Epitaxy of oligothiophenes on alkali metal hydrogen phthalates: Simulations and experiments.

Three alkali metal hydrogen phthalate salts (denoted as XAP, X = K+, Rb+, and Cs+) are chosen as substrates for the growth of quaterthiophene (4T) and hexathiophene (6T) thin films by organic molecular beam epitaxy to study the influence of gradual changes of surface unit cell parameters on the epitaxialgrowth. The increment of substrate lattice parameters increases the distance between the planes that define the furrows where oligothiophene molecules lie, while keeping unmodified the interactions between the overlayer and the substrate. Atom-atom potential simulations predict the preferential azimuthal orientations of the overlayer, which are compared with those experimentally observed. The agreement between simulations and experiments about contact planes and orientation of the crystalline domains in the films is satisfactory for both 4T/XAP and 6T/XAP. The increasing width of the surface furrows existing on moving from KAP to RbAP and CsAP does not cause any significant variation of the orientation and density of the overlayer domains, demonstrating that the interaction between overlayer and substrate is the key factor guiding organic epitaxialgrowth.

Inhibition of Hedgehog signalling by NVP-LDE225 (Erismodegib) interferes with growth and invasion of human renal cell carcinoma cells.

BACKGROUND: Multiple lines of evidence support that the Hedgehog (Hh) signalling has a role in the maintenance and progression of different human cancers. Therefore, inhibition of the Hh pathway represents a valid anticancer therapeutic approach for renal cell carcinoma (RCC) patients. NVP-LDE225 is a Smoothened (Smo) antagonist that induces dose-related inhibition of Hh and Smo-dependent tumour growth. METHODS: We assayed the effects of NVP-LDE225 alone or in combination with everolimus or sunitinib on the growth and invasion of human RCC models both in vitro and in vivo. To this aim, we used a panel of human RCC models, comprising cells with acquired resistance to sunitinib - a multiple tyrosine kinase inhibitor approved as a first-line treatment for RCC. RESULTS: NVP-LDE225 cooperated with either everolimus or sunitinib to inhibit proliferation, migration, and invasion of RCC cells even in sunitinib-resistant (SuR) cells. Some major transducers involved in tumour cell motility, including paxillin, were also efficiently inhibited by the combination therapy, as demonstrated by western blot and confocal microscopy assays. Moreover, these combined treatments inhibited tumour growth and increased animal survival in nude mice xenografted with SuR RCC cells. Finally, lung micrometastasis formation was reduced when mice were treated with NVP-LDE225 plus everolimus or sunitinib, as evidenced by artificial metastatic assays. CONCLUSIONS: Hedgehog inhibition by NVP-LDE225 plus sunitinib or everolimus bolsters antitumour activity by interfering with tumour growth and metastatic spread, even in SuR cells. Thus, this new evidence puts forward a new promising therapeutic approach for RCC patients.

The dual PI3K/mTOR inhibitor PKI-587 enhances sensitivity to cetuximab in EGFR-resistant human head and neck cancer models.

BACKGROUND: Cetuximab is the only targeted agent approved for the treatment of head and neck squamous cell carcinomas (HNSCC), but low response rates and disease progression are frequently reported. As the phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways have an important role in the pathogenesis of HNSCC, we investigated their involvement in cetuximab resistance. METHODS: Different human squamous cancer cell lines sensitive or resistant to cetuximab were tested for the dual PI3K/mTOR inhibitor PF-05212384 (PKI-587), alone and in combination, both in vitro and in vivo. RESULTS: Treatment with PKI-587 enhances sensitivity to cetuximab in vitro, even in the condition of epidermal growth factor receptor (EGFR) resistance. The combination of the two drugs inhibits cells survival, impairs the activation of signalling pathways and induces apoptosis. Interestingly, although significant inhibition of proliferation is observed in all cell lines treated with PKI-587 in combination with cetuximab, activation of apoptosis is evident in sensitive but not in resistant cell lines, in which autophagy is pre-eminent. In nude mice xenografted with resistant Kyse30 cells, the combined treatment significantly reduces tumour growth and prolongs mice survival. CONCLUSIONS: Phosphoinositide 3-kinase/mammalian target of rapamycin inhibition has an important role in the rescue of cetuximab resistance. Different mechanisms of cell death are induced by combined treatment depending on basal anti-EGFR responsiveness.

Palatability, digestibility and emotional pattern in 60 healthy volunteers after ingestion of an iced dessert presented in four different flavours: a subjective evaluation.

