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Nitro fatty acids (NO2-FAs) are endogenously generated lipid signaling mediators from metabolic and inflammatory reactions between conjugated diene fatty acids and nitric oxide or nitrite-derived reactive species. NO2-FAs undergo reversible Michael addition with hyperreactive protein cysteine thiolates to induce posttranslational protein modifications that can impact protein function. Herein, we report a novel mechanism of action of natural and non-natural nitroalkenes structurally similar to (E) 10-nitro-octadec-9-enoic acid (CP-6), recently de-risked by preclinical Investigational New Drug-enabling studies and Phase 1 and Phase 2 clinical trials and found to induce DNA damage in a TNBC xenograft by inhibiting homologous-recombination (HR)-mediated repair of DNA double-strand breaks (DSB). CP-6 specifically targets Cys319, essential in RAD51-controlled HR-mediated DNA DSB repair in cells. A nitroalkene library screen identified two structurally different nitroalkenes, a non-natural fatty acid [(E) 8-nitro-nonadec-7-enoic acid (CP-8)] and a dicarboxylate ester [dimethyl (E)nitro-oct-4-enedioate (CP-23)] superior to CP-6 in TNBC cells killing, synergism with three different inhibitors of the poly ADP-ribose polymerase (PARP) and γ-IR. CP-8 and CP-23 effectively inhibited γ-IR-induced RAD51 foci formation and HR in a GFP-reported assay but did not affect benign human epithelial cells or cell cycle phases. In vivo, CP-8 and CP-23's efficacies diverged as only CP-8 showed promising anticancer activities alone and combined with the PARP inhibitor talazoparib in an HR-proficient TNBC mouse model. As preliminary preclinical toxicology analysis also suggests CP-8 as safe, our data endorse CP-8 as a novel anticancer molecule for treating cancers sensitive to homologous recombination-mediated DNA repair inhibitors.

RAD51 is a critical recombinase that functions in concert with auxiliary mediator proteins to direct the homologous recombination (HR) DNA repair pathway. We show that Cys319 RAD51 possesses nucleophilic characteristics and is important for irradiation-induced RAD51 foci formation and resistance to inhibitors of poly (ADP-ribose) polymerase (PARP). We have previously identified that cysteine (Cys) oxidation of proteins can be important for activity and modulated via binding to peroxiredoxin 1 (PRDX1). PRDX1 reduces peroxides and coordinates the signaling actions of protein binding partners. Loss of PRDX1 inhibits irradiation-induced RAD51 foci formation and represses HR DNA repair. PRDX1-deficient human breast cancer cells and mouse embryonic fibroblasts display disrupted RAD51 foci formation and decreased HR, resulting in increased DNA damage and sensitization of cells to irradiation. Following irradiation cells deficient in PRDX1 had increased incorporation of the sulfenylation probe DAz-2 in RAD51 Cys319, a functionally-significant, thiol that PRDX1 is critical for maintaining in a reduced state. Molecular dynamics (MD) simulations of dT-DNA bound to a non-oxidized RAD51 protein showed tight binding throughout the simulation, while dT-DNA dissociated from an oxidized Cys319 RAD51 filament. These novel data establish RAD51 Cys319 as a functionally-significant site for the redox regulation of HR and cellular responses to IR.

Aluminum–Silicon (Al–Si) based materials are commonly preferred in engineering studies requiring high mechanical performance as an alternative to steel materials. These alloys are especially preferred in the automotive industry, aerospace components and heavy machinery parts. In post-casting processes, machining operations are of great importance for high geometric precision, surface quality and longer fatigue life in mechanical environments. In this research, the microstructural, mechanical and machining characteristics of the Al–5Si–1Cu–Mg material produced by sand casting method in both as-cast (AC) and heat-treated (HTed) (Solid solution, quenching and aging-SQA) states were experimentally investigated. Microstructural examinations were carried out with optical microscope and SEM images. Mechanical properties were determined by tensile and hardness tests. Then, drilling experiments were performed in the CNC vertical machining center with 8 mm diameter uncoated HSS (High Speed Steel) cutting tools at constant cutting conditions (i.e., cutting speed-V: 125 m/min, feed rate-f: 0.05 mm/rev and depth of cut-DoC: 15 mm). In microstructural investigations, it was determined that the microstructure of the Al–5Si–1Cu–Mg material in AC state consists of α-Al, eutectic Si, β-Fe (β-Al5FeSi) and π-Fe (π-Al8Mg3FeSi6) intermetallics. After the SQA, the existing phases generally exhibited a spherical structure, and it was seen that the β phase in the microstructure transformed into the Ɵ (Al7FeCu2) phase. SQA improved the hardness, yield and tensile durability of the material, whereas decreasing the elongation to fracture. SQA process improved the machining characteristics of the material by decreasing thrust force, moment, surface roughness and built-up edge (BUE) formation. The machined subsurface structure of HTed alloy under constant cutting conditions was determined to be more stable and smooth and the machined surface microhardness of HTed alloy was higher compared to as-cast alloy due to the effect of solid precipitation hardening. In addition, shorter and more broken chips occurred in the machining of HTed alloys due to the effect of low elongation to fracture.

