Links across disabilities: unveiling associations between functional domains.

BACKGROUND: Persons with disabilities experience higher risks of mortality as well as poorer health as compared to the general population. The aim of this study is to estimate the correlations between functional difficulties across several domains in six countries. METHODS: National census data with questions on disability from six countries (Mauritius, Morocco, Senegal, Myanmar, Vietnam, and Uruguay) was used in this study. We performed logistic regressions to assess the extent to which having a functional difficulty in one domain is correlated with having a functional difficulty in each of the other domains and report weighted odds ratios (ORs) overall and within age-groups ('18-44' years and '45+' years). Models adjust for age, sex, and location (rural or urban). Sensitivity analyses around different choices of predictors and response variables were conducted. FINDINGS: For all countries, reporting a functional difficulty in one domain was consistently and significantly positively correlated with reporting a functional difficulty in other domains (overall) and for each of the two age-groups considered - '18-44' years and '45+' years. All ORs were greater than one. Cognition, mobility, and hearing were the domains that were the most correlated ones with other domains. The highest pairwise correlations were for i/ hearing and cognition; ii/ mobility and cognition. Results were robust to changing the severity thresholds for functional difficulties. Across countries, Uruguay, the only high-income country among the six countries under study, had the lowest correlations between functional domains. CONCLUSIONS: There are consistent positive associations in the experience of functional difficulties in various domains in the six countries under study. Such correlations may reflect barriers to social services including healthcare services and resources (e.g. assistive devices) that may lead to an avoidable deterioration of functioning across domains. Further research is needed on the trajectories of functional difficulties and on structural barriers that people with functional difficulties may experience in their communities and in healthcare settings in particular. This is important as some functional difficulties may be preventable.

Control of electron and electron-hole pair dynamics on nonlinear lattice bilayers by strong solitons.

We consider the dynamics of electrons and holes moving in two-dimensional lattice layers and bilayers. As an example, we study triangular lattices with units interacting via anharmonic Morse potentials and investigate the dynamics of excess electrons and electron-hole pairs according to the Schrödinger equation in the tight binding approximation. We show that when single-site lattice solitons or M-solitons are excited in one of the layers, those lattice deformations are capable of trapping excess electrons or electron-hole pairs, thus forming quasiparticle compounds moving approximately with the velocity of the solitons. We study the temporal and spatial nonlinear dynamical evolution of localized excitations on coupled triangular double layers. Furthermore, we find that the motion of electrons or electron-hole pairs on a bilayer is slaved by solitons. By case studies of the dynamics of charges bound to solitons, we demonstrate that the slaving effect may be exploited for controlling the motion of the electrons and holes in lattice layers, including also bosonic electron-hole-soliton compounds in lattice bilayers, which represent a novel form of quasiparticles.

About electron transfer over long distances with tunable sub/supersonic velocities.

Provided in this paper is a theory of long-range electron transfer with near sound (supersonic or subsonic) velocity along one-dimensional crystal lattices. The theory represents the development of an earlier work by introducing Marcus formulation. To illustrate its application to a realistic case, the theory is used to offer an explanation of two puzzling observations made by Donovan and Wilson in transient photoconduction experiments with non-dopable perfectly crystalline polydiacetylene crystals in the presence of an electric field: transport velocity value close to sound velocity being independent of field for four orders of magnitude of field (102 V/m-106 V/m) and, in the low field values, an ultra-high mobility greater than 20 m2/V s. We also study factors eventually leading to lowering of the transport velocity.

Discrete-breather-assisted charge transport along DNA-like molecular wires.

