1,592 research outputs found
Pietro Verri’s Contribution to the Economic Theory of the 18th Century: Commercial Society, Civil Society and Governance of the Economy
No full text'Count Pietro Verri (1728-97) - Schumpeter writes (History, p. 178) - - would have to be included in any list of the greatest economists'. Within the Milanese school, he certainly stands out, alongside with Cesare Beccaria, during one of the most interesting periods from a history of analysis point of view. Luigi Cossa's famous introduction to the study of political economy rates Pietro Verri to be inferior to Beccaria in ingenuity and scientific cultivation, but greatly to be ahead of him as an economist.1 This judgement by Cossa, in particular, seems to echo the relative position of the two men in the history of ideas, particularly after Beccaria's rise to fame with a book - On crimes and punishments - which had in fact been largely inspired by Verri himself and defended by him.2 It is proposed in the present paper to revisit some of the basic tenets of Pietro Verri's political economy, with more in view than dwell on specific intuitions and theorems: namely relate those to Verri's own - quite original - conception of the economy. The scholarly work of Pietro Verri - with a special reference to his Meditazioni sulla economia politica of 1771 - provides the first systematic contribution stemming from the quarters of Lombard enlightenment in the field of political economy, especially so if one considers that Cesare Beccaria's parallel work - namely his Elementi di economia pubblica, conceived and drafted at the same time as Verri's Meditazioni - would only be published posthumously several years later. From the vantage point afforded by Verri's political economy, we gain a considerably attractive view of the most significant elements and characteristic concepts of Lombard enlightenment during the latter half of the 18th century; Verri, moreover, as we shall see, builds on a number of them in a new and original way. This paper is aimed at discussing Verri's political economy mainly along two distinct, but related, lines. In the first place the conception of commercial society is considered such as it is treated by the author particularly in his Meditazioni. In this perspective the analysis of such issues as competition and the market or money and taxation occupy a central place. Secondly it will be necessary to emphasise that Verri's approach has little to do either with forms of pure economics on one side - largely yet to be born throughout the 18th century - or, on the other side, with such conceptions of the polis - contrariwise well alive among his own contemporaries - as are founded on a sovereign authority conceived to be situated above the law. What Verri's political economy ultimately amounts to is an economic conception of civil society. The latter has natural strong connections with his own fact-mindedness - emphasised by Schumpeter - as well as with his deep practical involvement in administrative affairs and in the reforming process taking place during the latter half of the 18th century in Milan. In our view, a thorough investigation along the mentioned lines is the precondition for an understanding of the intellectual stature and of the scholarly contribution of Pietro Verri. His main ground is distinctly analytical and only by appreciating his analysis is it possible to shed light on the meaning and intellectual significance also of his practical contributions. Moreover Verri's pronouncements on the criticism of despotic government, the relevance of intermediate powers or bodies and on multiple levels of governance will be examined in a new and original light, showing how close they are to the gist of his analysis.
amp; pursue task
No full textCan haptic interaction improve the tracking performance in a fetch & pursue task, similar to clay pigeon shooting? In order to answer this question, we challenged the tracking movements of the subjects by a saddle-like moving force field, with the unstable manifold aligned along the moving target and the stable manifold orthogonal to it. The experimental results show a positive effect, suggesting that the internal model acquired by the subjects for compensating the target-linked haptic disturbance can improve the prediction capability of the subjects based on pure visuo-motor feedback
Effect of E134K pathogenic mutation of SMN protein on SMN-SmD1 interaction, with implication in spinal muscular atrophy: a molecular dynamics study
No full textSpinal muscular atrophy (SMA) is a disease that results from mutations in the Survival of Motor Neuron (SMN) gene 1, leading to muscle atrophy due to motor neurons degeneration. SMN plays a crucial role in the assembly of spliceosomal small nuclear ribonucleoprotein complexes via binding to the arginine-glycine rich C-terminal tails of Sm proteins recognized by SMN Tudor domain. E134K Tudor mutation, cause of the more severe type I SMA, compromises the SMN-Sm interaction without a perturbation of the domain fold. By molecular dynamics simulations, we investigated the mechanism of Tudor-SmD1 interaction, and the effects on it of E134K mutation. It was observed that E134 is crucial to catch the positive dimethylated arginines (DMRs) of the SmD1 tail that, wrapping around the acidic Tudor surface, enters a central DMR into an aromatic cage. The flexible cage residue Y130 must be blocked from the wrapped tail to assure a stable binding. The charge inversion in E134K mutation causes the loss of a critical anchor point, disfavoring the tail wrapping and leaving Y130 free to swing, leading to DMR detachments and exposition of the C-terminal region of the tail. This could suggest new hypotheses regarding a possible autoimmune response by anti-Sm autoantibodies
Molecular dynamics study of pathogenic mutations of SMN protein: effects on SMN-SmD1 protein complex formation and implication in Spinal Muscular Atrophy
No full textSpinal muscular atrophy (SMA) is a motor neuron disease that leads to muscle atrophy due to motor neurons degeneration. SMA is a major genetic cause of early childhood mortality and results from mutations in the Survival of Motor Neuron (SMN) gene 1. The SMN protein plays a crucial role in the assembly of spliceosomal small nuclear ribonucleoprotein complexes via binding to the spliceosomal Sm core proteins, in particular to their arginine-glycine (RG) rich C-terminal tails. SMN contains a central Tudor domain, directly involved in the SMN–Sm protein interaction by the recognition of symmetrically dimethylated arginine (DMR) residues in the RG repeats. In particular, an aromatic cage on Tudor domain seems to mediate this binding1-3.
