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Additive manufacturing (AM) technologies have advanced from rapid prototyping to becoming viable manufacturing solutions, offering users both design flexibility and mechanical properties that meet ISO/ASTM standards. Powder bed fusion using a laser beam (PBF-LB), a popular additive manufacturing process (aka 3D printing), is used for the cost-effective production of high-quality products for the medical, aviation, and automotive industries. Despite the growing variety of metallic powder materials available for the PBF-LB process, there is still a need for new materials and procedures to optimize the processing parameters before implementing them into the production stage. In this study, we explored the use of a checkerboard scanning strategy to create samples of various sizes (ranging from 130 mm3 to 8000 mm3 using parameters developed for a small 125 mm3 piece). During the PBF-LB process, all samples were fabricated using Ti grade 2 and were in situ alloyed with a precisely controlled amount of oxygen (0.1–0.4% vol.) to enhance their mechanical properties using a solid solution strengthening mechanism. The samples were fabricated in three sets: I. Different sizes and orientations, II. Different scanning strategies, and III. Rods for high-cycle fatigue (HCF). For the tensile tests, micro samples were cut using WEDM, while for the HCF tests, samples were machined to eliminate the influence of surface roughness on their mechanical performance. The amount of oxygen in the fabricated samples was at least 50% higher than in raw Ti grade 2 powder. The O2-enriched Ti produced in the PBF-LB process exhibited a tensile strength ranging from 399 ± 25 MPa to 752 ± 14 MPa, with outcomes varying based on the size of the object and the laser scanning strategy employed. The fatigue strength of PBF-LB fabricated Ti was 386 MPa, whereas the reference Ti grade 2 rod samples exhibited a fatigue strength of 312 MPa. Our study revealed that PBF-LB parameters optimized for small samples could be adapted to fabricate larger samples using checkerboard (“island”) scanning strategies. However, some additional process parameter changes are needed to reduce porosity.

Bacteria secrete various iron-chelators (siderophores), which scavenge Fe3+ from the environment, bind it with high affinity, and retrieve it inside the cell. After the Fe3+ uptake, bacteria extract the soluble iron(II) from the siderophore. Ferric siderophores are transported inside the cell via the TonB-dependent receptor system. Importantly, siderophore uptake paths have been also used by sideromycins, natural antibiotics. Our goal is to hijack the transport system for hydroxamate-type siderophores to deliver peptide nucleic acid oligomers into Escherichia coli cells. As siderophore mimics we designed and synthesized linear and cyclic Nδ-acetyl-Nδ-hydroxy-l-ornithine based peptides. Using circular dichroism spectroscopy, we found that iron(III) is coordinated by the linear trimer with hydroxamate groups but not by the cyclic peptide. The internal flexibility of the linear siderophore oxygen atoms and their interactions with Fe3+ were confirmed by all-atom molecular dynamics simulations. Using flow cytometry we found that the designed hydroxamate trimer transports PNA oligomers inside the E. coli cells. Growth recovery assays on various E. coli mutants suggest the pathway of this transport through the FhuE outer-membrane receptor, which is responsible for the uptake of the natural iron chelator, ferric-coprogen. This pathway also involves the FhuD periplasmic binding protein. Docking of the siderophores to the FhuE and FhuD receptor structures showed that binding of the hydroxamate trimer is energetically favorable corroborating the experimentally suggested uptake path. Therefore, this siderophore mimic, as well as its conjugate with PNA, is most probably internalized through the hydroxamate pathway.

This paper presents the research results on the influence of vibration abrasive machining parameters on the surface layer integrity of elements made by LPBF technology from Inconel 939. The research was carried out on samples of various sizes on vibrating smoothing machines. The influence of the size of the processed elements, the type of abrasive shapes, the processing time, and the supporting fluid on the surface roughness and microstructure of the processed elements was analyzed. Tests have shown that as a result of using vibration processing, it is possible to reduce the surface roughness five times to the value of Ra = 1.1 µm. A significant influence of the type of abrasive shapes was found. There was no significant effect of the machining fluid on the process.

In this study, we examined the effects of an aluminization process on the microstructure and texture of Haynes 282 nickel samples fabricated using the direct metal laser sintering technique. The aluminization process involved the use of chemical vapor deposition with AlCl3 vapors in a hydrogen atmosphere at a temperature of 1040 °C for 8 h. Following the 3D printing and aluminization steps, we analyzed the microstructure of the Haynes 282 nickel alloy samples using light microscopy and scanning electron microscopy. Additionally, we investigated the texture using X-ray diffractometry. A texture analysis revealed that after the process of direct laser sintering of metals, the texture of the Haynes 282 nickel alloy samples developed a texture typical of cast materials. Then, in the aluminization process, the texture was transformed—from foundry-type components to a texture characteristic of recrystallization.

