Some Preliminary Studies for Treating the Three-Body Scattering Problems

As a preliminary step for handling the three-body scattering problems, here we present the following three new methods: A method of acceleration for iterative calculations, a method for treating the scattering from a non-local potential, and a method for treating the three-body breakup channel. Convergence of elastic scattering channel is studied

IN SEARCH OF NEURAL MECHANISMS OF MIRROR NEURON DYSFUNCTION IN SCHIZOPHRENIA: RESTING STATE FUNCTIONAL CONNECTIVITY APPROACH

It has been repeatedly shown that schizophrenia patients have immense alterations in goal-directed behaviour, social cognition, and social interactions, cognitive abilities that are presumably driven by the mirror neurons system (MNS). However, the neural bases of these deficits still remain unclear. Along with the task-related fMRI and EEG research tapping into the mirror neuron system, the characteristics of the resting state activity in the particular areas that encompass mirror neurons might be of interest as they obviously determine the baseline of the neuronal activity. Using resting state fMRI, we investigated resting state functional connectivity (FC) in four predefined brain structures, ROIs (inferior frontal gyrus, superior parietal lobule, premotor cortex and superior temporal gyrus), known for their mirror neurons activity, in 12 patients with first psychotic episode and 12 matched healthy individuals. As a specific hypothesis, based on the knowledge of the anatomical inputs of thalamus to all preselected ROIs, we have investigated the FC between thalamus and the ROIs. Of all ROIs included, seed-to-voxel connectivity analysis revealed significantly decreased FC only in left posterior superior temporal gyrus (STG) and the areas in visual cortex and cerebellum in patients as compared to controls. Using ROI-to-ROI analysis (thalamus and selected ROIs), we have found an increased FC of STG and bilateral thalamus whereas the FC of these areas was decreased in controls. Our results suggest that: (1) schizophrenia patients exhibit FC of STG which corresponds to the previously reported changes of superior temporal gyrus in schizophrenia and might contribute to the disturbances of specific functions, such as emotional processing or spatial awareness; (2) as the thalamus plays a pivotal role in the sensory gating, providing the filtering of the redundant stimulation, the observed hyperconnectivity between the thalami and the STGs in patients with schizophrenia might explain the sequential overload with sensory inputs that leads to the abnormal cognitive processing

Theoretical Modeling of Cognitive Dysfunction in Schizophrenia by Means of Errors and Corresponding Brain Networks

The current evidence of cognitive disturbances and brain alterations in schizophrenia does not provide the plausible explanation of the underlying mechanisms. Neuropsychological studies outlined the cognitive profile of patients with schizophrenia, that embodied the substantial disturbances in perceptual and motor processes, spatial functions, verbal and non-verbal memory, processing speed and executive functioning. Standardized scoring in the majority of the neurocognitive tests renders the index scores or the achievement indicating the severity of the cognitive impairment rather than the actual performance by means of errors. At the same time, the quantitative evaluation may lead to the situation when two patients with the same index score of the particular cognitive test, demonstrate qualitatively different performances. This may support the view why test paradigms that habitually incorporate different cognitive variables associate weakly, reflecting an ambiguity in the interpretation of noted cognitive constructs. With minor exceptions, cognitive functions are not attributed to the localized activity but eventuate from the coordinated activity in the generally dispersed brain networks. Functional neuroimaging has progressively explored the connectivity in the brain networks in the absence of the specific task and during the task processing. The spatio-temporal fluctuations of the activity of the brain areas detected in the resting state and being highly reproducible in numerous studies, resemble the activation and communication patterns during the task performance. Relatedly, the activation in the specific brain regions oftentimes is attributed to a number of cognitive processes. Given the complex organization of the cognitive functions, it becomes crucial to designate the roles of the brain networks in relation to the specific cognitive functions. One possible approach is to identify the commonalities of the deficits across the number of cognitive tests or, common errors in the various tests and identify their common "denominators" in the brain networks. The qualitative characterization of cognitive performance might be beneficial in addressing diffuse cognitive alterations presumably caused by the dysconnectivity of the distributed brain networks. Therefore, in the review, we use this approach in the description of standardized tests in the scope of potential errors in patients with schizophrenia with a subsequent reference to the brain networks

Study of the anticancer properties of methyl- and phenyl-substituted carbon- and silicon-bridged ansa-titanocene complexes

The previously known complexes {[}Ti\{(Me2CMe2C)(eta(5)-C5H4)(2)\}Cl-2] (1), {[}Ti\{Me2C(eta(5)-C5H4)(2)\}Cl-2] (2), {[}Ti \{Me2Si(eta(5)-C5H4)(2)\}Cl-2] (4), {[}Ti\{MePhSi(eta(5)-C5H4)(2)\}Cl-2] (5) and {[}Ti\{MePhSi(eta(5)-C5Me4)(2)\}Cl-2] (6) have been prepared following reported procedures. The novel complex {[}Ti\{MePhC(eta(5)-C5H4)(2)\}Cl-2] (3) has been prepared and characterized. The cytotoxic activity of 1-6 has been tested after 72 h on melanoma A375 and B16, prostate cancer DU145 and LNCaP and colon cancer HCT116, SW620 and CT26CL25 cell lines observing a high cytotoxic activity of complexes 1 and 6 compared to the reference compound ({[}Ti(eta(5)-C5H5)(2)\}Cl-2]). 1 and 6 have also been tested against primary normal mouse keratinocytes and lung fibroblasts. While viability of both type of primary cells was significantly less affected by 1 in comparison to the reference compound {[}Ti(eta(5)-C5H5)(2)Cl-2], compound 6 was completely nontoxic for nonmalignant cells, indicating a potential selectivity of this compound towards cancer cell lines. In addition CFSE staining, cell cycle analysis, AnnexinV-FITC/PI staining, detection of caspase activity and mitochondrial potential showed that 1 and 6 were acting through inhibition of proliferation and subsequent induction of mitochondrial dependent apoptosis in colon cancer cell lines, HCT116 and SW620, which express low sensitivity to cisplatin. Compound 6 was found to be the leading drug in this group since it shows the fastest and most selective anticancer profile. (C) 2013 Elsevier B.V. All rights reserved.Ministerio de Educacion y Ciencia, Spain {[}CTQ-2011-24346, CTQ-2012-30762]; Ministry of Science and Technological Development of the Republic of Serbia {[}173013]; Grant Agency of the Czech Republic {[}P207/12/2368

Advances in Xmipp for cryo-electron microscopy: from Xmipp to Scipion

Xmipp is an open-source software package consisting of multiple programs for processing data originating from electron microscopy and electron tomography, designed and managed by the Biocomputing Unit of the Spanish National Center for Biotechnology, although with contributions from many other developers over the world. During its 25 years of existence, Xmipp underwent multiple changes and updates. While there were many publications related to new programs and functionality added to Xmipp, there is no single publication on the Xmipp as a package since 2013. In this article, we give an overview of the changes and new work since 2013, describe technologies and techniques used during the development, and take a peek at the future of the package

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

A Perturbative Approach to Scattering Problems with Short and Long Range Potentials

A Perturbative approach to the solution of Schrodinger equation proposed recently by Sasakawa and Sawada is studied for potentials containing a long range Coulomb tail. The rate of convergence is studied for nuclear as well as for atomic potentials