Mobile discrete breathers (MDBs) are here suggested as localized excitations underlying the trapping and transport of charged particles (electron or hole) along a DNA-like molecular wire with anchored ends such as attached to two electrodes. For illustration the Peyrard-Bishop-Dauxois-Holstein (PBDH) model is used. MDBs are excited by imposing appropriate disturbances to velocities or space positions of adjacent nucleotide pairs or lattice units of the wire. They can be directed either towards or away from the wire hence transverse to it. Numerical computer simulations show that a rather stable quasiparticle MDB + electron is possible when just a few of the nucleotide pairs near one of the fixed ends of the wire are excited. For the process to be effective, the charge, e.g., the electron, must be initially placed around the disturbed region of the molecule. Once the MDB + electron quasiparticle is formed it may be transported to quite a long distance up to ca. 60-70 nm in real space. Our findings show that such process does not demand intervention of an externally applied electric field and hence it may be considered as alternative to the polaron transport process.

Relationship between self-focused attention and mindfulness in people with and without hallucination proneness

The purpose of this work was to study the relationship between self-focused attention and mindfulness in participants prone to hallucinations and others who were not. A sample of 318 healthy participants, students at the universities of Sevilla and Almería, was given the Launay-Slade Hallucinations Scale-revised (LSHS-R, Bentall & Slade, 1985). Based on this sample, two groups were formed: participants with high (n = 55) and low proneness (n = 28) to hallucinations. Participants with a score higher than a standard deviation from the mean in the LSHS-R were included in the high proneness group, participants with a score lower than a standard deviation from the mean in the LSHR-R were included in the second one. All participants were also given the Self-Absorption Scale (SAS, McKenzie & Hoyle, 2008) and the Southampton Mindfulness Questionnaire (SMQ, Chadwick et al., 2008). The results showed that participants with high hallucination proneness had significantly higher levels of public (t(80) = 6.81, p < .001) and private (t(77) = 7.39, p < .001) self-focused attention and lower levels of mindfulness (t(81) = -4.56, p < .001) than participants in the group with low hallucination proneness. A correlational analysis showed a negative association between self-focused attention (private and public) and mindfulness (r = -0.23, p < .001; r = -0.38, p < .001 respectively). Finally, mindfulness was found to partly mediate between self-focused attention and hallucination proneness. The importance of self-focused attention and mindfulness in understanding the etiology of hallucinations discussed and suggest some approaches to their treatment (AU)

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Relationship between self-focused attention and mindfulness in people with and without hallucination proneness.

The purpose of this work was to study the relationship between self-focused attention and mindfulness in participants prone to hallucinations and others who were not. A sample of 318 healthy participants, students at the universities of Sevilla and Almería, was given the Launay-Slade Hallucinations Scale-revised (LSHS-R, Bentall & Slade, 1985). Based on this sample, two groups were formed: participants with high (n = 55) and low proneness (n = 28) to hallucinations. Participants with a score higher than a standard deviation from the mean in the LSHS-R were included in the high proneness group, participants with a score lower than a standard deviation from the mean in the LSHR-R were included in the second one. All participants were also given the Self-Absorption Scale (SAS, McKenzie & Hoyle, 2008) and the Southampton Mindfulness Questionnaire (SMQ, Chadwick et al., 2008). The results showed that participants with high hallucination proneness had significantly higher levels of public (t(80) = 6.81, p < .001) and private (t(77) = 7.39, p < .001) self-focused attention and lower levels of mindfulness (t(81) = -4.56, p < .001) than participants in the group with low hallucination proneness. A correlational analysis showed a negative association between self-focused attention (private and public) and mindfulness (r = -0.23, p < .001; r = -0.38, p < .001 respectively). Finally, mindfulness was found to partly mediate between self-focused attention and hallucination proneness. The importance of self-focused attention and mindfulness in understanding the etiology of hallucinations discussed and suggest some approaches to their treatment.

