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• MC activation is linked with actin changes meeting the functional requirements. • Chemoattractant-induced actin rearrangements support MC migration and inhibit degranulation. • The secretory actin phenotype overrides the migratory phenotype upon encounter of a secretagogue. • Actin rearrangements have a direct impact on FcεRI-elicited signaling. The application of high and super-resolution microscopy techniques has extended the possibilities of studying actin dynamics in mast cells (MCs). These studies demonstrated the close correlation between actin-driven changes in cell morphology and the functions that MC perform during their life cycle. Dynamic conversions between actin polymerization and depolymerization support MC degranulation and leading to the release of the preformed, secretory granule (SG)-contained, inflammatory mediators. Cell flattening inflicting an actin porous geometry and clearing of cortical actin, characterize the secretory actin phenotype. In contrast, pericentral actin clusters, that entrap the SGs, characterize the migratory actin phenotype, which supports MC migration, but restricts MC degranulation. Multiple actin binding and actin interacting proteins regulate these actin rearrangements, in compliance with the signals elicited by the respective activating receptors. Here, we review recent findings on the interplay between the actin cytoskeleton and MC migration and degranulation. [ABSTRACT FROM AUTHOR]

Actin remodeling is a key regulator of mast cell (MC) migration and secretion. However, the precise mechanism underlying the coordination of these processes has remained obscure. We sought to characterize the actin rearrangements that occur during MC secretion or chemotactic migration and identify the underlying mechanism of their coordination. Using high-resolution microscopy, we analyzed the dynamics of actin rearrangements in MCs triggered to migration by IL-8 or prostaglandin E 2 or to FcεRI-stimulated secretion. We show that a major feature of the actin skeleton in MCs stimulated to migration is the buildup of pericentral actin clusters that prevent cell flattening and converge the secretory granules (SGs) in the cell center. This migratory phenotype is replaced on encounter of an IgE cross-linking antigen that stimulates secretion through a secretory phenotype characterized by cell flattening, reduction of actin mesh density, ruffling of cortical actin, and mobilization of SGs. Furthermore, we show that knockdown of mammalian diaphanous-related formin 1 (mDia1) inhibits chemotactic migration and its typical actin rearrangements, whereas expression of an active mDia1 mutant recapitulates the migratory actin phenotype and enhances cell migration while inhibiting FcεRI-triggered secretion. However, mice deficient in mDia1 appear to have normal numbers of MCs in various organs at baseline. Our results demonstrate a unique role of actin rearrangements in clustering the SGs and inhibiting their secretion during MC migration. We identify mDia1 as a novel regulator of MC response that coordinates MC chemotaxis and secretion through its actin-nucleating activity. [ABSTRACT FROM AUTHOR]

Reactions of bis(2-pyridyl)diselenide, py 2 Se 2 (py = 2-C 5 H 4 N) with [(Ph 3 P)AuCl], [(Ph 3 P)CuCl] and CuCl 2 ·2H 2 O result in the formation of the complexes [Au(pyHSe) 2 ]Cl ( 1 ), [Cu 4 (pySe) 4 ] ( 2 ) and [Cu(py 2 Se 2 )Cl 2 ] ( 3 ) respectively. When the compounds 2 and 3 are exposed to air, they form the polymeric compound [Cu(pySeO 2 ) 2 ] n ( 4 ), which contains 2-pyridylseleninic species [pySeO 2 ] − . Compound 4 is also obtained by the reaction of py 2 Se 2 and CuBr followed by spontaneous oxidation in air. All compounds were characterized by single-crystal X-ray diffraction, elemental analysis, and infrared spectroscopy. [ABSTRACT FROM AUTHOR]

