Search

Formation of stable actin filaments, critically important for actin functions, is determined by the ionic strength of the solution. However, not much is known about the elements of the actin fold involved in ionic-strength-dependent filament stabilization. In this work, F-actin was destabilized by Cu2+ binding to Cys374, and the effects of solvent conditions on the dynamic properties of F-actin were correlated with the involvement of Segment 227-235 in filament stabilization. The results of our work show that the presence of Mg2+ at the high-affinity cation binding site of Cu-modified actin polymerized with MgCl2 strongly enhances the rate of filament subunit exchange and promotes the filament instability. In the presence of 0.1 M KCl, the filament subunit exchange was 2–3-fold lower than that in the MgCl2-polymerized F-actin. This effect correlates with the reduced accessibility of the D-loop and Segment 227-235 on opposite filament strands, consistent with an ionic-strength-dependent conformational change that modulates involvement of Segment 227-235 in stabilization of the intermonomer interface. KCl may restrict the mobility of the α-helix encompassing part of Segment 227-235 and/or be bound to Asp236 at the boundary of Segment 227-235. These results provide experimental evidence for the involvement of Segment 227-235 in salt-induced stabilization of contacts within the actin filament and suggest that they can be weakened by mutations characteristic of actin-associated myopathies.

This study aims to analyze the influence of the rolling process on the microstructure and corrosion properties of the Mg/Al bimetallic bars obtained by the explosive welding method. The bars investigated were rolled using two different types of rolling: classical rolling (Variant I) and modified rolling (Variant II). Two different temperatures (300 °C and 400 °C) for each of the variables were applied as well. In this study, rods with an aluminum plating layer constituting 16.8% of the cross-sectional area and an average thickness of about 0.93 mm were investigated. Based on the revealed results, it was found that after the rolling process, the material shows clearly lower values of both icor and current in the passive range. In the joint zone of Mg/Al rods rolled at 400 °C, Al3Mg2 and Mg17Al12 intermetallic phases are distinguished, localized next to the Mg core, and characterized by columnar, coarser grains. In the transition zone closer to the Al layer, only the Al3Mg2 phase is revealed, characterized by a refined, small grain size.

The aim of this investigation was to identify the effect of rolling at room temperature and under cryogenic conditions on selected properties and the microstructure of the AA2519-T62 aluminum alloy. The rolling processes were conducted with different variants of asymmetry (1.0—symmetry rolling; 1.2, 1.4 and 1.6). The investigation of the obtained samples involves microhardness distribution, microstrains, and microstructure observations using light and transmission electron microscopes. Both rolling at room temperature and under cryogenic conditions increased the micro-hardness of AA2519-T62 by at least 10%. The highest reported increase (25%) was obtained for the sample rolled at room temperature in the symmetry rolling process. The samples rolled under cryogenic conditions are characterized by a lower increase in microhardness than samples rolled at room temperature and by significantly lower values of microstrains. The application of rolling with the asymmetry ratio remaining within the range of 1.2–16 only slightly affected the microhardness values of the samples rolled at room temperature and under cryogenic conditions with respect to conventional symmetrical rolling.

The paper presents the theoretical and experimental research conducted to date regarding the possibility of obtaining round bars from AZ31 magnesium alloy with a bimodal structure rolled in the radial shear rolling process (RSR) technology. There is no analysis of the impact of the deformation path (distribution of deformation in individual passes) on the mechanical properties and the obtained bar structure. The feedstock, namely, AZ31 magnesium alloy round bars with a diameter of 30 mm, were rolled in RSR to the final diameter of 15 mm with different levels of deformation in successive passes, at a temperature of 400 °C. The bars obtained as a result of the RSR rolling process have different hardness on the cross-section as well as a characteristic gradient grain size distribution. Based on the conducted research, it can be concluded that the use of a larger number of passes with a smaller cross-section reduction will result in an improved formation of a bimodal structure consisting of a highly fragmented near-surface structure and in the half of the radius of the structure of fragmented grains at the boundaries of larger grains.

