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The objective of this work is to analyse the performance of clear aligners made of thermoplastic materials. Within this framework, the damage evolution stages and damage states of the aligners at different cycles of the compressive loading are evaluated using the Acoustic Emission (AE) technique. Three different clear aligner systems were prepared: thermoformed PET-g (polyethylene terephthalate glycol) and PU (polyurethane), and additively manufactured PU. Cyclic compression tests are performed to simulate 22500 swallows. The mechanical results show that the energy absorbed by the thermoformed PET-g aligner remains stable around 4 Nmm throughout the test. Although the PU-based aligners show a higher energy absorption of about 7 Nmm during the initial phase of the cyclic loading, this gradually decreases after 12500 cycles. The time-domain based, and frequency-based parameters of the stress wave acoustic signals generated by the aligners under compression loading are used to identify the damage evolution stages. The machine learning-based AE results reveal the initiation and termination of the different damage states in the aligners and the frequency-based results distinguish the different damage sources. Finally, the microscopy results validated the damage occurrences in the aligners identified by the AE results. The mechanical test results indicate that the thermoformed PET-g has the potential to match the performance and requirements of the dentistry of the popular Invisalign (additively manufactured PU). The AE results have the potential to identify at which cycles the aligners may start losing their functionality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Membrane-based devices typically used for serum protein binding determination are not fully applicable to highly lipophilic compounds because of nonspecific binding to the device membrane. Ultracentrifugation, however, completely eliminates the issue by using a membrane-free approach, although its wide application has been limited. This lack of utilization is mainly attributed to 2 factors: the high cost in acquiring and handling of radiolabeled compounds and low assay throughput owing to the difficulties in process automation. To overcome these challenges, we report a high-throughput workflow by cassette ultracentrifugation of nonradiolabeled compounds followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Twenty compounds with diverse physicochemical and protein binding properties were selected for the evaluation of the workflow. To streamline the working process, approaches of matrix balancing for all the samples for LC-MS/MS analysis and determining free fraction without analytical calibration curves were adopted. Both the discrete ultracentrifugation of individual compounds and cassette ultracentrifugation of all the test compounds followed by simultaneous LC-MS/MS analysis exhibited a linear correlation with literature values, demonstrating respectively the validity of the ultracentrifugation process and the cassette approach. The cassette ultracentrifugation using nonradiolabeled compounds followed by LC-MS/MS analysis has greatly facilitated its application for high-throughput protein binding screening in drug discovery., (Copyright © 2016. Published by Elsevier Inc.)

A stochastic model of intracellular calcium oscillations is analytically studied. The governing master equation is expanded under the linear noise approximation and a closed prediction for the power spectrum of fluctuations analytically derived. A peak in the obtained power spectrum profile signals the presence of stochastic, noise induced oscillations which extend also outside the region where a deterministic limit cycle is predicted to occur., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In the erythrocyte, ankyrin is the major adapter protein linking tetramers of band 3 to the spectrin-actin cytoskeleton. This linkage involves a direct interaction between ankyrin and the 14th-15th repeat unit of beta-spectrin. The spectrin cytoskeleton itself is stabilized by the self-association of spectrin heterodimers into tetramers and larger oligomers, a process mediated by the 17th repeat unit of beta-spectrin and a short NH(2) -terminal sequence in alpha-spectrin. The self-association of spectrin and its ankyrin-mediated membrane binding have generally been considered independent events. We now demonstrate that spectrin self-association, the binding of spectrin to ankyrin, and the binding of ankyrin to the 43-kDa cytoplasmic domain of band 3 (cdb3) are coupled in a positively cooperative way. In solution, [(125)I]-labeled ankyrin was found by ND-PAGE3 to enhance the affinity of spectrin self-association by 10-fold. The reciprocal process was also true, in that spectrin tetramers and oligomers bound ankyrin with enhanced affinity relative to dimer spectrin. Saturation of the beta-spectrin self-association site by an NH(2) -terminal 80-kDa alpha-spectrin peptide enhanced the affinity of spectrin dimer for ankyrin, indicating a direct relationship between ankyrin binding and the occupancy of the beta-spectrin self-association site. cdb3 accentuated these cooperative interactions. Several inherited spectrin mutations that cause hemolytic disease but that do not directly destabilize the self-association or ankyrin-binding sites can be explained by these results. Three classes of mutations appear to disrupt cooperative coupling between self-association and ankyrin binding: (i) mutation of the linker sequences that join helices C and A in repeat units that intervene between the two functional sites, mutations that presumably block repeat-to-repeat transfer of conformational information; (ii) mutations in alpha-spectrin repeats 4 to 6 that disrupt the ability of this region to trans-regulate ankyrin binding by the adjacent beta-spectrin repeats 14-15; and (iii) exon-skipping mutations that shorten alpha-spectrin and force repeats 4 to 6 to fall out-of-register with the ankyrin-binding motif in beta-spectrin. Collectively, these results demonstrate a molecular mechanism whereby a membrane receptor can directly promote cytoskeletal assembly., (Copyright 2001 Academic Press.)