Single Point Incremental Forming (SPIF) is an unconventional forming process that is suitable for prototype production and small lot production due to the economical tooling cost, short lead time, and the ability to create symmetrical and asymmetrical complex geometries without the use of expensive dies. This article presents the effect of the step size Δz of a forming tool made of 145Cr6 tool steel on the formability and maximum forming angle, mechanical properties, hardness, surface roughness, microstructure and texture of bimetallic Al/Cu sheets. Experiments were conducted at a constant rotational speed and feed rate, with the use of rapeseed oil as a lubricant. The tests were carried out with the use of a forming tool on both sides of the bimetallic sheet. The shape and dimensions of the formed elements are determined by non-contact optical 3D scanning. It has been proved that an increase in the step size Δz affects the deterioration of the surface quality of the specimens (an increase in the Ra parameter from 0.2 μm to approximately 3 μm for the step size of 1.2 mm), while a small step size down Δz favours the geometric stability of the samples. With increasing step size (at Δx = Δy = const.), the drawpiece wall continually thinned until the material fractured. Based on the results, it was shown that increasing the step size Δz over 1.1 mm causes cracking of the drawpieces. Furthermore, greater thinning of the Al/Cu sheet was observed in the range of step size Δz between 0.7 and 1.0 mm for aluminum side and step size Δz ≤ 0.6 mm and Δz ≥ 1.1 mm for copper side. It was also found that the mechanical properties of the bimetal sheet decreased as a result of incremental forming. The greatest decrease in strength and ductility was recorded for a pitch of 1.2 mm. Strength decreased from 230 MPa (for sheet in initial state) to approximately 80 MPa, elongation from 12% to approximately 8.5%, and hardness from 120 HV10 for Cu and 60 HV10 for Al to approximately 30 HV10 for both layers.

Novel evidence is presented allowing further clarification of the mechanism of the slow-binding thymidylate synthase (TS) inhibition by N4-hydroxy-dCMP (N4-OH-dCMP). Spectrophotometric monitoring documented time- and temperature-, and N4-OH-dCMP-dependent TS-catalyzed dihydrofolate production, accompanying the mouse enzyme incubation with N4-OH-dCMP and N5,10-methylenetetrahydrofolate, known to inactivate the enzyme by the covalent binding of the inhibitor, suggesting the demonstrated reaction to be uncoupled from the pyrimidine C(5) methylation. The latter was in accord with the hypothesis based on the previously presented structure of mouse TS (cf. PDB ID: 4EZ8), and with conclusions based on the present structure of the parasitic nematode Trichinella spiralis, both co-crystallized with N4-OH-dCMP and N5,10-methylenetetrahdrofolate. The crystal structure of the mouse TS-N4-OH-dCMP complex soaked with N5,10-methylenetetrahydrofolate revealed the reaction to run via a unique imidazolidine ring opening, leaving the one-carbon group bound to the N(10) atom, thus too distant from the pyrimidine C(5) atom to enable the electrophilic attack and methylene group transfer.

A homo-dimeric enzyme, thymidylate synthase (TS), has been a long-standing molecular target in chemotherapy. To further elucidate properties and interactions with ligands of wild-type mouse thymidylate synthase (mTS) and its two single mutants, H190A and W103G, spectroscopic and theoretical investigations have been employed. In these mutants, histidine at position 190 and tryptophan at position 103 are substituted with alanine and glycine, respectively. Several emission-based spectroscopy methods used in the paper demonstrate an especially important role for Trp 103 in TS ligands binding. In addition, the Advanced Poisson–Boltzmann Solver (APBS) results show considerable differences in the distribution of electrostatic potential around Trp 103, as compared to distributions observed for all remaining Trp residues in the mTS family of structures. Together, spectroscopic and APBS results reveal a possible interplay between Trp 103 and His190, which contributes to a reduction in enzymatic activity in the case of H190A mutation. Comparison of electrostatic potential for mTS complexes, and their mutants, with the substrate, dUMP, and inhibitors, FdUMP and N4-OH-dCMP, suggests its weaker influence on the enzyme–ligand interactions in N4OH-dCMP-mTS compared to dUMP-mTS and FdUMP-mTS complexes. This difference may be crucial for the explanation of the ”abortive reaction” inhibitory mechanism of N4OH-dCMP towards TS. In addition, based on structural analyses and the H190A mutant capacity to form a denaturation-resistant complex with N4-OH-dCMP in the mTHF-dependent reaction, His190 is apparently responsible for a strong preference of the enzyme active center for the anti rotamer of the imino inhibitor form.

