The field of organic, or molecular, electronics is currently dominated by both polymeric and molecular organic materials, while considerably less research efforts are devoted to transition metal based complexes. Despite this, such compounds can offer advantages including additional tuneability of the spatial distribution and energy levels of the frontier orbitals or stable paramagnetic species by manipulating the metal-ligand interactions which may be accomplished selectively modifying the ligand framework or changing the central metal. A series of Ni(II) and Cu(II) acenaphthenequinone bis(thiosemicarbazonato) complexes were prepared and characterised using X-ray diffraction, cyclic voltammetry, UV/Vis and EPR spectroscopy, as well as magnetic susceptibility and field effect transistor measurements and computational calculations. The observed charge transport properties are discussed in terms of the structural and electronic trends both within the series and in the context of the two more established analogue series, namely the bis(3-thiosemicarbazonato) and the diacetyl bis(3-thiosemicarbazonato) metal complexes. The Ni(II) analogues of the acenaphthenequinone bis(thiosemicarbazonato) family were found to exhibit p-type charge transport with mobilities between 10¯9 and 10¯5 cm2V¯1s¯1 depending on the exocyclic substitutent and resulting packing pattern. The observed results were rationalised in terms of the reorganisation energy and the charge transfer integrals. A series of 4,4`-phenyl-substituted nickel dithiolene complexes was synthesised and characterised. Initially with the aim of investigating the effect of varying the para-substituent of the phenyl ring on the charge transport properties, these efforts were undermined by the poor processability of these molecules by both vapour and solution phase methods. As a result, n-type charge transport could be observed under ambient conditions only for the phenyl and 4-bromo-phenyl substituted analogues, but the device performance was extremely poor. Nonetheless, the calculated reorganisation energies, charge transfer integrals and predicted mobilities were encouraging and may prompt further work on these materials. An all-organic analogue series of 4,4`-(4-halogen-phenyl)-substituted tetrathiafulvalenes was also investigated. The hole transport materials displayed mobilities of between 10¯3 and 10¯7 cm2V¯1s¯1 for both solution and vapour processed devices, depending on the nature of the halogen. These results are discussed in terms of their molecular properties and the calculated charge transport parameters and put in context of the performance of the 4,4`-bis(phenyl)-substituted benchmark analogue. Interestingly, the obtained crystal structure of the bromo-substituted analogue showed the molecule to be in the cis conformation, an observation that is unprecedented for simple, 4-phenyl,5-hydrogen substituted tetrathiafulvalenes, and indicates that both conformers are initially formed. Finally, a series of 4,4`-(2-alkyl)thienyl substituted nickel dithiolene salts and tetrathiafulvalenes was synthesised and characterised. While the charge transport properties of the former were not further investigated due to the low solubility of the neutral species, the tetrathiafulvalenes were incorporated into FET devices via solution processing. All exhibited comparatively high conductivity at room temperature (1.6x10¯3S m¯1), exceeding that of their quarterthiophene analogues. This masked the observed gate effects but indicates potential applications as conducting or charge transfer materials. While the two resolved analogues displayed trans geometry in the single crystal structures, powder diffraction and preliminary DSC measurements indicate that the materials displayed at least one additional phase, which once again likely corresponded to the cis conformer.

No description available.

This thesis describes the design, construction and application of a novel vacuum system for the preparation of thin films of organic charge-transfer compounds. The method of thermal evaporation was used for four materials: tetrathiafulvalene (TTF) and three of its derivatives, dimethyltetrathiafiilvalene (DiMe-TTF), trimethyltetrathiafiilvalene (TriMe-TTF) and bis(ethylenedithio)tetrathiafiilvalene (BEDT-TTF). The resulting thin layers were characterised using optical and electron microscopy, infrared/visible spectroscopy and dc conductivity measurements down to 77K.Thin films of tetrathiafulvalene, after doping with iodine, exhibited a maximum value of dc, in-plane room temperature conductivity σ of 8.0+2.4 S cm(^-1). Semiconducting behaviour was exhibited over the range 77-300 K with AE = 0.09+0.02 eV. The effect of the deposition rate on fihn morphology is reported. TTF iodide layers were also prepared by co- evaporating the two components. These films exhibited a maximum conductivity of 2.9+0.4 S cm(^-1) at room temperature. Again, semiconducting behaviour was noted over the range 77- 300 K with AE = 0.2+0.02 eV. A comparison of the optical, structural and electrical properties of the two types of films is made. DiMe-TTF and TriMe-TTF thin films were also successfully prepared. Doping with iodine resulted in in-plane, dc room temperature conductivities of 10(^-6) and 10(^-7) S cm(^-1), respectively. These values, together with data from optical spectroscopy, suggested that both salts were in the full charge-transfer state. (BEDT-TTF) iodide thin films were deposited by evaporating the organic compound and subsequent doping. Doped films possessed a dc, in-plane room temperature conductivity of 10(^-3) S cm(^-1).Annealing these layers at 60ºC resulted in an increase in conductivity with a final value of 1.6 S cm(^-1). Semiconducting behaviour over the range 77-300 K was exhibited by the annealed films (ΔE = 0.028 eV).Finally, thin film transistors, incorporating TTF and BEDT-TTF doped layers, were fabricated and their electrical characteristics measured.

