Abstract basins of attraction

Abstract basins appear naturally in different areas of several complex variables. In this survey we want to describe three different topics in which they play an important role, leading to interesting open problems

Experimental determination of the frequency and field dependence of Specific Loss Power in Magnetic Fluid Hyperthermia

Magnetic nanoparticles are promising systems for biomedical applications and in particular for Magnetic Fluid Hyperthermia, a promising therapy that utilizes the heat released by such systems to damage tumor cells. We present an experimental study of the physical properties that influences the capability of heat release, i.e. the Specific Loss Power, SLP, of three biocompatible ferrofluid samples having a magnetic core of maghemite with different core diameter d= 10.2, 14.6 and 19.7 nm. The SLP was measured as a function of frequency f and intensity of the applied alternating magnetic field H, and it turned out to depend on the core diameter, as expected. The results allowed us to highlight experimentally that the physical mechanism responsible for the heating is size-dependent and to establish, at applied constant frequency, the phenomenological functional relationship SLP=cH^x, with 2<x<3 for all samples. The x-value depends on sample size and field frequency/ intensity, here chosen in the typical range of operating magnetic hyperthermia devices. For the smallest sample, the effective relaxation time Teff=19.5 ns obtained from SLP data is in agreement with the value estimated from magnetization data, thus confirming the validity of the Linear Response Theory model for this system at properly chosen field intensity and frequency

NMR and μ+\mu^{+}SR detection of unconventional spin dynamics in Er(trensal) and Dy(trensal) molecular magnets

Measurements of proton Nuclear Magnetic Resonance (1H NMR) spectra and relaxation and of Muon Spin Relaxation ($\mu^{+}$SR) have been performed as a function of temperature and external magnetic field on two isostructural lanthanide complexes, Er(trensal) and Dy(trensal) featuring crystallographically imposed trigonal symmetry. Both the nuclear 1/T1 and muon $\lambda$ longitudinal relaxation rates, LRR, exhibit a peak for temperatures T lower than 30K, associated to the slowing down of the spin dynamics, and the width of the NMR absorption spectra starts to increase significantly at T ca. 50K, a temperature sizably higher than the one of the LRR peaks. The LRR peaks have a field and temperature dependence different from those previously reported for all Molecular Nanomagnets. They do not follow the Bloembergen-Purcell-Pound scaling of the amplitude and position in temperature and field and thus cannot be explained in terms of a single dominating correlation time $\tau$c determined by the spin slowing down at low temperature. Further, for T lower than 50K the spectral width does not follow the temperature behavior of the magnetic susceptibility chi. We suggest, using simple qualitative considerations, that the observed behavior is due to a combination of two different relaxation processes characterized by the correlation times $\tau$LT and $\tau$HT, dominating for T lower than 30K and T higher than 50K, respectively. Finally, the observed flattening of LRR for T lower than 5K is suggested to have a quantum origin

AEROBIC TRAINING WITH LIMBS INTERMITTENT ISCHEMIA IMPROVES MYOCARDIAL FUNCTION AND WALL STRETCH IN PATIENTS WITH CLAUDICATION

Background: peripheral arterial disease (PAD) is a chronic disease determining functional impairment and increased risk of cardiovascular events. Physical training improves cardiac performance and reduces NTproBNP concentration, marker of risk of cardiovascular events, in cardiac patients. Aim: we aimed to examine the effects training conducted till ischemic pain at the leg of PAD patients on myocardial function and peripheral flux.Methods: we enrolled 22 patients affected by peripheral arterial disease without cardiac disease. All patients undergone a physical training of 15 days, with treadmill test at the begin and at the end of training. Results: at the end of training patients increased walking distance (450\ub1180 m vs 250\ub1108 m; p<0.05). We documented at rest, at the end of physical training, an increase in flow volume of common femoral artery of the symptomatic leg (2,55\ub12,13 L/min vs 1,86\ub11,30 L/min; p<0.05); NTproBNP concentration at rest was lower al the end of training (210\ub1130 pg/mL vs 188\ub1108 pg/mL; p<0.005), an increase of NTproBNP concentration after maximal exercise on treadmill before treatment, with a reduced increase at the end of training period (24\ub121 vs 12\ub110 pg/mL; p<0.0005); a reduction of end-diastolic diameter of left ventricle at rest (48\ub14 mm vs 50\ub15 mm; p<0.05). The ejection fraction did not changed, while heart rate reduced after training (66\ub19 bpm vs 71\ub112 bpm; p<0.05). Conclusions: this study documented an improvement of hemodynamic and cardiac performance in response of physical training in peripheral arterial disease patients not affected by cardiac disease. Further trials will be necessary to evaluate the use of NTproBNP as a marker of good response to physical training in these patients

Effects of training on reticulated reactive platelets and erytrocyte fragments in patients with peripheral atherosclerosis.

