200 research outputs found
L’innovazione nelle medie imprese bresciane. Un’indagine empirica
L’articolo presenta i risultati di una indagine empirica su un campione di medie imprese della provincia di Brescia con particolare riferimento all’innovazione di prodotto e di processo. Le evidenze empiriche sugli investimenti in ricerca e sviluppo, sull’innovazione di prodotto e processo e sugli investimenti in nuove tecnologie mostrano la presenza di un gruppo di promettenti medie imprese innovative. Ma in generale il sistema delle imprese della provincia di Brescia è ancora segnato da alcune debolezze, quali una innovazione prevalentemente incrementale e non basata sulla ricerca, un basso livello di investimenti in ricerca e sviluppo, una bassa qualità del capitale umano impiegato, un debole impegno alla protezione delle innovazioni introdotte. L’articolo inquadra queste debolezze nei limiti sia dimensionali e organizzativi delle imprese che culturali di sistema dell’imprenditorialità del territorio indagato
Room Temperature Organic Superconductor?
The electron--phonon coupling in fullerene C28 has been calculated from first
principles. The value of the associated coupling constant lambda/N(0) is found
to be a factor three larger than that associated with C60. Assuming similar
values of the density of levels at the Fermi surface N(0) and of the Coulomb
pseudopotential for C28-based solids as those associated with alkali-doped
fullerides A3C60, one obtains Tc(C28) \approx 8 Tc(C60).Comment: 10 pages, 2 figure
Metadynamic sampling of the free energy landscapes of proteins coupled with a Monte Carlo algorithm
Metadynamics is a powerful computational tool to obtain the free energy
landscape of complex systems. The Monte Carlo algorithm has proven useful to
calculate thermodynamic quantities associated with simplified models of
proteins, and thus to gain an ever-increasing understanding on the general
principles underlying the mechanism of protein folding. We show that it is
possible to couple metadynamics and Monte Carlo algorithms to obtain the free
energy of model proteins in a way which is computationally very economical.Comment: Submitted to Gen
A folding inhibitor of the HIV-1 Protease
Being the HIV-1 Protease (HIV-1-PR) an essential enzyme in the viral life
cycle, its inhibition can control AIDS. The folding of single domain proteins,
like each of the monomers forming the HIV-1-PR homodimer, is controlled by
local elementary structures (LES, folding units stabilized by strongly
interacting, highly conserved, as a rule hydrophobic, amino acids). These LES
have evolved over myriad of generations to recognize and strongly attract each
other, so as to make the protein fold fast and be stable in its native
conformation. Consequently, peptides displaying a sequence identical to those
segments of the monomers associated with LES are expected to act as competitive
inhibitors and thus destabilize the native structure of the enzyme. These
inhibitors are unlikely to lead to escape mutants as they bind to the protease
monomers through highly conserved amino acids which play an essential role in
the folding process. The properties of one of the most promising inhibitors of
the folding of the HIV-1-PR monomers found among these peptides is demonstrated
with the help of spectrophotometric assays and CD spectroscopy
Designability of lattice model heteropolymers
Protein folds are highly designable, in the sense that many sequences fold to
the same conformation. In the present work we derive an expression for the
designability in a 20 letter lattice model of proteins which, relying only on
the Central Limit Theorem, has a generality which goes beyond the simple model
used in its derivation. This expression displays an exponential dependence on
the energy of the optimal sequence folding on the given conformation measured
with respect to the lowest energy of the conformational dissimilar structures,
energy difference which constitutes the only parameter controlling
designability. Accordingly, the designability of a native conformation is
intimately connected to the stability of the sequences folding to them.Comment: in press on Phys. Rev.
Simple models of protein folding and of non--conventional drug design
While all the information required for the folding of a protein is contained
in its amino acid sequence, one has not yet learned how to extract this
information to predict the three--dimensional, biologically active, native
conformation of a protein whose sequence is known. Using insight obtained from
simple model simulations of the folding of proteins, in particular of the fact
that this phenomenon is essentially controlled by conserved (native) contacts
among (few) strongly interacting ("hot"), as a rule hydrophobic, amino acids,
which also stabilize local elementary structures (LES, hidden, incipient
secondary structures like --helices and --sheets) formed early
in the folding process and leading to the postcritical folding nucleus (i.e.,
the minimum set of native contacts which bring the system pass beyond the
highest free--energy barrier found in the whole folding process) it is possible
to work out a succesful strategy for reading the native structure of designed
proteins from the knowledge of only their amino acid sequence and of the
contact energies among the amino acids. Because LES have undergone millions of
years of evolution to selectively dock to their complementary structures, small
peptides made out of the same amino acids as the LES are expected to
selectively attach to the newly expressed (unfolded) protein and inhibit its
folding, or to the native (fluctuating) native conformation and denaturate it.
These peptides, or their mimetic molecules, can thus be used as effective
non--conventional drugs to those already existing (and directed at neutralizing
the active site of enzymes), displaying the advantage of not suffering from the
uprise of resistance
Deriving amino acid contact potentials from their frequencies of occurence in proteins: a lattice model study
The possibility of deriving the contact potentials between amino acids from
their frequencies of occurence in proteins is discussed in evolutionary terms.
This approach allows the use of traditional thermodynamics to describe such
frequencies and, consequently, to develop a strategy to include in the
calculations correlations due to the spatial proximity of the amino acids and
to their overall tendency of being conserved in proteins. Making use of a
lattice model to describe protein chains and defining a "true" potential, we
test these strategies by selecting a database of folding model sequences,
deriving the contact potentials from such sequences and comparing them with the
"true" potential. Taking into account correlations allows for a markedly better
prediction of the interaction potentials
Electron-phonon interaction in C70
The matrix elements of the deformation potential of C are calculated
by means of a simple, yet accurate solution of the electron-phonon coupling
problem in fullerenes, based on a parametrization of the ground state
electronic density of the system in terms of hybridized orbitals.
The value of the calculated dimensionless total electron-phonon coupling
constant is , an order of magnitude smaller than in
C, consistent with the lack of a superconducting phase transition in
CA fullerite, and in overall agreement with measurements of the
broadening of Raman peaks in CK. We also calculate the photoemission
cross section of C, which is found to display less structure than that
associated with C, in overall agreement with the experimental
findings.Comment: To be published in Phys. Rev.
Role of bulk and of interface contacts in the behaviour of model dimeric proteins
Some dimeric proteins first fold and then dimerize (three--state dimers)
while others first dimerize and then fold (two--state dimers). Within the
framework of a minimal lattice model, we can distinguish between sequences
obeying to one or to the other mechanism on the basis of the partition of the
ground state energy between bulk than for interface contacts. The topology of
contacts is very different for the bulk than for the interface: while the bulk
displays a rich network of interactions, the dimer interface is built up a set
of essentially independent contacts. Consequently, the two sets of interactions
play very different roles both in the the folding and in the evolutionary
history of the protein. Three--state dimers, where a large fraction of the
energy is concentrated in few contacts buried in the bulk, and where the
relative contact energy of interface contacts is considerably smaller than that
associated with bulk contacts, fold according to a hierarchycal pathway
controlled by local elementary structures, as also happens in the folding of
single--domain monomeric proteins. On the other hand, two--state dimers display
a relative contact energy of interface contacts which is larger than the
corresponding quantity associated with the bulk. In this case, the assembly of
the interface stabilizes the system and lead the two chains to fold. The
specific properties of three--state dimers acquired through evolution are
expected to be more robust than those of two--state dimers, a fact which has
consequences on proteins connected with viral diseases
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