Background: Floxuridine (FUDR) and alpha-interferon (IFN) are active agents in advanced renal cell carcinoma, with different dose-limiting toxic effects and antitumor synergism in experimental models. The main purpose of this phase II study was to assess the activity and toxic effects of a combination of FUDR and alpha 2b-IFN in metastatic renal cell carcinoma., Patients and Methods: Metastatic renal cell carcinoma patients with measurable disease entered the study. FUDR was administered as a constant-rate continuous infusion for 14 days every 28 days at a starting daily dose of 0.1 mg/kg and with dose escalations of 0.025 mg/kg/day at each subsequent cycle if WHO > or = 2 toxicity had not occurred. IFN-alpha 2b 10 x 10(6) I.U. was administered intramuscularly 3 times per week., Results: Forty-two patients entered the study and a total of 272 cycles of FUDR + alpha 2b-IFN were administered. In 41 evaluable patients WHO grade III-IV toxic effects included nausea and vomiting (22%), diarrhea (32%), stomatitis (12%), fatigue (27%) and anorexia (12%). It was possible to increase the initial FUDR does in 21 (50%) patients; the median FUDR dose intensity was 0.35 mg/kg/week (range 0.18-0.54). Among 39 evaluable patients, 3 (7.5%) complete and 10 (25.5%) partial responses were observed (response rate 33%, 95% confidence interval (CI) 19%-50%) which lasted a median of 13 months (5.5-40+). Responses also occurred in liver (2), in patients pretreated with systemic therapy (5) and in patients who had other unfavourable prognostic characteristics (7). Median progression-free and survival times were 9 and 16 months, respectively., Conclusions: In this study FUDR + alpha 2b-IFN demonstrated interesting activity in metastatic renal cell carcinoma, showing promise also in patients with unfavourable prognostic characteristics. The antitumor activity of FUDR and alpha 2b-IFN seems to be cumulative, but cumulative toxicity is also observed. These results require confirmation in randomised trials.

Background: Cancer chemotherapy in elderly patients is an important and under-researched area. Doxifluridine is a fluoropyrimidine derivative and is activated to 5-fluorouracil by uridine phosphorylase, which is more highly expressed in malignant cells. Because of the high bioavailability and low toxicity of oral doxifluridine we conducted this phase II trial to evaluate the feasibility, toxicity and activity of a home therapy with oral doxifluridine in elderly metastatic colorectal cancer patients., Patients and Methods: Forty-three elderly metastatic colorectal cancer patients entered the study: their median ECOG performance status was 1 (0-2) and median age 74 years (69-83), the predominant site of metastasis was liver and all but one of the patients had received no previous chemotherapy. Doxifluridine was given orally at the initial daily total dose of 2250 mg for 4 consecutive days every week. The daily dose was reduced to 1500 mg if toxicities greater than grade 2 (WHO) occurred., Results: Forty-two patients are evaluable for toxicity: treatment was well tolerated, with the most common side effect being diarrhea, severe in 7 (17%) patients (6 grade 3 and 1 grade 4). Thirty-six patients are evaluable for response and 2 complete and 3 partial responses have been observed (response rate 14%; 95% confidence limit interval 5%-29%)., Conclusions: This study demonstrates that a home therapy with oral doxifluridine in elderly advanced colorectal cancer patients is feasible, with a relatively low rate of toxicity, and has moderate activity, comparable to that of intravenous 5-fluorouracil. Therefore, this treatment may be considered for the management of advanced colorectal cancer in the elderly.

A soluble Newcastle disease virus (NDV) agar gel precipitin (AGP) antigen was prepared by treating 100-fold concentrated NDV with a nonionic detergent. Virus concentration prior to detergent treatment was best accomplished by ultracentrifugation or by a simple, less expensive, and more practical method involving acid (HCl) precipitation of NDV. Virus concentrated by polyethylene glycol precipitation was found to have a low antigen titer and was not considered suitable as an AGP antigen. Antigens derived from the LaSota, Roakin, and Texas GB strains formed at least two lines of identity in the AGP test as early as 24 hr after inoculation of the agar gels. Virus used for AGP antigen production could be grown in chicken embryos from an NDV-immune as well as susceptible breeder flock. The NDV AGP antigen was found to be stable after 20 consecutive freezing and thawing cycles and storage at -20 C or 4 C for at least 6 months. Detergent-treated NDV was used as an AGP test antigen to determine serum antibody responses of chickens following infection and vaccination. Hemagglutination-inhibition, virus neutralization, and enzyme-linked immunosorbent assay antibody production was also evaluated for comparative purposes. The AGP test was found to be useful as an aid in diagnosing field infections and assessing inactivated virus vaccination responses. These purposes were achieved by demonstrating an increase in the number of AGP positive chickens between preinfection and postinfection or vaccination bleedings. The ease of performance and low cost of the AGP test favors its use for screening large numbers of serum samples, perhaps in conjunction with a quantitative serological test.(ABSTRACT TRUNCATED AT 250 WORDS)