Dilemas bioéticos y sus posibles soluciones en las unidades de terapia intensiva pediátrica del Distrito Federal (México) / Dilemas bioéticos e suas possíveis soluções nas Unidades de Terapia Intensiva Pediátrica do Distrito Federal (México) / Bioethics dilemmas and their possible solutions in pediatric intensive therapy units of Federal District (Mexico)

El proceso de toma de decisiones en las unidades de terapia intensiva pediátrica (UTIP) se sustenta en un marco científico, legal y ético, el cual suele ser más complejo que en la práctica para adultos e involucra a los padres o tutores, en consecuencia, debe ser resuelto con seriedad, con calma y rigor metodológico. Se diseñó una encuesta por expertos, con aplicación anónima y voluntaria, en forma no institucional, en la que se plantearon cuestiones referentes a dilemas bioéticos generados en los servicios de UTIP y los procedimientos para su solución. La aplicación de este instrumento fue el método Delphi, en dos rondas. Los resultados más importantes, entre otros, consistieron en reconocer que la totalidad de los médicos encuestados enfrentan en su unidad dilemas éticos, siendo el más frecuente la obstinación terapéutica, en un 32 por ciento, resultado que se enlaza al de la dificultad de establecer el diagnóstico de paciente terminal, en un 13 por ciento. Incluir materias de bioética y toma de decisiones con contenido moral en la formación de estos profesionistas, así como implementar la comunicación asertiva entre el equipo de salud y la familia, y promover el funcionamiento adecuado de comités de bioética hospitalarios con funciones consultivas de emergencia, son propuestas que emergen de las conclusiones de este estudio.

The process of decision making in pediatric intensive therapy units (PITU) is based on an ethical, legal and scientific framework, which generally is more complex that with adults and involves parents or tutors, thus, it must be solved carefully, with time and methodological precision. A survey was design for experts with anonymous and voluntary application, in a non institutional way, in which questions arise referring to bioethical dilemmas generated in PITU services and proceedings for their solution are proposed. Delphi method was used as instrument in two rounds. The most important results, among others, consisted in recognizing that all physician surveyed face in their unit ethical dilemmas, the most frequent being obstinacy in therapy in 32 percent cases, result linked to the difficulty to establish the diagnosis of terminal patient in 13 percent cases. To include bioethics topics and decision making with moral content in training professionals, as well as implementing assertive communication among health care team and families, and promoting adequate functioning of hospital bioethics committees with emergency consulting functions, are proposals which arise from the conclusions of this study.

O processo da tomada de decisões nas Unidades de Terapia Intensiva Pediátrica (UTIP) se sustenta num marco científico, legal e ético, que deve ser mais complexo do que na prática para adultos, e envolve os pais ou tutores; em consequência, deve ser resolvido com seriedade, calma e rigor metodológico. Planejou-se uma enquete por especialistas, com aplicação anônima e voluntária, de forma não institucional, na qual foram propostas questões referentes a dilemas bioéticos gerados nos serviços de UTIP e os procedimentos para a sua solução. A aplicação deste instrumento se deu pelo método Delphi, em duas etapas. Os resultados mais importantes, entre outros, consistiram em reconhecer que a totalidade dos médicos pesquisados enfrentam em sua unidade dilemas éticos, sendo o mais frequente a obstinação terapéutica, em 32 por cento dos casos, resultado que se relaciona ao de dificuldade em estabelecer o diagnóstico de paciente terminal, em 13 por cento. Incluir matérias de bioética e tomada de decisões com conteúdo moral na formação destes profissionais, assim como implementar a comunicação assertiva entre a equipe de saúde e a família, e promover o funcionamento adequado de Comitês de Bioética hospitalares com funções consultivas de emergência, são propostas que emergem das conclusões deste estudo.

