Single Breaks Research Articles

Yenilebilir mantar Macrolepiota procera kullanılarak yeşil sentez yöntemiyle sentezlenen gümüş nanopartiküllerinin in-vitro biyolojik aktivitelerinin araştırılması

Aim: Mushrooms known that to be used in traditional treatment among the people as they can generate a large diversity of secondary metabolites. In the present study, it was aimed to synthesized silver nanoparticles (AgNPs) mediated Macrolepiota procera, which is known to have diverse biological activities such as anticancer, antioxidant, antimicrobial in previous studies, and to investigated various in-vitro biological activities of these AgNPs. Materials and Methods: Synthesized Mp-AgNPs were characterized using transmission electron microscopy (TEM). Various biological activities including antimicrobial, biofilm inhibition and cell viability inhibition, DNA cleavage, DPPH activity of synthesized AgNPs were investigated in-vitro. Results: The highest DPPH scavenging activity of Mp-AgNPs was found as 92.72%, at 200 mg/L concentration. Mp-AgNPs caused single strain break in the E. coli pBR322 plasmid DNA. Mp-AgNPs showed moderate antimicrobial activity against tested microorganisms. Furthermore, the biofilm inhibition activity of Mp-AgNPs toward P. aeruginosa and S. aureus was 65.80% and 72.60% at 200 mg/L, respectively. Inhibition activity of E. coli cell viability of Mp-AgNPs was found as 99.99% at 500 mg/L. Conclusion: From the findings obtained in the study , the use of M. procera in the AgNPs synthesis it is important private regard due to its low cost, eco-friendly, high yield and non-toxicity human health. In addition, newly synthesized AgNPs can be used effectively for different applications after further studies.

Modelling of grain breakage of in a vertical rice mill based on DEM simulation combining particle replacement model

Rice milling is a common practice for the post-harvest processing of rice grains. However, the production of broken rice during the milling is an inevitable and universal problem. Thus, it is important to understand the grain breakage mechanisms for improving the final quality of milled rice. The work aims to propose a development of numerical methodology combining discrete element method (DEM) and particle replacement model (PRM) for modelling grain breakage in a vertical rice mill. Using dimensional analysis and fracture mechanics, a mass-specific threshold dissipation energy was determined that, if exceeded, allowed the contribution to grain breakage to be determined. Based on the continuum damage mechanics, the damage accumulation coefficient describing the amenability of a material to sustain damage prior to breakage was obtained. Then a mathematical model characterising particle strength weakening when subjected to repeated low-energy loading was established. Furthermore, the breakage criterion that judges whether rice grain breaks was also set up. On the basis of the numerical method established, the number and size of the post breakage daughter particles was determined from rice milling tests. The required material parameters were determined by single breakage and fracture when subjected to repeated loading tests. Finally, the required number of impacts before a particle breaks and the subsequent breakage ratio during milling predicted from the simulation were shown to be consistent with experimental results. The proposed numerical method is useful for providing theoretical guidance to further clarify the breakage mechanisms that occur in a rice mill. • A numerical method based on DEM and PRM is used to simulate rice grain breakage. • Mass-specific threshold dissipation energy judging effective collision is applied. • Damage accumulation coefficient describes strength weakening by repeated stressing. • Proposed method is validated by comparing simulated and experimental results.

Fibre failure assessment in carbon fibre reinforced polymers under tensile loading using in situ synchrotron X-ray computed tomography

In situ synchrotron radiation computed tomography (SRCT) was used to compare the fibre damage progression in five configurations of (902/02)s carbon-epoxy coupons loaded to failure. The effects of different sizing types, surface treatments and fibre diameters on the macroscopic properties, for example, ultimate tensile strength (UTS), and on the damage accumulation at a microscopic scale, for example, fibre break accumulation, were assessed. A semi-automated approach was adopted to process the large amount of data obtained from the SRCT scans and further method applicability areas can be envisaged. Single fibre break accumulation was seen to be influenced by the fibre type, while the formation of interacting fibre break groups by the surface treatment and the sizing type. For the materials presented, it can be suggested that an increased defect tolerance can be obtained by moving from stronger to weaker fibre-matrix adhesion, with sub-critical multiplet behaviour emerging as independent of the average UTS value.