Six of the pathogenic mutations causing SMA occur in the SMN Tudor domain. The only one that prevents the binding to the Sm proteins without a perturbation of the domain fold is E134K, that is the cause of the more severe type I SMA3.
To gain more understanding about the mechanism by which SMN interacts with the Sm proteins, and which are the structural effects on binding of its deleterious mutation E134K, we investigated the behavior of the native and mutated structure of the SMN Tudor domain in the presence of the C-terminal tail of SmD1, by means of molecular dynamics simulations.
We observed that the interaction of the SmD1 tail with the Tudor domain is electrostatic driven by the acidic residues near the entrance of the aromatic cage. In the native protein, a central DMR of the tail enters into the cage rapidly and stably, forming a network of both hydrophobic and cationic-pi interactions, both in stacking and T-shaped. The complex is stabilized also by the salt-bridges formed by the other DMRs and arginine residues wrapped around the acidic surface of the Tudor domain.
The charge inversion of E134K mutation leads to a non-correct interaction of the SmD1 tail with the acidic residues at the Tudor surface, causing the detachment the C-terminal region of the tail. In addition, the E134K mutation destabilizes the cage, not only with the disruption of the strong 134-136-127 H-bonds network, but also with the formation of new electrostatic and cationic-pi interactions. The cage collapses and expands, preventing a stable binding of the DMR.
The results are in agreement with what experimentally observed1-3 and clarify the key role of E134 in the interaction of the SmD1 tail with the Tudor domain. The loss of a strong Tudor-SmD1 interaction, if by one side causes the loss of a functional splicing machinery, by the other side causes the exposition of the detached Sm tails, that could stimulate the recognition by anti-Sm autoantibodies, as is reported for other diseases as lupus erithematosus4, giving rise to the innovative hypothesis of SMA as an autoimmune disease.
1. Selenko, P. et al., Nat. Struct. Biol. 8, 27–31 (2001).
2. Sprangers, R. et al., J. Mol. Biol. 327, 507–520 (2003).
3. Tripsianes, K. et al., Nat. Struct. Mol. Biol. 18, 1414–20 (2011).
4. Brahms, H. et al., J. Biol. Chem. 275, 17122–17129 (2000)
Wrist proprioception: amplitude or position coding?
No full textThis work examines physiological mechanisms underlying the position sense of the wrist, namely the codification of proprioceptive information related to pointing movements of the wrist towards kinesthetic targets. Twenty-four healthy subjects participated to a robot-aided assessment of their wrist proprioceptive acuity to investigate if the sensorimotor transformation involved in matching targets located by proprioceptive receptors relies on amplitude or positional cues. A joint position matching test was performed in order to explore such dichotomy. In this test, the wrist of a blindfolded participant is passively moved by a robotic device to a preset target position and, after a removal movement from this position, the participant has to actively replicate and match it as accurately as possible. The test involved two separate conditions: in the first the matching movements started from the same initial location; in the second one the initial location was randomly assigned. Target matching accuracy, precision and bias in the two conditions were then compared. Overall results showed a consistent higher performance in the former condition than in the latter, thus supporting the hypothesis that the joint position sense is based on vectorial or amplitude coding rather than positional
About twin primes and distribution of primes
No full textThis paper give us a demonstration of twin primes conjecture using approximation of function �(iupsilon) that we introduce in section 6. Section 1-5 give us introduction to terminology and a clarification on (iupsilon) terms. In particular section
5 is really important because of its Lemma. Section 7 reassume foregoing explanations and it give us two theorems and one corollary;the theorem 7.2 give us exact approximation of twin primes counting function
Robot-Aided Mapping of Wrist Proprioceptive Acuity across a 3D Workspace.
