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SuFEx chemistry is based on the unique reactivity of the sulfonyl fluoride group with a range of nucleophiles. Accordingly, sulfonyl fluorides label multiple nucleophilic amino acid residues, making these reagents popular in both chemical biology and medicinal chemistry applications. The reactivity of sulfonyl fluorides nominates this warhead chemotype as a candidate for an external, activation-free general labelling tag. Here, we report the synthesis and characterization of a small sulfonyl fluoride library that yielded the 3-carboxybenzenesulfonyl fluoride warhead for tagging tractable targets at nucleophilic residues. Based on these results, we propose that coupling diverse fragments to this warhead would result in a library of sulfonyl fluoride bits (SuFBits), available for screening against protein targets. SuFBits will label the target if it binds to the core fragment, which facilitates the identification of weak fragments by mass spectrometry. [ABSTRACT FROM AUTHOR]

In a search for novel therapeutic options for head and neck squamous cell carcinomas (HNSCCs) generally treated with limited therapeutic success, we synthesized a series of novel erlotinib–chalcone molecular hybrids with 1,2,3-triazole and alkyne linkers and evaluated them for their anticancer activity on Fadu, Detroit 562 and SCC-25 HNSCC cell lines. Time- and dose-dependent cell viability measurements disclosed a significantly increased efficiency of the hybrids compared to the 1:1 combination of erlotinib and a reference chalcone. The clonogenic assay demonstrated that hybrids eradicate HNSCC cells in low micromolar concentrations. Experiments focusing on potential molecular targets indicate that the hybrids trigger the anticancer effect by a complementary mechanism of action that is independent of the canonical targets of their molecular fragments. Confocal microscopic imaging and real-time apoptosis/necrosis detection assay pointed to slightly different cell death mechanisms induced by the most prominent triazole- and alkyne-tethered hybrids (6a and 13, respectively). While 6a featured the lowest IC50 values on each of the three HNSCC cell lines, in Detroit 562 cells, this hybrid induced necrosis more markedly compared to 13. The therapeutic potential indicated by the observed anticancer efficacy of our selected hybrid molecules validates the concept of development and justifies further investigation to reveal the underlying mechanism of action. [ABSTRACT FROM AUTHOR]

Thioether-phosphite ligands (SP's) with axially chiral (S)-H0- or (S)-H8-binaphthyl moiety and their [Rh(COD)(SP)]BF4 complexes have been synthesized to study their coordination chemistry and catalytic features and to compare them to those of the structurally analogous phosphine-phosphites (PP's). NMR exchange studies on [Rh(COD)(SP)]BF4 complexes showed selective 1,5-cyclooctadiene dynamics. Firm evidence has been found that this fluxional process involves dissociation of the Rh-sulfur bond. Based on in situ NMR studies, SP ligands can form two types of bis-ligated species at ligand-to-metal ratio higher than 1. Unlike bis-ligated phosphine-phosphite complexes, bis-ligated thioether-phosphite Rh-complexes can efficiently catalyze asymmetric hydrogenation reactions due to their distinct coordination chemistry. [ABSTRACT FROM AUTHOR]

Detection and characterization of hidden industrial inflows causing high fluctuations of the inlet load, is a challenging issue pushing plant operators for a cost-effective solution at regional wastewater treatment plants (WWTPs). On the other hand, carbon source of food industrial origin may have a good use at WWTPs facing otherwise inlet carbon source deficiency. In a case study of a regional domestic WWTP receiving seasonally organic carbon-rich discharge from a fruit juice factory, a new method combining on-site measurements and mathematical modelling was developed and successfully applied for estimating the quality and quantity of both industrial influent load and incoming domestic wastewater streams properly. The originally un-staged bioreactor system operated at low dissolved oxygen (low DO) concentration was unable to meet effluent nitrogen requirements with an additional constant risk of encouraging filament growth. A novel screening method based on special sampling campaigns for estimating carbon availability and C:N ratios of influent wastewater streams coming separately from the large catchment area, was developed and applied. Staging of the previously low DO basins into a flexible system containing non-aerated selectors proved to be efficient for enhancing both biological nitrogen removal and sculpturing appropriately settling biomass. [ABSTRACT FROM AUTHOR]