Networks and Islands of Genome Nano-architecture and Their Potential Relevance for Radiation Biology : (A Hypothesis and Experimental Verification Hints).

The cell nucleus is a complex biological system in which simultaneous reactions and functions take place to keep the cell as an individualized, specialized system running well. The cell nucleus contains chromatin packed in various degrees of density and separated in volumes of chromosome territories and subchromosomal domains. Between the chromatin, however, there is enough "free" space for floating RNA, proteins, enzymes, ATPs, ions, water molecules, etc. which are trafficking by super- and supra-diffusion to the interaction points where they are required. It seems that this trafficking works somehow automatically and drives the system perfectly. After exposure to ionizing radiation causing DNA damage from single base damage up to chromatin double-strand breaks, the whole system "cell nucleus" responds, and repair processes are starting to recover the fully functional and intact system. In molecular biology, many individual epigenetic pathways of DNA damage response or repair of single and double-strand breaks are described. How these responses are embedded into the response of the system as a whole is often out of the focus of consideration. In this article, we want to follow the hypothesis of chromatin architecture's impact on epigenetic pathways and vice versa. Based on the assumption that chromatin acts like an "aperiodic solid state within a limited volume," functionally determined networks and local topologies ("islands") can be defined that drive the appropriate repair process at a given damage site. Experimental results of investigations of the chromatin nano-architecture and DNA repair clusters obtained by means of single-molecule localization microscopy offer hints and perspectives that may contribute to verifying the hypothesis.

Oxidative Stress, Cancer and Antioxidant: A symbiosis?

The imbalance production of free radicals and reactive metabolites known as reactive oxygen species (ROS) and their elimination, will developed oxidative stress. ROS are playing dual roles as deleterious or beneficial species. At low level, they act as messengers in cell signaling and play a role in maintaining homeostasis whereas at higher concentration will cause cellular redox imbalance. This event is commonly occurred in cancer cells compared to normal cells. The oxidative DNA damage occurs as a result of elevated level of ROS causing single or double strand DNA breaks, replication errors, base modification, base oxidation, DNA cross-linking which leads to cell dysfunction and cell death. Taking antioxidant such as polyphenolic compounds is believed to exert anticancer effect due to ROS manifestations. Studies with flavonoids compounds exerted anticancer activity through modulation of ROS-scavenging enzyme activities, cell cycle arrest, induction of apoptosis, autophagy, and suppression of cancer cell proliferation and invasiveness. However, the mechanisms responsible for this anticancer effect have not been fully understood. Most of the laboratory and animal studies exhibited increased levels of exogenous antioxidants which prevent the types of free radical damage associated with cancer development. Few clinical studies in human were conducted with aim to observe possibilities of lowering risk of developing or dying from cancer upon taking dietary supplements. The dietary antioxidant supplements which were tested on human subjects were beta carotene, tocopherol, alpha tocopherol, vitamin C, selenium and zinc. These studies have yielded mixed results. In some preclinical studies, antioxidants have been found to promote tumor growth and metastasize. In tumor-bearing mice the supplements given had increased the ability to circulate tumor cells to metastasize. In conclusion, the mechanism of antioxidant action in cancer treatment is poorly understood. Many factors need to be considered before taking or giving antioxidant supplement since there were reports pertaining to benefits and disadvantages of antioxidant in cancer treatment.