Utilización de Duodopa en el paciente con enfermedad de Parkinson / Use of duodenal levodopa infusion therapy in advanced Parkinson's disease patients

El tratamiento con infusión continua de levodopa/carbidopa intraduodenal (Duodopa®) constituye una opción de tratamiento para pacientes con enfermedad de Parkinson (EP) avanzada que no responden de forma satisfactoria al tratamiento convencional. Publicaciones previas han reportado que Duodopa mejora las complicaciones motoras, síntomas no motores, calidad de vida y autonomía de los pacientes así como el grado de estrés y sobrecarga del cuidador. Asegura la mayoría de las veces la monoterapia evitando otros fármacos con efectos secundarios. Las complicaciones graves son excepcionales, mientras que las menores relacionadas con el estoma y el dispositivo son frecuentes. El presente trabajo revisa la evidencia científica existente sobre Duodopa y aspectos prácticos para el manejo de los pacientes con EP tratados con dicha terapia (AU)

The treatment with continuous intraduodenal levodopa/carbidopa infusion (Duodopa ®) is an option in the treatment of patients with advanced Parkinson's disease (PD) who do not respond satisfactorily to the conventional treatment. Earlier publications have reported that Duodopa improves the motor complications, non-motor symptoms, quality of life and autonomy of patients, as well as the level of stress and burden on caregivers. It can usually be administered in monotherapy, thus avoiding the need for other drugs with secondary effects. Severe complications are exceptional, while minor ones related with the stoma and the device are frequent. This work reviews the existing scientific evidence on Duodopa and practical aspects for the management of patients with PD treated with this therapy (AU)

Otros parkinsonismos de base genética: ataxias espinocerebelosas, síndrome temblor-ataxia asociado a premutación X frágil y xantomatosis cerebrotendinosa / Other genetically-based parkinsonisms: spinocerebellar ataxias, tremor-ataxia syndrome associated to fragile X premutation and cerebrotendinous xanthomatosis

Las ataxias espinocerebelosas autosómicas dominantes, el síndrome temblor-ataxia asociado a premutación X frágil y la xantomatosis cerebrotendinosa son enfermedades de base genética que cursan con manifestaciones neurológicas diversas. Aunque habitualmente no es el rasgo clínico principal, los trastornos extrapiramidales, incluido el parkinsonismo, pueden aparecer con frecuencia e intensidad variable. Durante las últimas décadas los avances en el campo de la genética molecular de han permitido profundizar en el conocimiento de estos trastornos. Realizamos una revisión sobre los aspectos etiopatogénicos, clínicos, neuropatológicos y diagnósticos de estas entidades (AU)

Autosomal dominant spinocerebellar ataxias, tremor-ataxia syndrome associated to fragile X premutation syndrome and cerebrotendinous xanthomatosis are diseases with a genetic base that are accompanied by diverse neurological manifestations. Although they are not usually the main clinical feature, extrapyramidal disorders, including parkinsonism, may appear with varying frequency and intensity. Over the last few decades, the progress made in the field of molecular genetics has enabled researchers to gain a deeper understanding of these disorders. We conduct a review of the aetiopathogenic, clinical, neuropathological and diagnostic aspects of these condition (AU)

Response of adult mouse uterus to early disruption of estrogen receptor-alpha signaling is influenced by Krüppel-like factor 9.

Inappropriate early exposure of the hormone-responsive uterus to estrogenic compounds is associated with increased risk for adult reproductive diseases including endometrial cancers. While the dysregulation of estrogen receptor-alpha (ESR1) signaling is well acknowledged to mediate early events in tumor initiation, mechanisms contributing to sustained ESR1 activity later in life and leading to induction of oncogenic pathways remain poorly understood. We had shown previously that the transcription factor Krüppel-like factor 9 (KLF9) represses ESR1 expression and activity in Ishikawa endometrial glandular epithelial cells. We hypothesized that KLF9 functions as a tumor suppressor, and that loss of its expression enhances ESR1 signaling. Here, we evaluated the contribution of KLF9 to early perturbations in uterine ESR1 signaling pathways elicited by the administration of synthetic estrogen diethylstilbestrol (DES) to wild-type (WT) and Klf9 null (KO) mice on postnatal days (PNDs) 1-5. Uterine tissues collected at PND84 were subjected to histological, immunological, and molecular analyses. Compared with WT mice, KO mice demonstrated larger endometrial glands and lower endometrial gland numbers; DES exposure exacerbated these differences. Loss of KLF9 expression resulted in increased glandular ESR1 immunoreactivity with DES, without effects on serum estradiol levels. Quantitative RT-PCR analyses indicated altered expression of uterine genes commonly dysregulated in endometrial cancers (Akt1, Mmp9, Slpi, and Tgfbeta1) and of those involved in growth regulation (Fos, Myc, Tert, and Syk), with loss of Klf9, alone or in concert with DES. Our data support a molecular network between KLF9 and ESR1 in the uterus, and suggest that silencing of KLF9 may contribute to endometrial dysfunctions initiated by aberrant estrogen action.