Background: training is a documented effective treatment in patients affected from peripheral arterial disease (PAD). Platelet activation plays a pivotal role in atherosclerosis progression and cardiovascular events. Reticulated platelets (IPF) reflects activity of bone marrow , recently they have been associated to cardiovascular complications and atherosclerosis with unstable conditions (e.g. acute coronary syndrome). Presence of a width blood red cell distribution is considered recently as a prognostic factor for coronary artery disease, a high RDW value depends greatly on presence of red blood cells fragmentation (FRC); this parameter may depend on different conditions such as inflammation, and oxidation and is connected with different risk factors such as hypertension and diabetes. Few data can be found for patients with peripheral arterial disease on training. We aimed to evaluate the effects of aerobic training on IPF and FRC at rest and after maximal walking exercise before and after training. Methods and Results: we enrolled 12 patients with intermittent claudication. They were submitted to a 15 days aerobic training period (cycling and treadmill exercise under maximal walking capacity). IPF, MPV, PLT count and FRC were analyzed at rest, 1 hour after maximal treadmill test and after 24 hours, these evaluations were performed at the beginning and at the end of the training period. The Lab parameters were analyzed with impedentiometry, fluorimetry (oxazyne) and optical methods (Sysmex Xn-1000, Sysmex Corporation, Kobe, Japan). Walking distance was measured with treadmill (3,2 km/h, 2-10% slope), maximal test was prolonged to the maximal tolerated claudication pain. Platelets count was within normal range (216,9 \ub1 40 109/l ) and did not changed throughout the study; also MPV was unchanged (11,6\ub11,9 vs 11.45\ub10,8 fl ) before and after the training ; plateletcrit was slightly reduced (0,246\ub10,061 vs 0,282 \ub10,018 %). IPF count (figure) slightly changed during maximal stress at the beginning of training with increase after 24 hours; after training the count decreased significantly (*p<0,05) at rest and 1 hour after, while it increased significantly after 24 hours (** p<0,05 vs rest ad vs 24 h-pre) but less than before training. FRC decreased after triaining (0,381\ub10,121 vs 0,542\ub10,220 %; p<0,05), maximal test slightly increased FRC after 1 hour , no significant change after 24 hours. At the end of training, absolute walking distance increased (450\ub1180 vs 250\ub1108 m; p<0,05). Discussion: training reduces IPF in patients with peripheral arterial disease, IPF increase after acute maximal test and this phenomenon can be attenuated by training. We also observed a reduction in FRC. Presence of FRC in these patients may be caused by mechanical forces throughout a large surface of atherosclerotic plaques fragmenting red cells, ischemia reperfusion in claudication is another mechanism that can elicit formation of FRC and in addition high oxidative stress may contribute. IPF are associated with an increase platelets activity and a higher turnover; in this pathology both these condition can be found associated with oxidative stress, inflammation and endothelial dysfunction. Training improves oxidation, inflammation and endothelium function with favorable effects on platelets activation and turnover, furthermore these parameters may influence also FRC count. Conclusion: training in PAD patients reduces IPF and FRC with potential improvement in risk profile for atherosclerosis progression and reduction of cardiovascular events. References: 1. Cesari F, Marcucci R, Gori AM, et al . Reticulated platelets predict cardiovascular death in acute coronary syndrome patients. Thrombosis and Haemostasis 2013; 109: 846-853. 2. Hoffmann JJ . Reticulated platelets: analytical aspects and clinical utility. Clin Chem Lab. 2014; 52: 1107-17. 3. Bujak K, Wasilewski J, Osadnik T, et al. Prognostic role of red blood cell distribution width in coronary artery disease: a review of the pathophysiology. Disease Markers 2015, vol 1 ; 1-12

Supervised training improves endothelial function measured during induced ischemia in peripheral arterial disease.

