Escacs, un sistema intel·ligent

Des dels inicis dels ordinadors com a màquines programables, l’home ha intentat dotar-los de certa intel•ligència per tal de pensar o raonar el més semblant possible als humans. Un d’aquests intents ha sigut fer que la màquina sigui capaç de pensar de tal manera que estudiï jugades i guanyi partides d’escacs. En l’actualitat amb els actuals sistemes multi tasca, orientat a objectes i accés a memòria i gràcies al potent hardware del que disposem, comptem amb una gran varietat de programes que es dediquen a jugar a escacs. Però no hi ha només programes petits, hi ha fins i tot màquines senceres dedicades a calcular i estudiar jugades per tal de guanyar als millors jugadors del món. L’objectiu del meu treball és dur a terme un estudi i implementació d’un d’aquests programes, per això es divideix en dues parts. La part teòrica o de l’estudi, consta d’un estudi dels sistemes d’intel•ligència artificial que es dediquen a jugar a escacs, estudi i cerca d’una funció d’avaluació vàlida i estudi dels algorismes de cerca. La part pràctica del treball es basa en la implementació d’un sistema intel•ligent capaç de jugar a escacs amb certa lògica. Aquesta implementació es porta a terme amb l’ajuda de les llibreries SDL, utilitzant l’algorisme minimax amb poda alfa-beta i codi c++. Com a conclusió del projecte m’agradaria remarcar que l’estudi realitzat m’ha deixat veure que crear un joc d’escacs no era tan fàcil com jo pensava però m’ha aportat la satisfacció d’aplicar tot el que he après durant la carrera i de descobrir moltes altres coses noves.

Atrial assist device, a new alternative to lifelong anticoagulation?

OBJECTIVE: Atrial fibrillation is a very common heart arrhythmia, associated with a five-fold increase in the risk of embolic strokes. Treatment strategies encompass palliative drugs or surgical procedures all of which can restore sinus rhythm. Unfortunately, atria often fail to recover their mechanical function and patients therefore require lifelong anticoagulation therapy. A motorless volume displacing device (Atripump) based on artificial muscle technology, positioned on the external surface of atrium could avoid the need of oral anticoagulation and its haemorrhagic complications. An animal study was conducted in order to assess the haemodynamic effects that such a pump could provide. METHODS: Atripump is a dome-shape siliconecoated nitinol actuator sewn on the external surface of the atrium. It is driven by a pacemaker-like control unit. Five non-anticoagulated sheep were selected for this experiment. The right atrium was surgically exposed, the device sutured and connected. Haemodynamic parameters and intracardiac ultrasound (ICUS) data were recorded in each animal and under three conditions; baseline; atrial fibrillation (AF); atripump assisted AF (aaAF). RESULTS: In two animals, after 20 min of AF, small thrombi appeared in the right atrial appendix and were washed out once the pump was turned on. Assistance also enhanced atrial ejection fraction. 31% baseline; 5% during AF; 20% under aaAF. Right atrial systolic surfaces (cm2) were; 5.2 +/- 0.3 baseline; 6.2 +/- 0.1 AF; 5.4 +/- 0.3 aaAF. CONCLUSION: This compact and reliable pump seems to restore the atrial "kick" and prevents embolic events. It could avoid long-term anticoagulation therapy and open new hopes in the care of end-stage heart failure.

Hypertension is an independent predictor of mean platelet volume in patients with acute ischaemic stroke.