In international practice, the performance of public finance management is usually assessed on the basis of quality indicators of the subsystems of the public finance system. The experts of the State Audit Office of Hungary have developed an evaluation system capable of measuring the performance of public finance management on the basis of quantitative indicators and quantifying the contribution of the factors that determine performance most. This article describes this system. It also shows how the assessment system was used to analyse the risks to the ongoing reduction of Hungarian public debt. [ABSTRACT FROM AUTHOR]

SUMMARY: In international practice, the performance of public finance management is usually assessed on the basis of quality indicators of the subsystems of the public finance system. The experts of the State Audit Office of Hungary have developed an evaluation system capable of measuring the performance of public finance management on the basis of quantitative indicators and quantifying the contribution of the factors that determine performance most. This article describes this system. It also shows how the assessment system was used to analyse the risks to the ongoing reduction of Hungarian public debt. [ABSTRACT FROM AUTHOR]

International credit rating agencies regularly (twice a year) assess the risk level of sovereign debt, and thus that of a given country. In order to identify risks, each credit rating agency has developed its own methodology to assess economic and public finance processes and identify the emerging risks. The evaluations carried out influence at the international level the financing possibilities of a given country and its conditions. The improving result of evaluations by international credit rating agencies has become one of the requirements for the success of economic policy. However, this can only be a realistic condition and a measure of success if the evaluation made is methodologically sound and the evaluations resulting from their consistent implementation are scientifically credible. This article describes in detail the evaluation methodology applied by the three major international credit rating agencies to evaluate the individual countries and sovereign debt. After presenting the general aspects, the article draws attention to the fact that the principles of objectivity, authenticity and methodological determination are enforced in practice in the evaluations of international credit rating agencies to a limited extent. [ABSTRACT FROM AUTHOR]

Prior to modern seismic codes, several road bridges were not designed for earthquakes in many moderate seismic regions. The seismic performance of these bridges is questionable. A portfolio of 30 non-seismically designed bridges is compiled for seismic reliability assessment. Fragility analysis is conducted, and the reliability of each structure is determined considering typical moderate seismic areas. The study shows that slab and multi-girder bridges with elastomeric bearings perform worse, whereas girder bridges with conventional bearings and multi-girder bridges with monolithic joints have better behavior. It is also shown that seismic design per Eurocode 8 leads to a reliability index of ~2. [ABSTRACT FROM AUTHOR]

Nowadays the quality of budget management and the availability of reliable budget information are becoming increasingly important. A key area of these changes is the continuous development of public accounting, including the application of accrual accounting. The characteristics of development in public accounting vary by country since EU member states have different public finance systems. The process is constantly monitored by the supreme audit institutions, including the State Audit Office of Hungary. The article presents the most important areas of change in public accounting, especially the role of standards. In addition, the purpose of the article is to give a detailed description of how the public accounting system in two countries developed, highlighting the aspects of supreme audit institutions. The experiences and the perspective of supreme audit institutions regarding the issue are presented through the examples of the countries. Finally, the aim of the article is to give an overview of the main changes in the Hungarian public accounting system, also from the point of view of the supreme audit institution. [ABSTRACT FROM AUTHOR]

Nowadays, the quality of fiscal management is increasingly significant. The generation and use of budget appropriation residues is an important, however, hardly analysed topic in either the Hungarian or the international literature. This article outlines the role of appropriation residues in fiscal management, as well as the cases of its generation. It underlines that both the large-scale generation and the use of residues represent budgetary risks. Based on the final accounts data of the period between 2007 and 2016, it analyses the characteristics of the generation and use of the residues of the central budget. It underlines that although the balance of residues generated and used fluctuated in different years, there has been a trend of increase in the value of residues generated and used. Next, the study aims to investigate the reasons behind the generation of residues by analysing individual budget headings. Finally, the article draws attention to the fact that several tools are available for the government (such as the application of "pool technique" or accrual-based accounting) to manage the risks associated with residues. [ABSTRACT FROM AUTHOR]

In lack of seismic provisions in the pre-Eurocode ages, most of the existing Hungarian bridges were not designed for seismic actions, therefore their seismic performance is questionable. The most commonly used structural type in highway construction is the integral precast multi-girder bridge. These bridges are typically constructed as continuous multi-support systems with monolithic joints at each support, thus their behavior may be significantly different from those applying simply supported beams and conventional bearings. A parametric fragility analysis of a wide range of different layouts is carried out using detailed and advanced non-linear numerical models. The results indicate that the abutment joints are highly vulnerable and piers are also critical for longer bridges. The study implies that without seismic design, integral precast multi-girder bridges are highly susceptible to pier shear failure, the probability of collapse is relatively high. The results also provide a solid basis for retrofit planning as well as for development of design concepts of newly built structures in moderate seismic zones. [ABSTRACT FROM AUTHOR]