Dans ce manuscrit, le premier chapitre introduit la cible matériaux multifonctionnels, y compris les connaissances nécessaires sur les différentes propriétés physiques sélectionnées telles que le magnétisme, la luminescence, et la conductivité, ainsi des contributions précédents de nos et d'autres groupes.Dans le chapitre deux, le ligand à base de tétrathiafulvalène avec deux accepteurs dpp (L1 et L2) (TTF = tétrathiafulvalène, dpp = 2,6-di(pyrazol-1-yl)pyridine) et des complexes lanthanide correspondant sont présentés, y compris la synthèse et les caractérisations physiques: structures cristallographique, voltamétrie cyclique, le spectre d'absorption rationalisée par des calculs TD-DFT, des spectres d'émission, et les mesures d’ aimantation AC et DC. Les complexes Eu, Yb, et Er sont emissives.Dans le chapitre trois, un ligand à base de TTF avec deux sites de coordination hétéro L7 et ses deux Dy(III) complexes (C7-1 et C7-2) ont été présentés avec les caractérisations physiques similaires. Les deux complexes Dy révèlent un caractère de molécule aimant. / In this manuscript, the Chapter one introduces the target multifunctional materials, including the necessary knowledge of different selected physical properties such as magnetism, luminescence, and conductivity, as well as some of the previous contributions by our and other groups. In Chapter two, the tetrathiafulvalene-based ligand with two dpp acceptors (L1 and L2) (TTF = tetrathiafulvalene, dpp = 2,6-di(pyrazol-1-yl)-pyridine) and the corresponding lanthanide complexes are presented including the synthesis and physical characterizations: single crystal structure, cyclic voltammetry, absorption spectra that rationalized by TD-DFT calculations, emission spectra, and DC and AC magnetic measurements. The complexes Eu, Yb, and Er are emissive. In the Chapter three, a TTF-based ligand with two hetero coordinating sites L7 and its two Dy(III) complexes (C7-1 and C7-2) were presented, which show multi-relaxation SMM behavior.

Yes / Purpose The purpose of this paper is to identify and examine the most important factors that could predict the Saudi customer’s continued intention towards adoption of mobile banking. Design/methodology/approach The proposed conceptual model was based on the technology acceptance model (TAM) and task-technology fit (TTF) model. This is also expanded by considering two additional factors: perceived privacy and perceived security. By using a self-administered questionnaire, the data were collected from a convenience sample of Saudi banking customers from different parts of Saudi Arabia. Findings The main results based on structural equation modelling analyses supported the impact of perceived privacy, perceived security, perceived usefulness and TTF on the customers’ continued intention to use mobile banking. Research limitations/implications The moderation influence of the demographic factors (i.e. age, gender, income level, educational level) was not tested. The data were also collected using a self-report questionnaire; however, it would be more accurate to utilise more statistics from the bank database about the users of m-banking. Originality/value This study represents a worthy attempt to test such novel technology (m-banking) in the KSA where there is a scarcity of literature. A considerable theoretical contribution was also made by integrating the TTF model with the TAM in addition to consider privacy and security in one single model. Moreover, considering both perceived privacy and security in the current model creates an accurate picture about the adoption of m-banking especially as there are a limited number of m-banking studies that have considered privacy and security alongside the TTF model and TAM in the same model.