Introduction: Mean platelet volume (MPV) was shown to be significantly increased in patients with acute ischaemic stroke, especially in non-lacunar strokes. Moreover, some studies concluded that increased MPV is related to poor functional outcome after ischaemic stroke, although this association is still controversial. However, the determinants of MPV in patients with acute ischaemic stroke have never been investigated. Subjects and methods: We recorded the main demographic, clinical and laboratory data of consecutive patients with acute (admitted within 24 h after stroke onset) ischaemic stroke admitted in our Neurology Service between January 2003 and December 2008. MPV was generated at admission by the Sysmex XE-2100 automated cell counter (Sysmex Corporation, Kobe, Japan) from ethylenediaminetetraacetic acid blood samples stored at room temperature until measurement. The association of these parameters with MPV was investigated in univariate and multivariate analysis. Results: A total of 636 patients was included in our study. The median MPV was 10.4 ± 0.82 fL. In univariate analysis, glucose (β= 0.03, P= 0.05), serum creatinine (β= 0.002, P= 0.02), haemoglobin (β= 0.009, P < 0.001), platelet count (β=-0.002, P < 0.001) and history of arterial hypertension (β= 0.21, P= 0.005) were found to be significantly associated with MPV. In multivariate robust regression analysis, only hypertension and platelet count remained as independent determinants of MPV. Conclusions: In patients with acute ischaemic stroke, platelet count and history of hypertension are the only determinants of MPV.

Central Horner's syndrome with contralateral ataxic hemiparesis: a diencephalic alternate syndrome.

OBJECTIVE: To assess whether thalamic strokes presenting with a central Horner's syndrome (HS) show specific clinicoanatomic patterns. METHODS: From the Lausanne Stroke Registry (period 1993 to spring 2002), the authors selected all patients with thalamic stroke presenting with ipsilateral HS. Patients with complete infarction of the posterior cerebral artery territory, with involvement of middle cerebral artery territory or bilateral lesions, were excluded. Lesions on brain MRI were correlated with standard neuroanatomic templates. RESULTS: Nine patients with thalamic infarction presenting with central HS were found; all showed contralateral ataxic hemiparesis (AH). Lesions involved the anterior or paramedian thalamus and extended to the hypothalamic or rostral paramedian mesencephalic area in all but one subject. Associated clinical signs included dysphasia (two patients), somnolence (six), vertical gaze paresis (two), asterixis (two), and hemihypesthesia (three). CONCLUSION: The alternate clinical pattern of central HS with contralateral AH is a stroke syndrome of the diencephalic-mesencephalic junction, resulting from the involvement of the common arterial supply to the paramedian/anterior thalamus, the posterior hypothalamus and the rostral paramedian midbrain.

Neuromuscular fatigue in racquet sports

This article describes the physiologic and neural mechanisms that cause neuromuscular fatigue in racquet sports: table tennis, tennis, squash, and badminton. In these intermittent and dual activities, performance may be limited as a match progresses because of a reduced central activation, linked to changes in neurotransmitter concentration or in response to afferent sensory feedback. Alternatively, modulation of spinal loop properties may occur because of changes in metabolic or mechanical properties within the muscle. Finally, increased fatigue manifested by mistimed strokes, lower speed, and altered on-court movements may be caused by ionic disturbances and impairments in excitation-contraction coupling properties. These alterations in neuromuscular function contribute to decrease in racquet sports performance observed under fatigue.

Temporal distribution and magnitude of the vulnerability period around stroke depend on stroke subtype.

Background: We aimed to analyze the rate and time distribution of pre- and post-morbid cerebrovascular events in a single ischemic stroke population, and whether these depend on the etiology of the index stroke. Methods: In 2,203 consecutive patients admitted to a single stroke center registry (ASTRAL), the ischemic stroke that led to admission was considered the index event. Frequency distribution and cumulative relative distribution graphs of the most recent and first recurrent event (ischemic stroke, transient ischemic attack, intracranial or subarachnoid hemorrhage) were drawn in weekly and daily intervals for all strokes and for all stroke types. Results: The frequency of events at identical time points before and after the index stroke was mostly reduced in the first week after (vs. before) stroke (1.0 vs. 4.2%, p < 0.001) and the first month (2.7 vs. 7.4%, p < 0.001), and then ebbed over the first year (8.4 vs. 13.1%, p < 0.001). On daily basis, the peak frequency was noticed at day -1 (1.6%) with a reduction to 0.7% on the index day and 0.17% 24 h after. The event rate in patients with atherosclerotic stroke was particularly high around the index event, but 1-year cumulative recurrence rate was similar in all stroke types. Conclusions: We confirm a short window of increased vulnerability in ischemic stroke and show a 4-, 3- and 2-fold reduction in post-stroke events at 1 week, 1 month and 1 year, respectively, compared to identical pre-stroke periods. This break in the 'stroke wave' is particularly striking after atherosclerotic and lacunar strokes.