Introduction: favorable effect of training on cardiovascular pathology is well documented in literature. Mechanisms evoked are the following: increased NO availability for reduction of oxidative stress, inflammation decrease, improvement of glucidic and lipidic metabolism, resetting of neuro-endocrine balance (1). These mechanism are also involved in the improvement of patients with peripheral arterial disease (PAD) treated with training. PAD is a model of inducible ischemia, in fact claudication is a condition in which ischemia/reperfusion phenomenon is present when walking is conducted till maximum pain (2). This phenomenon may produce a great amount of radical oxygen species with possible consequence on endothelium function. Xanthine oxidase is one of the most relevant enzyme involved in this process. Different types of training are proposed for PAD patients and there is not a consensus whether the ischemic pain should be reached during exercise. So we aimed to verify if maximal treadmill test (till pain) causes endothelial dysfunction, if oxidative stress is acutely aroused and if xanthine oxidase is involved. Therefore we aimed to verify if a training performed under the onset of ischemic pain can improve endothelial function ether at rest and after maximum tolerated exercise. Patients and methods: we enrolled 20 patients with PAD (16 males, 4 females, aged 65-77). Endothelium dependent dilation (EDD) was measured at humeral artery by ultrasound method, before and after maximal treadmill test (speed 3,2 km/h; slope 10%). We administered allopurinol 600 mg the day before and 600 mg 6 hours before a new treadmill test. Serum uric acid and lactate were determined throughout the study. Afterwards patients performed supervised training under pain onset for 20 days with physiotherapist overview. Every 7 days a new treadmill test was performed for updating training distance. At the end of the training period EDD was measured before and after a maximal treadmill test. Furthermore microcirculatory endothelium dependent dilation was measured at the skin of the forefoot by means of laser-Doppler (LD) after iontophoretic acetylcholine administration. Results: maximal treadmill test acutely reduced EDD (6,1\uf0b10,7 vs 9,2\uf0b10,9 %; p<0,05;). Allopurinol improved EDD (10,1\uf0b10,3 vs 9,4\uf0b10,6 %; p<0,05) with a reduced fall after maximal test (delta decrease -21,3\uf0b12,2 vs \u201333,2\uf0b11,2%; p<0,05). Training increased pain free walking distance (131\uf0b112 vs 66,6\uf0b121 m; p<0,05) and absolute walking distance (275\uf0b115 vs 125,8\uf0b140 m; p<0,05). EDD improved after training period (11,3\uf0b10,7 vs 9,2\uf0b10,9; p<0,05). The fall in EDD, observed during maximal treadmill test at the end of training period, was smaller than the one measured before training (delta decrease -15,5\uf0b12,4 vs \u201333,2\uf0b11,2%; p<0,005). Microcirculatory endothelium dependent dilation measured with LD increased after training (table). Table: microcirculatory flux with LD after iontophoretic acetylcholine. Acetylcholine 0,10 mA 10 s 20 s 40 s T 0 (% incr) 35\uf0b19 70\uf0b115 120\uf0b115 T 20 (%incr) 147\uf0b138* 182\uf0b122* 470\uf0b154* (*p<0.005 T20 vs T0) Conclusions: we demonstrate that walking through maximal pain causes impairment of EDD, this is caused by oxidative stress and can be reduced by inhibition of xanthine oxidase. Aerobic training improves EDD and microcirculatory endothelial function, furthermore training reduces the drop of EDD during maximal exercise and increased oxidative stress. As a consequence these results suggest the training should be performed under the maximal pain. References 1. Brendle DC, Joseph LJ, Corretti MC, Gardner AW, Katzel LI. Effects of exercise rehabilitation on endothelial reactivity in older patients with peripheral arterial disease. Am J Cardiol 2001;87:324-9. 2. Andreozzi GM, Leone A, Laudani R, Deinite G, Martini R. Acute impairment of the endothelial function by maximal treadmill exercise in patients with intermittent claudication, and its improvement after supervised physical training. Int Angiol. 2007; 26:12-7

2q37 deletions in patients with an albright hereditary osteodystrophy phenotype and PTH resistance

Pseudohypoparathyroidism (PHP) is a rare endocrine disorder derived from the defective activation of the cAMP pathway by the parathyroid hormone secondary to GNAS molecular defects. PHP subtypes are defined by the presence/absence of specific clinical/biochemical features. PHP1A is characterized by resistance to multiple hormones with features of Albright hereditary osteodystrophy (AHO), while pseudopseudohypoparathyroidism (PPHP) is characterized by AHO in the absence of PTH resistance. Small subsets of PHP and PPHP patients without known molecular defects have been re-diagnosed as being affected by the brachydactyly-mental retardation syndrome (BDMR), also known as the AHO-like syndrome. This study aimed to analyse 24 PHP1A and 51 PPHP patients without a molecular diagnosis for the presence of BDMR-associated 2q37 deletions to improve the differential diagnosis and to identify features that might help to avoid a misdiagnosis. Molecular investigations identified 4 deletions in 4 unrelated patients. The affected patients showed a combination of the most pathognomonic AHO features. Of note, 3 of the patients also displayed mild PTH resistance, and none of the patients developed ectopic ossifications. Our work confirmed the rarity of the misdiagnosis of BDMR in PHP patients through the identification of 4 patients bearing a 2q37 deletion in a cohort of 73 PHP patients (5.3%). Three patients with the deletion presented a PHP1A phenotype in the absence of any BDMR-specific findings. Further studies on larger case series are needed to elucidate the overlap between these clinical entities and to allow the early identification of patients