Several variables lead to changes in human and animal eating behaviour and food choices. A pivotal role is played by food palatability, represented by food, smell, taste, texture, appearance and temperature. The aim of our study is to assess the potential differences in palatability and digestibility of four different flavoured iced desserts, consumed at the end of a standardized meal, and their impact on the emotional status of 60 healthy volunteers. Sixty healthy volunteers, after ENT and psychological assessment, were asked to fill out a Psycho-Emotional Questionnaire (PEQ) to assess their basal emotional pattern before the consumption of an iced dessert at the end of a standard meal, after which they completed an Organoleptic-Sensory Questionnaire (OSQ), a Dynamic Digestibility Questionnaire (DDQ) and again the PEQ. Four different flavors (lemon, tangerine, pineapple and chocolate) were tested on 4 consecutive days on the same subjects. Most of the 60 subjects, by means of OSQ, found taste, aspect, texture and smell of the 4 flavours pleasant, lemon and tangerine were the freshest and lightest. The DDQ identified pineapple and chocolate dessert as those less digestible. By means of PEQ we recorded an improvement in joy, mood and activation, associated with good data of digestibility and palatability after the consumption of all flavors. Our data showed that all flavors improve joy, mood and activation, after their consumption, without statistically significant differences. However, among the tested flavours, lemon and tangerine appear to be the most pleasant and those which facilitate the digestive process.

Digestibility, palatability and emotional status after ingestion of an iced dessert: analysis of subjective responses in 100 healthy volunteers.

Food choices are influenced by many factors, perhaps the most important being availability. However, the desire to consume one item over another may be viewed as an outcome of sensory hedonic likes, situation and current internal state. In a previous preliminary report, an improvement of joy and mood, associated with good data of digestibility and palatability, was observed in a group of 30 healthy female subjects who consumed a coffee-flavoured iced dessert immediately after a standardized meal. The aim of this study is to confirm the results previously obtained in a smaller population and to investigate whether any differences between male and female subjects could be observed concerning the digestive process and emotional status. One hundred volunteers, after ENT and psychological assessment, were asked to fill out a Psycho-Emotional Questionnaire to assess their basal emotional pattern before the consumption of an iced coffee-flavoured dessert after a standard meal. After the meal they completed an Organoleptic-Sensory questionnaire, a Dynamic Digestibility questionnaire and again the Psycho-Emotional Questionnaire. In our study, most of the 100 subjects found the tested coffee-flavoured iced dessert pleasant according to the Organoleptic-Sensorial Questionnaire (OSQ), in terms of taste, aspect, texture and smell; moreover, the Dynamic Digestibility Questionnaire (DDQ) showed a good digestive experience in 71 subjects. According to the Psycho-Emotional Questionnaire (PEQ), an improvement of joy, activation and mood, associated with good data of digestibility and palatability was recorded. All these observations are statistically significant and the results seem to show a positive correlation between pleasure in eating such a product and emotional status. No statistically significant differences were recorded between male and female subjects.

[Clinical and biological prognostic factors in 135 patients affected by sinonasal carcinoma treated in Piedmont]. / Fattori prognostici clinici e biologici in 135 casi di carcinomi naso-sinusali trattati in Piemonte.

Clinical and biological prognostic factors in 135 patients affected by sinonasal carcinoma treated in Piedmont. Long-term survival of patients with sinonasal carcinoma remains disappointing in spite of aggressive treatment. The aim of the study is the assessment of overall survival in a group of patients treated with a fixed protocol and the positivity of proliferation and neoangiogenesis markers (Ki-67 and VEGF). From our data it comes out that staging, histological type and treatment are the most important clinical and pathological prognostic factors, moreover surgery +/- radiotherapy is the first line treatment for these tumors. Proliferation index and neoangiogenesis plays a pivotal role in the natural history of such neoplasms.

[Effect of noise and reverberation on vocal effort and fatigue of primary school teachers]. / Effetto del rumore e della riverberazione sullo sforzo vocale degli insegnati di scuola primaria.

Teachers are at a higher risk for occupation-related voice disorders than the general population. The aim of this work is the investigations on the relationships between vocal doses and clinical status, acoustical conditions (noise and reverberation) in the classrooms and subjective evaluations of vocal effort and fatigue. At clinical evaluation 41% of the teachers showed no sign of vocal disease. Students talking in the classroom is the most annoying, noise source in classrooms. The consequence of the poor acoustics in all the schools was the decrease in students question perception. The main cause of a vocal pathology was time dose.

[The monitoring role of otoacoustic emission and oxidative stress markers in the protective effects of antioxidant administration in noise-exposed subjects: a pilot study]. / Il ruolo del monitoraggio delle emissioni otoacustiche e dei marcatori dello stress ossidativo negli effetti protettivi dello somministrazione di antiossidanti in soggetti esposti al rumore: uno studio pilota.