Validation of the DRAGON Score in 12 Stroke Centers in Anterior and Posterior Circulation.

BACKGROUND AND PURPOSE: The DRAGON score predicts functional outcome in the hyperacute phase of intravenous thrombolysis treatment of ischemic stroke patients. We aimed to validate the score in a large multicenter cohort in anterior and posterior circulation. METHODS: Prospectively collected data of consecutive ischemic stroke patients who received intravenous thrombolysis in 12 stroke centers were merged (n=5471). We excluded patients lacking data necessary to calculate the score and patients with missing 3-month modified Rankin scale scores. The final cohort comprised 4519 eligible patients. We assessed the performance of the DRAGON score with area under the receiver operating characteristic curve in the whole cohort for both good (modified Rankin scale score, 0-2) and miserable (modified Rankin scale score, 5-6) outcomes. RESULTS: Area under the receiver operating characteristic curve was 0.84 (0.82-0.85) for miserable outcome and 0.82 (0.80-0.83) for good outcome. Proportions of patients with good outcome were 96%, 93%, 78%, and 0% for 0 to 1, 2, 3, and 8 to 10 score points, respectively. Proportions of patients with miserable outcome were 0%, 2%, 4%, 89%, and 97% for 0 to 1, 2, 3, 8, and 9 to 10 points, respectively. When tested separately for anterior and posterior circulation, there was no difference in performance (P=0.55); areas under the receiver operating characteristic curve were 0.84 (0.83-0.86) and 0.82 (0.78-0.87), respectively. No sex-related difference in performance was observed (P=0.25). CONCLUSIONS: The DRAGON score showed very good performance in the large merged cohort in both anterior and posterior circulation strokes. The DRAGON score provides rapid estimation of patient prognosis and supports clinical decision-making in the hyperacute phase of stroke care (eg, when invasive add-on strategies are considered).

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Protein destabilization by mutations or external stresses may lead to misfolding and aggregation in the cell. Often, damage is not limited to a simple loss of function, but the hydrophobic exposure of aggregate surfaces may impair membrane functions and promote the aggregation of other proteins. Such a "proteinacious infectious" behavior is not limited to prion diseases. It is associated to most protein-misfolding neurodegenerative diseases and to aging in general. With the molecular chaperones and proteases, cells have evolved powerful tools that can specifically recognize and act upon misfolded and aggregated proteins. Whereas some chaperones passively prevent aggregate formation and propagation, others actively unfold and solubilize stable aggregates. In particular, ATPase chaperones and proteases serve as an intracellular defense network that can specifically identify and actively remove by refolding or degradation potentially infectious cytotoxic aggregates. Here we discuss two types of molecular mechanisms by which ATPase chaperones may actively solubilize stable aggregates: (1) unfolding by power strokes, using the Hsp100 ring chaperones, and (2) unfolding by random movements of individual Hsp70 molecules. In bacteria, fungi, and plants, the two mechanisms are key for reducing protein damages from abiotic stresses. In animals devoid of Hsp100, Hsp70 appears as the core element of the chaperone network, preventing the formation and actively removing disease-causing protein aggregates.

Aortic arch atheroma and the risk of stroke.

Brain infarction of unknown cause, known as cryptogenic stroke, represents 30% to 40% of all ischemic strokes, or approximately 400,000 cases each year in western Europe. In this category of patients new potential causes, such as aortic arch atheroma in the elderly, have been investigated in the past two decades.

An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke.

OBJECTIVE: We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO. METHODS: Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates. RESULTS: Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%-26%) in those with 0 to 3 points to 73% (95% CI: 66%-79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%-28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%-4%) in the highest. CONCLUSION: Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk.

Frequency, characterisation and therapies of fatigue after stroke.