The Thermodynamic Formalism and the Central Limit Theorem for Stochastic Perturbations of Circle Maps with a Break

Let $T\in C^{2+\varepsilon}(S^{1}\setminus\{x_{b}\})$, $\varepsilon>0$, be an orientation preserving circle homeomorphism with rotation number $\rho_{T}=[k_{1},k_{2},\ldots,k_{m},1,1,\ldots]$, $m\geq 1$, and a single break point $x_{b}$. Stochastic perturbations $\overline{z}_{n+1}=T(\overline{z}_{n})+\sigma\xi_{n+1}$, $\overline{z}_{0}:=z\in S^{1}$ of critical circle maps have been studied some time ago by Diaz-Espinoza and de la Llave, who showed for the resulting sum of random variables a central limit theorem and its rate of convergence. Their approach used the renormalization group technique. We will use here Sinai’s et al. thermodynamic formalism approach, generalised to circle maps with a break point by Dzhalilov et al., to extend the above results to circle homemorphisms with a break point. This and the sequence of dynamical partitions allows us, following earlier work of Vul at al., to establish a symbolic dynamics for any point ${z\in S^{1}}$ and to define a transfer operator whose leading eigenvalue can be used to bound the Lyapunov function. To prove the central limit theorem and its convergence rate we decompose the stochastic sequence via a Taylor expansion in the variables $\xi_{i}$ into the linear term $L_{n}(z_{0})=\xi_{n}+\sum\limits_{k=1}^{n-1}\xi_{k}\prod\limits_{j=k}^{n-1}T^{% \prime}(z_{j})$, ${z_{0}\in S^{1}}$ and a higher order term, which is possible in a neighbourhood $A_{k}^{n}$ of the points $z_{k}$, ${k\leq n-1}$, not containing the break points of $T^{n}$. For this we construct for a certain sequence $\{n_{m}\}$ a series of neighbourhoods $A_{k}^{n_{m}}$ of the points $z_{k}$ which do not contain any break point of the map $T^{q_{n_{m}}}$, $q_{n_{m}}$ the first return times of $T$. The proof of our results follows from the proof of the central limit theorem for the linearized process.

Structural Change in Rice-Wheat Crop Yield in India: A Multiple Breakpoint Analysis

Rice and wheat are grown in sequence on the same land in the same year in South and South-East Asian cropping land to meet the demand for food of a rapidly increasing population. However, the rice-wheat system being the dominant cropping system in India is exhibiting a declining trend in recent times. This study aims at investigating a structural break in annual crop yield of two major foodgrains in India namely rice and wheat following multiple structural break analysis due to Bai-Peron for the period 1961 to 2018 using FAO(Food & Agricultural Organization) dataset of the United Nations following semi-logarithmic growth model both at level and growth. The results show that both rice and wheat yield are non-stationary at level but stationary in the first difference. The Bai-Perron multiple breakpoint test shows the presence of a structural break in both rice and wheat yield and these are present only in level but not in growth. This study has found a single break in rice yield in the year 1988, and two structural breakpoints in the years 1969 and 1998 for wheat yield. The yield growth has fallen for both rice and wheat in the post-break period compared to the pre-break period. Although the growth of rice yield in the post-break period was 1.388% compared to the pre-break period of 1.772%, the wheat yield exhibited acceleration after the green revolution with growth of 3.018% in the post-break period. The wheat growth, however, has slowed down since the late 1990s due to several ecological constraints including climate change. The above observations are quite consistent with the view that the dual goals of self-reliance and sustainable resource management are mutually incompatible. Resource-conserving technologies and crop diversification are required to be implemented to ensure the sustainability of the rice-wheat cropping system in the Indo-Gangetic plains to overcome food security problems in the region. Appropriate policy reform both at the macro level as well as at the sectoral level is necessary for arresting and reversing the present degradation trends. caused by both institutional and ecological factors

The Bardeen–Petterson effect in accreting supermassive black hole binaries: disc breaking and critical obliquity

ABSTRACT The inspiral of supermassive black hole (BH) binaries in a gas-rich environment is driven by the presence of an accretion disc and viscous interactions tend to align the spin of the BHs with the orbital angular momentum of the disc. Recent work introduced a new iterative approach to describe the alignment process and the resulting non-linear evolution of the surrounding warped accretion disc. Their model predicted that BH spins reach either full alignment or a ‘critical obliquity’ where solutions to the warp equations cease to exist. In this paper, we show that this critical region corresponds to the disc breaking phenomenon, where the disc is disrupted into two or more discrete sections. We use 3D hydrodynamical simulations to (i) recover the predictions of the semi-analytic model and (ii) unveil a richer phenomenology where the disc exhibits either unsuccessful, single and multiple breaks. We additionally identify hydrodynamic effects such as spiral arms that are able to stabilize the disc against breaking beyond criticality. Our results show that when disc breaking occurs, the ability of BHs and disc to align is compromised and in some cases even prevented as the binary inspirals.