The paper presents the results of experimental tests of the rolling process of Mg/Al bimetallic bars in two systems of classic passes (horizontal oval-circle-horizontal oval-circle variant I) and modified (multi-radial horizontal oval-multi-radial vertical oval-multi-radial horizontal oval-circle-variant II). The feedstock in the form of round bimetallic bars with a diameter of 22 mm and 30% of the outer aluminum layer was made through explosive welding. The bimetallic bars consisted of an AZ31 magnesium core and a 1050A aluminum outer layer. Bars with a diameter of 17 mm were obtained as a result of rolling in four passes. The rolling process in the passes was conducted at two temperatures of 300 and 400 °C. Based on the analysis of the test results, it was found that the use of modified passes and a lower rolling temperature (300 °C) ensures a more homogenous distribution of the plating layer around the circumference of the core and results in an even grain decreasing, which improves the corrosion resistance of bimetallic bars compared to rolling bars in a classic system of passes and at a higher temperature (400 °C).

Controlling stability of dynamical systems is one of the most important challenges in science and engineering. Hence, there appears to be continuous need to study and develop numerical algorithms of control methods. One of the most frequently applied invariants characterizing systems’ stability are Lyapunov exponents (LE). When information about the stability of a system is demanded, it can be determined based on the value of the largest Lyapunov exponent (LLE). Recently, we have shown that LLE can be estimated from the vector field properties by means of the most basic mathematical operations. The present article introduces new methods of LLE estimation for continuous systems and maps. We have shown that application of our approaches will introduce significant improvement of the efficiency. We have also proved that our approach is simpler and more efficient than commonly applied algorithms. Moreover, as our approach works in the case of dynamical maps, it also enables an easy application of this method in noncontinuous systems. We show comparisons of efficiencies of algorithms based our approach. In the last paragraph, we discuss a possibility of the estimation of LLE from maps and for noncontinuous systems and present results of our initial investigations.

Mycoplankton of Vistula River and its main tributaries biomass as well as the number and morphotype diversity was studied in summer and autumn 2011. Summer mycoplankton biomass was within the range of 0.2 - 0.5 μg/l, while in the autumn it was two times wider range (0.1 - 1.3 μg/l). The number of fungi in river water most often did not exceed 1000 - 2000 CFU/ml. Fungi colonies isolated from rivers water were sensitive to the commonly used amphotericine B (10 μg) and gentamicin (10 μg). It seems to be plausible that aquatic fungi can acquire immunity to drugs as a result of horizontal transfer of a gene responsible for drug resistance or as an effect of antibiotics and antimycotics getting into the aquatic ecosystems from wastewaters. [ABSTRACT FROM AUTHOR]

DOI: http://doi.org/10.26333/sts.xxxii1.07 Celem niniejszego artykułu jest wyznaczenie kierunków badań edukacyjnych w działalności Polskiej Szkoły Argumentacji (http://argdiap.pl) oraz zainicjowanie dyskusji w polskim środowisku filozoficznym i wśród nauczycieli szkolnych. Opierając się na dotychczasowej działalności Szkoły w badaniach nad edukacją i tworzeniu standardów nauczania sztuki argumentacji (część 1) oraz wątków edukacyjnych wyeksponowanych podczas XV konferencji ArgDiaP (część 2), formułujemy postulaty, które mogą stanowić część planu edukacyjnego w najbliższych latach (część 3). Realizacja tych postulatów może stanowić punkt odniesienia do realizacji długoterminowego planu tworzenia standardów nauczania sztuki argumentacji (część 4).

DOI: http://doi.org/10.26333/sts.xxxii1.04 Arystoteles wyodrębnił w Organonie dwa rodzaje rozumowań: analityczne i dialektyczne. Badaniami rozumowań analitycznych, które podjął w Analitykach I i II, zasłużył sobie na miano ojca logiki formalnej. Według Chaima Perelmana, współczesnym logikom umknął z pola widzenia fakt, że rozważania Arystotelesa na temat rozumowań dialektycznych – podjęte w Topikach, Retoryce i O dowodach sofistycznych – czynią zeń także ojca teorii argumentacji. Niniejszy artykuł jest próbą odpowiedzi na tę diagnozę. Jego celem jest potwierdzenie tezy Perelmana o jednorodności Arystotelesowskiej koncepcji sylogizmu teoretycznego i praktycznego. W tym potwierdzeniu kluczową rolę odgrywa pojęcie entymematu. W artykule odpowiadamy na pytanie, jakie miejsce zajmuje ono w teorii retoryki Arystotelesa i porównujemy je z ogólnym pojęciem sylogizmu. Szkicujemy też strukturę argumentacji przez entymemat oraz przedstawiamy dwa typy entymematów omawiane przez Arystotelesa: pozorne i obalające.

