Pd-catalyzed intramolecular addition of active methylene compounds to alkynes with subsequent cross-coupling with (hetero)aryl halides

We report an efficient protocol for tandem Pd-catalyzed intramolecular addition of active methylene compounds to alkynes, followed by subsequent cross-coupling with (hetero)aryl bromides and chlorides. The reaction proceeds under mild conditions, providing excellent functional group tolerance, including unprotected OH, NH₂ groups, enolizable ketones, or a variety of heterocycles. Mechanistic studies point towards a catalytic cycle involving oxidative addition, intramolecular nucleophilic addition to the Pd(ii)-activated alkyne, and reductive elimination, with 5-exo-dig cyclization being the rate limiting step.

A tandem cyclization/coupling of acetylenic active methylene compounds with aryl halides features broad scope and excellent functional group compatibility. Mechanistic studies identified 5-exo-dig cyclization as the rate limiting step.     

Juvenile polyposis syndrome

Juvenile polyposis syndrome (JPS) is an autosomal dominant predisposition to the occurrence of hamartomatous polyps in the gastrointestinal tract. Diagnosis of JPS is based on the occurrence of numerous colon and rectum polyps or any number of polyps with family history and, in the case of juvenile polyps, their occurrence also outside the large intestine. The JPS is caused by mutations in SMAD4 and BMPR1A. Products of the SMAD4 gene are involved in signal transduction in the transforming growth factor β pathway and BMPR1A protein is a receptor belonging to the family of transmembrane serine/threonine kinases. Both proteins are responsible for processes determining appropriate development of colonic mucosa. The JPS belongs to the group of hamartomatous polyposes. The hamartomatous polyposis syndromes constitute a group of diseases in which manifestations differ slightly and only molecular diagnostics gives the possibility of verifying the clinical diagnosis.     

Comparison of Numerical Simulation Techniques of Ballistic Ceramics under Projectile Impact Conditions

This article presents an analysis of the effectiveness of available numerical techniques in mapping the characteristic behavior of ballistic ceramics under projectile impact conditions. As part of the work, the ballistic tests were performed on the layered ceramic/steel composite armor and tested with the 7.62 × 39 mm, armor-piercing incendiary (API) BZ projectile. The experimental tests were then mapped using computer simulations. In numerical analyses, four different techniques were used to describe cubic ceramic tiles Al₂O₃ placed on the ARMOX 500T steel backing plate, i.e.,: the Finite Element Method without Erosion (FEM), Finite Element with erosion (FEM + Erosion), Smoothed Particles Hydrodynamics (SPH) and a hybrid method that converts finite elements to SPH particles after exceeding the defined failure criteria (FEM to SPH conversion). The effectiveness of the individual methods was compared in terms of quality (mapping of characteristic phenomena occurring during the penetration process), quantity (bulge height of the backing plate) and time needed to complete the calculations. On the basis of the results of the experiments and numerical simulations, it was noticed that the most accurate reproduction of the phenomenon of ballistic impact of AP projectiles on ceramic/steel composite armor can be obtained by using a hybrid method, incorporating the conversion of finite elements into SPH particles. This method should be used in cases where accuracy of the results is more important than the time required to complete the calculations. In other situations where the purpose of the calculation is not to determine, for example, the exact value of penetration depth but only to observe a certain trend, the FEM method with defined erosion criteria (variant 2), which is more than 10 times faster, can be successfully used.     

Bioconjugation Strategy for Ceramic Membranes Decorated with Candida Antarctica Lipase B—Impact of Immobilization Process on Material Features

