196,851 research outputs found
Heme binding by the N-terminal fragment 1-44 of human growth hormone
No full textFragment 1-44 of human growth hormone (hGH), prepared in vitro by limited proteolysis of the hormone with pepsin at low pH, encompasses in full the N-terminal helix of this four-helix bundle protein [Spolaore, B., Polverino de Laureto, P., Zambonin, M., and Fontana, A. (2004) Biochemistry 40, 9460-9468]. Here, we report the new and interesting observation that fragment 1-44 can bind heme. The binding property is specific for the N-terminal helix of hGH, since heme binding does not occur with fragment 45-191 or the entire protein. The spectral characteristics of Fe-protoporphyrin IX are those of a low-spin, hexacoordinated iron ligated by two imidazole rings of His residues or His and Met residues. Far-UV circular dichroism (CD) measurements revealed that fragment 1-44 acquires a helical secondary structure upon heme binding. Heme appears to be bound to the fragment in a stereospecific way, since an induced dichroic signal is observed in the Soret region of the CD spectrum. The heme-fragment complex occurs in a 1:1 molar ratio, as determined by spectrophotometric titration, as well as by electrospray-ionization mass spectrometric analysis of the complex. The fragment alone is much more susceptible to tryptic digestion than the heme complex, implying a more folded and rigid structure of this last species. It is proposed that the molecular features of fragment 1-44 determining its heme-binding property reside in the amphipathic character of the helix adopted by the fragment, as well as in the presence in its polypeptide chain of His18, His21, and Met14. These residues can act as specific ligands for the heme-iron, as observed with cytochromes
Agency and fictional truth: a formal study on fiction-making
No full textFictional truth, or truth in fiction/pretense, has been the object of extended scrutiny among philosophers and logicians in recent decades. Comparatively little attention, however, has been paid to its inferential relationships with time and with certain deliberate and contingent human activities, namely, the creation of fictional works. The aim of the paper is to contribute to filling the gap. Toward this goal, a formal framework is outlined that is consistent with a variety of conceptions of fictional truth and based upon a specific formal treatment of time and agency, that of so-called stit logics. Moreover, a complete axiomatic theory of fiction-making TFM is defined, where fiction-making is understood as the exercise of agency and choice in time over what is fictionally true. The language L of TFM is an extension of the language of propositional logic, with the addition of temporal and modal operators. A distinctive feature of L with respect to other modal languages is a variety of operators having to do with fictional truth, including a ‘fictionality’ operator M (to be read as “it is a fictional truth that”). Some applications of TFM are outlined, and some interesting linguistic and inferential phenomena, which are not so easily dealt with in other frameworks, are accounted for
Design and realization of a magnetron sputtering device for deposition of electromagnetic shields
No full textA system for sputtering deposition of thin electromagnetic shields has been developed. A double source magnetron sputtering system, with planar commercial cathodes, has been chosen, in order to realize film depositions in low pressure plasmas with two different targets. A rotating system, with external manual movement, for the location of the sustaining structure of the substrates has been realized, and different vertical positions are obtained by an adjustable fixing of the supporting stem. Finally the system is monitored by a safety system, with interlocks
The number and size of nations revisited: Endogenous border formation with non-uniform population distributions
No full textThe endogenous border formation model of Alesina and Spolaore (1997) has received a lot of attention in the economics community. One of its central messages is that in a democratic world in equilibrium there is an ineciently large number of nation states. However, this result is obtained under very specic assumptions like a uniform population distribution and no population mobility. In this paper, I generalize the model of Alesina and Spolaore allowing for population distributions other than the uniform distribution. Since this generalization is accompanied by the loss of tractability in closed form, I calculate the equilibria by means of numerical computation. It turns out that the above-mentioned central result is highly sensitive to the choice of population distribution and that the model shows four different regimes depending on the chosen distribution. Furthermore, the behaviour implied by the Alesina and Spolaore model with uniform population distribution is the exception, not the rule.Size of Nations; Endogenous Border Formation; Computational Economics
Characterization of nanostructured copper films for electromagnetic shield
No full textPurpose – The purpose of this paper is to obtain a multidisciplinary characterization of nanostructured copper films for electromagnetic shields. Design/methodology/approach – Structural and electrical analysis have been applied, on copper nanometric films produced by a magnetron sputtering device. Findings – Data are provided for copper films realized by magnetron sputtering deposition on glass, in different operating conditions. Practical implications – A multidisciplinary comprehension of shielding effectiveness of nanostructured thin films can be important in many applications where there are electromagnetic
compatibility problems. Originality/value – The paper gives a valuable set of information for the characterization of
nanometric copper thin films
Structural polymorphism within a regulatory element of the human KRAS promoter: formation of G4-DNA recognized by nuclear proteins
No full textThe human KRAS proto-oncogene contains a critical nuclease hypersensitive element (NHE) upstream of the major transcription initiation site. In this article, we demonstrate by primer-extension experiments, PAGE, chemical footprinting, CD, UV and FRET experiments that the G-rich strand of NHE (32R) folds into intra-molecular G-quadruplex structures. Fluorescence data show that 32R in 100 mM KCl melts with a biphasic profile, showing the formation of two distinct G-quadruplexes with T(m) of approximately 55 degrees C (Q(1)) and approximately 72 degrees C (Q(2)). DMS-footprinting and CD suggest that Q(1) can be a parallel and Q(2) a mixed parallel/antiparallel G-quadruplex. When dsNHE (32R hybridized to its complementary) is incubated with a nuclear extract from Panc-1 cells, three DNA-protein complexes are observed by EMSA. The complex of slower mobility is competed by quadruplex 32R, but not by mutant oligonucleotides, which cannot form a quadruplex structure. Using paramagnetic beads coupled with 32R, we pulled down from the Panc-1 extract proteins with affinity for quadruplex 32R. One of these is the heterogeneous nuclear ribonucleoprotein A1, which was previously reported to unfold quadruplex DNA. Our study suggests a role of quadruplex DNA in KRAS transcription and provides the basis for the rationale design of molecular strategies to inhibit the expression of KRAS
A Mereology for the Change of Parts
No full textA theory of temporal mereology is formulated in which the principles of Existence and of Uniqueness of Composition hold. The theory is consistent both with a three-dimensionalist ontology and with the change of parts, that is, with the view that at least one object has distinct parts at distinct times. Some interesting consequences of the theory joined with the change of parts, taken as an axiom, are proven. It is usually held that certain well known ontological puzzles must be solved either by adopting a four-dimensionalist ontology or by restricting some mereological principles. Here a solution to those puzzles is stated, which allows to keep all mereological principles in their generality, without adopting a four-dimensionalist ontology. The solution is achieved by denying the persistence of some of the entities involved, along the “Chrysippean” lines advocated by M. Burke and M. Rea. Although good reasons for this move are provided, some problems of the solution are also highlighted and tentatively answered
Complementation of protein fragments: novel systems derived from cytochrome c and apomyoglobin
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