MPK-09, a small molecule inspired from bioactive styryllactone restores the wild-type function of mutant p53

In the search for more efficacious and less toxic cancer drugs, the tumor suppressor p53 protein has long been a desirable therapeutic target. In the recent past, few independent studies have demonstrated that the antitumor activity of wild-type p53 can be restored in cancer cells harboring mutant form of p53 using small molecule activators. In this study, we describe a novel small molecule MPK-09, which is selective and highly potent against allele specific p53 mutations mainly, R175H, R249S, R273H, R273C, and E285K. Except E285K, all other mutations tested are among the six ``hot spot'' p53 mutations reported in majority of human cancer. Furthermore, our study conclusively demonstrates that the apoptotic activity of the small molecule MPK-09 against cancer cells harboring R273C and E285K mutations is due to restoration of the wild-type conformation to the corresponding mutant form of p53.

Targeting the dopamine receptor in schizophrenia: investigational drugs in Phase III trials

Introduction: Antipsychotic drugs date back to the 1950s and chlorpromazine. Soon after, it was established that blockade of dopamine and, in particular, the D-2 receptor was central to this effect. Dopamine continues to represent a critical line of investigation, although much of the work now focuses on its potential in other symptom domains. Areas covered: A search was carried out for investigational drugs using the key words `dopamine', `schizophrenia' and `Phase III' in an American clinical trial registry (clinicaltrials.gov), published articles using the National Library of Medicine's PubMed database, and supplemented results with a manual search of cross-references and conference abstracts. Drugs were excluded that were already FDA approved. Expert opinion: There remains interest, albeit diminished, in developing better antipsychotic compounds. The greatest enthusiasm currently centres on dopamine's role in negative and cognitive symptom domains. With theories conceptualising hypodopaminergic activity as underlying these deficits, considerable effort is focused on drug strategies that will enhance dopamine activity. Finally, a small body of research is investigating dopaminergic compounds vis-a-vis side-effect treatments. In domains beyond psychosis, however, dopamine arguably is not seen as so central, reflected in considerable research following other lines of investigation.

The basics and advances of immunomodulators and antigen presentation: a key to development of potent memory response against pathogens

Introduction: Immunomodulators are agents, which can modulate the immune response to specific antigens, while causing least toxicity to the host system. Being part of the modern vaccine formulations, these compounds have contributed remarkably to the field of therapeutics. Despite the successful record maintained by these agents, the requirement of novel immunomodulators keeps increasing due to the increasing severity of diseases. Hence, research regarding the same holds great importance. Areas covered: In this review, we discuss the role of immunomodulators in improving performance of various vaccines used for counteracting most threatening infectious diseases, mechanisms behind their action and criteria for development of novel immunomodulators. Expert opinion: Understanding the molecular mechanisms underlying immune response is a prerequisite for development of effective therapeutics as these are often exploited by pathogens for their own propagation. Keeping this in mind, the present research in the field of immunotherapy focuses on developing immunomodulators that would not only enhance the protection against pathogen, but also generate a long-term memory response. With the introduction of advanced formulations including combination of different kinds of immunomodulators, one can expect tremendous success in near future.

Structure, stability and elasticity of DNA nanotubes

DNA nanotubes are tubular structures composed of DNA crossover molecules. We present a bottom up approach for the construction and characterization of these structures. Various possible topologies of nanotubes are constructed such as 6-helix, 8-helix and tri-tubes with different sequences and lengths. We have used fully atomistic molecular dynamics simulations to study the structure, stability and elasticity of these structures. Several nanosecond long MD simulations give the microscopic details about DNA nanotubes. Based on the structural analysis of simulation data, we show that 6-helix nanotubes are stable and maintain their tubular structure; while 8-helix nanotubes are flattened to stabilize themselves. We also comment on the sequence dependence and the effect of overhangs. These structures are approximately four times more rigid having a stretch modulus of similar to 4000 pN compared to the stretch modulus of 1000 pN of a DNA double helix molecule of the same length and sequence. The stretch moduli of these nanotubes are also three times larger than those of PX/JX crossover DNA molecules which have stretch moduli in the range of 1500-2000 pN. The calculated persistence length is in the range of a few microns which is close to the reported experimental results on certain classes of DNA nanotubes.

