudio Santiago de Chile 1994-2003

Expansión Urbana en áreas rurales; Normativa territorial y mercado inmobiliario Caso de estudio Santiago de Chile 1994-2003.Postprint (published version

Co-Design quantum simulation of nanoscale NMR

Quantum computers have the potential to efficiently simulate the dynamics of nanoscale NMR systems. In this work, we demonstrate that a noisy intermediate-scale quantum computer can be used to simulate and predict nanoscale NMR resonances. In order to minimize the required gate fidelities, we propose a superconducting application-specific Co-Design quantum processor that reduces the number of SWAP gates by over 90% for chips with more than 20 qubits. The processor consists of transmon qubits capacitively coupled via tunable couplers to a central co-planar waveguide resonator with a quantum circuit refrigerator (QCR) for fast resonator reset. The QCR implements the nonunitary quantum operations required to simulate nuclear hyperpolarization scenarios.The authors would like to thank Caspar Ockeloen-Korppi, Alessandro Landra, and Johannes Heinsoo for their help in de- veloping the idea of the star-architecture chip, Jani Tuorila for his support in developing the gate theory, Amin Hosseinkhani and Tianhan Liu for reviewing the manuscript, and Hen- rikki Mäkynen and Hoang-Mai Nguyen for graphic design. J.C. additionally acknowledges the Ramón y Cajal program (RYC2018-025197-I). We further acknowledge support from Atos with the Quantum Learning Machine (QLM). Finally, the authors acknowledge financial support to BMBF through the Q-Exa Project No. FZK: 13N16062

Focal adhesion genes refine the intermediate-risk cytogenetic classification of acute myeloid leukemia

© 2018 by the authors.In recent years, several attempts have been made to identify novel prognostic markers in patients with intermediate-risk acute myeloid leukemia (IR-AML), to implement risk-adapted strategies. The non-receptor tyrosine kinases are proteins involved in regulation of cell growth, adhesion, migration and apoptosis. They associate with metastatic dissemination in solid tumors and poor prognosis. However, their role in haematological malignancies has been scarcely studied. We hypothesized that PTK2/FAK, PTK2B/PYK2, LYN or SRC could be new prognostic markers in IR-AML. We assessed PTK2, PTK2B, LYN and SRC gene expression in a cohort of 324 patients, adults up to the age of 70, classified in the IR-AML cytogenetic group. Univariate and multivariate analyses showed that PTK2B, LYN and PTK2 gene expression are independent prognostic factors in IR-AML patients. PTK2B and LYN identify a patient subgroup with good prognosis within the cohort with non-favorable FLT3/NPM1 combined mutations. In contrast, PTK2 identifies a patient subgroup with poor prognosis within the worst prognosis cohort who display non-favorable FLT3/NPM1 combined mutations and underexpression of PTK2B or LYN. The combined use of these markers can refine the highly heterogeneous intermediate-risk subgroup of AML patients, and allow the development of risk-adapted post-remission chemotherapy protocols to improve their response to treatment.Pallarès, VictorThis work was supported by Instituto de Salud Carlos III (Co-funding from FEDER) [CD13/00074 to V.P., PI15/00378 and PIE15/00028 to R.M., FIS PI17/01246, RD12/0036/0071 and FIS PI14/00450 to J.S., RD12/0036/0069 to M.G.., ISCIII-PS13/1640 and PI16/0665 to E.B., and RD12/0036/0014 and PIE13/00046 to M.A.S.] CIBERONC [CB16/12/00284 to M.A.S.]; CIBER-BBN [CBV6/01/1031 and Nanomets3 to R.M.]; AGAUR [2017 FI_B 00680 to A.F.; 2017-SGR-865 and 2014PROD0005 to R.M. and 2014-SGR-1281 to J.S.]; Fundació La Marató TV3 [416/C/2013-2030 to R.M., 100830/31/32 to J.S., M.G.. and M.A.S.]; Josep Carreras Leukemia Research Institute [P/AG 2017 to R.M.]; Spanish Health Research Program [PI12/02321 to M.G..]; Spanish Association Against Cancer (AECC) [to M.C.C.]; a grant from the Cellex Foundation, Barcelona [to J.S.]; a grant from La Generalitat de Catalunya (PERIS) [SLT002/16/00433 to J.S.]; and a grant from Fundación Española de Hematología y Hemoterapia (FEHH) [to V.P.]

NEDD9, an independent good prognostic factor in intermediate-risk acute myeloid leukemia patients

Altres ajuts: Fundació La Marató TV3 [416/C/2013-2030,100830/31/32]; Josep Carreras Leukemia Research Institute [P/AG 2014]; Spanish Health Research Program [PI12/02321]; Spanish Association Against Cancer (AECC) [to MCC]; and a grant from the Cellex Foundation, Barcelona.Intermediate-risk acute myeloid leukemia (IR-AML) is the largest subgroup of AML patients and is highly heterogeneous. Whereas adverse and favourable risk patients have well-established treatment protocols, IR-AML patients have not. It is, therefore, crucial to find novel factors that stratify this subgroup to implement risk-adapted strategies. The CAS (Crk-associated substrate) adaptor protein family regulates cell proliferation, survival, migration and adhesion. Despite its association with metastatic dissemination and prognosis of different solid tumors, the role of these proteins in hematological malignancies has been scarcely evaluated. Nevertheless, previous work has established an important role for the CAS family members NEDD9 or BCAR1 in the migratory and dissemination capacities of myeloid cells. On this basis, we hypothesized that NEDD9 or BCAR1 expression levels could associate with survival in IR-AML patients and become new prognostic markers. To that purpose, we assessed BCAR1 and NEDD9 gene expression in a cohort of 73 adult AML patients validating the results in an independent cohort (n = 206). We have identified NEDD9, but not BCAR1, as a new a marker for longer overall and disease-free survival, and for lower cumulative incidence of relapse. In summary, NEDD9 gene expression is an independent prognostic factor for favourable prognosis in IR-AML patients