The aims of this study is to assess how DPOAEs can discriminate normal subjects with a risk of damage induced by noise, the effectiveness of OAEs in monitoring the effect of Q-Ter, and the role of blood tests to monitor therapy. In the placebo group, the amplitude of DPOAEs was reduced 1 hour and 16 hours after exposure, the group treated with Q-Ter showed normal DPOAEs. This pilot study confirms that DPOAEs represent a sensitive test for monitoring the effects of noise in preclinical conditions and pharmacological treatment.

[Coenzyme Q10 (Q-ter) in treatment of functional voice disorders]. / Il Coenzima Q10 (Q-ter) nel trattamento dei disordini funzionali della voce.

Aim of this study was to evaluate the effectivness of Coenzyme Q-Ter and Vitamin A in functional voice disorders. Twenty two patients were treated with CoQ10-ter and vitamin A twice a day for ten days. A general otolaryngological/foniatric and logopedic examination were performed. Videolaringostroboscopy, GIRBAS, Voice Handicap Index questionnaire and Multi-Dimensional Voice analysis were carried out before and after treatment. In all patients an improvement was observed in almost all parameters considered after treatment. CoQ10-ter and Vitamin A risulted effective in treatment of patients with functional voice disorders (caused by vocal "malmenage" or "surmenage").

Subjective assessment of palatability, digestibility and emotions in healthy volunteers after ingestion of an iced dessert: preliminary report.

Dietary habits can be influenced by several factors such as emotional status and food palatability represented by food smell, taste, texture, appearance and temperature. The aim of this study is to assess the palatability and digestibility of a coffee-flavored iced dessert ingested at the end of a standardized meal and its impact on emotional status in a sample of 30 healthy female volunteers. Thirty healthy female volunteers, after ENT and psychological assessment, were asked to fill in a Psycho-Emotional Questionnaire to assess their basal emotional pattern before the consumption of an iced coffee-flavored dessert after a standard meal. After the meal they filled in an Organoleptic-Sensory questionnaire, a Dynamic Digeribility questionnaire and again a Psycho-Emotional Questionnaire. In our study, most of the subjects found the tested coffee-flavoured iced dessert pleasant according to the Organoleptic-Sensorial Questionnaire (OSQ), in terms of taste, aspect, texture and smell; moreover, in 29 subjects the Dynamic Digestibility Questionnaire (DDQ) resulted in a good digestive experience. By means of the Psycho-Emotional Questionnaire (PEQ), an improvement of feelings and mood, associated with good data of digestibility and palatability was recorded. Although this observation is not statistically significant, the results seem to show a positive correlation between pleasure in eating such a product and emotional status. These data are preliminary and need further investigations on a larger population, in order to confirm this association, also in a mixed population, comparing male and female eating behaviour.

Objective and subjective assessment of digestion after ingestion of an iced dessert in healthy volunteers.

The aim of our study is to assess, with objective measures, the impact on digestion of a coffee-flavoured iced dessert ingested at the end of a standardized meal; moreover, a subjective assessment, using a specific questionnaire, was carried out in order to compare objective and subjective data. Ten healthy male volunteers, after ENT and psychological assessment, underwent two scintigraphic evaluations (standardized meal without and with coffee-flavoured iced dessert) and, after the meal, filled in a specific questionnaire named dynamic digestibility questionnaire. In our sample the ingestion of the coffee-flavoured iced dessert seemed to improve the digestibility of a standardized meal: the difference between the curves of gastric emptying without and with iced dessert is statistically significant. These data are strongly confirmed by subjective assessment: the dynamic digestibility questionnaire (DDQ) showed a higher digestibility of a standardized meal with the coffee-flavoured iced dessert in comparison to a normal meal. The current study represents a preliminary report on this topic with a small sample of healthy volunteers: further studies on larger population are requested in order to confirm all the encouraging results herein discussed.

Dielectric tensor of tetracene single crystals: the effect of anisotropy on polarized absorption and emission spectra.

The full UV-visible dielectric tensor and the corresponding directions of the principal axes of triclinic tetracene crystals are reported as deduced either by polarized absorption and ellipsometry measurements or by calculations based on the molecular and crystallographic data. The results allow the attribution of the polarized bands observed in both absorption and photoluminescence emission spectra. In particular, the spectral line shape and polarization of the emission are found to depend on the sample thickness, and the effect is attributed to the modification of the state of polarization of the emitted light during its propagation inside the crystal. Indeed, the directions of polarization of the lowest optical transitions and the directions of the principal axes of the dielectric tensor are demonstrated not to coincide, in contrast to the assumptions typically made in the literature, thus causing the mixed transverse/longitudinal character of light propagation.

Reclassifying exciton-phonon coupling in molecular aggregates: evidence of strong nonadiabatic coupling in oligothiophene crystals.

