273 research outputs found
Germanium-on-Glass solar cells: fabrication and characterization
We report on Germanium on Glass solar cells realized by wafer bonding, layer splitting and epitaxial regrowth. We provide a detailed description of the layer transfer process and discuss the material characterization. The solar cells are fabricated and tested to extract the most significant figures of merit, evaluating their performance versus device area and operating temperature. The cells exhibit typical conversion efficiencies exceeding 2.4% under AM1.5 irradiation and a maximum efficiency of 3.7% under concentrated excitation. This Germanium on Glass approach is promising in terms of added flexibility in multi-junction engineering and allows a significant cost reduction thanks to the re-usability of the Ge substrates
Engineering REST-Specific Synthetic PUF Proteins to Control Neuronal Gene Expression: A Combined Experimental and Computational Study
Regulation of gene transcription is an essential mechanism for differentiation and adaptation of organisms. A key actor in this regulation process is the repressor element 1 (RE1)-silencing transcription factor (REST), a transcriptional repressor that controls more than 2000 putative target genes, most of which are neuron-specific. With the purpose of modulating REST expression, we exploited synthetic, ad hoc designed, RNA binding proteins (RBPs) able to specifically target and dock to REST mRNA. Among the various families of RBPs, we focused on the Pumilio and FBF (PUF) proteins, present in all eukaryotic organisms and controlling a variety of cellular functions. Here, a combined experimental and computational approach was used to design and test 8- and 16-repeat PUF proteins specific for REST mRNA. We explored the conformational properties and atomic features of the PUF-RNA recognition code by Molecular Dynamics simulations. Biochemical assays revealed that the 8- and 16-repeat PUF-based variants specifically bind the endogenous REST mRNA without affecting its translational regulation. The data also indicate a key role of stacking residues in determining the binding specificity. The newly characterized REST-specific PUF-based constructs act as excellent RNA-binding modules and represent a versatile and functional platform to specifically target REST mRNA and modulate its endogenous expression
Interfacing Graphene-Based Materials With Neural Cells
The scientific community has witnessed an exponential increase in the applications of graphene and graphene-based materials in a wide range of fields, from engineering to electronics to biotechnologies and biomedical applications. For what concerns neuroscience, the interest raised by these materials is two-fold. On one side, nanosheets made of graphene or graphene derivatives (graphene oxide, or its reduced form) can be used as carriers for drug delivery. Here, an important aspect is to evaluate their toxicity, which strongly depends on flake composition, chemical functionalization and dimensions. On the other side, graphene can be exploited as a substrate for tissue engineering. In this case, conductivity is probably the most relevant amongst the various properties of the different graphene materials, as it may allow to instruct and interrogate neural networks, as well as to drive neural growth and differentiation, which holds a great potential in regenerative medicine. In this review, we try to give a comprehensive view of the accomplishments and new challenges of the field, as well as which in our view are the most exciting directions to take in the immediate future. These include the need to engineer multifunctional nanoparticles (NPs) able to cross the blood-brain-barrier to reach neural cells, and to achieve on-demand delivery of specific drugs. We describe the state-of-the-art in the use of graphene materials to engineer three-dimensional scaffolds to drive neuronal growth and regeneration in vivo, and the possibility of using graphene as a component of hybrid composites/multi-layer organic electronics devices. Last but not least, we address the need of an accurate theoretical modeling of the interface between graphene and biological material, by modeling the interaction of graphene with proteins and cell membranes at the nanoscale, and describing the physical mechanism(s) of charge transfer by which the various graphene materials can influence the excitability and physiology of neural cells
Colored-noise thermostats \`a la carte
Recently, we have shown how a colored-noise Langevin equation can be used in
the context of molecular dynamics as a tool to obtain dynamical trajectories
whose properties are tailored to display desired sampling features. In the
present paper, after having reviewed some analytical results for the stochastic
differential equations forming the basis of our approach, we describe in detail
the implementation of the generalized Langevin equation thermostat and the
fitting procedure used to obtain optimal parameters. We discuss in detail the
simulation of nuclear quantum effects, and demonstrate that, by carefully