Thiocarbamoylbenzimidophenylselenide and -telluride have been prepared from N -[ N ′, N′ -methylphenylamino(thiocarbonyl)]benzimidoyl chloride and the in situ -prepared phenylselenolate or -tellurolate, and their structures have been determined by X-ray diffraction. The air-stable compounds react with metal ions such as HgCl 2 , PdCl 2 or Pd(acetate) 2 under cleavage of their C N or C–Se/Te bonds. The decomposition fragments react with the transition metal ions under formation of stable products such as [HgCl(SePh)] ∞ , (3-methylphenylamino-5-phenyl-1,2,4-dithiazolium) 2 [HgCl 4 ], [Pd(MePhbtu) 2 ] (HMePhbtu = N -methyl- N -phenyl-N′-benzoylthiourea) or [Pd(MePhtu) 4 ]Cl 2 (MePhtu = N -methyl- N -phenylthiourea). The products have been isolated in crystalline form and characterized spectroscopically and by X-ray structure analysis. [ABSTRACT FROM AUTHOR]

Abstract: (NEt4)2[Re(CO)3Br3] or (NEt4)2[Tc(CO)3Cl3] react with bis(2-pyridyl)phenylphosphine (PPhpy2) or tris(2-pyridyl)phosphine (Ppy3) under formation of neutral tricarbonyl complexes of the composition [M(CO)3X(L)] (M=Re, X=Br; M=Tc, X=Cl; L=PPhpy2 or Ppy3). In all isolated products, the ligands coordinate solely via two of their nitrogen atoms. All attempts to force a tripodal coordination of the phosphinopyridines failed. Removal of the bromo ligands from (NEt4)2[Re(CO)3Br3] by the addition of AgNO3 in THF/water, and subsequent reaction of the resulting [Re(CO)3(THF)3](NO3)with Ppy3 yielded the complex [Re(CO)3(NO3)(Ppy3-N,N′)] with a monodentate coordinated nitrato ligand. The products have been characterized spectroscopically and by X-ray structure analyses. [Copyright &y& Elsevier]

Cyclization reactions dominated attempts to synthesize N -alkyl- or N -dialkyl- N ′-benzoylthiourea ligands having an alkyne group at the amine residue. While exclusively thiazolidine or thiazole derivatives could be isolated during reactions of benzoyl chloride, (NH 4 )SCN and N -methypropargylamine, an open-chain benzoylthiourea was obtained with unsubstituted propargylamin. But also the latter product isomerized under the influence of a strong base and heat to the corresponding cyclic derivatives. The resulting heterocycles, a 5-methylenthiazolidine (HL4) and a 5-methylthiazole (HL5), react with (NBu 4 )[ReOCl 4 ]/PPh 3 mixtures or [ReOCl 3 (PPh 3 ) 2 ] under formation of the neutral Re(III) complex [ReCl 2 (PPh 3 ) 2 (L4)] and the cationic Re(V) compound [ReO 2 (PPh 3 ) 2 (HL5)], respectively. The products have been isolated in crystalline form and studied spectroscopically and by X-ray diffraction. [ABSTRACT FROM AUTHOR]

