45 research outputs found
Quantum technology for 3D imaging of single molecules
© 2018 Viktor PerunicicBiochemical processes are conducted by interactions of individual molecules that comprise cells. It is the transient physical shape of proteins that dictates their specific functionality. However, imaging individual instances of single molecular structures is one of the notable challenges in structural biology. Presently available protein structure reconstruction techniques, Nuclear Magnetic Resonance (NMR) spectroscopy, X-ray crystallography and cryogenic Electron microscopy (cryo-EM), cannot provide images of individual molecules. Despite their power and their complementary capabilities, said techniques produce only average molecular information. They achieve this by sampling large ensembles of molecules in nearly identical conformational states. As a result, individual instances of a generic, inhomogeneous or unstable atomic structures presently remain beyond reach.
We seek to address this problem in a novel way by leveraging quantum technologies. In quantum computing, qubits are usually arranged in grids and coupled to one another in a highly organised manner. However, what if a qubit was coupled to an organic cluster of nuclear spins instead, e.g. that of a single molecule? What can be done with such a system in the context of quantum control and 3D imaging of individual molecular systems? What are its ultimate limits and possibilities? We explore those questions in stages throughout the chapters of this thesis.
We begin in Chapter 2 by investigating dipole-dipole interactions present between the nuclear spins in a target molecule, on one side, and between an electron-spin based qubit and each of the nuclear target spins on the other. We consider the Nitrogen Vacancy (NV) centre in diamond as an example of a suitable qubit with an active community interest as a biocompatible nano-magnetometer. Our intention is to lay down foundations that will help us advance from magnetometry to 3D molecular imaging.
Our inspiration comes from drawing parallels between the single molecule sensing in the qubit-target system and the clinical Magnetic Resonance Imaging (MRI). An MRI machine directly images a single, specific sample in its native state regardless of its characteristics. That is precisely what we would like to achieve on the molecular level. In Chapter 3, we develop a framework that allows a spin qubit to serve as a platform for 3D atomic imaging of molecules with Angstrom resolution. It uses an electron spin qubit simultaneously as a detector and as a gradient field provider for MRI-style imaging. We develop a theoretical quantum control methodology that allows dipole-dipole decoupling sequences used in solid-state NMR to be interleaved with the gradient field provided by the qubit.
In Chapter 4, we propose group-V donors in silicon as a novel qubit platform for bioimaging. Actively researched for quantum computing purposes, such qubits have not been considered in the biological context. A prime example of this class of qubits is the phosphorus donor in silicon (Si:P). We show how its specific set of properties, including long coherence times, large wave function and low operational temperatures can be leveraged for the purposes of atomic level imaging. Finalising the work in Chapter 5, we simulate the imaging process for one transmembrane protein of the influenza virus embedded in a lipid membrane. This demonstration highlights the potential of silicon spin qubits in the future development of in situ single molecule imaging at sub-Angstrom resolution
P03-298 - Dimensions Of Personality And Suicidal Attempts
Background and aimsDepression is among the most prevalent psychiatric conditions in general population. Previous reports established a link between suicidal attempts and major depressive disorder (MDD). There is a large number of risk factors which can participate in suicidal behavior. Many studies showed the role of personality dimensions such as borderline personality dimensions risk factors of suicidal behavior. The aim of this study was to assess dimensions of personality in inpatients who were hospitalized after suicidal attempt.MethodThe sample consisted of sixty inpatients with MDD diagnosed with ICD X. There were thirty patients with suicidal attempt and thirty with no history of suicidal attempts. The assessment of personality dimensions was carried out by the Millon Clinical Multiaxial Inventory III (MCMI III).ResultsOur findings have shown that borderline and masochistic dimensions were more frequently present in the group of patients with suicidal attempts. Compulsive dimensions were more present in the group of patients with no history of suicidal attempt.ConclusionBorderline personality dimensions with underlying impulsivity and low level of self-confidence might be potential risk factor for suicidal behavior, while the patients with a rigid system of organization and conscientiousness are less prone to suicidal behavior. Assessing personality dimensions is recommended in the process of psychodiagnostics and might be useful in preventive interventions.</jats:sec
Clinical - pathological significance of leptin receptor (LEPR) expression in squamous cell carcinoma of the skin
