Neurocomputing strategies in structural design — on analysing weights of feedforward neural networks

The sequel of two papers explores the applicability of selected neurocomputing strategies in the optimization of structural systems. The present paper describes the use of interconnection weights of a multilayer, feedforward neural network to extract information pertinent to a design space modelled by such a network. It is shown that aweights analysis provides a technique to assess the effect of all input quantities on a given output. Such dependencies are expressed in the form of atransition matrix, and their evaluation is reduced to the inspection of elements of a matrix row. Explicit formulae are derived for networks with one and two hidden layers and can easily be generalized to networks with an arbitrary number of hidden layers. In addition to its use as a tool to partition design spaces, the weights analysis may be employed to assist in determining the size of hidden layers and an adequate number of training patterns (input-output pairs). Several numerical examples from the field of structural analysis are provided, and the paper underscores the utility of the present technique in decomposition driven optimal design; such optimization is treated in full in the companion paper.     

The Importance of Immunological Disorders in the Pathogenesis of Lichen Sclerosus in Pediatric Patients: A Systematic Review

Lichen sclerosus (LS) is defined as a chronic mucocutaneous inflammatory disease with a localization predominantly to the anus and genitals (vulvar sclerosus (VLS)). Pediatric lichen sclerosus (LS) is a chronic inflammatory skin condition with predilection for the anogenital area that if untreated can lead to scarring. Vulvar LS is characterized by two peaks in incidence: it occurs in prepubertal girls and in postmenopausal women. To date, several mechanisms and risk factors have been proposed in the pathogenesis of pediatric vulvar LS; however, the etiology of this condition is still not fully understood and constitutes a challenge for scientists and clinicians. The presented research aimed to systematically review the existing literature on the pathogenesis of pediatric LS and to identify possible underlying autoimmune mechanisms and molecular networks. The clinical presentation of pediatric lichen sclerosus and available treatment modalities are also presented to acquaint a broader audience with this underdiagnosed and undertreated condition. As a result of our review, we discuss several potential mechanisms, molecules, and pathways that have been recognized in this disease. The purpose of our review was also to summarize what we can induce in further studies, which will ultimately help to identify the mechanism responsible for the disease and aid in the development of new, more effective treatment strategies for diagnosis and treatment by clinicians and researchers.     

CTLA-4 Expression Is a Promising Biomarker of Idiopathic Pulmonary Arterial Hypertension and Allows Differentiation of the Type of Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) is an increasingly frequently diagnosed disease, the molecular mechanisms of which have not been thoroughly investigated. The aim of our study was to investigate subpopulations of lymphocytes to better understand their role in the molecular pathomechanisms of various types of PAH and to find a suitable biomarker that could be useful in the differential diagnosis of PAH. Using flow cytometry, we measured the frequencies of lymphocyte subpopulations CD4+CTLA-4+, CD8+ CTLA-4+ and CD19+ CTLA-4+ in patients with different types of PAH, namely pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH), pulmonary arterial hypertension associated with connective tissue disorders (CTD-PAH), chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH), and in an age- and sex-matched control group in relation to selected clinical parameters. Patients in the iPAH group had the significantly highest percentage of CD4+CTLA-4+ T lymphocytes among all PAH groups, as compared to those in the control group (p < 0.001), patients with CTEPH (p < 0.001), CTD-PAH (p < 0.001) and CHD-PAH (p < 0.01). In iPAH patients, the percentages of CD4+CTLA-4+ T cells correlated strongly positively with the severity of heart failure New York Heart Association (NYHA) Functional Classification (r = 0.7077, p < 0.001). Moreover, the percentage of B CD19+CTLA-4+ cells strongly positively correlated with the concentration of NT-proBNP (r = 0.8498, p < 0.001). We have shown that statistically significantly higher percentages of CD4+CTLA-4+ (p ≤ 0.01) and CD8+ CTLA-4+ (p ≤ 0.001) T cells, measured at the time of iPAH diagnosis, were found in patients who died within 5 years of the diagnosis, which allows us to consider both of the above lymphocyte subpopulations as a negative prognostic/predictive factor in iPAH. CTLA-4 may be a promising biomarker of noninvasive detection of iPAH, but its role in planning the treatment strategy of PAH remains unclear. Further studies on T and B lymphocyte subsets are needed in different types of PAH to ascertain the relationships that exist between them and the disease.     

Acute Kidney Injury in COVID-19

COVID-19 is mainly considered a respiratory illness, but since SARS-CoV-2 uses the angiotensin converting enzyme 2 receptor (ACE2) to enter human cells, the kidney is also a target of the viral infection. Acute kidney injury (AKI) is the most alarming condition in COVID-19 patients. Recent studies have confirmed the direct entry of SARS-CoV-2 into the renal cells, namely podocytes and proximal tubular cells, but this is not the only pathomechanism of kidney damage. Hypovolemia, cytokine storm and collapsing glomerulopathy also play an important role. An increasing number of papers suggest a strong association between AKI development and higher mortality in COVID-19 patients, hence our interest in the matter. Although knowledge about the role of kidneys in SARS-CoV-2 infection is changing dynamically and is yet to be fully investigated, we present an insight into the possible pathomechanisms of AKI in COVID-19, its clinical features, risk factors, impact on hospitalization and possible ways for its management via renal replacement therapy.     