A strategy for the bioconjugation of the enzyme Candida antarctica lipase B onto titania ceramic membranes with varied pore sizes (15, 50, 150, and 300 kDa) was successfully performed. The relationship between the membrane morphology, i.e.,the pore size of the ceramic support, and bioconjugation performance was considered. Owing to the dimension of the enzyme (~33 kDa), the morphology of the ceramics allowed (50, 150, and 300 kDa) or did not allow (15 kDa) the entrance of the enzyme molecules into the porous structure. Such a strategy made it possible to better understand the changes in the material (morphology) and physicochemical features (wettability, adhesiveness, and surface charge) of the samples, which were systematically examined. The silane functionalization and enzyme immobilization were accomplished via the covalent route. The samples were characterized after each stage of the modification, which was very informative from the material point of view. As a consequence of the modification, significant changes in the contact angle, roughness, adhesion, and zeta potential were observed. For instance, for the 50 kDa membrane, the contact angle increased from 29.1 ± 1.5° for the pristine sample to 72.3 ± 1.5° after silane attachment; subsequently, it was reduced to 57.2 ± 1.5° after the enzyme immobilization. Finally, the contact angle of the bioconjugated membrane used in the enzymatic process rose to 92.9 ± 1.5°. By roughness (S_q) controlling, the following amendments were noticed: for the pristine 50 kDa membrane, S_q = 1.87 ± 0.21 µm; after silanization, S_q = 2.33 ± 0.30 µm; after enzyme immobilization, S_q = 2.74 ± 0.26 µm; and eventually, after the enzymatic process, S_q = 2.37 ± 0.27 µm. The adhesion work of the 50 kDa samples was equal to 136.41 ± 2.20 mN m⁻¹ (pristine membrane), 94.93 ± 2.00 mN m⁻¹ (with silane), 112.24 ± 1.90 mN m⁻¹ (with silane and enzyme), and finally, 69.12 ± 1.40 mN m⁻¹ (after the enzymatic process). The materials and physicochemical features changed substantially, particularly after the application of the membrane in the enzymatic process. Moreover, the impact of ceramic material morphology on the zeta potential value is here presented for the first time. With an increase in the ceramic support cut-off, the amount of immobilized lipase rose, but the specific productivity was higher for membranes possessing smaller pores, owing to the higher grafting density. For the enzymatic process, two modes of accomplishment were selected, i.e., stirred-tank and cross-flow. The latter method was characterized by a much higher effectiveness, with a resulting productivity equal to 99.7 and 60.3 µmol h⁻¹ for the 300 and 15 kD membranes, respectively.     

Method of Data Selection for Turning of Inconel 718 Alloy Obtained by Casting and Laser Sintering Powder

This article focuses on the issues related to the machining of DMLS (Direct Metal Laser Sintering) laser sintered parts made of Inconel 718 alloy. Longitudinal turning with CBN (cubic boron nitride) tool inserts is analyzed. The authors made an attempt to establish a procedure to find the optimal finishing cutting parameters while minimizing the specific cutting force and taking into account the machined surface quality criterion. During experiments the influence of cutting data on the values of cutting force and specific cutting force were performed. Moreover, the results of measurements of surface roughness parameters and the results of analysis of chip form are presented as well. Cast Inconel 718 has also been tested for comparative purposes. The variability of the material’s hardening state during machining was found, as well as the variability of the specific cutting force value as a function of the cross-sectional shape of the cutting layer. The values of all components of the total cutting force for turning the material obtained by the additive method are lower than for turning the cast material by approximately 32%. At the end of the article, the authors present an application of the proposed optimization algorithm. It was established that by changing the cross-section shape of the cutting layer, it was possible to perform the turning process at a specific cutting force value of 22% less, which is achieved by reducing the cross-section size.     

Coronary Stent Thrombosis in COVID-19 Patients: A Systematic Review of Cases Reported Worldwide

Approximately 5 million percutaneous coronary interventions are performed worldwide annually. Therefore, stent-related complications pose a serious public health concern. Stent thrombosis, although rare, is usually catastrophic, often associated with extensive myocardial infarction or death. Because little progress has been made in outcomes following stent thrombosis, ongoing research is focusing on further understanding the predictors as well as frequency and timing in various patient subgroups. Coronavirus disease-2019 (COVID-19), a viral illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), activates inflammatory mechanisms that potentially create a prothrombotic environment and increases the risk of local micro thromboembolism and all types of stent thrombosis. In-stent thrombosis occurrence increased during the COVID-19 pandemic, however, there is still lack of comprehensive studies describing this population. This review and worldwide analysis of coronary stent thrombosis cases related to COVID-19 summarizes all available data.