To encapsulate the clinical and technical insights from three years of implementing pelvic online adaptive radiotherapy (oART) using a Cone Beam Computed Tomography (CBCT)-guided system at a single institution. Our study seeks to identify the predominant failure modes observed from our experience and outline potential strategies for system and process enhancement. An in-depth review was conducted on over 1000 adaptive sessions for nearly 50 patients undergoing pelvic oART. The review encompasses the entire oART workflow: reference treatment planning, session imaging, contouring, treatment planning, plan selection, quality assurance (QA), and delivery, with a focus on identifying primary failure modes. Failure modes were analyzed through detailed root cause analysis with a team of physicists, dosimetrists, therapists, and radiation oncologists. Our investigation revealed several failure modes: (1) significant intra-fractional gas changes affecting target and organ-at-risk (OAR) deformation and positioning, sometimes leading to aborting the session and restarting later; (2) unintended alignment issues due to hardcoded auto-matching; (3) creation of excessively high dose areas > 125% in adaptive plans due to limited MLC range and imaging shifts; (4) process termination from contour extensions beyond body limits; (5) operator errors in manual contour importing; (6) alterations in root structure(s) after Boolean contour operations leading to automated structures failing to propagate; (7) reduced auto-contouring accuracy due to imaging artifacts; (8) RT intent not optimal for adaptive plan optimization due to anatomy changes; and (9) variability in monitor unit (MU), hot spot occurrences, and locations caused by the stochastic nature of the oART optimizer. Root causes of these failure modes originated primarily in treatment planning (modes 3, 5, 6, and 8), on-couch workflow (modes 2, 4, 7, 8, and 9), and patient changes (modes 1, 2, 3, 4, 7, 8, and 9). Detailed root causes and strategies to address these issues will be discussed. CBCT-guided oART emerges as an integrated and efficient solution for tailoring daily radiation treatment plans to changing anatomies, thereby restoring optimal therapeutic ratios. Unique and unanticipated failure modes will exist in any new technology. Our retrospective analysis sheds light on failure modes observed in our clinical experience. Periodic review and team learning from encountered failures is an important step in continual quality improvement for emerging techniques and workflows. [ABSTRACT FROM AUTHOR]

PhTe(CH 2 ) 3 NH 3 Cl ( 1 ) is readily converted to [PhTeX 2 (CH 2 ) 3 NH 3 ]X (X = Cl: 2 , X = Br: 3 ) either by reactions with X 2 (X = Cl, Br) or by air oxidation after treatment with concentrated HX (X = Cl, Br). Similar reactions with HI or I 2 resulted in the formation of unattractive viscous oils only. Solutions of compound 1 are stable on air under slightly acidic conditions, but undergo a reaction with CO 2 from the air under formation of the corresponding carbamate, when aqueous ammonia or NEt 3 are added. The reaction is more efficient when CO 2 is bubbled through the solution. The ion pair [PhTe(CH 2 ) 3 NH 3 ] + [PhTe(CH 2 ) 3 NHCO 2 ] − is formed from such solutions in high yields. The products have been studied spectroscopically and by X-ray diffraction. [ABSTRACT FROM AUTHOR]

Abstract: Reactions of 3,3,3′,3′-tetraethyl-1,1-isophthaloylbis(thiourea), H2L1a, with InCl3, Pb(acetate)2, [AuCl(PPh3)] and [CuCl(PPh3)]4 gave complexes of the compositions [In2(L1a-κO,S)3], [{Pb(L1a-κO,S)}2]∞, [{Au(PPh3)}2(L1a-κS)] and [{Cu(L1a-κO,S)}2], respectively. The products have been studied spectroscopically and by single-crystal X-ray diffraction. Depending on the specific requirements of the metal ions used, complexes of completely different basic structures have been obtained: a binuclear complex with two octahedrally coordinated indium atoms, a polymeric lead compound with two differently coordinated Pb2+ ions, a binuclear gold compound in which two {Au(PPh3)}+ building blocks are connected by a L1a2− ligand and a binuclear copper(II) complex with two cis-coordinated metal centers. [Copyright &y& Elsevier]

Abstract: Potentially tetradentate, binegative thiocarbamoylbenzamidines derived from o-phenylenediamines (H2L or H3L) are shown to be suitable ligand systems for oxidorhenium(V) cores. They readily react with (NBu4)[ReOCl4] or [ReOCl3(PPh3)2] under formation of monoxido complexes of the composition [ReO{(H)L}(Y)] with various co-ligands (Y=ReO4 −, F3CCO2 −, Cl− or methanol) or μ-oxido dimers depending on the reaction conditions applied. Representative products were isolated and studied spectroscopically and by X-ray diffraction. Substitutions in the periphery of the ligands allow the introduction of a carboxylic substituent, which may serve as anchor group for future bioconjugation of appropriate rhenium (or technetium) complexes. [Copyright &y& Elsevier]