With the aim to identify novel inhibitors of parasitic nematode thymidylate synthase (TS), we screened in silico an in-house library of natural compounds, taking advantage of a model of nematode TS three-dimensional (3D) structure and choosing candidate compounds potentially capable of enzyme binding/inhibition. Selected compounds were tested as (i) inhibitors of the reaction catalyzed by TSs of different species, (ii) agents toxic to a nematode parasite model (C. elegans grown in vitro), (iii) inhibitors of normal human cell growth, and (iv) antitumor agents affecting human tumor cells grown in vitro. The results pointed to alvaxanthone as a relatively strong TS inhibitor that causes C. elegans population growth reduction with nematocidal potency similar to the anthelmintic drug mebendazole. Alvaxanthone also demonstrated an antiproliferative effect in tumor cells, associated with a selective toxicity against mitochondria observed in cancer cells compared to normal cells.

Additive Manufacturing (AM) methods are generally used to produce an early sample or near net-shape elements based on three-dimensional geometrical modules. To date, publications on AM of metal implants have mainly focused on knee and hip replacements or bone scaffolds for tissue engineering. The direct fabrication of metallic implants can be achieved by methods, such as Selective Laser Melting (SLM) or Electron Beam Melting (EBM). This work compares the SLM and EBM methods used in the fabrication of titanium bone implants by analyzing the microstructure, mechanical properties and cytotoxicity. The SLM process was conducted in an environmental chamber using 0.4–0.6 vol % of oxygen to enhance the mechanical properties of a Ti-6Al-4V alloy. SLM processed material had high anisotropy of mechanical properties and superior UTS (1246–1421 MPa) when compared to the EBM (972–976 MPa) and the wrought material (933–942 MPa). The microstructure and phase composition depended on the used fabrication method. The AM methods caused the formation of long epitaxial grains of the prior β phase. The equilibrium phases (α + β) and non-equilibrium α’ martensite was obtained after EBM and SLM, respectively. Although it was found that the heat transfer that occurs during the layer by layer generation of the component caused aluminum content deviations, neither methods generated any cytotoxic effects. Furthermore, in contrast to SLM, the EBM fabricated material met the ASTMF136 standard for surgical implant applications.

Abstract In this work we investigate the spin-dependent transport through a double quantum dot embedded in a ferromagnetic tunnel junction and side attached to a topological superconducting nanowire hosting Majorana zero-energy modes. We focus on the transport regime when the Majorana mode leaks into the double quantum dot competing with the two-stage Kondo effect and the ferromagnetic-contact-induced exchange field. In particular, we determine the system’s spectral properties and analyze the temperature dependence of the spin-resolved linear conductance by means of the numerical renormalization group method. Our study reveals unique signatures of the interplay between the spin-resolved tunneling, the Kondo effect and the Majorana modes, which are visible in the transport characteristics. In particular, we uncover a competing character of the coupling to topological superconductor and that to ferromagnetic leads, which can be observed already for very low spin polarization of the electrodes. This is signaled by an almost complete quenching of the conductance in one of the spin channels which is revealed through perfect conductance spin polarization. Moreover, we show that the conductance spin polarization can change sign depending on the magnitude of spin imbalance in the leads and strength of interaction with topological wire. Thus, our work demonstrates that even minuscule spin polarization of tunneling processes can have large impact on the transport properties of the system.

Enterobacterales (especially carbapenem-resistant) are considered an urgent threat to public health. The available antibiotic therapy is limited due to the increase of multidrug-resistant (MDR) strains. Tigecycline, a minocycline derivative, has emerged as a potential key agent in the treatment of MDR isolates. The aim of the study was to evaluate the synergistic effect of tigecycline in combination with nine antimicrobial agents—ceftazidime/avibactam, colistin, ertapenem, gentamicin, imipenem, levofloxacin, meropenem/vaborbactam, polymyxin B, and rifampicin. Eighty clinical Enterobacter cloacae strains were obtained from patients of two University Hospitals in Bialystok, Poland. The E-test method was used to determine synergistic interactions. Among all combinations, synergy was reported in 61% of cases, addition in 32%, and indifference in 7%. The highest synergy rates were observed in tigecycline combinations with: ceftazidime/avibactam (60/80; 75%), imipenem (60/80; 75%), polymyxin B (55/80; 68.75%) and rifampicin (55/80; 68.75%), while the lowest synergy rate was noted in tigecycline-levofloxacin (26/80; 32.5%). The tigecycline-gentamicin showed the highest rate of indifference; antagonism, was not observed in any combination. In conclusion, tigecycline appears more suitable for use in combination therapy rather than as monotherapy and can be effectively paired with various antimicrobial agents against MDR E. cloacae. Further research will be necessary to confirm these results.