Multivariate Approach to Single-Molecule Thermopower and Electrical Conductance Measurements

We report a method using scanning tunneling microscope single molecular break junction to simultaneously measure and correlate the single-molecule thermopower and electrical conductance. In contrast to previously reported approaches, it does not require custom-built electronics and takes advantage of a trace-by-trace calibration of the thermal offset at the Au/Au contact, thus greatly facilitating thermoelectric measurements at the single-molecule level. We report measurements of three molecules, 1,4-di(4-(ethynyl(phenylthioacetate))) benzene, 1,8-octanedithiol, and 4,4′-bipyridine, and determine single-molecule Seebeck coefficients of 12(3), 5(2), and −5(2) μV K–1, respectively. Furthermore, the method statistically correlates the Seebeck voltage offset, electrical conductance, and stretching displacement of the single-molecule junction and allows for direct comparison with current-distance spectroscopy results obtained at constant bias.

Early Clinical Evaluation of Potential Synergy of Targeted Radiotherapy with Lintuzumab-Ac225 and Venetoclax in Relapsed/Refractory AML

Early Clinical Evaluation of Potential Synergy of Targeted Radiotherapy with Lintuzumab-Ac225 and Venetoclax in Relapsed/Refractory AML

Produced means of production and the chain of comparative advantages

We study the effects of income distribution on comparative costs and show that the presence of produced means of production dramatically affects the possibility to build a “chain of comparative advantages” to explain the direction of trade. Specifically, we show that: i) comparative autarky costs are bad predictors of the trade pattern because comparative costs are no longer proportional to relative wages; ii) to ensure that a single break in the chain suffices to separate imported from exported commodities, at most one tradable capital good may be employed in production. With heterogeneous capital goods, the chain may need to be broken into many segments. iii) A change in the profit rate may alter the ordering of the links, even if the chain is well behaved for a constant profit rate. And iv) the plausibility of the chain of comparative advantages requiring multiple links for the same industry increases with the profit rate.

P59.27 Complementary Utility of Combined ALK/ROS1 FISH with Immunohistochemistry for ALK/ROS1 Rearrangement Testing in Lung Cancer

Testing for EGFR mutations, ALK and ROS1 rearrangements and BRAF mutations are now recommended as the essential minimum predictive biomarkers to be tested in primary non-squamous NSCLC patients presenting with advanced disease. While the ALK D5F3 Ventana immunohistochemistry (IHC) Assay is approved for detection of ALK rearrangements and for targeted therapy, ROS1 IHC only serves as a screening tool for ROS1 rearrangements with demonstration of gene fusions by molecular methods required for confirmation and targeted treatment. Nevertheless, equivocal IHC results, although uncommon, still occur with the D5F3 ALK assay necessitating complementary methods for confirmation. The recent availability of combined ALK/ROS1 break-apart fluorescence in-situ hybridisation (FISH) probes offer the advantage of tissue conservation with ability to analyse both gene alterations in a single tissue section. The aim of the present study was to study the utility of the combined ALK/ROS1 FISH assay as a complement to ALK and ROS1 IHC in routine predictive biomarker testing algorithms. Over a 6-year study period, all EGFR wild type NSCLC samples were subject to automated ALK D5F3 Ventana IHC assay and ROS1 IHC using the D4D6 (Cell signalling technology) clone as a manual lab developed test. Diffuse strong granular staining in tumor cells for ALK and ROS1 protein was interpreted as positive. All cases of equivocal ALK staining and positive ROS1 staining was subject to combined ALK/ROS1 FISH using the FlexISH ALK/ROS1 DistinguISH Probe (Vysis) performed as per manufacturers’ instructions. Presence of ALK/ROS1 break apart signals and/or isolated ALK/ROS1 3’ signals in >15% of interpretable tumour nuclei was considered as positive for ALK or ROS1 rearrangement. The ALK Ventana Assay was performed in 711 formalin fixed paraffin embedded EGFR wild type NSCLC samples including biopsies, lymph node excisions and cell blocks. Of these, 12% (85/711) were positive, 2% (13/711) were equivocal, 75% (539/711) were negative, while in the remaining 11% (76/711), result could not be evaluated due to exhaustion of tumor tissue. FISH analysis in four of the ALK IHC equivocal cases show absence of ALK translocations while no tissue remained for FISH analysis in the remaining equivocal cases. ROS1 IHC was performed in 434 cases of the above cohort of which 7% (30/434) were positive. ROS1 immunopositivity was enriched among ALK IHC positive cases with 43% (19/44) of ALK IHC positive cases also showing protein expression of ROS1. FISH analysis revealed ROS1 translocation in two cases (both showing diffuse strong ROS1 protein expression and negative ALK IHC) while all dual ALK/ROS IHC positive cases tested by FISH showed presence of only ALK rearrangements with non-rearranged ROS1 signals. Tissue adequacy remains the major limiting factor for predictive biomarker testing in lung cancer. The use of combined ALK-ROS FISH allows for excellent demonstration of ALK and ROS1 rearrangements in the same section using the same criteria validated in single gene break apart FISH probes. ROS1 protein is commonly overexpressed in ALK rearranged NSCLC and may represent cross reactivity with ALK or a related protein.