The emerging role of Krüppel-like factors in endocrine-responsive cancers of female reproductive tissues.

Krüppel-like factors (KLFs), of which there are currently 17 known protein members, belong to the specificity protein (Sp) family of transcription factors and are characterized by the presence of Cys(2)/His(2) zinc finger motifs in their carboxy-terminal domains that confer preferential binding to GC/GT-rich sequences in gene promoter and enhancer regions. While previously regarded to simply function as silencers of Sp1 transactivity, many KLFs are now shown to be relevant to human cancers by their newly identified abilities to mediate crosstalk with signaling pathways involved in the control of cell proliferation, apoptosis, migration, and differentiation. Several KLFs act as tumor suppressors and/or oncogenes under distinct cellular contexts, underscoring their prognostic potential for cancer survival and outcome. Recent studies suggest that a number of KLFs can influence steroid hormone signaling through transcriptional networks involving steroid hormone receptors and members of the nuclear receptor family of transcription factors. Since inappropriate sensitivity or resistance to steroid hormone actions underlies endocrine-related malignancies, we consider the intriguing possibility that dysregulation of expression and/or activity of KLF members is linked to the pathogenesis of endometrial and breast cancers. In this review, we focus on recently described mechanisms of actions of several KLFs (KLF4, KLF5, KLF6, and KLF9) in cancers of the mammary gland and uterus. We suggest that understanding the mode of actions of KLFs and their functional networks may lead to the development of novel therapeutics to improve current prospects for cancer prevention and cure.

[Rivastigmine in a case of autopsy proved frontotemporal dementia (Pick's disease)]. / Rivastigmina en un caso de demencia frontotemporal, enfermedad de Pick verificada por autopsia.

INTRODUCTION: Cholinesterase inhibitors are useful in the treatment of behavioural and psychological symptoms in Alzheimer's disease. Their effectiveness in frontotemporal dementia has not been proved, since such a claim has only been backed by the publication of one open-label trial in which the behavioural and psychological symptoms of the patients treated with rivastigmine over a 12-month period improved significantly with respect to those belonging to a group that were given a placebo. We report a case of frontotemporal dementia, Pick's disease, which improved with rivastigmine treatment. CASE REPORT: A 61-year-old male who presented a progressive clinical picture of behavioural disorders and executive-cognitive impairment that had begun two years earlier. Magnetic resonance imaging of the head revealed severe frontotemporal atrophy. Neuropsychological Inventory (NPI). Overall score 36/144 (6/12: anxiety, disinhibition and aberrant motor behaviour, 4/12: agitation, irritability and apathy; 3/12: sleep and eating disorders. After three months' treatment with rivastigmine, the overall score on the NPI was 10/144. This improvement remained stable over the months that followed. The patient died eight months later after developing liver cancer with metastasis. The microscopic study of the brain showed tau-positive neuronal inclusions, gliosis and neuronal loss. The inclusions were well-circumscribed Pick bodies, which were present in the frontal and temporal cortices and in the dentate gyrus of the hippocampus. CONCLUSIONS: This case confirms the idea that treatment with cholinesterase inhibitors can be effective in the behavioural and psychological symptoms of frontotemporal dementia.