This paper aimed to propose the fabrication of light, Al/Mg/Al multilayered composite. Initially prepared three-layered feedstock was subjected to deformation during four rolling cycles (passes) using the conventional and modified accumulative roll bonding (ARB) processes at 400 °C, thanks to which 24-layered composite materials were produced. The modification of the ARB process was based on the application of the rotational speed asymmetry (asymmetric accumulative roll bonding, AARB). It was adopted that the initial thickness of the composite stack amounted to 3 mm (1 mm for each composite). The rolling was done in the laboratory duo D150 rolling mill with the application of the roll rotational speed asymmetry and symmetry av = 1.0 (ARB) and av = 1.25 and 1.5 (AARB). In this manuscript, it was proved that introducing the asymmetry into the ARB process for the tested Al/Mg/Al composite has an impact on the activation of additional shear bands, which results in higher fragmentation of the structure in comparison to the symmetrical process. Due to the application of the AARB, the reduction of the grain size by 17% was obtained, in comparison to the conventional ARB. Not to mention that at the same time there was an increase in strength of the fabricated multilayered composite.

The paper describes an investigation of an explosively welded Mg/Al/Ti multilayer composite. Following the welding, the composite was subjected to hot-rolling in three different temperatures: 300 °C, 350 °C and 400 °C, with a total relative strain of 30%. The rolling speed was 0.2 m/s. The investigation of the composite properties involves microhardness analysis and mini-specimen tensile tests of the joints. The composite Mg/Al and Al/Ti bonds in the as-welded state and after rolling in 400 °C were subjected to microstructure analysis using scanning electron (SEM) and transmission electron microscopy (TEM). In the Al/Ti interface, the presence of melted zones with localized intermetallic precipitates has been reported in the as-welded state, and it has been stated that hot-rolling results in precipitation of intermetallic particles from the melted zone. The application of the hot-rolling process causes the formation of a continuous layer in the Mg/Al joint, consisting of two intermetallic phases, Mg2Al3 (β) and Mg17Al12 (γ).

A genome-wide association scan of type 1 diabetic patients from the GoKinD collections previously identified four novel diabetic nephropathy susceptibility loci that have subsequently been shown to be associated with diabetic nephropathy in unrelated patients with type 2 diabetes. To expand these findings, we examined whether single nucleotide polymorphisms (SNPs) at these susceptibility loci were associated with diabetic nephropathy in patients from the Joslin Study of Genetics of Nephropathy in Type 2 Diabetes Family Collection. Six SNPs across the four loci identified in the GoKinD collections and 7 haplotype tagging SNPs, were genotyped in 66 extended families of European ancestry. Pedigrees from this collection contained an average of 18.5 members, including 2 to 14 members with type 2 diabetes. Among diabetic family members, the 9q21.32 locus approached statistical significance with advanced diabetic nephropathy (P = 0.037 [adjusted P = 0.222]). When we expanded our definition of diabetic nephropathy to include individuals with high microalbuminuria, the strength of this association improved significantly (P = 1.42×10−3 [adjusted P = 0.009]). This same locus also trended toward statistical significance with variation in urinary albumin excretion in family members with type 2 diabetes (P = 0.032 [adjusted P = 0.192]) and in analyses expanded to include all relatives (P = 0.019 [adjusted P = 0.114]). These data increase support that SNPs identified in the GoKinD collections on chromosome 9q21.32 are true diabetic nephropathy susceptibility loci.

