On Quasiperiodic Morphisms

Weakly and strongly quasiperiodic morphisms are tools introduced to study quasiperiodic words. Formally they map respectively at least one or any non-quasiperiodic word to a quasiperiodic word. Considering them both on finite and infinite words, we get four families of morphisms between which we study relations. We provide algorithms to decide whether a morphism is strongly quasiperiodic on finite words or on infinite words.Comment: 12 page

Repetitions in infinite palindrome-rich words

Rich words are characterized by containing the maximum possible number of distinct palindromes. Several characteristic properties of rich words have been studied; yet the analysis of repetitions in rich words still involves some interesting open problems. We address lower bounds on the repetition threshold of infinite rich words over 2 and 3-letter alphabets, and construct a candidate infinite rich word over the alphabet $\Sigma_2=\{0,1\}$ with a small critical exponent of $2+\sqrt{2}/2$. This represents the first progress on an open problem of Vesti from 2017.Comment: 12 page

Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours.

Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase II studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m(-2) and ifosfamide doses from 2.5 to 5.0 g m(-2). Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m(-2) of docetaxel combined with 5.0 g m(-2) ifosfamide appeared to be manageable. Schedule A was advocated for further treatment

A Comparative Study of Ultrasmall Calcium Carbonate Nanoparticles for Targeting and Imaging Atherosclerotic Plaque

therosclerosis is a complex disease that can lead to life-threatening events, such as myocardial infarction and ischemic stroke. Despite the severity of this disease, diagnosing plaque vulnerability remains challenging due to the lack of effective diagnostic tools. Conventional diagnostic protocols lack specificity and fail to predict the type of atherosclerotic lesion and the risk of plaque rupture. To address this issue, technologies are emerging, such as noninvasive medical imaging of atherosclerotic plaque with customized nanotechnological solutions. Modulating the biological interactions and contrast of nanoparticles in various imaging techniques, including magnetic resonance imaging, is possible through the careful design of their physicochemical properties. However, few examples of comparative studies between nanoparticles targeting different hallmarks of atherosclerosis exist to provide information about the plaque development stage. Our work demonstrates that Gd (III)-doped amorphous calcium carbonate nanoparticles are an effective tool for these comparative studies due to their high magnetic resonance contrast and physicochemical properties. In an animal model of atherosclerosis, we compare the imaging performance of three types of nanoparticles: bare amorphous calcium carbonate and those functionalized with the ligands alendronate (for micro- calcification targeting) and trimannose (for inflammation targeting). Our study provides useful insights into ligand-mediated targeted imaging of atherosclerosis through a combination of in vivo imaging, ex vivo tissue analysis, and in vitro targeting experiments.We acknowledge M. Spuch for his scientific drawings and the Basque Government for the R&D Project in Health (grant number 2022333041). S.C.R. acknowledges the Spanish Ministerio de Ciencia e Innovación (MCIN)/Agencia Estatal de Investigación (AEI) Grant PID2019-106139RA-100 funded by MCIN/AEI/10.13039/501100011033 and the Ramon y Cajal Grant RYC2020-030241-I. C.S.C. acknowledges financial support from the Spanish State Research Agency (grant PID2020-118176RJ-I100), and the Gipuzkoa Foru Aldundia (Gipuzkoa Fellows program; grant number 2019-FELL- 000018-01/62/2019). This work was performed under the Severo Ochoa Centers of Excellence Program of the Spanish State Research Agency − Grant No. CEX2018-000867-S (DIPC). SXRF analysis was carried out with the support of Diamond Light Source, beamline I18 (proposal SP27720). J.R.C. is funded by MCIN/AEI/10.13039/501100011033 (PID2021-123238OB-I00) and from La Caixa Foundation (Health Research Call 2020: HR20-00075). A.M.G. and C.U. acknowledge the Spanish Ministerio de Ciencia e Innovación (MCIN)/Agencia Estatal de Investigación (AEI) Grant: PID2021-122504NB-I00 funded by MCIN/AEI/10.13039/ 501100011033 and by “ERDF A way of making Europe. W.J.P. acknowledges funding from the Cluster of Excellence “Advanced Imaging of Matter” of the Deutsche Forschungsge- meinschaft (DFG) - EXC 2056 - project ID 390715994. F.H. acknowledges MCIN (PID2019-104059RB-I00) and M.J.S.G. the Spanish Ministerio de Educación y Formación Profesional (PRE2018-083691). REFERENCES (1) Libby, P. The changing landscape of atherosclerosPeer reviewe

A phase II study of docetaxel in patients with metastatic squamous cell carcinoma of the head and neck

This study was designed to evaluate the activity, safety and tolerance of docetaxel (D) in a selected population with metastatic squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients with no prior palliative therapy were enrolled and received D 100 mg m−2 by 1 h of infusion, every 3 weeks. All but two patients had been evaluated for efficacy on lung metastatic sites. No prophylactic administration of anti-emetics or growth factors was given. A pharmacokinetic study was performed in 22 patients. Twenty-one patients were assessable for response and 24 for toxicity. One hundred and four cycles were administered with a median of 4.5 (range 1–9) per patient. The median cumulative dose was 449 mg m−2. Partial responses were achieved in five patients with a median duration of 18.7 weeks (range 13.1–50.3). The overall response rate was 20.8% with a median duration of 11.0 weeks (range 2.4–52.6). The most frequent side-effect was neutropenia (79.2% grade IV) but with a short duration (median 4 days) and no febrile neutropenia. The incidence of moderate/severe fluid retention was 29.2% with one treatment discontinuation. Other toxicities (all grades) were common (skin 75%, asthenia 50%, infection 29.2%, nausea 16.7%, diarrhoea 12.5%, stomatitis 16.7%, vomiting 8.3% and HSR 8.3%). A mean clearance of 19.6 l h−1 m−2 and an area under the curve of 6.00 μg ml−1 h−1 was found in the pharmacokinetic analysis. Docetaxel is active in this selected population with metastatic SCCHN, with a good tolerance. © 1999 Cancer Research Campaig

ZAK beta is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle

Mechanical inputs give rise to p38 and JNK activation, which mediate adaptive physiological responses in various tissues. In skeletal muscle, contraction-induced p38 and JNK signaling ensure adaptation to exercise, muscle repair, and hypertrophy. However, the mechanisms by which muscle fibers sense mechanical load to activate this signaling have remained elusive. Here, we show that the upstream MAP3K ZAK beta is activated by cellular compression induced by osmotic shock and cyclic compression in vitro, and muscle contraction in vivo. This function relies on ZAKO's ability to recognize stress fibers in cells and Z-discs in muscle fibers when mechanically perturbed. Consequently, ZAK-deficient mice present with skeletal muscle defects characterized by fibers with centralized nuclei and progressive adaptation towards a slower myosin profile. Our results highlight how cells in general respond to mechanical compressive load and how mechanical forces generated during muscle contraction are translated into MAP kinase signaling.Peer reviewe

Pectin aerogels for controlled release

National audienc

Pectin aerogels for controlled release

National audienc