Rivastigmina en un caso de demencia frontotemporal, enfermedad de Pick verificada por autopsia / Rivastigmine in a case of autopsy proved frontotemporal dementia (pick´s disease)

Introducción. Los inhibidores de la colinesterasa son útiles en el tratamiento de los síntomas conductuales y psicológicos en la enfermedad de Alzheimer. Su eficacia en la demencia frontotemporal no está demostrada, pues sólo la avala la publicación de un estudio abierto en el que los síntomas conductuales y psicológicos de los pacientes tratados con rivastigmina durante 12 meses mejoraron significativamente respecto de los del grupo placebo. Describimos un caso de demencia frontotemporal, enfermedad de Pick, que mejoró con el tratamiento con rivastigmina. Caso clínico. Varón de 61 años de edad que presentaba un cuadro clínico progresivo de alteraciones de conducta y afectación ejecutivocognitiva de dos años de evolución. En la resonancia magnética craneal se observó una atrofia frontotemporal grave. En el inventario neuropsicológico (NPI) alcanzó una puntuación global de 36/144 (6/12: ansiedad, desinhibición y conducta motora aberrante, 4/12: agitación, irritabilidad y apatía; 3/12: alteraciones del sueño y de la conducta alimentaria). Tras tres meses de tratamiento con rivastigmina, la puntuación global en el NPI fue de 10/144. Esta mejoría se mantuvo estable en los siguientes meses. Falleció ocho meses después tras desarrollar un hepatocarcinoma con metástasis. En el estudio microscópico del cerebro se observaron inclusiones neuronales tau positivas, pérdida neuronal y gliosis. Las inclusiones eran cuerpos de Pick, bien circunscritos, presentes en la corteza frontal, temporal y en el giro dentado del hipocampo. Conclusión. Este caso confirma que el tratamiento con inhibidores de la colinesterasa puede ser eficaz en los síntomas conductuales y psicológicos de demencia frontotemporal (AU)

Introduction. Cholinesterase inhibitors are useful in the treatment of behavioural and psychological symptoms in Alzheimer's disease. Their effectiveness in frontotemporal dementia has not been proved, since such a claim has only been backed by the publication of one open-label trial in which the behavioural and psychological symptoms of the patients treated with rivastigmine over a 12-month period improved significantly with respect to those belonging to a group that were given a placebo. We report a case of frontotemporal dementia, Pick’s disease, which improved with rivastigmine treatment. Case report. A 61-year-old male who presented a progressive clinical picture of behavioural disorders and executive-cognitive impairment that had begun two years earlier. Magnetic resonance imaging of the head revealed severe frontotemporal atrophy. Neuropsychological Inventory (NPI). Overall score 36/144 (6/12: anxiety, disinhibition and aberrant motor behaviour, 4/12: agitation, irritability and apathy; 3/12: sleep and eating disorders. After three months’ treatment with rivastigmine, the overall score on the NPI was 10/144. This improvement remained stable over the months that followed. The patient died eight months later after developing liver cancer with metastasis. The microscopic study of the brain showed tau-positive neuronal inclusions, gliosis and neuronal loss. The inclusions were well-circumscribed Pick bodies, which were present in the frontal and temporal cortices and in the dentate gyrus of the hippocampus. Conclusions. This case confirms the idea that treatment with cholinesterase inhibitors can be effective in the behavioural and psychological symptoms of frontotemporal dementia (AU)

Nuclear receptor co-regulator Krüppel-like factor 9 and prohibitin 2 expression in estrogen-induced epithelial cell proliferation in the mouse uterus.