choosing parameters, one can successfully model strongly anharmonic solids such
as neon. For the reader's convenience, a library of thermostat parameters and
some demonstrative code can be downloaded from an on-line repository
Maximum Flux Transition Paths of Conformational Change
Given two metastable states A and B of a biomolecular system, the problem is
to calculate the likely paths of the transition from A to B. Such a calculation
is more informative and more manageable if done for a reduced set of collective
variables chosen so that paths cluster in collective variable space. The
computational task becomes that of computing the "center" of such a cluster. A
good way to define the center employs the concept of a committor, whose value
at a point in collective variable space is the probability that a trajectory at
that point will reach B before A. The committor "foliates" the transition
region into a set of isocommittors. The maximum flux transition path is defined
as a path that crosses each isocommittor at a point which (locally) has the
highest crossing rate of distinct reactive trajectories. (This path is
different from that of the MaxFlux method of Huo and Straub.) It is argued that
such a path is nearer to an ideal path than others that have been proposed with
the possible exception of the finite-temperature string method path. To make
the calculation tractable, three approximations are introduced, yielding a path
that is the solution of a nonsingular two-point boundary-value problem. For
such a problem, one can construct a simple and robust algorithm. One such
algorithm and its performance is discussed.Comment: 7 figure
ACTH-producing tumorlets and carcinoids of the lung: clinico-pathologic study of 63 cases and review of the literature.
Adrenocorticotropic hormone (ACTH)-secreting lung carcinoids represent the principal cause of ectopic Cushing syndrome, but the prevalence of ACTH expression and the association between ACTH production and Cushing syndrome in lung carcinoids have scarcely been investigated. In addition, available information on the prognostic meaning of ACTH production is controversial. The aims of this multicentric retrospective study, also including a review of the literature, were to describe the clinico-pathologic features of ACTH-producing lung carcinoids, to assess recurrence and specific survival rates, and to evaluate potential prognostic factors. To identify ACTH production in 254 unselected and radically resected lung carcinoids, we used a double approach including RT-PCR (mRNA encoding for pro-opiomelanocortin) and immunohistochemistry (antibodies against ACTH and β-endorphin). Sixty-three (24.8%) tumors produced ACTH and 11 of them (17.4%), representing 4.3% of the whole series, were associated with Cushing syndrome. The median follow-up time was 71 months. The 10-year overall and specific survival rates were 88.5% and 98.2%, respectively, with difference neither between functioning and nonfunctioning tumors nor between ACTH-positive and ACTH-negative carcinoids. At univariate analysis, histological type (typical or atypical) and Ki67 index significantly correlated with tumor recurrence. The literature review identified 172 previously reported patients with functioning ACTH-secreting lung carcinoids, and the meta-analysis of survival showed that 92% of them were alive after a mean follow-up time of 50 months. Our results demonstrate that ACTH-producing lung carcinoids are not rare, are not always associated with Cushing syndrome, and do not represent an aggressive variant of lung carcinoid
A weak characterization of slow variables in stochastic dynamical systems
We present a novel characterization of slow variables for continuous Markov
processes that provably preserve the slow timescales. These slow variables are
known as reaction coordinates in molecular dynamical applications, where they
play a key role in system analysis and coarse graining. The defining
characteristics of these slow variables is that they parametrize a so-called
transition manifold, a low-dimensional manifold in a certain density function
space that emerges with progressive equilibration of the system's fast
variables. The existence of said manifold was previously predicted for certain
classes of metastable and slow-fast systems. However, in the original work, the
existence of the manifold hinges on the pointwise convergence of the system's
transition density functions towards it. We show in this work that a
convergence in average with respect to the system's stationary measure is
sufficient to yield reaction coordinates with the same key qualities. This
allows one to accurately predict the timescale preservation in systems where
the old theory is not applicable or would give overly pessimistic results.
Moreover, the new characterization is still constructive, in that it allows for
the algorithmic identification of a good slow variable. The improved
characterization, the error prediction and the variable construction are
demonstrated by a small metastable system
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