Heat Shock Protein 90 Inhibitors as Broad Spectrum Anti-Infectives

Combating stress is one of the prime requirements for any organism. For parasitic microbes, stress levels are highest during the growth inside the host. Their survival depends on their ability to acclimatize and adapt to new environmental conditions. Robust cellular machinery for stress response is, therefore, both critical and essential especially for pathogenic microorganisms. Microbes have cleverly exploited stress proteins as virulence factors for pathogenesis in their hosts. Owing to its ability to sense and respond to the stress conditions, Heat shock protein 90 (Hsp90) is one of the key stress proteins utilized by parasitic microbes. There are growing evidences for the critical role played by Hsp90 in the growth of pathogenic organisms like Candida, Giardia, Plasmodium, Trypanosoma, and others. This review, therefore, explores potential of exploiting Hsp90 as a target for the treatment of infectious diseases. This molecular chaperone has already gained attention as an effective anti-cancer drug target. As a result, a lot of research has been done at laboratory, preclinical and clinical levels for several Hsp90 inhibitors as potential anti-cancer drugs. In addition, lot of data pertaining to toxicity studies, pharmacokinetics and pharmacodynamics studies, dosage regime, drug related toxicities, dose limiting toxicities as well as adverse drug reactions are available for Hsp90 inhibitors. Therefore, repurposing/repositioning strategies are also being explored for these compounds which have gone through advanced stage clinical trials. This review presents a comprehensive summary of current status of development of Hsp90 as a drug target and its inhibitors as candidate anti-infectives. A particular emphasis is laid on the possibility of repositioning strategies coupled with pharmaceutical solutions required for fulfilling needs for ever growing pharmaceutical infectious disease market.

Generating Efficient Data Movement Code for Heterogeneous Architectures with Distributed-Memory

Programming for parallel architectures that do not have a shared address space is extremely difficult due to the need for explicit communication between memories of different compute devices. A heterogeneous system with CPUs and multiple GPUs, or a distributed-memory cluster are examples of such systems. Past works that try to automate data movement for distributed-memory architectures can lead to excessive redundant communication. In this paper, we propose an automatic data movement scheme that minimizes the volume of communication between compute devices in heterogeneous and distributed-memory systems. We show that by partitioning data dependences in a particular non-trivial way, one can generate data movement code that results in the minimum volume for a vast majority of cases. The techniques are applicable to any sequence of affine loop nests and works on top of any choice of loop transformations, parallelization, and computation placement. The data movement code generated minimizes the volume of communication for a particular configuration of these. We use a combination of powerful static analyses relying on the polyhedral compiler framework and lightweight runtime routines they generate, to build a source-to-source transformation tool that automatically generates communication code. We demonstrate that the tool is scalable and leads to substantial gains in efficiency. On a heterogeneous system, the communication volume is reduced by a factor of 11X to 83X over state-of-the-art, translating into a mean execution time speedup of 1.53X. On a distributed-memory cluster, our scheme reduces the communication volume by a factor of 1.4X to 63.5X over state-of-the-art, resulting in a mean speedup of 1.55X. In addition, our scheme yields a mean speedup of 2.19X over hand-optimized UPC codes.

High specific surface area alpha-Fe2O3 nanostructures as high performance electrode material for supercapacitors

Porous alpha-Fe2O3 nanostructures have been synthesized by a simple sol-gel route. The alpha-Fe2O3 nanostructures are poorly crystalline and porous with BET surface area of 386 m(2) g(-1). The high discharge capacitance of alpha-Fe2O3 electrodes is 300 F g(-1) when the electrodes are cycled in 0.5 M Na2SO3 at a current density of 1 A g(-1). The capacitance retention after 1000 cycles is about 73% of the initial capacitance at a current density of 2 A g(-1). The high discharge capacitance of alpha-Fe2O3 in comparison with the literature reports are attributed to high surface area and porosity of the iron oxide prepared in the present study. As the iron oxides are inexpensive, the capacity of alpha-Fe2O3 is expected to be of potential use for supercapacitor application. (C) 2014 Elsevier B.V. All rights reserved.

A modified auxiliary excitation signal for achieving unidirectional ion ejection in quadrupole ion trap mass spectrometers operating in the resonance ejection mode

This paper proposes a technique to cause unidirectional ion ejection in a quadrupole ion trap mass spectrometer operated in the resonance ejection mode. In this technique a modified auxiliary dipolar excitation signal is applied to the endcap electrodes. This modified signal is a linear combination of two signals. The first signal is the nominal dipolar excitation signal which is applied across the endcap electrodes and the second signal is the second harmonic of the first signal, the amplitude of the second harmonic being larger than that of the fundamental. We have investigated the effect of the following parameters on achieving unidirectional ion ejection: primary signal amplitude, ratio of amplitude of second harmonic to that of primary signal amplitude, different operating points, different scan rates, different mass to charge ratios and different damping constants. In all these simulations unidirectional ejection of destabilized ions has been successfully achieved. (C) 2015 Elsevier B.V. All rights reserved.

Disorder, oscillatory dynamics and state switching: the role of c-Myc

In this paper, using the intrinsically disordered oncoprotein Myc as an example, we present a mathematical model to help explain how protein oscillatory dynamics can influence state switching. Earlier studies have demonstrated that, while Myc overexpression can facilitate state switching and transform a normal cell into a cancer phenotype, its downregulation can reverse state-switching. A fundamental aspect of the model is that a Myc threshold determines cell fate in cells expressing p53. We demonstrate that a non-cooperative positive feedback loop coupled with Myc sequestration at multiple binding sites can generate bistable Myc levels. Normal quiescent cells with Myc levels below the threshold can respond to mitogenic signals to activate the cyclin/cdk oscillator for limited cell divisions but the p53/Mdm2 oscillator remains nonfunctional. In response to stress, the p53/Mdm2 oscillator is activated in pulses that are critical to DNA repair. But if stress causes Myc levels to cross the threshold, Myc inactivates the p53/Mdm2 oscillator, abrogates p53 pulses, and pushes the cyclin/cdk oscillator into overdrive sustaining unchecked proliferation seen in cancer. However, if Myc is downregulated, the cyclin/cdk oscillator is inactivated and the p53/Mdm2 oscillator is reset and the cancer phenotype is reversed. (C) 2015 Elsevier Ltd. All rights reserved.