NMR Study of Spin Dynamics in V\u3csub\u3e7\u3c/sub\u3eZn and V\u3csub\u3e7\u3c/sub\u3eNi Molecular Rings

We present a 1H NMR investigation of spin dynamics in to finite integer spin molecular nanomagnetic rings, namely V7Zn and V7Ni. This study could be put in correlation with the problem of Haldane gap in infinite integer spin chains. While V7Zn is an approximation of a homometallic broken chain due to the presence of s = 0 Zn2+ ion uncoupled from nearest neighbor V2+ s = 1 ions, the V7Ni compound constitutes an example of a closed periodical s = 1 heterometallic chain. From preliminary susceptibility measurements on single crystals and data analysis, the exchange coupling constant J/kB results in the order of few kelvin. At room temperature, the frequency behavior of the 1H NMR spin–lattice relaxation rate 1/T1 allowed to conclude that the spin–spin correlation function is similar to the one observed in semi-integer spin molecules, but with a smaller cutoff frequency. Thus, the high-T data can be interpreted in terms of, e.g., a Heisenberg model including spin diffusion. On the other hand, the behavior of 1/T1 vs temperature at different constant fields reveals a clear peak at temperature of the order of J/kB, qualitatively in agreement with the well-known Bloembergen–Purcell–Pound model and with previous results on semi-integer molecular spin systems. Consequently, one can suggest that for a small number N of interacting s = 1 ions (N = 8), the Haldane conjecture does not play a key role on spin dynamics, and the investigated rings still keep the quantum nature imposed mainly by the low number of magnetic centers, with no clear topological effect due to integer spins

Cyclic RGD peptidomimetics containing bifunctional diketopiperazine scaffolds as new potent integrin ligands

The synthesis of eight bifunctional diketopiperazine (DKP) scaffolds is described; these were formally derived from 2,3-diaminopropionic acid and aspartic acid (DKP-1-DKP-7) or glutamic acid (DKP-8) and feature an amine and a carboxylic acid functional group. The scaffolds differ in the configuration at the two stereocenters and the substitution at the diketopiperazinic nitrogen atoms. The bifunctional diketopiperazines were introduced into eight cyclic peptidomimetics containing the Arg-Gly-Asp (RGD) sequence. The resulting RGD peptidomimetics were screened for their ability to inhibit biotinylated vitronectin binding to the purified integrins \u3b1 v\u3b2 3 and \u3b1 v\u3b2 5, which are involved in tumor angiogenesis. Nanomolar IC 50 values were obtained for the RGD peptidomimetics derived from trans DKP scaffolds (DKP-2-DKP-8). Conformational studies of the cyclic RGD peptidomimetics by 1H NMR spectroscopy experiments (VT-NMR and NOESY spectroscopy) in aqueous solution and Monte Carlo/Stochastic Dynamics (MC/SD) simulations revealed that the highest affinity ligands display well-defined preferred conformations featuring intramolecular hydrogen-bonded turn motifs and an extended arrangement of the RGD sequence [C\u3b2(Arg)-C\u3b2(Asp) average distance 658.8 \uc5]. Docking studies were performed, starting from the representative conformations obtained from the MC/SD simulations and taking as a reference model the crystal structure of the extracellular segment of integrin \u3b1 v\u3b2 3 complexed with the cyclic pentapeptide, Cilengitide. The highest affinity ligands produced top-ranked poses conserving all the important interactions of the X-ray complex. Copyright \ua9 2012 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim

Effective targeting of DC-sign by &#945;-fucosylamide functionalized gold nanoparticles

Dendritic Cells (DCs), the most potent antigenpresenting cells, play a critical role in the detection of invading pathogens, which are recognized also by multiple carbohydrate-specific receptors. Among them, DC-SIGN is one of the best characterized, with high-mannose and Lewis-type glycan specificity. In this study, we present a potent DC-SIGN targeting device developed using gold nanoparticles functionalized with \u3b1-fucosyl-\u3b2-alanyl amide. The nanoparticles bound to cellular DC-SIGN and induced internalization as effectively as similar particles coated with comparable amounts of LewisX oligosaccharide. They were found to be neutral toward dendritic cell maturation and IL-10 production, thus envisaging a possible use as targeted imaging tools and antigen delivery devices