Estrogen, acting through its cognate receptor estrogen receptor-alpha (ESR1), is a critical regulator of uterine endometrial epithelial proliferation. Although the dynamic communication between endometrial stromal (ST) and epithelial cells is considered to be an important component in this process, key molecular players in particular compartments remain poorly defined. Here, we used mice null for Krüppel-like factor 9 (KLF9) to evaluate the contribution of this nuclear protein in ST-epithelial interactions underlying proliferative effects of estrogen. We found that in ovariectomized mice administered estradiol-17beta (E(2)) for 24 h, Klf9 null mutation resulted in lack of E(2)-induced proliferative response in all endometrial compartments. We demonstrated a negative association between Klf9 expression and nuclear levels of ESR1 transcriptional corepressor prohibitin (PHB) 2 in uterine ST and epithelial cells of E(2)-treated wild-type (WT) and Klf9 null mice. In early pregnancy uteri of WT mice, the temporal pattern of Klf9 transcript levels was inversely associated with that of Phb2. Deletion of Klf9 up-regulated uterine Phb2 expression and increased PHB2 nuclear localization in endometrial ST and epithelial cells, with no effects on the expression of the related Phb1. In the human endometrial ST cell line treated with E(2) for 24 h, Klf9 siRNA targeting augmented PHB2 transcript and increased nuclear PHB2 protein levels, albeit this effect was not to the extent seen in vivo with Klf9 null mutants. Our findings suggest a novel mechanism for control of estrogen-induced luminal epithelial proliferation involving ST KLF9 regulation of paracrine factor(s) to repress epithelial expression of corepressor PHB2.

Surface forces and wetting phenomena.

Conditions for thermodynamic equilibrium of liquid drops on solid substrates are presented. It is shown that if surface force (disjoining/conjoining Derjaguin pressure) action in a vicinity of the three-phase contact line is taken into account the condition of thermodynamic equilibrium is duly satisfied. Then the thermodynamic expressions for equilibrium contact angles of drops on solid substrates and menisci in thin capillaries are expressed in terms of the corresponding Derjaguin isotherm. It is shown that equilibrium contact angles of drops vary significantly depending on the vapour pressure in the ambient atmosphere, while there is a single, unique equilibrium contact angle in thin capillaries. It is also shown that the static advancing contact angle of a drop depends on its volume, in agreement with experimental data. In the case of menisci in capillaries, the expression for the receding contact angle is deduced, with results that are also in agreement with known experimental data.

Compounds of paired electrons and lattice solitons moving with supersonic velocity.

We study the time evolution of two correlated electrons of opposite spin in an anharmonic lattice chain. The electrons are described quantum mechanically by the Hubbard model while the lattice is treated classically. The lattice units are coupled via Morse-Toda potentials. Interaction between the lattice and the electrons arises due to the dependence of the electron transfer-matrix element on the distance between neighboring lattice units. Localized configurations comprising a paired electron and a pair of lattice deformation solitons are constructed such that an associated energy functional is minimized. We investigate long-lived, stable pairing features. It is demonstrated that traveling pairs of lattice solitons serve as carriers for the paired electrons realizing coherent transport of the two correlated electrons. We also observe dynamical narrowing of the states, that is, starting from an initial double-peak profile of the electron probability distribution, a single-peak profile is adopted going along with enhancement of localization of the paired electrons. Interestingly, a parameter regime is identified for which supersonic transport of paired electrons is achieved.

Electron capture and transport mediated by lattice solitons.

We study electron transport in a one-dimensional molecular lattice chain. The molecules are linked by Morse interaction potentials. The electronic degree of freedom, expressed in terms of a tight binding system, is coupled to the longitudinal displacements of the molecules from their equilibrium positions along the axis of the lattice. More specifically, the distance between two sites influences in an exponential fashion the corresponding electronic transfer matrix element. We demonstrate that when an electron is injected in the undistorted lattice it causes a local deformation such that a compression results leading to a lowering of the electron's energy below the lower edge of the band of linear states. This corresponds to self-localization of the electron due to a polaronlike effect. Then, if a traveling soliton lattice deformation is launched a distance apart from the electron's position, upon encountering the polaronlike state it captures the latter dragging it afterwards along its path. Strikingly, even when the electron is initially uniformly distributed over the lattice sites a traveling soliton lattice deformation gathers the electronic amplitudes during its traversing of the lattice. Eventually, the electron state is strongly localized and moves coherently in unison with the soliton lattice deformation. This shows that for the achievement of coherent electron transport we need not start with the polaronic effect.