Quantifying the Transmit Diversity Order of Euclidean Distance Based Antenna Selection in Spatial Modulation

In this letter, we quantify the transmit diversity order of the SM system operating in a closed-loop scenario. Specifically, the SM system relying on Euclidean distance based antenna subset selection (EDAS) is considered and the achievable diversity gain is evaluated. Furthermore, the resultant trade-off between the achievable diversity gain and switching gain is studied. Simulation results confirm our theoretical results. Specifically, at a symbol error rate of about 10(-4) the signal-to-noise ratio gain achieved by EDAS is about 7 dB in case of 16-QAM and about 5 dB in case of 64-QAM.

A 1 V supercapacitor device with nanostructured graphene oxide/polyaniline composite materials

Polyaniline and graphene oxide composite on activated carbon cum reduced graphene oxide-supported supercapacitor electrodes are fabricated and electrochemically characterized in a three-electrode cell assembly. Attractive supercapacitor performance, namely high-power capability and cycling stability for graphene oxide/polyaniline composite, is observed owing to the layered and porous-polymeric-structured electrodes. Based on the materials characterization data in a three-electrode cell assembly, 1 V supercapacitor devices are developed and performance tested. A comparative study has also been conducted for polyaniline and graphene oxide/polyaniline composite-based 1 V supercapacitors for comprehending the synergic effect of graphene oxide and polyaniline. Graphene oxide/polyaniline composite-based capacitor that exhibits about 100 F g(-1) specific capacitance with faradaic efficiency in excess of 90% has its energy and power density values of 14 Wh kg(-1) and 72 kW kg(-1), respectively. Cycle-life data for over 1000 cycles reflect 10% capacitance degradation for graphene oxide/polyaniline composite supercapacitor.

Mechano-fluorochromic Pt-II Luminogen and Its Cysteine Recognition

A new triphenylamine-based organometallic Pt-II luminogen (1) and its analogous organic compound (2) are reported. The molecules are decorated with aldehyde functionality to improve their photophysical properties by utilising donor-acceptor interactions. The single crystal X-ray structure analysis of PtII analogue 1 revealed that the neighbouring molecules were loosely organised by weak intermolecular C-H center dot center dot center dot pi interactions. Because of the twisted nature of the triphenylamine backbone the compounds showed aggregation-induced emission enhancement in THF/water mixture. Due to their loose crystal packing, upon application of external stimuli these luminogens exhibited mechano-fluorochromic behaviour. The crystalline forms of the compounds displayed a more superior emission efficiency than the grinded samples. Moreover, the compounds showed crystallization-induced emission enhancement (CIEE) and exhibited chemodosimetric response towards cysteine under physiological condition.

Ice induced low temperature fatigue crack propagation in offshore structural steel A131

To investigate the low temperature fatigue crack propagation behavior of offshore structural steel A131 under random ice loading, three ice failure modes that are commonly present in the Bohai Gulf are simulated according to the vibration stress responses induced by real ice loading. The test data are processed by a universal software FCPUSL developed on the basis of the theory of fatigue crack propagation and statistics. The fundamental parameter controlling the fatigue crack propagation induced by random ice loading is determined to be the amplitude root mean square stress intensity factor K-arm. The test results are presented on the crack propagation diagram where the crack growth rate da/dN is described as the function of K-arm. It is evident that the ice failure modes have great influence on the fatigue crack propagation behavior of the steel in ice-induced vibration. However, some of the experimental phenomena and test results are hard to be physically explained at present. The work in this paper is an initial attempt to investigate the cause of collapse of offshore structures due to ice loading.

Composición química de la biomasa verde y amonificada con diferentes niveles de urea del pasto Gamba (Andropogon gayanus), cv CIAT-621 en etapa fonológica de pansoneo, Santa Rosa, Sabana Grande, Managua