Effects of 2-hour nighttime nap on melatonin concentration and alertness during 12-hour simulated night work.

A nighttime nap is expected to mitigate melatonin suppression during night work by blocking light input to the retina, but it is unclear. In the present study, we investigated the effects of a nap break on melatonin level, subjective sleepiness, and vigilance performance during simulated night work. Eleven healthy young males (mean ± SD age: 22.2 ± 4.1 years) participated in counterbalanced crossover design experiments with two conditions (nap vs. no nap). The subjects performed 12-hour simulated night work from 21:00 to 09:00 h (illuminance: ∼500 lx). Subjects with a nap condition took a nap for 2 hours in a dark room from 03:00, while subjects with a no nap condition continued the simulated night work. The results showed that immediately after the 2-h nap break, the melatonin level at 05:00 h temporarily recovered from light-induced melatonin suppression during the simulated night work but significantly suppressed again at 07:00 and 09:00 h. Subjective alertness and vigilance performance were impaired immediately after the nap break but subsequently enhanced. The results suggest that a single nap break for 2 hours could be a strategy to enhance alertness during the last part of night shift but inadequate for mitigating melatonin suppression.

A revisit of the unemployment rate, interest rate, GDP growth and Inflation of Pakistan: Whether Structural break or unit root?

The study investigates the query of structural break or unit root considering four macroeconomic indicators; unemployment rate, interest rate, GDP growth, and inflation rate of Pakistan. The previous studies create ambiguity regarding the stationarity and non-stationarity of these variables. We employ Zivot & Andrews (1992) unit root test and Step Indicator Saturation (SIS) method for multiple break detection in mean. GDP growth and inflation rate are stationary at level whereas unit root tests fail to reject the null hypothesis of the unemployment rate and interest rate at level. However, Zivot and Andrew unit root test with a single endogenous break indicates that the unemployment rate and interest rate are stationary at level with a single endogenous break. On the other hand, the SIS method reveals that the series are stationary with multiple structural breaks. It is inferred that it is inappropriate to take the first difference of the unemployment rate and interest rate to attain stationarity. The results of this study confirmed that there exist multiple breaks in the macroeconomic variables considered in the context of Pakistan.