Post-stroke objective or subjective fatigue occurs in around 50% of patients and is frequent (30%) even after minor strokes. It can last more than one year after the event, and is characterised by a different quality from usual fatigue and good response to rest. Associated risk factors include age, single patients, female, disability, depression, attentional impairment and sometimes posterior strokes, but also inactivity, overweight, alcohol and sleep apnoea syndrome. There are few therapy studies, but treatment may include low-intensity training, cognitive therapy, treatment of associated depression, wakefulness-promoting agents like modafinil, correction of risk factors and adaptation of activities.

Safety of thrombolysis in stroke mimics: results from a multicenter cohort study.

BACKGROUND AND PURPOSE: Intravenous thrombolysis for acute ischemic stroke is beneficial within 4.5 hours of symptom onset, but the effect rapidly decreases over time, necessitating quick diagnostic in-hospital work-up. Initial time strain occasionally results in treatment of patients with an alternate diagnosis (stroke mimics). We investigated whether intravenous thrombolysis is safe in these patients. METHODS: In this multicenter observational cohort study containing 5581 consecutive patients treated with intravenous thrombolysis, we determined the frequency and the clinical characteristics of stroke mimics. For safety, we compared the symptomatic intracranial hemorrhage (European Cooperative Acute Stroke Study II [ECASS-II] definition) rate of stroke mimics with ischemic strokes. RESULTS: One hundred stroke mimics were identified, resulting in a frequency of 1.8% (95% confidence interval, 1.5-2.2). Patients with a stroke mimic were younger, more often female, and had fewer risk factors except smoking and previous stroke or transient ischemic attack. The symptomatic intracranial hemorrhage rate in stroke mimics was 1.0% (95% confidence interval, 0.0-5.0) compared with 7.9% (95% confidence interval, 7.2-8.7) in ischemic strokes. CONCLUSIONS: In experienced stroke centers, among patients treated with intravenous thrombolysis, only a few had a final diagnosis other than stroke. The complication rate in these stroke mimics was low.

Mécanismes moléculaires de l'homodimérisation de la protéine Scaffold IB1 et son implication dans la sécrétion d'insuline