Beige adipocytes are special cells situated in the white adipose tissue. Beige adipocytes, lacking thermogenic cues, morphologically look quite similar to regular white adipocytes, but with a markedly different response to adrenalin. White adipocytes respond to adrenergic stimuli by enhancing lipolysis, while in beige adipocytes adrenalin induces mitochondrial biogenesis too. A key step in the differentiation and function of beige adipocytes is the deacetylation of peroxisome proliferator-activated receptor (PPARγ) by SIRT1 and the consequent mitochondrial biogenesis. AMP-activated protein kinase (AMPK) is an upstream activator of SIRT1, therefore we set out to investigate the role of AMPK in beige adipocyte differentiation using human adipose-derived mesenchymal stem cells (hADMSCs) from pericardial adipose tissue. hADMSCs were differentiated to white and beige adipocytes and the differentiation medium of the white adipocytes was supplemented with 100 μM [(2R,3S,4R,5R)-5-(4-Carbamoyl-5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate (AICAR), a known activator of AMPK. The activation of AMPK with AICAR led to the appearance of beige-like morphological properties in differentiated white adipocytes. Namely, smaller lipid droplets appeared in AICAR-treated white adipocytes in a similar fashion as in beige cells. Moreover, in AICAR-treated white adipocytes the mitochondrial network was more fused than in white adipocytes; a fused mitochondrial system was characteristic to beige adipocytes. Despite the morphological similarities between AICAR-treated white adipocytes and beige cells, functionally AICAR-treated white adipocytes were similar to white adipocytes. We were unable to detect increases in basal or cAMP-induced oxygen consumption rate (a marker of mitochondrial biogenesis) when comparing control and AICAR-treated white adipocytes. Similarly, markers of beige adipocytes such as TBX1, UCP1, CIDEA, PRDM16 and TMEM26 remained the same when comparing control and AICAR-treated white adipocytes. Our data point out that in human pericardial hADMSCs the role of AMPK activation in controlling beige differentiation is restricted to morphological features, but not to actual metabolic changes. [ABSTRACT FROM AUTHOR]

This study focuses on domes the ground plan of which, instead of the more common circular shape, is an oval, and aims at finding the minimally necessary uniform wall thickness for domes of different geometries loaded by their selfweight. The discrete element code 3DEC was applied because of its capability of simulating the collapse mechanisms of masonry structures. Results on the minimal wall thickness, corresponding masonry volume and failure mechanisms for different dome geometries are presented. Three ranges of the friction coefficient were found. For very low frictional resistance collapse happens with pure frictional sliding, for any arbitrarily large wall thickness. In the range of relatively high (i.e., realistic) friction coefficients the structure collapses without any sliding if the wall is not sufficiently thick, and in the observed range of the friction coefficient the necessary wall thickness is nearly insensitive to its value (collapse initiates with hinging cracks only). Between the two domains an intermediate behavior was found: combined cracking and sliding collapse modes occur for insufficient wall thickness, and the minimal thickness strongly depends on the friction coefficient. The critical and transitional friction coefficients separating the failure modes were determined for different eccentricities of the groundplan. [ABSTRACT FROM AUTHOR]

In this study, seismic performance of the existing M0 Háros Highway Bridge in Hungary is evaluated. The large-span bridge is designed with minimal consideration of seismic actions, seismic resistance of certain piers, bearings and pile foundations is not adequate. Eight different demand mitigation methods are evaluated considering quasi-elastic configurations as well as non-linear systems adopted with non-linear anti-seismic devices (NLASD). To accelerate the preliminary design phase, an equivalent linear analysis (ELA) methodology is worked out. Keeping in mind the limitations of the ELA method, non-linear time-history analysis (NLTHA) is also applied for the retrofitted configuration for validation purposes. Comparison of the two methods shows that the ELA method gives the designer adequate, still conservative results for optimal retrofit decisions. [ABSTRACT FROM AUTHOR]

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