Palm Oil-Rich Diet Affects Murine Liver Proteome and S-Palmitoylome

Palmitic acid (C16:0) is the most abundant saturated fatty acid in animals serving as a substrate in synthesis and β-oxidation of other lipids, and in the modification of proteins called palmitoylation. The influence of dietary palmitic acid on protein S-palmitoylation remains largely unknown. In this study we performed high-throughput proteomic analyses of a membrane-enriched fraction of murine liver to examine the influence of a palm oil-rich diet (HPD) on S-palmitoylation of proteins. HPD feeding for 4 weeks led to an accumulation of C16:0 and C18:1 fatty acids in livers which disappeared after 12-week feeding, in contrast to an accumulation of C16:0 in peritoneal macrophages. Parallel proteomic studies revealed that HPD feeding induced a sequence of changes of the level and/or S-palmitoylation of diverse liver proteins involved in fatty acid, cholesterol and amino acid metabolism, hemostasis, and neutrophil degranulation. The HPD diet did not lead to liver damage, however, it caused progressing obesity, hypercholesterolemia and hyperglycemia. We conclude that the relatively mild negative impact of such diet on liver functioning can be attributed to a lower bioavailability of palm oil-derived C16:0 vs. that of C18:1 and the efficiency of mechanisms preventing liver injury, possibly including dynamic protein S-palmitoylation.     

Role of HMOX1 Promoter Genetic Variants in Chemoresistance and Chemotherapy Induced Neutropenia in Children with Acute Lymphoblastic Leukemia

Whilst the survival rates of childhood acute lymphoblastic leukemia (ALL) have increased remarkably over the last decades, the therapy resistance and toxicity are still the major causes of treatment failure. It was shown that overexpression of heme oxygenase-1 (HO-1) promotes proliferation and chemoresistance of cancer cells. In humans, the HO-1 gene (HMOX1) expression is modulated by two polymorphisms in the promoter region: (GT)n-length polymorphism and single-nucleotide polymorphism (SNP) A(−413)T, with short GT repeat sequences and 413-A variants linked to an increased HO-1 inducibility. We found that the short alleles are significantly more frequent in ALL patients in comparison to the control group, and that their presence may be associated with a higher risk of treatment failure, reflecting the role of HO-1 in chemoresistance. We also observed that the presence of short alleles may predispose to develop chemotherapy-induced neutropenia. In case of SNP, the 413-T variant co-segregated with short or long alleles, while 413-A almost selectively co-segregated with long alleles, hence it is not possible to determine if SNPs are actually of phenotypic significance. Our results suggest that HO-1 can be a potential target to overcome the treatment failure in ALL patients.     

Arylene bisimides with triarylamine N-substituents as new solution processable organic semiconductors: Synthesis,spectroscopic, electrochemical and electronic properties

New solution processable organic semiconductors, consisting of pyrromelitic, naphthalene or perylene bisimide core and triarylamine N-substituents, have been synthesized. All three compounds are electrochemically active and undergo quasi-reversible oxidation and reduction as evidenced by cyclic voltammetry investigations. The oxidation process involves the transformation of the triarylamine substituents into radical cations as proven spectroscopically and spectroelectrochemically. The reduction process occurs at the arylene bisimide core leading to the formation of a radical anion and eventually a dianion in the second step. These findings are in perfect agreement with the DFT calculations which show that in the synthesized molecules the HOMO orbital is located on the triarylamine moiety whereas the LUMO one on the bisimide core. In all molecules studied the electrochemically determined ionization potential (IP) is slightly higher than 5.0 eV whereas in naphthalene and perylene derivatives the electron affinity (EA) is close to ?3.9 eV. These values fulfill the requirements for n-type (electron) semiconductors in air operating n-channel field effect transistors (FETs) as well as for p-type (hole) conductors in p-channel FETs. To verify whether the newly synthesized compounds exhibit the expected electrical transport properties all organic (CYTOP dielectric) test transistors were fabricated. All three semiconductors showed no field effect in the n-channel configuration. To the contrary, they could be used in p-channel FETs showing, in the saturation regime, the hole mobility approaching 10^?4 cm² V^?1 s^?1 – the value which slightly exceeds that measured for low molecular weight, amorphous triarylamine semiconductors.     

Distribution of impurities in lithium iodate crystals

The ability of single crystals α - lithium iodate to transmit polarized light in the wavelength band 0.25 to 0.7 μm has been studied. An impurity absorption band has been observed near the fundamental optical absorption edge. At the chosen conditions for crystal growth, the extent to which impurities were absorbed into the crystal lattice was a function of distance from the original seed crystal and so was dependent on the position of the crystal relative to the beam and the polarization of the beam.