ATLANTIC ‐ PRIMATES : a dataset of communities and occurrences of primates in the Atlantic Forests of South America

Primates play an important role in ecosystem functioning and offer critical insights into human evolution, biology, behavior, and emerging infectious diseases. There are 26 primate species in the Atlantic Forests of South America, 19 of them endemic. We compiled a dataset of 5,472 georeferenced locations of 26 native and 1 introduced primate species, as hybrids in the genera Callithrix and Alouatta. The dataset includes 700 primate communities, 8,121 single species occurrences and 714 estimates of primate population sizes, covering most natural forest types of the tropical and subtropical Atlantic Forest of Brazil, Paraguay and Argentina and some other biomes. On average, primate communities of the Atlantic Forest harbor 2 ± 1 species (range = 1–6). However, about 40% of primate communities contain only one species. Alouatta guariba (N = 2,188 records) and Sapajus nigritus (N = 1,127) were the species with the most records. Callicebus barbarabrownae (N = 35), Leontopithecus caissara (N = 38), and Sapajus libidinosus (N = 41) were the species with the least records. Recorded primate densities varied from 0.004 individuals/km2 (Alouatta guariba at Fragmento do Bugre, Paraná, Brazil) to 400 individuals/km2 (Alouatta caraya in Santiago, Rio Grande do Sul, Brazil). Our dataset reflects disparity between the numerous primate census conducted in the Atlantic Forest, in contrast to the scarcity of estimates of population sizes and densities. With these data, researchers can develop different macroecological and regional level studies, focusing on communities, populations, species co‐occurrence and distribution patterns. Moreover, the data can also be used to assess the consequences of fragmentation, defaunation, and disease outbreaks on different ecological processes, such as trophic cascades, species invasion or extinction, and community dynamics. There are no copyright restrictions. Please cite this Data Paper when the data are used in publications. We also request that researchers and teachers inform us of how they are using the data.Fil: Culot, Laurence. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Pereira, Lucas Augusto. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Agostini, Ilaria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Universidad Nacional de Misiones. Instituto de Biología Subtropical; Argentina. Centro de Investigaciones del Bosque Atlántico; ArgentinaFil: de Almeida, Marco Antônio Barreto. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Alves, Rafael Souza Cruz. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Baldovino, María Celia. Centro de Investigaciones del Bosque Atlántico; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Naturales e Instituto Miguel Lillo. Instituto Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; ArgentinaFil: Di Bitetti, Mario Santiago. Centro de Investigaciones del Bosque Atlántico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú; ArgentinaFil: Oklander, Luciana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú; ArgentinaFil: Holzmann, Ingrid. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Bio y Geociencias del NOA. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Museo de Ciencias Naturales. Instituto de Bio y Geociencias del NOA; ArgentinaFil: Dums, Marcos. RUMO S.A. Licenciamento Ambiental; BrasilFil: Lombardi, Pryscilla Moura. RUMO S.A. Licenciamento Ambiental; BrasilFil: Bonikowski, Renata Twardowsky Ramalho. RUMO S.A. Licenciamento Ambiental; BrasilFil: Age, Stéfani Gabrieli. RUMO S.A. Licenciamento Ambiental; BrasilFil: Souza Alves, João Pedro. Universidade Federal de Pernambuco; BrasilFil: Chagas, Renata. Universidade Federal da Paraíba; BrasilFil: da Cunha, Rogério Grassetto Teixeira. Universidade Federal de Alfenas; BrasilFil: Valença Montenegro, Monica Mafra. Centro Nacional de Pesquisa e Conservaçao de Primates Brasileiros; BrasilFil: Ludwig, Gabriela. Centro Nacional de Pesquisa e Conservaçao de Primates Brasileiros; BrasilFil: Jerusalinsky, Leandro. Centro Nacional de Pesquisa e Conservaçao de Primates Brasileiros; BrasilFil: Buss, Gerson. Centro Nacional de Pesquisa e Conservaçao de Primates Brasileiros; BrasilFil: de Azevedo, Renata Bocorny. Centro Nacional de Pesquisa e Conservaçao de Primates Brasileiros; BrasilFil: Filho, Roberio Freire. Universidade Federal de Pernambuco; BrasilFil: Bufalo, Felipe. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Milhe, Louis. Université D'Avignon et des Pays du Vaucluse; FranciaFil: Santos, Mayara Mulato dos. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Sepulvida, Raíssa. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Ferraz, Daniel da Silva. Universidade do Estado de Minas Gerais; BrasilFil: Faria, Michel Barros. Universidade do Estado de Minas Gerais; BrasilFil: Ribeiro, Milton Cezar. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Galetti, Mauro. Universidade Estadual Paulista Julio de Mesquita Filho; Brasi

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362