Principal Foliations of Surfaces near Ellipsoids

The lines of curvature of a surface embedded in $\R^3$ comprise its principal foliations. Principal foliations of surfaces embedded in $\R^3$ resemble phase portraits of two dimensional vector fields, but there are significant differences in their geometry because principal foliations are not orientable. The Poincar\'e-Bendixson Theorem precludes flows on the two sphere $S^2$ with recurrent trajectories larger than a periodic orbit, but there are convex surfaces whose principal foliations are closely related to non-vanishing vector fields on the torus $T^2$. This paper investigates families of such surfaces that have dense lines of curvature at a Cantor set $C$ of parameters. It introduces discrete one dimensional return maps of a cross-section whose trajectories are the intersections of a line of curvature with the cross-section. The main result proved here is that the return map of a generic surface has \emph{breaks}; i.e., jump discontinuities of its derivative. Khanin and Vul discovered a qualitative difference between one parameter families of smooth diffeomorphisms of the circle and those with breaks: smooth families have positive Lebesgue measure sets of parameters with irrational rotation number and dense trajectories while families of diffeomorphisms with a single break do not. This paper discusses whether Lebesgue almost all parameters yield closed lines of curvature in families of embedded surfaces.

Mononuclear π-complexes of Pd(II) and Pt(II) with 1-allyl-3-(2-hydroxyethyl)thiourea: Synthesis, structure, molecular docking, DNA binding ability and genotoxic activity

Five π-complexes [M(HL)X2] (M = Pd2+, Pt2+; X = Cl−, Br−, I−) have been obtained by the reactions of [MCl4]2− with 1-allyl-3-(2-hydroxyethyl)thiourea (HL) in the presence of HCl and/or KBr/KI. (Br/I)-Containing chelated π-type complexes of this type are presented for the first time. A comprehensive structural and spectral characterization has revealed an identical atomic arrangement, with the Cl- and Br-bearing phases adopting the same triclinic structure (space group P), while [Pt(HL)I2] crystallizes in the monoclinic P21/n space group. The molecules of HL are coordinated in a bidentate manner with the formation of six-membered chelate metallocycles. The diagonal arrangement of “soft-hard” donor atoms (S–X, C–X) in the coordination sphere leads to Pearson's effect of “molecular antisymbiosis in the trans effect” that causes the interaction of M:L in a ratio of 1:1. The similarity of the structures of the synthesized complexes with that of cisplatin implies the same mechanism for their antitumor action, whilst different halide anions in the coordination sphere of the metal affects the cytotoxic activity of the complexes. Among the new cisplatin analogues, two of the platinum π-complexes are promising compounds, the action of which slows or completely stops cell division, causes a decrease in nucleus size and increases the proportion of heterochromatin in the structure of interphase nuclei, thus reducing the activity of transcriptional processes. A molecular docking study showed that the general mechanism of action for the complexes can be characterized by the formation of single and double-stranded breaks of DNA plasmid. The presence of the OH-group has a positive impact on the “ligand – DNA binding”.

Rhegmatogenous retinal detachment: A brief overview

Rhegmatogenous retinal detachment (RRD) is one of the major causes of blindness worldwide. It is caused by single or multiple breaks in the retina and is defined by the separation of the neurosensory retina from the retinal pigment epithelium (1). Treatment for these cases is time sensitive with many studies advising for treatment within 24 hours to improve visual outcomes, thus early recognition and management of these cases is important particularly in cases involving the macula. This article will discuss the clinical features associated with rhegmatogenous retinal detachment, its underlying pathogenesis as well as the steps taken in managing patients with this condition.

Ecological footprint, public-private partnership investment in energy, and financial development in Brazil: a gradual shift causality approach.

The present study assesses the effect of public-private partnerships in energy and financial development on Brazil's ecological footprint and also takes into account the role of renewable energy and economic growth using data spanning from 1983 to 2017. The study utilized several techniques including autoregressive distributive lag (ARDL) and dynamic ordinary least square (DOLS) to examine the relationship between ecological footprint and the determinants, while the gradual shift causality test was utilized to capture the causal linkage between the series in the presence of a single structural break. The outcomes of the Maki co-integration test revealed evidence of a long-run association among the variables of interest. Furthermore, the results of the ARDL and DOLS tests revealed that economic growth and public and private investment in energy increase environmental degradation, while it is mitigated by both renewable energy and financial development. Moreover, the gradual shift causality test revealed a bidirectional causal linkage between ecological footprint and economic growth. The present study recommends the establishment of a forum that will foster public and private partnerships to enhance communication, which will promote collaboration on new initiatives involving green technological innovations.