Implementation of semi-automated cloning and prokaryotic expression screening: the impact of SPINE.

The implementation of high-throughput (HTP) cloning and expression screening in Escherichia coli by 14 laboratories in the Structural Proteomics In Europe (SPINE) consortium is described. Cloning efficiencies of greater than 80% have been achieved for the three non-ligation-based cloning techniques used, namely Gateway, ligation-indendent cloning of PCR products (LIC-PCR) and In-Fusion, with LIC-PCR emerging as the most cost-effective. On average, two constructs have been made for each of the approximately 1700 protein targets selected by SPINE for protein production. Overall, HTP expression screening in E. coli has yielded 32% soluble constructs, with at least one for 70% of the targets. In addition to the implementation of HTP cloning and expression screening, the development of two novel technologies is described, namely library-based screening for soluble constructs and parallel small-scale high-density fermentation.

The secretory leukocyte protease inhibitor gene is a target of epidermal growth factor receptor action in endometrial epithelial cells.

The over-expression of epidermal growth factor receptor (EGFR) and its ligands, epidermal growth factor (EGF) and transforming growth factor-alpha, is a common feature of epithelial carcinomas and correlates with neoplastic progression. Secretory leukocyte protease inhibitor (SLPI), a member of the Kazal superfamily of serine anti-proteases, induces proliferation and promotes malignancy of epithelial cells and is expressed at high levels in multiple tumor types. In the present study, we have demonstrated that EGF increases SLPI expression in the human endometrial epithelial cell line Ishikawa in a dose- and time-dependent manner. We have shown that this effect of EGF occurs, in part, at the level of the SLPI promoter and involves the MAP kinase signaling pathway. We have further shown that EGF promotion of cell proliferation, but not induction of cyclin D1 gene expression, involves SLPI. Our results suggest that the regulation of SLPI expression by EGFR ligand(s) may represent a 'feed-forward' mechanism by which the enhanced proliferative and migratory properties of EGFR over-expressing cancer cells are sustained. Increased SLPI expression is likely an important component of altered EGFR signaling in human tumors and may have significant therapeutic implications in cancer progression.

Factores de riesgo cardiovascular en niños con diabetes tipo 1 y su relación con el control de la glucemia / Cardiovascular risk factors in children with type 1 diabetes and their relationship with the glycemic control

Diabetics have an increased risk of cardiovascular disease (CVD). The objective of this work was to evaluate the cardiovascular risk factors in infant-juvenile type 1 diabetics and their association with the degree of glycemic control. A total of 52 patients, aged 5-15 years, were studied and compared with 37 control subjects. The degree of glycemic control, lipid profile, plasma fibrinogen, microalbuminuria and blood pressure were investigated. The patients were grouped in diabetics with good glycemic control [DGGC, glycosilated hemoglobin (HbA1c) < 8%] and poor glycemic control [DPGC, HA1c > or = 8%]. Diabetic patients presented incremented values of total cholesterol (4.1 +/- 0.9 vs. 3.1 +/- 0.7 mmol/l, p = 0.0008), LDL-cholesterol (2.4 +/- 0.9 vs. 1.7 +/- 0.7 mmol/l, p = 0.0001), HDL-cholesterol (1.2 +/- 0.3 vs. 1.0 +/- 0.2 mmol/l, p = 0.0002), with respect to control group. Eighty three per cent of diabetics showed a poor glycemic control. There were not significant differences in lipid profile between DGGC and DPGC, excepting HDL-cholesterol which was higher in DPGC group (p = 0.007). Plasma fibrinogen levels were similar in diabetics and controls, but they were higher in DPGC than in DGGC (265 +/- 46 vs. 229 +/- 22 mg/dl, p = 0.02). Three patients with microalbuminuria and none with hypertension were detected. In these patients the most pronounced risk factors for CVD were dyslipidemia and hyperglycemia, which justify the need for the early detection of these factors as well as strict metabolic control.