As the growth of the E-commerce and mobile technology, value-added services have attracted a substantial amount of attention in mobile applications. Many reports indicate that those mobile value-added services will be the next generation of Internet access and a potential profit maker in the future. However, the actual use of mobile value-added services is not as good as our expectation and the available services as well as user¡¦s intention to use them are not very high. The objective of this research is to explore how contextual factors and different types of value-added services may affect the user¡¦s intention to use. The theory underlying the study is the TPB model. An empirical study was conducted to examine the factors that affect the intention of adopting mobile services. The results show that (1) For all kind of services, a better task-technology fit resulted in a more positive attitude towards using the value-added services; (2). For all kind of services, user attitude on mobile value-added services was positively related to the user¡¦s willingness to use; (3) For communication, entertainment, and information services, perceive behavior control had a positive effect on user¡¦s willingness to use; (4) Social norms affected the willingness to use only when the nature of services is mobile entertainment or business transaction; (5) Contextual variables such as time pressure and location had mediate effects between attitudes and willingness to use.

Le sujet choisi a nécessité une étude bibliographique pour les études de recherche publiées dans les domaines de la Thermodynamique à Vitesse Finie (TVF) et Thermodynamique en Temps Fini (TTF), et pas seulement. Le premier chapitre est dédié à l’état de l’art bibliographique en ce qui concerne le sujet. Une synthèse des aspects énergétiques du Monde, les principales considérations sur les machines de Stirling, les principales méthodes d’analyse et optimisation thermodynamique sont présentés. La comparaison entre la TVF et TTF est présentée, car le développement original s’appuie sur deux méthodes, une de la TVF et l’autre de la TTF, ou plutôt en Dimension Finie. Le deuxième chapitre est dédié aux contributions originales dans le domaine de la TVF: l’adaptation de la Méthode Directe à l’étude et optimisation des machines à cycle inverse avec des irréversibilités internes et externes; amélioration de la méthode de Schmidt en considérant la cinématique effective de la machine considérée ; présentation d’une étude de sensibilité qui permet de séparer les irréversibilités par causes et analyser les effets séparément ; adaptation de la Méthode Directe à l’étude et optimisation de moteurs de Stirling solaires et des ensembles solaire récepteur – concentrateur - moteur Stirling solaire- générateur électrique ; validation de schéma par la comparaison avec les données expérimentales; mise en valeur de la recherche par une application pratique: système de génération d’énergie électrique à partir de l’énergie solaire et hydrogène comme vecteur d’énergie. Le troisième chapitre est dédié aux contributions originales dans le domaine de la TTF. Un modèle thermodynamique pour l’étude et optimisation des machines thermiques est proposé et appliqué pour le cycle de Carnot, pour plusieurs cas, pour des lois de transfert de chaleur linéaires et non linéaires convectif et radiatif. L‘existence des données expérimentales a fait possible la simulation du fonctionnement avec le modèle analytique et la validation. Les conclusions générales et perspectives attendues sont présentées. / The stated subject needed an important bibliographic research for the publications in the field of Thermodynamics with Finite Speed (TFS) and Thermodynamics in Finite Time (TFT), and more than that. The first chapter is dedicated to the current status in the chosen subject. A synthesis of worldwide energetic aspects, main considerations on Stirling machines, main methods for analysis and optimization are presented. An important paragraph is the comparison between TFS and TFT, since the original contributions represent two methods, one from TFS and the other one from TFT. The second chapter is dedicated to the original contributions in the field of TFS: adjustment of the Direct Method to the study and optimization of reverse cycle machines with internal and external irreversibilities; correction of the Schmidt method by considering the effective kinematics of the studied machine; development of a sensitivity study to analyze the effects of each irreversibility; adaptation of the Direct Method to the study and optimization of Stirling solar engines and solar assemblies receiver – concentrator - Stirling engine - electric generator; validation of the proposed scheme par comparison with experimental data; research practical utilization: a proposed solar system for electric energy and hydrogen (as an energy career) production. The third chapter is dedicated to the original contributions in the field of TFT. A thermodynamic model pour for the study and optimization of thermal machines is proposed and applied to the Carnot cycle, for more cases, for linear and non linear convective and radiative heat transfer laws. Existence of experimental data allowed the operating simulation and validation of the model. The general conclusions and perspectives are presented.

