Small and large scale segmental motion in polymers: Estimating cooperativity length by ordinary relaxation experiments

We derive a suitable expression for estimating the size of the cooperatively rearranging regions (CRRs) in supercooled polymer melts by fitting data worked out by ordinary relaxation experiments carried out in isothermal conditions. As an example, the average CRR size in poly(n-butyl methacrylate) in proximity to the glass transition temperature is derived from a stress relaxation experiment performed by means of an atomic force microscopy setup. Good agreement is found with results in the literature derived from measurements of temperature fluctuations (the so-called Donth method). The temperature dependence of the CRR size is explored for poly(butadiene); in this case the segmental relaxation function is derived through a novel method for the analysis of the efficiency with which free induction decay echoes are refocused in 1H NMR experiments. It is found that the CRR size increases upon cooling. The results derived from the analysis of the NMR data are found to be in satisfactory agreement with those worked out from broadband dielectric spectroscopy data in the literatur

Tyr78Phe Transthyretin Mutation with Predominant Motor Neuropathy as the Initial Presentation

Transthyretin (TTR) amyloidosis, the most frequent form of hereditary amyloidosis, is caused by dominant mutations in the TTR gene. More than 100 mutations have been identified. Clinical manifestations of TTR amyloidosis are usually induced by extracellular amyloid deposition in several organs. The major neurological manifestation is motor-sensory neuropathy associated with dysautonomic impairment. Here, we describe a 63-year-old man who came to our institution due to a suspected motor neuron disease. During a 4-year follow-up period, he underwent extensive clinical examination, electromyographic studies, sural nerve biopsy and TTR gene analysis by direct sequencing. Despite the predominant motor involvement, the detailed clinical examination also showed some mild sensory and dysautonomic signs. In addition, his clinical and family history included multiorgan disorders, such as carpal tunnel syndrome, as well as conditions with cardiac, renal, eye, and hepatic involvement. The sural nerve biopsy disclosed amyloid deposition, and the sequence analysis of the TTR gene detected a heterozygous Tyr78Phe substitution. The TTR gene variant found in our patient had only been described once so far, in a French man of Italian origin presenting with late-onset peripheral neuropathy and bilateral carpal tunnel syndrome. The predominant motor involvement presented by our patient is an uncommon occurrence and demonstrates the clinical heterogeneity of TTR amyloidosis

Green tea catechins suppress the DNA synthesis marker MCM7 in the TRAMP model of prostate cancer.

Green tea catechins (GTCs) exert chemopreventive effects in many cancer models. Several studies implicate the DNA synthesis marker minichromosome maintenance protein 7 (MCM7) in prostate cancer progression, growth and invasion; representing a novel therapeutic target. In this study, we investigated the effect of GTCs on MCM7 expression in the transgenic adenocarcinoma mouse prostate model (TRAMP). DNA microarray, immunohistochemistry and western blot analysis showed that GTCs significantly suppressed MCM7 in the TRAMP mice treated with GTCs. Our study indicates that the cellular DNA replication factor MCM7 is involved in prostate cancer (CaP) and MCM7 gene expression was reduced by GTCs. Together, these results suggest a possible role of GTCs in CaP chemoprevention in which MCM7 plays a critical role

NMR as evaluation strategy for cellular uptake of nanoparticles

Advanced nanostructured materials, such as gold nanoparticles, magnetic nanoparticles, and multifunctional materials, are nowadays used in many state-of-the-art biomedical application. However, although the engineering in this field is very advanced, there remain some fundamental problems involving the interaction mechanisms between nanostructures and cells or tissues. Here we show the potential of 1H NMR in the investigation of the uptake of two different kinds of nanostructures, that is, maghemite and gold nanoparticles, and of a chemotherapy drug (Temozolomide) in glioblastoma tumor cells. The proposed experimental protocol provides a new way to investigate the general problem of cellular uptake for a variety of biocompatible nanostructures and drugs. © 2014 American Chemical Society

Glycogen storage disease type III: A novel Agl knockout mouse model

AbstractGlycogen storage disease type III is an autosomal recessive disease characterized by a deficiency in the glycogen debranching enzyme, encoded by AGL. Essential features of this disease are hepatomegaly, hypoglycemia, hyperlipidemia, and growth retardation. Progressive skeletal myopathy, neuropathy, and/or cardiomyopathy become prominent in adults. Currently, there is no available cure. We generated an Agl knockout mouse model by deletion of the carboxy terminus of the protein, including the carboxy end of the glucosidase domain and the glycogen-binding domain. Agl knockout mice presented serious hepatomegaly, but we did not observe signs of cirrhosis or adenomas. In affected tissues, glycogen storage was higher than in wild-type mice, even in the central nervous system which has never been tested in GSDIII patients. The biochemical findings were in accordance with histological data, which clearly documented tissue impairment due to glycogen accumulation. Indeed, electron microscopy revealed the disruption of contractile units due to glycogen infiltrations. Furthermore, adult Agl knockout animals appeared less prompt to move, and they exhibited kyphosis. Three-mo-old Agl knockout mice could not run, and adult mice showed exercise intolerance. In addition, older affected animals exhibited an accelerated respiratory rate even at basal conditions. This observation was correlated with severe glycogen accumulation in the diaphragm. Diffuse glycogen deposition was observed in the tongues of affected mice. Our results demonstrate that this Agl knockout mouse is a reliable model for human glycogenosis type III, as it recapitulates the essential phenotypic features of the disease