Exciton-phonon (EP) coupling in molecular aggregates is reexamined in cases where extended intermolecular interactions result in low-energy excitons with high effective masses. The analysis is based on a single intramolecular vibrational mode with frequency omega0 and Huang-Rhys factor lambda2. When the curvature Jc at the exciton band bottom is much smaller than the free-exciton Davydov splitting W, the strength of the EP coupling is determined by comparing the nuclear relaxation energy lambda2omega0 with the curvature. In this way, weak (lambda2omega0<<4piJc), intermediate I (lambda2omega0 approximately 4piJc), and strong I (lambda2omega0>>4piJc) coupling regimes are introduced. The conventional intermediate (lambda2omega0 approximately W) and strong (lambda2omega0>>W) EP coupling regimes originally defined by Simpson and Peterson [J. Chem. Phys. 26, 588 (1957)] are based solely on the Davydov splitting and are referred to here as intermediate II and strong II regimes, respectively. Within the intermediate I and strong I regimes the near degeneracy of the low-energy excitons allows efficient nonadiabatic coupling, resulting in a spectral splitting between the b- and ac-polarized first replicas in the vibronic progression characterizing optical absorption. Such spectral signatures are clearly observed in OT4 thin films and crystals, where splittings for the lowest energy mode with omega0=161 cm(-1) are as large as 30 cm(-1) with a small variation due to sample disorder. Numerical calculations using a multiphonon BO basis set and a Hamiltonian including linear EP coupling yield excellent agreement with experiment.

Exciton self-trapping in tetrafluoro-dimethyl-aminoacridine single crystals.

The UV-visible optical spectra of 1,2,3,4-tetrafluoro-7-(N,N)dimethyl-amino-acridine single crystals are reported. The results are discussed on the basis of the molecular transitions and crystal packing in the framework of the theory of molecular excitons under a fluctuating potential field due to dynamic disorder. A strong local geometry distortion is demonstrated by applying the Urbach rule to the absorption tails, which is the amplitude of the local potential fluctuation being larger than the intermolecular transfer energy. The lineshape and linewidth of the emission band and its temperature dependence give further evidence of exciton self-trapping.

Effect of static and dynamic disorder on exciton mobility in oligothiophenes.

The polarized optical absorption spectra of different quaterthiophene single crystals in the energy region of the exciton bands originating from the first molecular transition are reported as measured in the temperatures ranging from 7 to 140 K. The intrinsic higher mobility of the b-polarized 0-0 a(u) exciton both with respect to its replicas and to the a-polarized structures is demonstrated in high quality crystals at the lowest temperatures. The influence of structural disorder on mobility is discussed considering, for the different samples, the measured lineshape and linewidth of the absorption peaks, and the relative lineshift and intensity ratio between the 0-0 a(u) line and its first replica at the lowest temperature. The influence of dynamic disorder is discussed considering the lineshape and linewidth of the measured peaks as a function of temperature for both polarizations in the framework of the exciton-phonon coupling theory.

Measured Davydov splitting in oligothiophene crystals.

The polarized absorption spectra of single crystals of oligothiophenes in a wide spectral range are reported. The experimental procedure is discussed, underlying several details which are relevant to obtain reliable spectra particularly for samples of increasing thickness. On the basis of these considerations, it has been possible to fully detect the transition to the upper Davydov exciton originating from the first molecular state. The position and shape of the main exciton peak in these materials are compared and discussed, taking into consideration the molecular arrangement and the longitudinal contribution which depends on the transition moment orientation. The Davydov splitting values as deduced from the experimental data at room temperature are also reported either for the first vibronic replica or for the electronic transition as a whole. The difference between the purely transverse and the measured Davydov splitting is discussed.

Optical transverse excitation in quaterthiophene crystals by ultraviolet-visible internal and attenuated total reflection.

We report internal and attenuated total reflection of light at the interface between glass and a quaterthiophene crystal in the spectral region of the electronic transitions. The bands corresponding to the absorption of the a(u) and b(u) Frenkel exciton states are detected for different polarization of the incident light. In particular, the wave-normal vector being almost perpendicular to the b(u) transition dipole moment allows its transverse component to be accessed, whose excitation in conventional external reflection or transmission spectroscopies is forbidden.

Primary adsorption site of phage PBS1: the flagellum of Bacillus subtilis.

The adsorption of Bacillus subtilis phage PBS1 was studied, and it was demonstrated that the primary adsorption site for this phage is the flagellum of B. subtilis. The capacity of flagella to function for motility may be lost without the loss of their capacity to adsorb the phage and permit infection. Deoxyribonucleic acid injection by the phage is inhibited by cyanide, suggesting the requirement for cellular energy in the infection process.