TTFields sind eine Therapieoption des GBM, welche als alternierende elektrische Felder den Aufbau des mitotischen Spindelapparates stören. Gleichzeitig überwacht der SAC, mit seiner Schlüsselkomponente der Kinase MPS1, eine korrekte Anheftung der Spindelfasern an die Kinetochore der Chromosomen. Eine Inhibition des SAC durch den Inhibitor MPS1-IN-3 in Kombination mit Vincristin führt zu einem synergistischen Effekt auf das Tumorwachstum in vitro und in vivo. Aus diesen Erkenntnissen folgerten wir die Hypothese, dass eine SAC-Inhibition die Wirkung von TTFields verstärken könnte. Um dies zu testen, wurden Zellen der Zelllinien U87 und GaMG über 72h mit TTFields, MPS1-IN-3 oder einer Kombination aus den beiden behandelt. Anschließend wurden die Zellen gezählt, es wurde eine Analyse des Zellzyklus vorgenommen und apoptotische Zellen wurden via TUNEL-Assay detektiert. Die Kombinationsbehandlung aus TTFields und MPS1-IN-3 führte zu einer Reduktion der Zellzahl (U87: -54,3% vs. TTFields, p=0,0046; -52,9% vs. MPS1-IN-3, p=0,0026; GaMG: -74,3% vs. TTFields, p=0,0373; -84% vs. MPS1-IN-3, p<0,00001). Nur 28,1% mehr Zellen als ausgesät waren bei der Zelllinie U87 zu finden (TTFields: 179,1%; MPS1-IN-3: 168,3%), während es bei GaMG-Zellen sogar 62% weniger Zellen als ausgesät waren. Im Zellzyklus zeigte sich eine Abnahme der Zellen von der G1-Phase (U87: -59,9% vs. TTFields, p=0,0007; -42,1% vs. IN-3, p=0,0426; GaMG: -45,1% vs. TTFields, p=0,0276; -51,6% vs. IN-3, p=0,0020), während es zu einem massiven Anstieg von toten Zellen kam (U87: 2,9fach vs. TTFields, p=0,0022; 2,2fach vs. IN-3, p=0,0046; GaMG: 5,6fach vs. TTFields, p=0,0078; 7,8fach vs. IN-3, p=0,0005). Diese Zellen ließen sich im TUNEL-Assay als durch Apoptose zu Grunde gegangene Zellen weiter identifizieren (U87: 5,4fach vs. TTFields, p=0,0489; 6,2fach vs. IN-3, p=0,0278; GaMG: 8,9fach vs. IN-3, p=0,0110). Diese Ergebnisse sind erste und wichtige Hinweise für eine Verstärkung der Wirkung von TTFields durch eine Inhibition des SAC und liefern eine gute Grundlage für weitere Forschung zur Verbesserung der Therapie des GBM. / TTFields are -in addition to the standard therapy- approved for GBM therapy. TTFields are alternating electric fields at a low intensity, which cause disruption of the mitotic spindle fibers. Whether spindle fibers are properly attached to the kinetochores is surveilled by the SAC. An inhibition of the kinase MPS1, a key component of the SAC, in combination with Vincristine treatment, results in a synergistic effect on GBM growth in vitro an in vivo (Tannous, Kerami et al. 2013). We hypothesized that a combination of inhibition of SAC in combination with TTFields increases TTFields efficacy. Cells of the cell lines U87 and GaMG were treated either with TTFields alone, the inhibitor MPS1-IN-3 alone or in combination of both. After 72h cells were counted, an analysis of the cell cycle was performed and apoptotic cells were detected by using a TUNEL-Assay. The combined treatment of TTFields and inhibition of SAC led to a significant decrease of cells (U87: -54.3% vs. TTFields, p=0.0046; -52.9% vs. MPS1- IN-3, p=0.0026; GaMG: -74.3% vs. TTFields, p=0.0373; -84% vs. MPS1-IN-3, p<0.00001). U87 cells proliferated only by 28.1% compared to the cells seeded at the beginning, while cells of the GaMG cell line diminished by 62% compared to the number of cells seeded (TTFields: 179.1%; MPS1-IN-3: 168.3%). The cell cycle analysis showed -among other effects- a reduction of the cells in phase G1 (U87: - 59.9% vs. TTFields, p=0.0007; -42.1% vs. IN-3, p=0.0426; GaMG: -45.1% vs. TTFields, p=0.0276; -51.6% vs. IN-3, p=0.0020), and an increase of dead cells (U87: 2.9x vs. TTFields, p=0.0022; 2.2x vs. IN-3, p=0.0046; GaMG: 5.6x vs. TTFields, p=0.0078; 7.8x vs. IN-3, p=0.0005). Those dead cells were identified by the TUNEL- Assay as cells, which had undergone apoptosis (U87: 5.4x vs. TTFields, p=0.0489; 6.2x vs. IN-3, p=0.0278; GaMG: 8.9x vs. IN-3, p=0.0110). These results strengthen the hypothesis that TTFields’ efficacy is increased by a combined treatment with an inhibition of the SAC and provide a basis for further research to improve GBM therapy.