RÉSUMÉ Les kinases activées par des mitogènes (MAPKs) constituent une importante famille d'enzymes conservée dans l'évolution. Elles forment un réseau de signalisation qui permet à la cellule de réguler spécifiquement divers processus impliqués dans la différenciation, la survie ou l'apoptose. Les kinases formant le module MAPK sont typiquement disposées en cascades de trois partenaires qui s'activent séquentiellement par phosphorylation. Le module minimum est constitué d'une MAPK kinase kinase (MAPKKK), d'une MAPK kinase (MAPKK) et d'une MAPK. Une fois activée, la MAPK phosphoryle différents substrats tels que des facteurs de transcription ou d'autres protéines. Chez les mammifères, trois groupes principaux de MAPKs ont été identifiés. Il s'agit du groupe des kinases régulées par des signaux extracellulaires du type «mitogènes » (ERK), ainsi que des groupes p38 et cJun NH2-terminal kinase (JNK), ou SAPK pour stress activated protein kinase, plutôt activées par des stimuli de type «stress ». De nombreuses études ont impliqué JNK dans la régulation de différents processus physiologiques et pathologiques, comme le diabète, les arthrites rhumatoïdes, l'athérosclérose, l'attaque cérébrale, les maladies de Parkinson et d'Alzheimer. JNK, en particulier joue un rôle dans la mort des cellules sécrétrices d'insuline induite par l'interleukine (IL)-1 β, lors du développement du diabète de type 1. IB1 est une protéine scaffold (échafaud) qui participe à l'organisation du module de JNK. IB1 est fortement exprimée dans les neurones et les cellules β du pancréas. Elle a été impliquée dans la survie des cellules, la régulation de l'expression du transporteur du glucose de type 2 (Glut-2) et dans le processus de sécrétion d'insuline glucose-dépendante. IBl est caractérisée par plusieurs domaines d'interaction protéine-protéine : un domaine de liaison à JNK (JBD), un domaine homologue au domaine 3 de Src (SH3) et un domaine d'interaction avec des tyrosines phosphorylées (PID). Des partenaires d'IB1, incluant les membres de la familles des kinases de lignée mélangée (MLKs), la MAPKK MKK7, la phosphatase 7 des MAPKs (MKP-7) ainsi que la chaîne légère de la kinésine, ont été isolés. Tous ces facteurs, sauf les MLKs et MKK7 interagissent avec le domaine PID ou l'extrême partie C-terminale d'IBl (la chaîne légère de la kinésine). Comme d'autres protéines scaffolds déjà décrites, IBl et un autre membre de la famille, IB2, sont capables d'homo- et d'hétérodimériser. L'interaction a lieu par l'intermédiaire de leur région C-terminale, contenant les domaines SH3 et PID. Mais ni le mécanisme moléculaire, ni la fonction de la dimérisation n'ont été caractérisés. Le domaine SH3 joue un rôle central lors de l'assemblage de complexes de macromolécules impliquées dans la signalisation intracellulaire. Il reconnaît de préférence des ligands contenant un motif riche en proline de type PxxP et s'y lie. Jusqu'à maintenant, tous les ligands isolés se liant à un domaine SH3 sont linéaires. Bien que le domaine SH3 soit un domaine important de la transmission des signaux, aucun partenaire interagissant spécifiquement avec le domaine SH3 d'IB1 n'a été identifié. Nous avons démontré qu'IBl homodimérisait par un nouveau set unique d'interaction domaine SH3 - domaine SH3. Les études de cristallisation ont démontré que l'interface recouvrait une région généralement impliquée dans la reconnaissance classique d'un motif riche en proline de type PxxP, bien que le domaine SH3 d'IB1 ne contienne aucun motif PxxP. L'homodimère d'IB1 semble extrêmement stable. Il peut cependant être déstabilisé par trois mutations ponctuelles dirigées contre des résidus clés impliqués dans la dimérisation. Chaque mutation réduit l'activation basale de JNK dépendante d'IB 1 dans des cellules 293T. La déstabilisation de la dimérisation induite par la sur-expression du domaine SH3, provoque une diminution de la sécrétion d'insuline glucose dépendant. SUMMARY Mitogen activated kinases (MAPK) are an important and conserved enzyme family. They form a signaling network required to specifically regulate process involved in cell differentiation, proliferation or death. A MAPK module is typically organized in a threekinase cascade which are activated by sequential phosphorylation. The MAPK kinase kinase (MAPKKK), the MAPK kinase (MAPKK) and the MAPK constitute the minimal module. Once activated, the MAPK phosphorylates its targets like transcription factors or other proteins. In mammals, three major groups of MAPKs have been identified : the group of extra-cellular regulated kinase (ERK) which is activated by mitogens and the group of p38 and cJun NH2-terminal kinase (JNK) or SAPK for stress activated protein kinase, which are activated by stresses. Many studies implicated JNK in many physiological or pathological process regulations, like diabetes, rheumatoid arthritis, arteriosclerosis, strokes or Parkinson and Alzheimer disease. In particular, JNK plays a crucial role in pancreatic β cell death induced by Interleukin (IL)-1 β in type 1 diabetes. Islet-brain 1 (IB 1) is a scaffold protein that interacts with components of the JNK signal-transduction pathway. IB 1 is expressed at high levels in neurons and in pancreatic β-cells, where it has been implicated in cell survival, in regulating expression of the glucose transporter type 2 (Glut-2) and in glucose-induced insulin secretion. It contains several protein-protein interaction domains, including a JNK-binding domain (JBD), a Src homology 3 domain (SH3) and a phosphotyrosine interaction domain (PID). Proteins that have been shown to associate with IB 1 include members of the Mixed lineage kinase family (MLKs), the MAPKK MKK7, the MAPK phosphatase-7 MKP7, as well as several other ligands including kinesin light chain, LDL receptor related family members and the amyloid precursor protein APP. All these factors, except MLK3 and MKK7 have been shown to interact with the PID domain or the extreme C-terminal part (Kinesin light chain) of IB 1. As some scaffold already described, IB 1 and another member of the family, IB2, have previously been shown to engage in oligomerization through their respective C-terminal regions that include the SH3 and PID domains. But neither the molecular mechanisms nor the function of dimerization have yet been characterized. SH3 domains are central in the assembly of macromolecular complexes involved in many intracellular signaling pathways. SH3 domains are usually characterized by their preferred recognition of and association with canonical PxxP motif. In all these cases, a single linear sequence is sufficient for binding to the SH3 domain. However, although SH3 domains are important elements of signal transduction, no protein that interacts specifically with the SH3 domain of IB 1 has been identified so far. Here, we show that IB 1 homodimerizes through a navel and unique set of SH3-SH3 interactions. X-ray crystallography studies indicate that the dieter interface covers a region usually engaged in PxxP-mediated ligand recognition, even though the IB 1 SH3 domain lacks this motif. The highly stable IB 1 homodimer can be significantly destabilized in vitro by individual point-mutations directed against key residues involved in dimerization. Each mutation reduces IB 1-dependent basal JNK activity in 293T cells. Impaired dimerization induced by over-expression of the SH3 domain also results in a significant reduction in glucose-dependent insulin secretion in pancreatic β-cells.