[This corrects the article DOI: 10.1371/journal.pgen.1005950.].

Political behaviors have an important place in human life in terms of providing benefits. For this reason, while political behaviors are revealed in achieving the desired goals, the importance of political skill increases. In the organizational field, especially the political skill levels of the managers are seen as an important factor in the achievement of the goals of the organization. In this context, the political skill levels of kickboxing trainers and referees working in the field of sports are also an important factor in the spread of kickboxing and achieving sporting goals. With this study, it is aimed to reveal the political skill levels of Kickboxing trainers and referees in terms of different variables. The total number of participants is 303. 80.5% of the participants are male and 19.5% are female. In the data analysis of this study, in which the scanning model was used, Independent Sample T-Test was used for binary variables and One-Way ANOVA was used for variables with more than two categories. As a result of the analysis made according to the level of coaching, it was determined that there was a statistically significant difference in the sub-dimensions of networking ability and apparent sincerity, and general political skill levels (p<,05). However, the political skill levels of kickboxing coaches and referees were found above the average. As a result, it is suggested that kickboxing coaches and referees should be subjected to in-service training that can improve their political skills and therefore their communication skills.

This study aimed to determine the athletic burnout of the under-18 (U18) women's ice hockey national team players and examine their burnout levels in terms of age, education level, sports history, training frequency, inability to participate in a match due to COVID-19, and history of injury. The research population consisted of the U18 women's ice hockey national team players in Turkey. The sample comprised 27 athletes randomly selected from the target population based on voluntariness. A questionnaire consisting of two parts was used as a data collection tool. The first part of the questionnaire included a personal information form developed by the researcher to determine the characteristics of the participants, such as age, education level, sports history, training frequency, whether they missed any ice hockey matches due to COVID-19, and history of injury. In the second part, the Athlete Burnout Questionnaire, developed by Raedeke and Smith in 2001 and adapted to Turkish by Kelecek et al. in 2016, was administered to measure the athletic burnout levels of the participants. The research findings revealed that the athletes' burnout levels were generally low, but those with a history of disability lasting longer than three months and those that missed ice hockey matches due to COVID-19 had higher burnout levels compared to the remaining participants.

IntroductionWe previously reported that a 6-day continuous peripheral nerve block reduces established postamputation phantom pain. To provide patients and providers with the information to best inform treatment decisions, here we reanalyze the data and present the results in a more patient-centered format. We also provide information on patient-defined clinically relevant benefits to facilitate evaluation of available studies and guide future trial design.MethodsThe original trial enrolled participants with a limb amputation and phantom pain who were randomized to receive a 6-day continuous peripheral nerve block(s) of either ropivacaine (n=71) or saline (n=73) in a double-masked fashion. Here we calculate the percentage of each treatment group that experienced a clinically relevant improvement as defined by previous studies as well as present what the participants of our study defined as small, medium, and large analgesic improvements using the 7-point ordinal Patient Global Impression of Change scale.ResultsAmong patients who were given a 6-day ropivacaine infusion, 57% experienced at least a 2-point improvement on the 11-point numeric rating scale in their average and worst phantom pain 4 weeks postbaseline as compared with 26% (p