No description available.

O mecanismo de controle da secreção de GnRH inclui diversas vias neuronais. Estudos em modelos animais identificaram genes que codificam fatores de transcrição, tais como TTF-1 (thyroid transcription factor 1) e EAP1 (enhanced at puberty), que atuam no controle transcricional de genes codificadores de fatores excitatórios (KiSS1 e GnRH) e inibitórios (preproencefalinas) regulando a secreção de GnRH. Em primatas, a expressão de EAP1 e TTF-1 aumenta, no início da puberdade, nas regiões hipotalâmicas envolvidas na secreção de GnRH. Nos modelos animais, a deleção pós-natal de TTF-1 e o silenciamento do EAP1 provocam atraso puberal e prejuízo na função reprodutiva. TTF-1 também está envolvido na morfogênese diencefálica, por meio da via de sinalização da família Sonic-Hedgehog. Anormalidades na secreção de GnRH resultam em distúrbios puberais, que variam de puberdade precoce central (PPC) a hipogonadismo hipogonadotrófico. Hipotetizamos que anormalidades genéticas no TTF-1 e EAP1 estejam envolvidas na patogênese dos distúrbios puberais centrais. A PPC pode ser idiopática ou devido a causas orgânicas, sendo o hamartoma hipotalâmico, uma malformação congênita não neoplásica, a mais conhecida. Os pacientes com PPC devido a hamartoma hipotalâmico podem cursar com alterações neurológicas e cognitivas. Nossos objetivos foram: estudar as regiões codificadora do TTF-1 e do EAP1 e a região promotora do TTF-1 em pacientes com distúrbios puberais centrais; estabelecer a prevalência, taxa de penetrância e modo de herança da forma familial de PPC e caracterizar as manifestações neurológicas e neurocognitivas de pacientes com PPC devido a hamartoma hipotalâmico. Foram selecionados 133 pacientes com distúrbios puberais centrais - PPC idiopática (n=71), PPC devido a hamartoma hipotalâmico (n=15) e hipogonadismo hipogonadotrópico isolado normósmico (HHIn) (n=47) - e controles (n=53). Os genes TTF-1 e EAP1 foram amplificados e submetidos a sequenciamento automático. Os tratos de poliglutamina e polialanina no EAP1 foram estudados por software de análise de tamanho de fragmento (GeneScan). A avaliação neurológica e neurocognitiva dos pacientes com PPC devido a hamartoma hipotalâmico consistiu de exame neurológico, eletroencefalograma, ressonância magnética de encéfalo e aplicação da escala de inteligência (WISC-III, WAIS-III, WPPSIR). Identificamos 25% de casos familiais de PPC, com modo de herança autossômica dominante e taxa de penetrância de 67,5%. Variantes alélicas no TTF-1 não foram identificadas nos pacientes estudados. No gene EAP1 foram identificadas quatro variantes alélicas sinônimas: p.E87E, p.A163A, p.Y415Y e uma nova variante alélica p.C758C, encontradas em pacientes com PPC e HHIn. A distribuição das frequências alélica e genotípica das variantes alélicas do EAP1 não diferiram entre pacientes com PPC, HHIn e controles (p >0,05). Nas regiões poliglutamina e polialanina 5 distal foi identificada variação similar no número de repetições glutamina e alanina em pacientes e controles. Não houve diferença significativa da frequência alélica em relação ao número de repetições glutamina e alanina entre os grupos PPC e HHIn (p >0,05). A avaliação neurológica dos pacientes com PPC devido a hamartoma hipotalâmico revelou epilepsia gelástica e crises focais com generalização em 3/15 (20%) pacientes. Não houve diferença significativa entre a mediana do maior diâmetro dos hamartomas dos pacientes com PPC com e sem epilepsia (13 e 10 mm, respectivamente). Quanto à forma, 10 hamartomas eram sésseis e 5 pedunculados, sendo que a forma pedunculada foi detectada exclusivamente em pacientes sem epilepsia. A avaliação neurocognitiva em 11 dos 15 pacientes com PPC devido a hamartoma hipotalâmico detectou 2 pacientes com epilepsia com QI significativamente menor que o grupo sem epilepsia (p <0,05). Em conclusão, (i) a considerável prevalência de casos familiais de PPC reforça a influência dos fatores genéticos na puberdade humana; (ii) mutações germinativas no TTF-1 e no EAP1 não estão envolvidas na patogênese dos distúrbios puberais centrais; (iii) a função neurocognitiva reduzida nos pacientes com