First order sensitivity analysis of flexible multibody systems using absolute nodal coordinate formulation

Design sensitivity analysis of flexible multibody systems is important in optimizing the performance of mechanical systems. The choice of coordinates to describe the motion of multibody systems has a great influence on the efficiency and accuracy of both the dynamic and sensitivity analysis. In the flexible multibody system dynamics, both the floating frame of reference formulation (FFRF) and absolute nodal coordinate formulation (ANCF) are frequently utilized to describe flexibility, however, only the former has been used in design sensitivity analysis. In this article, ANCF, which has been recently developed and focuses on modeling of beams and plates in large deformation problems, is extended into design sensitivity analysis of flexible multibody systems. The Motion equations of a constrained flexible multibody system are expressed as a set of index-3 differential algebraic equations (DAEs), in which the element elastic forces are defined using nonlinear strain-displacement relations. Both the direct differentiation method and adjoint variable method are performed to do sensitivity analysis and the related dynamic and sensitivity equations are integrated with HHT-I3 algorithm. In this paper, a new method to deduce system sensitivity equations is proposed. With this approach, the system sensitivity equations are constructed by assembling the element sensitivity equations with the help of invariant matrices, which results in the advantage that the complex symbolic differentiation of the dynamic equations is avoided when the flexible multibody system model is changed. Besides that, the dynamic and sensitivity equations formed with the proposed method can be efficiently integrated using HHT-I3 method, which makes the efficiency of the direct differentiation method comparable to that of the adjoint variable method when the number of design variables is not extremely large. All these improvements greatly enhance the application value of the direct differentiation method in the engineering optimization of the ANCF-based flexible multibody systems.     

Influence of the tank shape on the electrostatic field generated by space charge

Contents The paper provides results of calculations of electric field for parallelepiped and ellipsoidal tanks. The calculations reported in the paper indicate that even at a relatively small volumetric density of charge (q=100 C/m³) the intensity of the electric field in the vapour/air mixture may exceed the critical value (3 MV/m), which may cause a spark discharge. They also show the maximum of the electric field intensity, the maximum potential and energy after the change in shape of the tank, while the volume of the stored liquid remains the same. The calculations of these quantities can be used as a basis for reduction or elimination of the electrostatic ignition hazard.

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Einfluß der Behälterform auf das elektrostatische Feld infolge einer Raumladung

Übersicht Der Beitrag behandelt elektrische Felder in Behältern von der Form eines Parallelepipeds und eines Ellipsoids. Die Berechnungen zeigen, daß selbst bei relativ kleinen Werten der Raumladung (100 C/m³) die elektrische Feldstärke im Dampf-Luftgemisch den kritischen Wert (3 ÖMV/m) überschreiten und einen Durchschlag verursachen kann. Außerdem werden die Maxima der elektrischen Feldstärke, des Potentials und der Energie in Abhängigkeit der Behälterform angegeben unter der Voraussetzung, daß das Volumen der enthaltenen Flüssigkeit konstant bleibt. Die Rechenergebnisse lassen sich als Basis für die Verminderung oder Elimination der Gefahr von Überschlägen verwenden.

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List of symbols A, B, C factors of the ellipsoidal tank - a, b, H length, width and height of the parallelepiped tank, respectively [m] - E electrical field strength [V/m] - h liquid height in the tank [m] - q volumetric charge density [C/m³] - R radius of the sphere [m] - V electric potential [V] - W _E electric field energy [J] - V volume of the tank - _r relative dielectric constant - _O absolute dielectric constant 8.854×10^–12 [As/Vm]     

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.     

Inhibitors of Cyclin-Dependent Kinases: Types and Their Mechanism of Action

Recent studies on cyclin-dependent kinase (CDK) inhibitors have revealed that small molecule drugs have become very attractive for the treatment of cancer and neurodegenerative disorders. Most CDK inhibitors have been developed to target the ATP binding pocket. However, CDK kinases possess a very similar catalytic domain and three-dimensional structure. These features make it difficult to achieve required selectivity. Therefore, inhibitors which bind outside the ATP binding site present a great interest in the biomedical field, both from the fundamental point of view and for the wide range of their potential applications. This review tries to explain whether the ATP competitive inhibitors are still an option for future research, and highlights alternative approaches to discover more selective and potent small molecule inhibitors.     