Background: In patients with Type 1 Diabetes (T1D) who develop microalbuminuria, progressive decline in glomerular filtration rate (GFR) may be initiated by leakage into the urine of toxic proteins (txUPs). This study tested this hypothesis. Methods: After archiving baseline urine, we followed T1D patients with microalbuminuria for 8–12 years to distinguish those in whom GFR declined (Decliners) and those in whom it remained stable (Non-decliners). Human proximal tubular cells (HK-2 cells) were grown in serum-free medium enriched with pooled urines from Decliners or Non-decliners. We determined genome-wide expression profiles in extracted mRNA. Results: The two pooled urines induced differential expression of 312 genes. In terms of gene ontology, molecular functions of the 119 up-regulated genes were enriched for protein binding and peptidase inhibitor activities. Their biologic processes were enriched for defense response, responses to other organisms, regulation of cellular processes, or response to stress or stimulus, and programmed cell death. The 195 down-regulated genes were disproportionately represented in molecular functions of cation binding, hydrolase activity, and DNA binding. They were disproportionately represented in biological processes for regulation of metabolic processes, nucleic acid metabolic processes, cellular response to stress and macromolecule biosynthesis. The set of up-regulated genes in HK-2 cells overlaps significantly with sets of over-expressed genes in tubular and interstitial compartments of kidney biopsies from patients with advanced DN (33 genes in one study and 25 in the other compared with 10.3 expected by chance, p<\(10^{−9}\) and p<\(10^{−4}\), respectively). The overlap included genes encoding chemokines and cytokines. Overlap of down-regulated genes was no more than expected by chance. Conclusions: Molecular processes in tubules and interstitium seen in advanced diabetic nephropathy can be induced in vitro by exposure to urine from patients with minimal microalbuminuria who subsequently developed progressive renal function decline, presumably due to putative txUPs.

Introduction: Recent studies demonstrated that circulating fibroblast growth factor (FGF)-23 was associated with risk of end stage renal disease (ESRD) and mortality. This study aims to examine whether the predictive effect of FGF-23 is independent from circulating levels of tumor necrosis factor receptor 1 (TNFR1), a strong predictor of ESRD in Type 2 diabetes (T2D). Methods: We studied 380 patients with T2D who were followed for 8–12 years and were used previously to examine the effect of TNFR1. Baseline plasma FGF-23 was measured by immunoassay. Results: During follow-up, 48 patients (13%) developed ESRD and 83 patients (22%) died without ESRD. In a univariate analysis, baseline circulating levels of FGF-23 and TNFR1 were significantly higher in subjects who subsequently developed ESRD or died without ESRD than in those who remained alive. In a Cox proportional hazard model, baseline concentration of FGF-23 was associated with increased risk of ESRD, however its effect was no longer significant after controlling for TNFR1 and other clinical characteristics (HR 1.3, p = 0.15). The strong effect of circulating level of TNFR1 on risk of ESRD was not changed by including circulating levels of FGF-23 (HR 8.7, p<0.001). In the Cox multivariate model, circulating levels of FGF-23 remained a significant independent predictor of all-cause mortality unrelated to ESRD (HR 1.5, p<0.001). Conclusions: We demonstrated that the effect of circulating levels of FGF-23 on the risk of ESRD is accounted for by circulating levels of TNFR1. We confirmed that circulating levels of FGF-23 have an independent effect on all-cause mortality in T2D.

The risk of end-stage renal disease (ESRD) remains high in patients with type 1diabetes and proteinuria; however, little is known about the rate of decline in their renal function. To help determine this we enrolled patients with 1 diabetes and proteinuria whose estimated glomerular filtration rate (eGFR) was normal (equal to or above 60 ml/min/1.73\(m^2\)). Using a minimum of 5 serial measurements of serum creatinine for 161 patients, we determined individual trajectories of eGFR change and the occurrence of ESRD during 5–18 years of follow-up. The rates were linear for 110 patients, for 24 the non-linear rate was mild enough to satisfy a linear model, and the rates were clearly non-linear for only 27 patients. Overall, in more than one third of patients, the eGFR decline was less than 3.5 ml/min/1.73\(m^2\) per year and the lifetime risk of ESRD could be considered negligible. In the remainder of patients, eGFR declined with widely different slopes and ESRD developed within 2 to 18 years. Based on up to five years observation when renal function was within the normal range, the estimates of early eGFR slope predicted the risk of ESRD during subsequent follow-up better than the baseline clinical characteristics of glycated hemoglobin, blood pressure, or the albumin to creatinine ratio. Thus, the early slope of eGFR decline in patients with type 1diabetes and proteinuria can be used to predict the risk of ESRD.