BACKGROUND:We previously developed and validated a strategy for stimulating heart regeneration by administration of recombinant neuregulin (rNRG1), a growth factor, in mice. rNRG1 stimulated proliferation of heart muscle cells, cardiomyocytes, and was most effective when administration began during the neonatal period. Our results suggested the use of rNRG1 to treat pediatric patients with heart failure. However, administration in this age group may stimulate growth outside of the heart. METHODS:NRG1 and ErbB receptor expression was determined by RT-PCR. rNRG1 concentrations in serum were quantified by ELISA. Mice that received protocols of recombinant neuregulin1-β1 administration (rNRG1, 100 ng/g body weight, daily subcutaneous injection for the first month of life), previously shown to induce cardiac regeneration, were examined at pre-determined intervals. Somatic growth was quantified by weighing. Organ growth was quantified by MRI and by weighing. Neoplastic growth was examined by MRI, visual inspection, and histopathological analyses. Phospho-ERK1/2 and S6 kinase were analyzed with Western blot and ELISA, respectively. RESULTS:Lung, spleen, liver, kidney, brain, and breast gland exhibited variable expression of the NRG1 receptors ErbB2, ErbB3, ErbB4, and NRG1. Body weight and tibia length were not altered in mice receiving rNRG1. MRI showed that administration of rNRG1 did not alter the volume of the lungs, liver, kidneys, brain, or spinal cord. Administration of rNRG1 did not alter the weight of the lungs, spleen, liver, kidneys, or brain. MRI, visual inspection, and histopathological analyses showed no neoplastic growth. Follow-up for 6 months showed no alteration of somatic or organ growth. rNRG1 treatment increased the levels of phospho-ERK1/2, but not phospho-S6 kinase. CONCLUSIONS:Administration protocols of rNRG1 for stimulating cardiac regeneration in mice during the first month of life did not induce unwanted growth effects. Further studies may be required to determine whether this is the case in a corresponding human population.

New transferable parameters for polytetrafluoroethylene (PTFE) compatible with the Assisted Model Building with Energy Refinement (AMBER) force field were developed by including many conformational states to improve accuracy. The Austin–Frisch–Petersson functional with dispersion hybrid density functional theory, advantageous for treating dispersion, was used to obtain quantum mechanical reference data. The restrained electrostatic potential method was used to compute the partial charges. The bonds, angles, and dihedral parameters were obtained via Paramfit software fitted to quantum mechanical data. The optimization of van der Waals parameters was obtained in the condensed phase through molecular dynamics simulations and the simplex method. These parameters were transferred to various molecular weights of PTFE assembly systems to calculate the density, radial distribution functions, power spectrum, and specific heat capacity. The highest percent error in density was 1.4% for the modeled PTFE ensembles. The calculated vibrational spectrum peaks closely matched experimental peaks with a maximum wavenumber deviation of 19 cm⁻¹. The highest percent error to specific heat capacity was 5%. These results represent a significant improvement over pre-existing potentials in the literature and provide parameters that can be used to model PTFE in many existing simulation codes.

Doğum korkusu ile ilgili araştırmaları gözden geçirmek, yayınları bibliyometrik analiz yoluyla analiz etmek, değerlendirmek, ilgili alandaki eğilimi tespit etmek ve gelecekteki çalışmalar için öneriler sağlamak bu derlemenin amacıdır. Bibliyografik veriler Scopus veri tabanından çekilmiştir. 19/06/2023’e kadar konuyla ilgili yapılmış tüm makaleler taranmıştır. Analize 807 makale dahil edilmiştir. Bibliyografik veriler veri tabanından dışarı aktarılmış ve ardından Mendeley programında duplikasyon kontrolü yapılmıştır. Bulguları analiz etmek ve görselleştirmek için Microsoft Excel, VOSviewer ve R tabanlı Biblioshiny programları kullanılmıştır. 1955-2023 tarihleri arasında 807 çalışmaya ulaşılmıştır. Dünya genelinde İsveç, 149 (%18,46) makale ile en üretken ülke olmuştur. Acta Obstetricia et Gynecologica Scandinavica ve BMC Pregnancy and Childbirth dergilerinde 45’er doküman yayınlanmıştır. En üretken yazar, Hildingsson'du (n=25). “Psychometric aspects of the W-DEQ; A new questionnaire for the measurement of fear of childbirth” başlıklı çalışma en çok atıf yapılan makale olmuştur ve 509 atıf almıştır. Son yıllarda doğum korkusu araştırmalarına artan bir ilgi vardır. Doğum korkusu ve sonuçları önemli bir halk sağlığı sorunudur. Türkiye gibi doğum ve sezaryen doğum oranlarının yüksek olduğu ülkelerdeki araştırmacıların, bu alandaki araştırma projelerinin teşvik edilmesi önem arz etmektedir.