© 2020 The Authors Adipokine leptin functions through its transmembrane receptors (LEPR). In many malignant tumors it stimulates the growth, migration and invasion of malignant cells. The aim of our work is to examine the effect of LEPR expression on the clinical-morphological properties of squamous cell carcinoma of the skin (cSCC). The biopsy material obtained by excision of squamous cell skin cancer was used. The test group consisted of excision biopsies of squamous cell carcinoma of the skin (n = 62), and the control group (n = 62) consisted of excision biopsies of non-tumor tissue of the skin (from the tumor environment) from an operative preparation delivered to the Pathohistology Department. After routine processing and paraffin molding, histochemical Hematoxylin-Eosin and immunohistochemical ABC method with anti LEPR and Ki67 antibodies were applied at 4 μm sections. The statistical software package SPSS for Windows (26.0) was used to analyze obtained results. Intracytoplasmic and intramembranous LEPR expression was found in 100 % of examined cSCCs. LEPR expression was statistically significantly associated with proliferation index and histologic grade of tumors. Pronounced LEPR expression was associated with a high proliferation index in 66.7 % of cases and with poorly differentiated cSCC in 94.4 %. Multivariate regression analysis showed that cSCCs with pronounced LEPR expression were seven times more often poorly differentiated than tumors with moderate or LEPR expression in trace. Our results indicate that LEPR expression is a predictor of the malignant potential of cSCC, so that based on LEPR expression, it is possible to identify an aggressive cSCC phenotype, which provides the possibility of individualizing anti-tumor treatment using LEPR antagonists
MS404 INFLUENCE OF SMOKING AND DIABETES MELLITUS TYPE 2 ON THE DEVELOPMENT OF CORONARY DISEASE
P01-60 - Irrational Beliefs of Patients with Major Depressive Disorder
ObjectiveAccording to CBT theory, belief system has an important role in etiology of depression. Absolutistic, rigid and irrational beliefs might have influence on development and persistence of depressive psychopathology. The aim of our study was to examine characteristics of irrational beliefs in the cognitive scheme of patients with Major Depressive Disorder (MDD).MethodThe sample consisted of sixty inpatients diagnosed as MDD by using the ICD-X criteria. The assessment of irrational beliefs was carried out by Beck's Personality Belief Questionnaire (PBQ).ResultsOur findings have shown that irrational beliefs related to histrionic, schizoid and paranoid cognitive system were the most prevalent in patients with MDD. We also found significant and high correlation between opposite way of thinking - histrionic beliefs pattern correlated with avoidant and schizoid beliefs patterns. Also, dependent belief pattern was in a significant correlation with avoidant, schizoid and paranoid beliefs. In addition to rigidity, absolutistic and imperative cognitive schemes, we also found ambivalent cognitive tendencies. The existing ambivalence could be an important factor in the maintenance of depressive symptoms.ConclusionOur study has shown high prevalence of irrational beliefs in MDD patients. By recognizing the exact cognitive biases underlying depression, it might be possible to direct the therapeutic interventions more specifically and provide a highly personalized approach in the treatment of patients with MDD. We also believe that there is a need for a psychotherapeutic work on irrational beliefs during remission, which might prevent relapses.</jats:sec
Anemia is independently associated with NT-proBNP levels in asymptomatic predialysis patients with chronic kidney disease
Background: Although anemia and renal dysfunction are related to increased natriuretic peptides levels in heart failure patients, less is known about this relationship in asymptomatic predialysis patients with chronic kidney disease (CKD). The aim of this study was to investigate relationship between hemoglobin (Hb) concentration, N-terminal proBNP (NT-proBNP) levels and echocardiographic findings in these patients. Methods: The study included 61 patients with CKD stage IV-V (34 male, mean age 62.6 +/- 13.6 years) and 22 age-and sex -matched healthy persons as control group. All participants underwent clinical, laboratory and echocardiographic examination, including Tissue Doppler Imaging and colour M-mode Doppler. Results: Patients with CKD had lower Hb levels (p LT 0.001), and higher levels of NT-proBNP (p LT 0.001) than healthy controls. Patients were divided into two groups according to their mean Hb levels: group A, Hb LT 10.3 g/dL and group B, Hb >= 10.3 g/dL. Patients from group A was significantly older (p LT 0.001), left ventricular mass index was significantly higher (LVMI, p LT 0.001), LV diastolic function was worse (septal and lateral E'/A' ratio: p LT 0.05 and p LT 0.01, respectively), and the level NT-proBNP was higher (p LT 0.001) compared to patients from group B. The natural logarithm of NT-proBNP (lnNT-proBNP) showed highly significant correlation with Hb (p LT 0.001) and significant correlation with estimated glomerular filtration rate (p=0.035) in CKD patients. Multiple regression analysis revealed Hb levels (p LT 0.01), cholesterol (p LT 0.001), LV ejection fraction (p LT 0.001) and septal E/E' ratio (p LT 0.01) as the independent variables predicting as much as 54% variability of lnNTpro-BNP. Conclusions: The increased NT-proBNP levels in asymptomatic patients with advanced CKD were independently associated with echocardiographic parameters of LV function, but anemia may represent one of the important confounder of the relationship between NT-proBNP and cardiovascular abnormalities
