The Development of the Keyboard Through the Grand Piano and Its Effect on Piano Literature

The keyboard instrument was improved through a long series of developments until the pianoforte was developed, which reached beyond the capabilities of the harpsichord. Christofori developed the pianoforte which would lead to the ultimate development of the concert grand piano. Not all composers were privileged to have the pianoforte at their fingertips, let alone the grand piano with all of its improvements. Therefore, each composer’s musical style can be correlated to the piano’s development during each time period. Each musical era signifies where the piano was developmentally during that century. Through this progression the piano came to be a means of emotion and imagination, allowing audiences to see the colors, moods, and pictures that can be created through music

Inhibition of phosphoinositide 3-kinase/protein kinase B signaling hampers the vasopressin-dependent stimulation of myogenic differentiation

Arginine-vasopressin (AVP) promotes muscle differentiation, hypertrophy, and regeneration through the combined activation of the calcineurin and Calcium/Calmodulin-dependent Protein Kinase (CaMK) pathways. The AVP system is impaired in several neuromuscular diseases, suggesting that AVP may act as a physiological factor in skeletal muscle. Since the Phosphoinositide 3-kinases/Protein Kinase B/mammalian Target Of Rapamycin (PI3K/Akt/mTOR) signaling plays a significant role in regulating muscle mass, we evaluated its role in the AVP myogenic effect. In L6 cells AKT1 expression was knocked down, and the AVP-dependent expression of mTOR and Forkhead box O3 (FoxO) was analyzed by Western blotting. The effect of the PI3K inhibitor LY294002 was evaluated by cellular and molecular techniques. Akt knockdown hampered the AVP-dependent mTOR expression while increased the levels of FoxO transcription factor. LY294002 treatment inhibited the AVP-dependent expression of Myocyte Enhancer Factor-2 (MEF2) and myogenin and prevented the nuclear translocation of MEF2. LY294002 also repressed the AVP-dependent nuclear export of histone deacetylase 4 (HDAC4) interfering with the formation of multifactorial complexes on the myogenin promoter. We demonstrate that the PI3K/Akt pathway is essential for the full myogenic effect of AVP and that, by targeting this pathway, one may highlight novel strategies to counteract muscle wasting in aging or neuromuscular disorders

Effective interactions between parallel-spin electrons in two-dimensional jellium approaching the magnetic phase transition

We evaluate the effective interactions in a fluid of electrons moving in a plane, on the approach to the quantum phase transition from the paramagnetic to the fully spin-polarized phase that has been reported from Quantum Monte Carlo runs. We use the approach of Kukkonen and Overhauser to treat exchange and correlations under close constraints imposed by sum rules. We show that, as the paramagnetic fluid approaches the phase transition, the effective interactions at low momenta develop an attractive region between parallel-spin electrons and a corresponding repulsive region for antiparallel-spin electron pairs. A connection with the Hubbard model is made and used to estimate the magnetic energy gap and hence the temperature at which the phase transition may become observable with varying electron density in a semiconductor quantum well.Comment: 11 pages, 3 figure

Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild-type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N-terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium-labelled synthetic peptide. The labelled peptide permeated MCF-7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I- and 131I-labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro-apoptotic mechanism

Influence of innate immunity on cancer cell stemness

Even if cancer stem cells (CSCs) represent only a small proportion of the tumor mass, they significantly account for tumor maintenance, resistance to therapies, relapse and metastatic spread, due to their increased capacity of self-renewal, multipotency, tumorigenicity and quiescence. Emerging evidence suggests that the immune contexture within the tumor microenvironment (TME) determines both the response to therapy and the clinical outcome. In this context, CSCs acquire immune evasion skills by editing immune cell functions and sculpting the immunosuppressive landscape of TME. Reciprocally, infiltrating immune cells influence CSCs self-renewal, tumorigenicity and metastasis. In this review, we summarize the immunomodulatory properties of CSCs, as well as the impact of innate immune cells on cancer cells stemness in the different phases of cancer immunoediting process and neoplastic progression

The networking dynamics of the Italian biofuel industry in time of crisis: Finding an effective instrument mix for fostering a sustainable energy transition

This paper aims to design the effective instrument mixes for fostering a sustainable energy transition in times of crises. We focus on a sufficiently developed green niche – namely the Italian biofuel sector – implementing a two-step investigation: 1) a social network analysis, to study the effects of the crisis on the basic niche development mechanisms, with the aim of eliciting its development needs; 2) a fuzzy inference simulation based on a causal-effect map drawn from experts' knowledge to identify the most effective instrument mix for the development of the niche studied. The major needs emerged in the case investigated are for an increase of actors' expectations towards the further development of the sector, and a need for a tailored networking activity, devoted to attracting specific knowledgeable actors. The results indicate that, among others, effective policy instruments are, in this case, the cooperation that has the best outcome in terms of networking, and the public procurement, which remarkably increases the level of expectation. The analysis presented constitutes a model to evaluate single policy drivers and their combinations to find adequate policy actions to promote the green energy transition in times of crisis

Diritto d’interpello e certezza nei rapporti tra cittadino e pubblica amministrazione

La certezza dei rapporti giuridici tra cittadino e pubblica amministrazione costituisce un elemento fondamentale nello svolgimento della vita non solo sociale ma anche economica e produttiva. Il diritto tributario prevede specifici istituti per cercare di garantire, per quanto possibile, la certezza in via preventiva. Tale esigenza e` tuttavia avvertita in tutti i casi in cui il cittadino entra in rapporto con la p.a. alla quale compete l\u2019esercizio del potere amministrativo. Muovendo da un\u2019analisi dell\u2019istituto del diritto di interpello, viene effettuata una ricognizione di alcune importanti fattispecie in cui l\u2019ordinamento attribuisce espressamente agli amministrati il diritto di ottenere, in via diretta o indiretta, l\u2019incremento del grado di certezza e prevedibilita` delle scelte dell\u2019amministrazione. Piu` in generale, si evidenzia come, richiamando i principi costituzionali e tenendo conto del rilievo assunto dalle singole fattispecie, si possa pervenire all\u2019individuazione di un principio generale immanente nell\u2019ordinamento che consente al cittadino di rivolgersi alla pubblica amministrazione per conoscere quali potrebbero essere le determinazioni del decisore pubblico in relazione ad un specifico caso concreto qualora vi siano obiettive condizioni di incertezza