hamartoma e epilepsia sugere um efeito deletério das crises convulsivas no sistema nervoso central / GnRH secretion control involves multiple neuronal pathways. Animal studies have identified genes which codifies transcription factors, such as TTF-1 (thyroid transcription factor 1) and EAP1 (enhanced at puberty), that act in the transcriptional control of genes that codifies excitatory (KiSS1 and GnRH) and inhibitory factors (preproenkephalines) regulating GnRH secretion. In nonhuman primates, expression of EAP1 and TTF-1 are increased at the hypothalamic regions involved in GnRH secretion, at the beginning of puberty. In animal models, post-natal TTF-1 deletion and silencing of EAP1 lead to pubertal delay and damage of reproductive function. TTF-1 is also involved in diencephalic morphogenesis, through signalization via Sonic-Hedgehog family. Abnormalities in GnRH secretion are responsible for pubertal disorders, varying from central precocious puberty (CPP) to hypogonadotropic hypogonadism. We hypothesized that genetic anomalies at TTF-1 and EAP1 are involved in the pathogenesis of central pubertal disorders. CPP may be idiopathic or due to organic alterations and hypothalamic hamartoma, a non-neoplasic congenital malformation, is the most frequent known organic cause. Patients with CPP due to hypothalamic hamartoma may have neurological and cognitive disfunctions. Our aims were: to evaluated the codifying region of TTF-1 and EAP1 and the promoter region of TTF-1 in patients with central pubertal disorders; to establish the prevalence, penetrance rate and inheritance mode of familial CPP and to characterize neurologic and neurocognitive aspects of patients with CPP due to hypothalamic hamartoma. We selected 133 patients with central pubertal disorders idiopathic CPP (n=71), CPP due to hypothalamic hamartoma (n=15) and normosmic isolated hypogonadropic hypogonadism (nIHH) (n=47) - and controls (n=53). TTF-1 and EAP1 genes were amplified and sequenced. Polyglutamine and polyalanine tracts of EAP1 were studied by a fragment size analyser software (GeneScan). Neurologic and neurocognitive evaluation of CPP patients due to hypothalamic hamartoma consisted of neurologic exam, electroencephalogram, brain magnetic resonance and application of intelligence scale (WISC-III, WAIS-III, WPPSI-R). We identified 25% of familial CPP cases with autosomal dominant mode of inheritance and penetrance rate of 67.5%. No TTF-1 allelic variants were identified in the patients analysed. At EAP1 gene, four synonimous allelic variants were identified: p.E87E, p.A163A, p.Y415Y and a new allelic variant p.C758C, found in CPP and nIHH patients. The allelic and genotypic distribution of theses variants of EAP1 did not differ among patients with CPP and nIHH, and controls (p >0.05). At polyglutamine and 5 distal polyalanine region, similar glutamine and alanine repeats variation was found. No significative difference of allelic frequency distribution regarding the number of glutamines and alanines repeats was found among the studied groups (p >0.05). Neurologic evaluation of CPP patients due to hypothalamic hamartoma revealed epilepsy and focal crisis with generalization in 3/15 (20%) of the patients. No significant difference between the median of the larger diameter of hypothalamic hamartoma of CPP patients with and without epilepsy was found (10 mm and 13 mm, respectively). Regarding the shape, 10 hamartomas were sessile and 5 pedunculated, and the pedunculated shape was found only in non epileptic patients. Neurocognitive evaluation performed in 11 of the 15 patients with CPP due to hypothalamic hamartoma detected 2 patients with epilepsy whose IQ were significantly lower than the IQ found in the group without epilepsy (p <0.05). In conclusion, (i) the considerable prevalence of familial CPP cases reinforce the influence of genetic factors in human puberty; (ii) germinative mutations in TTF-1 and EAP1 are not involved in the pathogenesis of central pubertal disorders; (iii) reduced neurocognitive function in patients with hypothalamic hamartoma and epilepsy suggests a deleterious effect of crisis at the central nervous system