Objective: To examine the association between single nucleotide polymorphisms (SNPs) in the engulfment and cell motility 1 (ELMO1) gene, a locus previously shown to be associated with diabetic nephropathy in two ethnically distinct type 2 diabetic populations, and the risk of nephropathy in type 1 diabetes. Research Design and Methods: Genotypic data from a genome-wide association scan (GWAS) of the Genetics of Kidneys in Diabetes (GoKinD) study collection were analyzed for associations across the ELMO1 locus. In total, genetic associations were assessed using 118 SNPs and 1,705 individuals of European ancestry with type 1 diabetes (885 normoalbuminuric control subjects and 820 advanced diabetic nephropathy case subjects). Results: The strongest associations in ELMO1 occurred at rs11769038 (odds ratio [OR] 1.24; P = 1.7 × 10−3) and rs1882080 (OR 1.23; P = 3.2 × 10−3) located in intron 16. Two additional SNPs, located in introns 18 and 20, respectively, were also associated with diabetic nephropathy. No evidence of association for variants previously reported in type 2 diabetes was observed in our collection. Conclusions: Using GWAS data from the GoKinD collection, we comprehensively examined evidence of association across the ELMO1 locus. Our investigation marks the third report of associations in ELMO1 with diabetic nephropathy, further establishing its role in the susceptibility of this disease. There is evidence of allelic heterogeneity, contributed by the diverse genetic backgrounds of the different ethnic groups examined. Further investigation of SNPs at this locus is necessary to fully understand the commonality of these associations and the mechanism(s) underlying their role in diabetic nephropathy.

OBJECTIVE - The purpose of this study was to examine prospectively whether renal hyperfiltration is associated with the development of microalbuminuria in patients with type 1 diabetes, after taking into account known risk factors. RESEARCH DESIGN AND METHODS - The study group comprised 426 participants with normoalbuminuria from the First Joslin Kidney Study, followed for 15 years. Glomerular filtration rate was estimated by serum cystatin C, and hyperfiltration was defined as exceeding the 97.5th percentile of the sex-specific distribution of a similarly aged, nondiabetic population (134 and 149 ml/min per 1.73 m2 for men and women, respectively). The outcome was time to microalbuminuria development (multiple albumin excretion rate >30 μg/min). Hazard ratios (HRs) for microalbuminuria were calculated at 5, 10, and 15 years. RESULTS - Renal hyperfiltration was present in 24% of the study group and did not increase the risk of developing microalbuminuria. The unadjusted HR for microalbuminuria comparing those with and without hyperfiltration at baseline was 0.8 (95% CI 0.4–1.7) during the first 5 years, 1.0 (0.6–1.7) during the first 10 years, and 0.8 (0.5–1.4) during 15 years of follow-up. The model adjusted for baseline known risk factors including A1C, age at diagnosis of diabetes, diabetes duration, and cigarette smoking resulted in similar HRs. In addition, incorporating changes in hyperfiltration status during follow-up had minimal impact on the HRs for microalbuminuria. CONCLUSIONS - Renal hyperfiltration does not have an impact on the development of microalbuminuria in type 1 diabetes during 5, 10, or 15 years of follow-up.

OBJECTIVE—Despite extensive evidence for genetic susceptibility to diabetic nephropathy, the identification of susceptibility genes and their variants has had limited success. To search for genes that contribute to diabetic nephropathy, a genome-wide association scan was implemented on the Genetics of Kidneys in Diabetes collection. RESEARCH DESIGN AND METHODS—We genotyped 360,000 single nucleotide polymorphisms (SNPs) in 820 case subjects (284 with proteinuria and 536 with end-stage renal disease) and 885 control subjects with type 1 diabetes. Confirmation of implicated SNPs was sought in 1,304 participants of the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study, a long-term, prospective investigation of the development of diabetes- associated complications. RESULTS—A total of 13 SNPs located in four genomic loci were associated with diabetic nephropathy with P1105. The strongest association was at the FRMD3 (4.1 protein ezrin, radixin, moesin [FERM] domain containing 3) locus (odds ratio [OR]1.45, P5.0107). A strong association was also identified at the CARS (cysteinyl-tRNA synthetase) locus (OR 1.36, P3.1106). Associations between both loci and time to onset of diabetic nephropathy were supported in the DCCT/EDIC study (hazard ratio [HR]1.33, P0.02, and HR1.32, P 0.01, respectively). We demonstrated expression of both FRMD3 and CARS in human kidney. CONCLUSIONS—We identified genetic associations for susceptibility to diabetic nephropathy at two novel candidate loci near the FRMD3 and CARS genes. Their identification implicates previously unsuspected pathways in the pathogenesis of this important late complication of type 1 diabetes.