The LHCb ultra-fast simulation option, Lamarr: design and validation

Detailed detector simulation is the major consumer of CPU resources at LHCb, having used more than 90% of the total computing budget during Run 2 of the Large Hadron Collider at CERN. As data is collected by the upgraded LHCb detector during Run 3 of the LHC, larger requests for simulated data samples are necessary, and will far exceed the pledged resources of the experiment, even with existing fast simulation options. An evolution of technologies and techniques to produce simulated samples is mandatory to meet the upcoming needs of analysis to interpret signal versus background and measure efficiencies. In this context, we propose Lamarr, a Gaudi-based framework designed to offer the fastest solution for the simulation of the LHCb detector. Lamarr consists of a pipeline of modules parameterizing both the detector response and the reconstruction algorithms of the LHCb experiment. Most of the parameterizations are made of Deep Generative Models and Gradient Boosted Decision Trees trained on simulated samples or alternatively, where possible, on real data. Embedding Lamarr in the general LHCb Gauss Simulation framework allows combining its execution with any of the available generators in a seamless way. Lamarr has been validated by comparing key reconstructed quantities with Detailed Simulation. Good agreement of the simulated distributions is obtained with two-order-of-magnitude speed-up of the simulation phase.Comment: Under review in EPJ Web of Conferences (CHEP 2023

One-pot synthesis and characterization of size-controlled bimagnetic FePt-iron oxide heterodimer nanocrystals.

A one-pot, two-step colloidal strategy to prepare bimagnetic hybrid nanocrystals (HNCs), comprising size-tuned fcc FePt and inverse spinel cubic iron oxide domains epitaxially arranged in a heterodimer configuration, is described. The HNCs have been synthesized in a unique surfactant environment by temperature-driven sequential reactions, involving the homogeneous nucleation of FePt seeds and the subsequent heterogeneous growth of iron oxide. This self-regulated mechanism offers high versatility in the control of the geometric features of the resulting heterostructures, circumventing the use of more elaborate seeded growth techniques. It has been found that, as a consequence of the exchange coupling between the two materials, the HNCs exhibit tunable single-phase-like magnetic behavior, distinct from that of their individual components. In addition, the potential of the heterodimers as effective contrast agents for magnetic resonance imaging techniques has been examined

Changes in serum biomarker profiles after percutaneous mitral valve repair with the MitraClip system

Background: Mitral regurgitation (MR) is one of the most common valvular diseases. Percu­taneous mitral valve repair with the MitraClipTM system is a novel percutaneous mitral valve repair (PMVR) technique for high-surgical-risk patients. However, the effect of PMVR on cir­culating cardiac or inflammatory biomarkers and their association with individual functional, echocardiographic and clinical outcomes is poorly investigated. Methods: A group of 144 patients with functional or degenerative MR (age, 75 ± 11 years; 41% females) underwent PMVR with the MitraClip system at the University Heart Center Zu­rich. Serum biomarkers as N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and creatinine were obtained from venous sampling at baseline and follow-up of 3–6 months. Results: Median NT-proBNP decreased insignificantly from 2,942 (IQR 1,596–5,722) to 2,739 (IQR 1,440–4,296) ng/L, p = 0.21. NT-proBNP changes did not correlate with baseline left ventricular (LV) ejection fraction or LV dimensions, with New York Heart Association class on follow-up, or with clinical events on follow-up. CRP levels reached a peak on the third postoperative day at 34.0 mg/L with a subsequent slow decrease over the ensuing days. Conclusions: Despite successful PMVR, NT-proBNP remain fairly unchanged on follow-up and changes in NT-proBNP levels are poor predictors of functional improvement or clinical outcome after MitraClip treatment

Changes in serum biomarker profiles after percutaneous mitral valve repair with the MitraClip system

BACKGROUND Mitral regurgitation (MR) is one of the most common valvular diseases. Percu-taneous mitral valve repair with the MitraClipTM system is a novel percutaneous mitral valve repair (PMVR) technique for high-surgical-risk patients. However, the effect of PMVR on cir-culating cardiac or inflammatory biomarkers and their association with individual functional, echocardiographic and clinical outcomes is poorly investigated. METHODS A group of 144 patients with functional or degenerative MR (age, 75 ± 11 years; 41% females) underwent PMVR with the MitraClip system at the University Heart Center Zu-rich. Serum biomarkers as N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and creatinine were obtained from venous sampling at baseline and follow-up of 3-6 months. RESULTS Median NT-proBNP decreased insignificantly from 2,942 (IQR 1,596-5,722) to 2,739 (IQR 1,440-4,296) ng/L, p = 0.21. NT-proBNP changes did not correlate with baseline left ventricular (LV) ejection fraction or LV dimensions, with New York Heart Association class on follow-up, or with clinical events on follow-up. CRP levels reached a peak on the third postoperative day at 34.0 mg/L with a subsequent slow decrease over the ensuing days. CONCLUSIONS Despite successful PMVR, NT-proBNP remain fairly unchanged on follow-up and changes in NT-proBNP levels are poor predictors of functional improvement or clinical outcome after MitraClip treatment