A new self-expanding aortic stent valve with annular fixation: in vitro haemodynamic assessment.

OBJECTIVE: Balloon-expandable stent valves require flow reduction during implantation (rapid pacing). The present study was designed to compare a self-expanding stent valve with annular fixation versus a balloon-expandable stent valve. METHODS: Implantation of a new self-expanding stent valve with annular fixation (Symetis, Lausanne, Switzerland) was assessed versus balloon-expandable stent valve, in a modified Dynatek Dalta pulse duplicator (sealed port access to the ventricle for transapical route simulation), interfaced with a computer for digital readout, carrying a 25 mm porcine aortic valve. The cardiovascular simulator was programmed to mimic an elderly woman with aortic stenosis: 120/85 mmHg aortic pressure, 60 strokes/min (66.5 ml), 35% systole (2.8 l/min). RESULTS: A total of 450 cardiac cycles was analysed. Stepwise expansion of the self-expanding stent valve with annular fixation (balloon-expandable stent valve) resulted in systolic ventricular increase from 120 to 121 mmHg (126 to 830+/-76 mmHg)*, and left ventricular outflow obstruction with mean transvalvular gradient of 11+/-1.5 mmHg (366+/-202 mmHg)*, systolic aortic pressure dropped distal to the valve from 121 to 64.5+/-2 mmHg (123 to 55+/-30 mmHg) N.S., and output collapsed to 1.9+/-0.06 l/min (0.71+/-0.37 l/min* (before complete obstruction)). No valve migration occurred in either group. (*=p<0.05). CONCLUSIONS: Implantation of this new self-expanding stent valve with annular fixation has little impact on haemodynamics and has the potential for working heart implantation in vivo. Flow reduction (rapid pacing) is not necessary.

Mouvements anormaux et accident vasculaire cérébral [Movement disorders in stroke]

Dyskinesias are infrequent presentations in acute stroke (1%). They can be found more frequently as delayed presentations after a stroke, but the prevalence is not available from the literature. The full spectrum of hyper- and hypo-akinetic syndromes has been described, but three main pictures are rather specific of an acute stroke: limb shaking, hemichorea-hemiballism and unilateral asterixis. Besides limb shaking, that seems to reflect a transient diffuse ischemia of the frontosubcortical motor pathway, lesions are described at all levels of the frontosubcortical motor circuit including the sensorimotor frontoparietal cortex, the striatum, the pallidum, the thalamic nuclei, the subthalamic nucleus, the substantia nigra, the cerebellum, the brainstem and their interconnecting pathways, as ischemic or hemorrhagic strokes. The preferentially late development of dyskinesia could reflect the return to a more ancestral motor control level, the most functional possible with the remaining configuration of structures, elaborated by brain plasticity after stroke.