Abstract: A series was neutral platinum(II) complexes bearing OCH3- or F-substituted 3,4-bis(4-fluorophenyl)-1,6-bis(2-hydroxyphenyl)-2,5-diazahexa-1,5-dienes (diarylsalenes) were synthesized and tested for in vitro antitumour activity. The growth inhibitory effects depended on the configuration and the substitution pattern of the salicylidene moiety. The lead compound [meso-3,4-bis(4-fluorophenyl)-1,6-bis(2-hydroxyphenyl)-2,5-diazahexa-1,5-diene]platinum(II) (1-Pt) reduced the cell growth of MCF-7 (IC50 = 7.6 μM) and MDA-MB 231 cells (IC50 = 10.0 μM), but was inactive against HT-29 cells at the used concentration range (IC50 > 20 μM). The change of the configuration (meso→d,l) at the 1,2-diimino-1,2-diarylethane bridge and methoxy substitution led to completely inactive compounds, while fluorine substituents increased the antiproliferative effects depending on their position (3-F < 5-F < 4-F < 6-F). Complex 10-Pt (6-F: IC50(MCF-7) = 1.5 μM, IC50(MDA-MB 231) = 1.3 μM, IC50 (HT-29) = 2.6 μM) was as active as cisplatin (IC50(MCF-7) = 1.6 μM, IC50(MDA-MB 231) = 1.5 μM, IC50(HT-29) = 4.1 μM). [Copyright &y& Elsevier]

Abstract: A novel class of silver N-heterocyclic carbene complexes (5a–f) were synthesized in high yield by reacting silver(I) oxide with 4,5-diarylimidazolium halides (4a–f). The complexes were characterized using NMR and IR spectroscopy. The structure was confirmed on the example of bromo[1,3-diethyl-4,5-bis(4-fluorophenyl)imidazol-2-ylidene]silver(I) (5c) by crystal structure analysis. The X-ray structure indicated a three-dimensional coordination polymer with a repeating unit consisting of a Ccarben-Ag2-Br2-Ccarben cluster. Pharmacological investigations revealed that all silver complexes possessed growth inhibitory effects against breast cancer (MCF-7 and MDA-MB-231) as well as colon carcinoma (HT-29) cells. The most active compound 5c was slightly less active against MCF-7 cells, more active against MDA-MB-231 cells and comparable active as cisplatin against HT-29 cells. Further pharmacological investigations were performed with selected compounds on estrogen receptor (ER) binding, DNA intercalation, cyclooxygenase (COX) inhibition and antibacterial activity. The complexes were only marginally active at the DNA, ER and the COX enzymes, so these targets can be excluded to be involved in the mode of action. However, the growth of bacteria was significantly inhibited by 5c and 5f and opens a new application of this complex type. [Copyright &y& Elsevier]

• Thiosemicarbazonate complexes containing the (ReNPh)3+ core have been successfully prepared. • Three complexes were studied by single-crystal X-ray diffraction. • A "3 + 2" mixed-ligand complex was obtained in order to completely envelope the metal center. • A prototype compound with potential for couplings to biomolecules was designed by means of DFT calculation. Reactions of thiosemicarbazone ligands (H 2 L1) with [ReX 3 (NPh)(PPh 3) 2 ] (X = Cl or Br) led to the formation of stable rhenium(V) complexes of composition [ReX(NPh)(HL1)(PPh 3)]X. The Re(V) complexes have been characterized by diverse techniques including FTIR, 1H and 31P NMR, elemental analysis, HRMS and single-crystal X-ray diffraction analysis. The crystal structures of the complexes rhenium complexes showed the formation a distorted octahedron environment around the Re(V) metal center, with the axial positions being occupied by the halogen atom and by the nitrogen atom from the phenylimido moiety, while the equatorial positions are occupied by the S,N,S -thiosemicarbazonate and the triphenylphosphane ligands. Furthermore, the "3 + 2" mixed ligand complex [Re(NPh)(L1b)(Et 2 btu)], where HEt 2 btu is N,N -diethyl- N '-benzoylthiourea, could be obtained from an equimolar reaction of [ReCl(NPh)(HL1)(PPh 3)]Cl with the bidentate thiourea in the presence of NEt 3. Finally, DFT calculations were applied in order to propose a complex suitable for biocouplings upon substitution of a NH 2 group at the 4-position of the phenylimido ligand in [Re(NPh)(L1b)(Et 2 btu)]. The compounds studied here represent the first examples of phenilimidorhenium(V) complexes with thiosemicarbazones. [ABSTRACT FROM AUTHOR]