Objectives: Recently, an association was found between diabetic nephropathy and the D18S880 microsatellite, located in the carnosinase gene (CNDP1) on chromosome 18q. Alleles of this microsatellite encode for a variable number of leucine residues (from four to seven) in the leader peptide of the carnosinase precursor. The frequency of subjects homozygous for the five leucines was higher in control subjects than in case subjects in studies focusing on type 2 diabetic patients. To test whether this finding can be extended to type 1 diabetic patients, we carried out a comprehensive study on association between diabetic nephropathy and the D18S880 microsatellite and 21 additional SNPs that tagged the genomic region containing CNDP1 and CNDP2. Research Design & Methods: Overall, 1,269 Caucasian patients with type 1 diabetes were included in the study, including 613 patients with normoalbuminuria and a long duration of diabetes, 445 patients with persistent proteinuria, and 211 patients with end-stage renal disease (ESRD). All patients were genotyped for selected polymorphisms, the associations with diabetic nephropathy were tested by a χ2 test, and odds ratios were calculated. Results: We did not find any significant association between diabetic nephropathy and any examined genetic markers. The negative findings of the case-control study were supported further by negative findings obtained from the 6-year follow-up study of 445 patients with persistent proteinuria, during which 135 patients developed ESRD. Conclusions: Our large, comprehensive study did not find an association between the D18S880 microsatellite or any other polymorphisms in the CNDP2–CNDP1 genomic region and susceptibility for diabetic nephropathy in type 1 diabetes.

Objective: Epidemiological and family studies have demonstrated that susceptibility genes play an important role in the etiology of diabetic nephropathy, defined as persistent proteinuria or end-stage renal disease (ESRD) in type 1 diabetes. Research Design and Methods: To efficiently search for genomic regions harboring diabetic nephropathy genes, we conducted a scan using 5,382 informative single nucleotide polymorphisms on 100 sibpairs concordant for type 1 diabetes but discordant for diabetic nephropathy. In addition to being powerful for detecting linkage to diabetic nephropathy, this design allows linkage analysis on type 1 diabetes via traditional affected sibpair (ASP) analysis. In weighing the evidence for linkage, we considered maximum logarithm of odds score (maximum likelihood score [MLS]) values and corresponding allelic sharing patterns, calculated and viewed graphically using the software package SPLAT. Results: Our primary finding for diabetic nephropathy, broadly defined, is on chromosome 19q (MLS = 3.1), and a secondary peak exists on chromosome 2q (MLS = 2.1). Stratification of discordant sibpairs based on whether disease had progressed to ESRD suggested four tertiary peaks on chromosome 1q (ESRD only), chromosome 20p (proteinuria only), and chromosome 3q (two loci 58 cm apart, one for ESRD only and another for proteinuria only). Additionally, analysis of 130 ASPs for type 1 diabetes confirmed the linkage to the HLA region on chromosome 6p (MLS = 9.2) and IDDM15 on chromosome 6q (MLS = 3.1). Conclusions: This study identified several novel loci as candidates for diabetic nephropathy, none of which appear to be the sole genetic determinant of diabetic nephropathy in type 1 diabetes. In addition, this study confirms two previously reported type 1 diabetes loci.

El abate Konarski escribió una oda homenajeando al conde de Aranda cuando el gran político aragonés dejaba la embajada de Varsovia y se dirigía a Portugal, donde debía mandar las tropas que habían invadido el vecino país en 1762. Los resonantes triunfos que esperaba del conde el escolapio polaco no llegaron a producirse, pues la campaña militar fue un desastre; tampoco la oda era una ingenuidad del latinista polaco, pues escondía nada menos que el intento partidario de los valedores del rey Estanislao Augusto Poniatowski de estrechar lazos con las monarquías borbónicas.

We describe the method of estimation of the largest Lyapunov exponent of nonsmooth dynamical systems using the properties of chaos synchronization. The method is based on the coupling of two identical dynamical systems and is tested on two examples of Duffing oscillator: (i) with added dry friction, (ii) with impacts.