Abstract Background Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann’s procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P

Objectives The aim of the undertaken research was to present the role of a new specialist in the system of mainstream education, i.e. a special educator - in the perception of teachers Material and methods In order to gather empirical material, a diagnostic survey method was used, which included an author's questionnaire consisting of 20 open and closed questions. The survey covered 127 teachers of kindergartens, primary and secondary general public schools, mainly from the south of Poland. The selection of people for the study was purposive, but despite this, a distribution similar to the population structure was obtained Results The results of the study indicate that the vast majority of the surveyed teachers of mainstream schools, as many as 87%, see not only the need, but even the necessity for a special educator. He or she should play the role of coordinator in the team of specialists employed in mainstream educational institutions. The surveyed teachers indicated as the main tasks of the special educator the conduct of therapeutic classes, cooperation with the psychological-educational counselling centre, adaptation of the teaching process to the special needs of students. Conclusions Teachers of mainstream education consider the creation of a new position of special educator as a necessity in the current phase of development of inclusive education.

Abstract Purpose The objective of the study was to assess whether the history of psychiatric treatment was associated with (1) body weight and BMI on admission for bariatric surgery, (2) weight loss > 5 kg prior to bariatric surgery, and (3) postoperative body weight reduction. Methods Data from medical records of all consecutive patients admitted for surgical treatment of obesity in the 2nd Department of General Surgery Jagiellonian University Medical College were obtained. There were 1452 records of patients who underwent bariatric surgery between 2009 and 2021 included in the study. Results History of psychiatric treatment was found in 177 (12%) of the sample and was inversely associated with body weight and BMI on admission for surgery in women. Men with history of psychiatric treatment were 54% less likely to lose > 5 kg before the surgery (OR = 0.46 95% CI = 0.24–0.88). Both in men and women %TWL did not differ significantly by history of psychiatric treatment (Me: 40.7 vs. 45.9; p = 0.130 and Me: 27.0 vs. 23.9; p = 0.383, respectively). After adjustment for covariates no association was found between history of psychiatric treatment and body weight reduction one year after surgery. Conclusion Although men with preoperative history of psychiatric treatment had lower odds of losing weight before the surgery, psychiatric treatment did not differentiate the effectiveness of bariatric treatment in 1 year of observation. Bariatric surgery appears to be an effective obesity care for people treated for mental disorders. Level of evidence: III Evidence obtained from cohort or case-control analytic studies.

Abstract The increasing prevalence of bariatric surgery has resulted in a rise in the number of redo procedures as well. While redo bariatric surgery has demonstrated its effectiveness, there is still a subset of patients who may not derive any benefits from it. This poses a significant challenge for bariatric surgeons, especially when there is a lack of clear guidelines. The primary objective of this study is to evaluate the outcomes of patients who underwent Re-Redo bariatric surgery. We conducted a retrospective cohort study on a group of 799 patients who underwent redo bariatric surgery between 2010 and 2020. Among these patients, 20 individuals underwent a second elective redo bariatric surgery (Re-Redo) because of weight regain (15 patients) or insufficient weight loss, i.e. 50% EWL. The mean final %TWL was 34.2 ± 11.1% and final %EBMIL was 72.1 ± 20.8%. The mean BMI after treatment was 31.9 ± 5.3 kg/m2. Complications occurred in 3 of 20 patients (15%), with no reported mortality or need for another surgical intervention. The mean follow-up after Re-Redo was 35.3 months. Although Re-Redo bariatric surgery is an effective treatment for obesity, it carries a significant risk of complications.

In augmented reality scenarios, headphones obstruct the direct path of the sound to the ears, affecting the users’ abilities to localize surrounding sound sources and compromising the immersive experience. Unfortunately, the assessment of the perceptual implications of wearing headphones on localization in ecologically valid scenarios is costly and time-consuming. Here, we propose a model-based tool for automatic assessment of the dynamic localization degradation (DLD) introduced by headphones describing the time required to find a target in an auditory-guided visual search task. First, we introduce the DLD score obtained for twelve headphones and the search times with actual listeners. Then, we describe the predictions of the headphone-induced DLD score obtained by an auditory model designed to simulate the listener’s search time. Our results indicate that our tool can predict the degradation score of unseen headphones. Thus, our tool can be applied to automatically assess the impact of headphones on listener experience in augmented reality applications.