Reactive oxygen species, DNA damage and Solar-Earth communications

Reactive oxygen species play a significant role in regulating the main functions of the cell both in the normal conditions and when exposing the cell to exogenous and endogenous factors under electromagnetic and radiation emission at various levels of solar activity. The research studied the impact of low-intensity alternating magnetic field; the intensity level is comparable to the geomagnetic field, in the frequency range from 3 to 60 Hz and γ-radiation on the generation of the most stable ROS which are hydrogen peroxide, in vitro. A degree of oxidative DNA damage in the blood serum of health donors, after being exposed to the alternating magnetic field, was investigated by determining the content of 8- hydroxy-2-deoxyguanosine (8-OHdG) in the blood serum and DNA single breaks in the lymphocytes. An increase of the content of 8-OHdG in DNA by a factor of 1.5 – 2 in comparison with non-emitted samples, and non-linear change in the level of lipid peroxide in the blood serum with maxima at MF frequencies of 8 and 50 Hz. In lymphocytes are observed. When exposed to gamma radiation, the number of single-strand breaks (SSB) of DNA increased with increasing exposure time from 44.3 ± 0.4% (irradiation for 30 minutes) to 68.3 ± 0.8% (irradiation for 90 minutes) compared to the control samples. It is concluded that the obtained effects can be associated with the generation of reactive oxygen species in the aquatic environment with variations in solar activity and affect the adaptive capabilities of the human body as a whole.

Zinc organocomplexes containing non-steroid anti-inflammatories and plane aromatic diimines: New potential drugs

Strategies have been developing to obtain new medicines. Bioisosterism represents an approach used by medicinal chemists for the rational modification of lead compounds into safer and more clinically effective agents. Evidently, the synthesis of organocomplexes has been an important strategy in the planning of new drugs, and there are examples of great improvements in therapeutic efficacy. Thus, this work is aimed at the synthesis of new zinc complexes with nonsteroidal anti-inflammatory drugs (NSAIDs), the chemical characterization and the previous toxicity by cytotoxicity, and an evaluation of the ability of these compounds to interact with DNA. As a result, four new zinc II ternary complexes containing the NSAIDs diclofenac (Diclof) and ibuprofen (Ibup) and a zinc neutral linker were obtained by the two-step solvent metal–ligand complexation method (1. Zn-Ibup-Bipy, 2. Zn-Ibup-Phen, 3. Zn-Diclof-Bipy, 4. Zn-Diclof-Phen). Molecular structures were determined by NMR, FTIR, and HR-MS which demonstrated that the complexes are binuclear systems of the general formula [Zn(RCOO−)2N-binder]. In silico studies were performed for toxicity and physicochemical properties and biological target prediction. Cytotoxicity was determined by the MTT assay. The results indicated a relative absence of toxicity for these organometallic zinc derivatives. It was also observed that the compounds Zn-Diclof-Bipy and Zn-Diclof-Phen showed high potential without theoretical toxic effects, and they should be submitted to studies for evaluation of biological activity. Plasmidi DNA breakdown capacities were evaluated by producing single and double breaks (DNA FII and FIII) from plasmid incubation with complex solutions in the concentration range of 0 to 400 μmol·L−1 in experiments with the presence and absence of light. Both experiments did not show significant differences (P ≤ 0.05) in induced DNA cleavage activity between the maximum study concentrations (400 μmol·L−1) and the negative controls for both complexes. The types of complex 1 and 2 interactions with the secondary DNA structure were determined by titrating a CT-DNA solution with complex solutions and monitoring by circular dichroism spectrometry. Complex 1 was not cytotoxic at the concentrations tested against the Vero cell line. The results showed that both complexes interact with the grooves of the secondary structure of CT-DNA by electrostatic attraction but without evidence of alteration in the primary structure. Thus, four new compounds were synthesized and characterized, and their previous toxicities were determined. These compounds are promising new drugs, and the next step is to evaluate their activity.