Our department has recently commissioned a CBCT-guided online adaptive radiation therapy (ART) platform, one of the first of its kind in the United States. The implementation of this novel technology has revealed unique failure modes to the workflow with on-couch ART. We have performed root-cause analyses (RCA) on three unexpected failure modes, quantified the impact to patient care and clinical workflow, and implemented quality control measures to mitigate the likelihood of these failure modes from impacting patient care. We identified three unique failure modes in the first three months of operating the machine clinically. Each failure mode underwent RCA with a team of physicists, dosimetrists, therapists, and oncologists. Key items that contributed to the events reaching the patient were identified at each step in the planning and treatment workflow. Impact on patient treatment was rated following the guidance of TG-100. Mitigation measures were identified and implemented within our clinical workflows. The three unique failure modes identified were: incorrect on-couch target contouring, automated structures failing to propagate, and OAR contours existing outside the body resulting in on-couch session failures. RCA identified that the on-couch target contouring was a risk at each adaptive session, while the other two failure modes originated in the planning stage. Incorrect on-couch target contouring was rated as the highest risk for ART by our team as it was the most difficult failure to detect in real-time and prone to several contributing factors, such as poor initial target propagation and artifacts on the daily CBCT. Team familiarity with the new technology was a contributing factor, coupled with a lack of global warning messages within the system reporting. Mitigation strategies included establishing easily-identifiable anatomic landmarks for target extent, modification of existing checklists to systematically incorporate the RT Intent Report generated by the ART platform into our pre-existing Oncology Information System, and trimming of specific organs at risk away from the body contour. Product improvement requests for the on-couch structures outside of body and failure of derived structures to propagate failure modes have been lodged with the vendor to improve warnings presented to the user during final clinical review. We have not encountered further failures following implementation of these control measures. Unique and unanticipated failure modes will exist in any new technology. We have identified three failure modes unique to this CBCT-guided, online ART platform and implemented systematic controls to mitigate future failures. Periodic review and team learning from encountering failures is an important step in continual quality improvement for emerging techniques. [ABSTRACT FROM AUTHOR]

Abstract: N-(Dialkylthiocarbamoyl)-N′-picolylbenzamidines (HLEt and HLMorph) react with NiCl2, CuCl2 and [PdCl2(MeCN)2] with the formation of complexes of the general composition [M(LR)Cl] (M=Ni (1), Pd (2)) and the dimeric complexes [{Cu(LR)Cl}2] (3). The molecular structures of complexes 1 and 2 exhibit a square-planar coordination sphere, in which the organic ligands coordinate in a S,N,N coordination mode. The two subunits of 3, the arrangement of each is similar to those of 1 and 2, are connected via two weak Cu–Cl′ bonds. The copper complexes [{Cu(LR)Cl}2] (3) are slowly oxidized under aerobic conditions to give [{Cu(∗LR)Cl}2] complexes (4), where H∗LR =N-(dialkylthiocarbamoyl)-N′-picolinoylbenzamidines. Complexes 1 and 2 show a very weak reduction of the growth of human MCF-7 breast cancer cells. Complexes 4, however, possess a remarkable cytotoxicity with IC50 values within the range 0.40–1.05μM. Compounds 3 are likely converted to 4 under the conditions of the cytotoxicity assay, and consequently exhibit IC50 values very similar to those found for 4. [Copyright &y& Elsevier]