Se llevó a cabo un estudio con el objetivo de determinar el mejoramiento de la composición química de la biomasa verde y tratada con Urea como proceso de amonificación. El pasto utilizado fue el Gamba (Andropogon gayanus Kunth), cv CIAT- 621 el cual se encontraba en etapa fenológica de pansoneo. El muestreo se realizó durante el mes de noviembre del año 2009 en la Finca Santa Rosa, Universidad Nacional Agraria. Managua, Nicaragua. Los tratamiento consistieron en cuatro niveles de aplicación de Urea; 0, 1, 3 y 5 % en base al forraje verde a tratar, diluido en 0.5 lt de agua, y almacenados en bolsas de polietileno durante 21 días a temperatura ambiente. El diseño utilizado fue un DCA (Diseño completo al Azar) con tres repeticiones. Las variables de estudio para cada tratamiento fueron, porcentajes de; materia seca, proteína cruda, fibra ácido detergente (FAD), fibra neutro detergente (FND), calcio y fósforo. Se realizaron análisis de varianza (ANDEVA) y separaciones de medias, usando Duncan (P<0.05). Para el análisis estadístico las variables codificadas en porcentajes se transformaron, según, 2 arco seno p (Dos veces Arco seno de la raíz cuadrada de la proporción). Se encontró diferencias significativas (P ≤ 0.05) para las variables Proteína Cruda (PC), Fibra Ácido Detergente (FAD), Calcio y Fósforo. La PC varío de 5.24 % a 11.48 % para 0 % y 3 % de Urea respectivamente, mientras la FAD disminuyo de 56.06 % a 43.64 % para los mismos tratamientos. Los minerales evaluados presentaron una tendencia inversa con los tratamientos de Urea, incrementándose el Ca y disminuyendo el Fósforo a medida que aumentaba la dosis de Urea. La Fibra Neutro Detergente aunque no presentó diferencias estadísticas entre los distintos tratamiento fue mejorada (disminución del contenido fibroso) con el tratamiento 3 % de Urea. Se concluye que el tratamiento de 3 % de Urea es el más recomendado para la amonificación de forraje verde en etapa fenologica de pansoneo en Andropogon gayanus Kunth cv CIAT 621. Estos resultados son halagadores ya que con el uso de esta tecnología se evidencia la transformación de materiales maduros de baja o nula calidad en alimentos que provean nutrientes (Proteína – Energía y Minerales) al animal durante la época seca

Caracterización y evaluación preliminar de veintiún genotipos de maíz (Zea mays L.)

El presente trabajo trata sobre la caracterización y evaluación preliminar de 21 genotipos de maíz (Zea mays L.) de los cuales el 95% fue recolectado en diferentes regiones de Nicaragua por el programa Recursos Genéticos Nicaragüense (REGEN), y la variedad comercial NB-6 como Testigo. El experimento se llevó a cabo en Julio de 1992 en los terrenos del REGEN, adscrito a la Universidad Nacional Agraria (UNA) Km 12-1/2carretera norte. El diseño empleado fué un Látice Balanceado (modificado) contabilizándose 3 réplicas con un testigo en cada bloque. Se utilizaron 49 descriptores, de los cuales el 92% de ellos ayudaron a diferenciar los genotipos estudiados. El mayor rendimiento lo expresaron el Testigo y la accesión 2511 sobrepasando los 4,000 kg/ha, asimismo se evaluó el ciclo vegetativo de los cultivares sobresaliendo la accesión 3061 (Pujagua) como material precoz. También se elaboró un catálogo de las accesiones conteniendo loe valores máximos, medios, mínimos, desviación estándar y coeficientes de variación para los descriptores cuantitativos y la moda para los caracteres cualitativos

Escenas de la vida de Santo Domingo de Guzmán

Resumen: “Escenas de la Vida de Santo Domingo de Guzmán” es el título otorgado a la bella obra atribuida al pintor Pere Nicolau, uno de los máximos representantes del Gótico Internacional en Valencia. Esta obra nos informa de la imagen simbólica de Santo Domingo, creada a partir de la literatura hagiográfica y las manifestaciones artísticas en la Edad Media, “cada una en su lenguaje, su riqueza y sus límites, y en ellos reside su belleza, su capacidad de sugerir y de permitirnos soñar o recrearnos”.

“Ser” como interpretación de la realidad

Resumen: En un contexto de descrédito de la Metafísica, José Gómez Caffarena plantea una reflexión especulativa que, afianzada en lo humano, ‘diga’ de modo veraz y relevante lo esencial de la estructura última de lo real. Para ello desarrolla una ontología que, afianzada en unos presupuestos metodológicos genuinamente trascendentales, respete tanto el límite de lo fenoménico como la pretensión de verdad desde la que se hace. Este escrito discute la viabilidad última de dicha propuesta precisamente porque su posibilidad supondría ir más allá de lo que el método permite.