Subcellular Localization of Acyl-CoA: Lysophosphatidylethanolamine Acyltransferases (LPEATs) and the Effects of Knocking-Out and Overexpression of Their Genes on Autophagy Markers Level and Life Span of A. thaliana

Arabidopsis thaliana possesses two acyl-CoA:lysophosphatidylethanolamine acyltransferases, LPEAT1 and LPEAT2, which are encoded by At1g80950 and At2g45670 genes, respectively. Both single lpeat2 mutant and double lpeat1 lpeat2 mutant plants exhibit a variety of conspicuous phenotypes, including dwarfed growth. Confocal microscopic analysis of tobacco suspension-cultured cells transiently transformed with green fluorescent protein-tagged versions of LPEAT1 or LPEAT2 revealed that LPEAT1 is localized to the endoplasmic reticulum (ER), whereas LPEAT2 is localized to both Golgi and late endosomes. Considering that the primary product of the reaction catalyzed by LPEATs is phosphatidylethanolamine, which is known to be covalently conjugated with autophagy-related protein ATG8 during a key step of the formation of autophagosomes, we investigated the requirements for LPEATs to engage in autophagic activity in Arabidopsis. Knocking out of either or both LPEAT genes led to enhanced accumulation of the autophagic adaptor protein NBR1 and decreased levels of both ATG8a mRNA and total ATG8 protein. Moreover, we detected significantly fewer membrane objects in the vacuoles of lpeat1 lpeat2 double mutant mesophyll cells than in vacuoles of control plants. However, contrary to what has been reported on autophagy deficient plants, the lpeat mutants displayed a prolonged life span compared to wild type, including delayed senescence.     

Novel Cell Permeable Polymers of N-Substituted L-2,3-Diaminopropionic Acid (DAPEGs) and Cellular Consequences of Their Interactions with Nucleic Acids

The present study aimed to synthesize novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues (DAPEGs) and investigate their cell permeability, cytotoxicity, and DNA-binding ability. The most efficient cell membrane-penetrating compounds (O2Oc-Dap(GO2)_n-O2Oc-NH₂, where n = 4, 6, and 8) showed dsDNA binding with a binding constant in the micromolar range (0.3, 3.4, and 0.19 µM, respectively) and were not cytotoxic to HB2 and MDA-MB-231 cells. Selected compounds used in the transfection of a GFP plasmid showed high transfection efficacy and minimal cytotoxicity. Their interaction with plasmid DNA and the increasing length of the main chain of tested compounds strongly influenced the organization and shape of the flower-like nanostructures formed, which were unique for 5/6-FAM-O2Oc-[Dap(GO2)]₈-O2Oc-NH₂ and typical for large proteins.     

Mediator-Related Symptoms and Anaphylaxis in Children with Mastocytosis

Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier’s sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.     

The Role of TNF-α and Anti-TNF-α Agents during Preconception,Pregnancy, and Breastfeeding

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.     

基于字典的DNA序列压缩算法研究及应用*

在现有DNA序列数据压缩算法的基础上,以DNA序列数据的存储效率及生物学解释综合考虑,设计并实现了基于字典的DNA序列压缩算法DNADCompress.算法核心包括重复子串字典建立、字典项筛选、字串压缩编码三方面.实验数据表明,数据压缩算法压缩效果达到常用DNA序列压缩算法水平,并为序列生物学解释提供了基础.     

Computer-Aided Search for 5-Arylideneimidazolone Anticancer Agents Able To Overcome ABCB1-Based Multidrug Resistance

ABCB1 modulation is an interesting strategy in the search for new anticancer agents that can overcome multidrug resistance (MDR). Hence, 17 new 5-arylideneimidazolones containing an amine moiety, as potential ABCB1 inhibitors, were designed, synthesized, and investigated. The series was tested in both parental (PAR) and multidrug-resistant (MDR) ABCB1-overexpressing T-lymphoma cancer cells using cytotoxicity assays. The ABCB1-modulating activity was examined in rhodamine 123 accumulation tests, followed by Pgp-Glo™ Assay to determine the influence of the most active compounds on ATPase activity. Lipophilic properties were assessed both, in silico and experimentally (RP-TLC). Pharmacophore-based molecular modelling toward ABCB1 modulation was performed. The studies allowed the identification of anticancer agents (p-fluorobenzylidene derivatives) more potent than doxorubicin, with highly selective action on MDR T-lymphoma cells (selectivity index >40). Most of the investigated compounds showed ABCB1-modulating action; in particular, two 5-benzyloxybenzylidene derivatives displayed activity nearly as strong as that of tariquidar.