Четыре клеточно-автоматных алгоритма пермутаций матриц

Numerical calculation uses to describe the operation of matrix permutation algorithms based on cyclic shifts of rows and columns. This choice of discrete transformation algorithms justified by the convenience of the cellular automaton (CA) formulation, which is used. Obtained Empirical formulas for the permutation period and for the last algorithm, which period formula is recurrent. For a base scheme period has the asymptotics:  for a matrix  with pairwise different elements. Despite the complexity of the scheme, the other two modifications only give a polynomial growth of period, no higher than 3. Fourth scheme has a non-trivial period dependence, but no higher than the exponential. In some cases algorithms make special permutations: rotate, reflect, and rearrange blocks for the matrix . These formulas are closely related to individual cells paths. And paths connected with the influence of the boundaries that gives branching the matrix order by subtraction class modulo 3,4 or 12. Visualizations of these paths make in the extended CA-field. Two "mixing metrics" analyze as a parameter of CA dynamics on matrix permutations (compared to the initial). For all schemes and most branches, the behavior of these metrics shows in graphs and histograms (conditional density distribution) showing how often the permutation period occurs with the specified interval of metrics. The practical aim of this work is in the field of pseudorandom number generation and cryptography.С помощью численного расчета описывается работа алгоритмов пермутаций матриц, основанных на циклических сдвигах строк и столбцов. Такой выбор алгоритмов дискретного преобразования обоснован удобством клеточно-автоматных формулировок, которые и приводятся. Получены эмпирические формулы для периода пермутаций; для последнего алгоритма формула периода носит рекуррентный характер. Для базовой и наиболее простой схемы период N(n) имеет асимптотику exp(2n)/n для матрицы nxn с попарно различными элементами. Несмотря на усложнение схемы алгоритма, две другие модификации дают лишь полиномиальный рост степени не выше 3. Четвертая схема имеет нетривиальную зависимость периода, но не выше экспоненциальной. В ряде случаев алгоритмы порождают особые пермутации: поворот, отражение и перестановку блоков для матрицы 2kx2k. Эти формулы тесно связаны с индивидуальными траекториями элементов, а они – с влиянием границ, что дает ветвление порядка матрицы по классу вычета по модулю 3,4 или 12. Визуализации этих траекторий приводятся в расширенном поле КА. В качестве параметра динамики КА анализируются две «метрики перемешанности» на пермутациях матрицы (по сравнению с начальной). Для всех схем и большинства ветвей поведение этих метрик представлено на графиках и гистограммах (условно: плотности распределения), показывающих, как часто встречаются по периоду пермутации с заданным интервалом значений метрик. Практическое значение работы состоит в оценке применения КА в областях генерации псевдослучайных чисел и криптографии

Differences between familial and sporadic dilated cardiomyopathy: ESC EORP Cardiomyopathy & Myocarditis registry

Aims: Dilated cardiomyopathy (DCM) is a complex disease where genetics interplay with extrinsic factors. This study aims to compare the phenotype, management, and outcome of familial DCM (FDCM) and non‐familial (sporadic) DCM (SDCM) across Europe. / Methods and results: Patients with DCM that were enrolled in the prospective ESC EORP Cardiomyopathy & Myocarditis Registry were included. Baseline characteristics, genetic testing, genetic yield, and outcome were analysed comparing FDCM and SDCM; 1260 adult patients were studied (238 FDCM, 707 SDCM, and 315 not disclosed). Patients with FDCM were younger (P < 0.01), had less severe disease phenotype at presentation (P < 0.02), more favourable baseline cardiovascular risk profiles (P ≤ 0.007), and less medication use (P ≤ 0.042). Outcome at 1 year was similar and predicted by NYHA class (HR 0.45; 95% CI [0.25–0.81]) and LVEF per % decrease (HR 1.05; 95% CI [1.02–1.08]. Throughout Europe, patients with FDCM received more genetic testing (47% vs. 8%, P < 0.01) and had higher genetic yield (55% vs. 22%, P < 0.01). / Conclusions: We observed that FDCM and SDCM have significant differences at baseline but similar short‐term prognosis. Whether modification of associated cardiovascular risk factors provide opportunities for treatment remains to be investigated. Our results also show a prevalent role of genetics in FDCM and a non‐marginal yield in SDCM although genetic testing is largely neglected in SDCM. Limited genetic testing and heterogeneity in panels provides a scaffold for improvement of guideline adherence

Blood pressure and metabolic effects of acetyl-L-carnitine in type 2 diabetes: DIABASI randomized controlled trial