No full textProprioceptive signals from peripheral mechanoreceptors form the basis for bodily perception and are known to be essential for motor control. However we still have an incomplete understanding of how proprioception differs between joints, whether it differs among the various degrees-of-freedom (DoFs) within a particular joint, and how such differences affect motor control and learning. We here introduce a robot-aided method to objectively measure proprioceptive function: specifically, we systematically mapped wrist proprioceptive acuity across the three DoFs of the wrist/hand complex with the aim to characterize the wrist position sense. Thirty healthy young adults performed an ipsilateral active joint position matching task with their dominant wrist using a haptic robotic exoskeleton. Our results indicate that the active wrist position sense acuity is anisotropic across the joint, with the abduction/adduction DoF having the highest acuity (the error of acuity for flexion/extension is 4.64 ± 0.24°; abduction/adduction: 3.68 ± 0.32°; supination/pronation: 5.15 ± 0.37°) and they also revealed that proprioceptive acuity decreases for smaller joint displacements. We believe this knowledge is imperative in a clinical scenario when assessing proprioceptive deficits and for understanding how such sensory deficits relate to observable motor impairments
Self-adaptive robot training of stroke survivors for continuous tracking movements
No full textAbstract Background Although robot therapy is progressively becoming an accepted method of treatment for stroke survivors, few studies have investigated how to adapt the robot/subject interaction forces in an automatic way. The paper is a feasibility study of a novel self-adaptive robot controller to be applied with continuous tracking movements. Methods The haptic robot Braccio di Ferro is used, in relation with a tracking task. The proposed control architecture is based on three main modules: 1) a force field generator that combines a non linear attractive field and a viscous field; 2) a performance evaluation module; 3) an adaptive controller. The first module operates in a continuous time fashion; the other two modules operate in an intermittent way and are triggered at the end of the current block of trials. The controller progressively decreases the gain of the force field, within a session, but operates in a non monotonic way between sessions: it remembers the minimum gain achieved in a session and propagates it to the next one, which starts with a block whose gain is greater than the previous one. The initial assistance gains are chosen according to a minimal assistance strategy. The scheme can also be applied with closed eyes in order to enhance the role of proprioception in learning and control. Results The preliminary results with a small group of patients (10 chronic hemiplegic subjects) show that the scheme is robust and promotes a statistically significant improvement in performance indicators as well as a recalibration of the visual and proprioceptive channels. The results confirm that the minimally assistive, self-adaptive strategy is well tolerated by severely impaired subjects and is beneficial also for less severe patients. Conclusions The experiments provide detailed information about the stability and robustness of the adaptive controller of robot assistance that could be quite relevant for the design of future large scale controlled clinical trials. Moreover, the study suggests that including continuous movement in the repertoire of training is acceptable also by rather severely impaired subjects and confirms the stabilizing effect of alternating vision/no vision trials already found in previous studies.</p
Testing proprioception in intrinsic and extrinsic coordinate systems: Is there a difference?
No full textAn intact position sense is considered important for neuromotor recovery, but the available methods and protocols for its assessment are still limited. In the clinical practice it is generally tested trough a bimanual position matching test, that consists of replicating with one arm the angular positions of the other arm in space (intrinsic coordinates matching). However, the same test could be carried out by matching the hand location in space (extrinsic coordinates matching). Is there any difference between the procedures that may be relevant to the evaluation of position sense deficits? In this study we compared the performance of eight right handed subjects and two stroke survivors with left hemiparesis performing the test in the two conditions. A robotic manipulandum passively moved the left arm of the participants in twenty-four positions in the workspace. Subjects had to match the left arm position with their right arm either in intrinsic or extrinsic coordinates. The results show that all the subjects (impaired and controls) performed better when using the extrinsic paradigm
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