Growth and optical properties of peculiar ZnO tetrapods

Regular ZnO tetrapods with different morphologies have been obtained on Si(100) substrate via the chemical vapour deposition approach. Varying the growth temperature and gas rate, we have obtained different structured ZnO materials: tetrapods with a large hexagonal crown, a flat top and a small hexagonal crown. The results suggest that these tetrapods are all single crystals with a wurtzite structure that grow along the (0001) direction. However, photoluminescence spectra shows that their optical properties are quite different: for those with large hexagonal crown, the green emission overwhelms that of the near band-edge (NBE) ultraviolet (UV) peak, while others have only a strong NBE UV peak at ~386 nm.

Numerical Study Of Pile-Up In Bulk Metallic Glass During Spherical Indentation

Pile-up around indenter is usually observed during instrumented indentation tests on bulk metallic glass. Neglecting the pile-up effect may lead to errors in evaluating hardness, Young's modulus, stress-strain response, etc. Finite element analysis was employed to implement numerical simulation of spherical indentation tests on bulk metallic glass. A new model was proposed to describe the pile-up effect. By using this new model, the contact radius and hardness of Zr41.2Ti13.8Cu12.5Ni10Be22.5 bulk metallic glass were obtained under several different indenter loads with pile-up, and the results agree well with the data generated by numerical simulation.

Determinación de la precocidad de diez variedades de algodón (Gossypium hirsutum) en dos diferentes fechas de siembra

Se llevó a cabo el presente estudio en el centro experimental del algodón (CEA), Posoltega, con el objetivo de determinar las variedades más precoces y la fecha más óptima de siembra, manteniendo el rendimiento en el cultivo del algodón (gossypium), y observar cual es el efecto de la fecha de siembra sobre el rendimiento. Se determinó que de diez variedades, las precoces son paulikeni 73 y u-386 obteniendo su fecha media de maduración en las dos fechas con rangos de 23-25 días, se comportan como intermedias u-276, con al son y u-280 con un rango de maduración de 27-29 días en las dos fechas de siembra, el resto de variedades se consideraron como tardías, incluyendo a la variedad h-373 con rangos de maduración de 31-33 días. En la segunda fecha de siembra, obtuvieron los mejores rendimientos en producción las variedades u-280 y u-276, con respecto a la primera fecha lo obtuvieron h-373 (testigo), seguida de las variedades u-280 y u-276.

Comportamiento de nopal (Opuntia ficusindica L.) en asocio con seis cultivos prehispánicos, Ecolotes Ave Maria, Las Esquinas, Carazo 2013

El nopal (Opuntia ficus-indica L.), familia de las Cactáceas, es originario de América. Es una planta que se adapta muy bien en diferentes condiciones climáticas, se desarrolla exitosamente en zonas donde llueve muy poco; también tiene una gran importancia por sus diferentes usos que se le conocen. Para conocer de su comportamiento como cultivo asociado, se estableció un ensayo en la finca Ecolote Ave María, ubicada en Las Esquinas, Carazo, en el km 37 ½ carretera Managua – San Marcos, Carazo, en la época de primera 2013. Se utilizó un diseño de bloques completos al azar (BCA), con cuatro repeticiones y seis tratamientos: pipián cuarenteño (Cucúrbita angyrosperma J. C. Huber), amaranto (Amaranthus caudatus L.), chan (Hyptis suaveolens L.), frijol blanco (Phaseolus acutifolius, Gray), yuca (Manihot esculenta Crantz) y batata (Ipomoea batata L.), con el objetivo de conocer con cuál de estos cultivos en asocio se obtienen mejores rendimientos de cladodios de nopal. El análisis de los datos obtenidos del estudio reflejan que se obtuvo una supervivencia del 100 % en todo los tratamientos, el mejor número de brotes por planta fue de 2, el mejor ancho de cladodios (3.63 cm) y el mejor rendimiento fue de (2 386.5 kg/ha), en asocio con amaranto; el mejor largo de cladodios (7.65 cm) fue con el cultivo de Yuca, respecto al comportamiento de los cultivos prehispánicos, batata con una altura de 172.8 cm ha sido el más exitoso, seguido por el chan con 131.42 cm de largo de guía y la yuca con 111.3 cm de altura, los cultivos de amaranto, frijol blanco y pipián cuarenteño no lograron adaptarse a las condiciones climáticas del ensayo.

强脉冲CO_2激光对红外材料的破坏现象

实验表明强激光对红外材料的破坏分为两种类型:烧蚀和冲击破坏。在空气中,光功率密度低于大气的光学击穿阈值时,以烧蚀为主。超过击穿阈值时,冲击破坏是主要的。在我们的实验条件下,用强激光辐照红外脆性材料的靶,靶极易产生微裂纹或粉碎性破坏,其破坏效果与激光的脉冲能量、功率密度、脉冲宽度,以及着靶面积有关。为了直观,文中给出了不少辐照损伤的照片。

Relatório final de atividades 2008

Relatório de atividades de 2008 da Comissão de Minas e Energia da Câmara dos Deputados.