Context: Acetyl-L-carnitine (ALC), a mitochondrial carrier involved in lipid oxidation and glucose metabolism, decreased systolic blood pressure (SBP), and ameliorated insulin sensitivity in hypertensive nondiabetic subjects at high cardiovascular risk. Objective: To assess the effects of ALC on SBP and glycemic and lipid control in patients with hypertension, type 2 diabetes mellitus (T2D), and dyslipidemia on background statin therapy. Design: After 4-week run-in period and stratification according to previous statin therapy, patients were randomized to 6-month, double-blind treatment with ALC or placebo added-on simvastatin. Setting: Five diabetology units and one clinical research center in Italy. Patients: Two hundred twenty-nine patients with hypertension and dyslipidemic T2D &gt; 40 years with stable background antihypertensive, hypoglycemic, and statin therapy and serum creatinine &lt; 1.5 mg/ dL. Interventions: Oral ALC 1000 mg or placebo twice daily on top of stable simvastatin therapy. Outcome and Measures: Primary outcome was SBP. Secondary outcomes included lipid and glycemic profiles. Total-body glucose disposal rate and glomerular filtration rate were measured in subgroups by hyperinsulinemic-euglycemic clamp and iohexol plasma clearance, respectively. Results: SBP did not significantly change after 6-month treatment with ALC compared with placebo (-2.09mmHg vs-3.57mmHg, P = 0.9539). Serum cholesterol, triglycerides, and lipoprotein(a), as well as blood glucose, glycated hemoglobin, fasting insulin levels, homeostatic model assessment of insulin resistance index, glucose disposal rate, and glomerular filtration rate did not significantly differ between treatments. Adverse events were comparable between groups. Conclusions: Six-month oral ALC supplementation did not affect blood pressure, lipid and glycemic control, insulin sensitivity and kidney function in hypertensive normoalbuminuric and microalbuminuric T2D patients on background statin therapy

In vitro anti-cancer activity of a polyherbal preparation, VEDICINALS®9, against A549 human lung adenocarcinoma cells

PurposeNon-small cell lung cancer (NSCLC) is among the leading causes of morbidity and mortality worldwide. Despite the availability of several treatment options, the five-year survival rate of NSCLC is extremely low (&lt;20%). This underlines the necessity of more effective therapeutic alternatives. In this context, plant-derived extracts and bioactive molecules extracted from plants, known collectively as phytoceuticals, represent an extremely variegated source of bioactive compounds with potent anticancer potential. In the present study, we tested the in vitro anticancer activity of a polyherbal preparation, VEDICINALS®9, containing nine different bioactive principles extracted by medicinal plants.MethodsThe anticancer activity of VEDICINALS®9 was investigated by measuring its impact on A549 human NSCLC cell proliferation (MTT assay and trypan blue staining), migration (wound healing assay and transwell chamber assay) and by measuring the impact on the expression of cancer-related proteins (Human XL Oncology Protein Array).ResultsWe show that VEDICINALS®9 at a concentration of 0.2% v/v has potent anticancer effect, significantly inhibiting A549 cell proliferation and migration. Mechanistically, this was achieved by downregulating the expression of proteins involved in cancer cell proliferation (Axl, FGF basic, enolase 2, progranulin, survivin) and migration (Dkk-1, cathepsins B and D, BCL-x, amphiregulin, CapG, u-plasminogen activator). Furthermore, treatment with VEDICINALS®9 resulted in increased expression of the oncosuppressor protein p53 and of the angiogenesis inhibitor endostatin.ConclusionsTaken together, our results provide proof of principle of the potent anticancer activity of the polyherbal preparation VEDICINALS®9, highlighting its enormous potential as an alternative or adjuvant therapy for lung cancer.</p

Angiotensin-Neprilysin Inhibition and Left Ventricular Assist Device Therapy:Primary Results of the ENVAD-HF Trial

Background: The role of heart failure–specific therapies in left ventricular assist device (LVAD) recipients is unclear, and observational data suggest improved outcomes with neurohormonal blockers. Objectives: ENVAD-HF (Multicenter, Randomized, Open-Label, Parallel Group, Study to Evaluate the Use of Sacubitril/Valsartan in HeartMate 3 LVAD Recipients) sought to evaluate the safety and tolerability of the angiotensin-neprilysin inhibitor sacubitril/valsartan vs standard of care (SOC) for managing blood pressure (BP) in HeartMate 3 LVAD recipients. Methods:ENVAD-HF was a prospective multicenter, randomized, open-label study of sacubitril/valsartan vs SOC for managing BP (mean arterial pressure goal: 75-90 mm Hg) in stable LVAD recipients with 12-month follow-up. The composite primary endpoint was time to death, deterioration in renal function, hyperkalemia, or symptomatic hypotension leading to drug withdrawal. Exploratory endpoints included clinical and biomarker assessments and patient-reported outcomes. Results: In 60 randomized patients (30 in each arm), sacubitril/valsartan compared with SOC demonstrated an HR of 0.42 (95% CI: 0.08-2.18; P = 0.30) for the primary endpoint at 12 months. Two primary endpoints were reached in the sacubitril/valsartan group (1 death and 1 symptomatic hypotension event) compared with 5 in the SOC group (2 deaths, 2 worsening renal function events, and 1 symptomatic hypotension event). Numerical trends in favor of sacubitril/valsartan were noted for other exploratory endpoints, including a reduced number of BP medications (difference: −1.09 [95% CI: −1.52 to −0.66]; P &lt; 0.0001) and a significantly better Kansas City Cardiomyopathy Questionnaire–Overall Summary Score (improvement: +10.6 [95% CI: 2.6-18.7]; P = 0.011). Conclusions: ENVAD-HF, a prospective randomized controlled trial of angiotensin-neprilysin inhibition in stable HeartMate 3 LVAD recipients, demonstrated the safety and tolerability of this therapy in this unique population. The trial forms the basis for a pivotal trial to investigate the usefulness of HF-specific therapies in the LVAD population.</p