Heat Shock Protein 90 regulates encystation in Entamoeba

Enteric protozoan Entamoeba histolytica is a major cause of debilitating diarrheal infection worldwide with high morbidity and mortality. Even though the clinical burden of this parasite is very high, this infection is categorized as a neglected disease. Parasite is transmitted through feco-oral route and exhibit two distinct stages namely - trophozoites and cysts. Mechanism and regulation of encystation is not clearly understood. Previous studies have established the role of Heat shock protein 90 (Hsp90) in regulating stage transition in various protozoan parasites like Giardia, Plasmodium, Leishmania, and Toxoplasma. Our study for the first time reports that Hsp90 plays a crucial role in life cycle of Entamoeba as well. We identify Hsp90 to be a negative regulator of encystation in Entamoeba. We also show that Hsp90 inhibition interferes with the process of phagocytosis in Entamoeba. Overall, we show that Hsp90 plays an important role in virulence and transmission of Entamoeba.

First Structural View of a Peptide Interacting with the Nucleotide Binding Domain of Heat Shock Protein 90

The involvement of Hsp90 in progression of diseases like cancer, neurological disorders and several pathogen related conditions is well established. Hsp90, therefore, has emerged as an attractive drug target for many of these diseases. Several small molecule inhibitors of Hsp90, such as geldanamycin derivatives, that display antitumor activity, have been developed and are under clinical trials. However, none of these tested inhibitors or drugs are peptide-based compounds. Here we report the first crystal structure of a peptide bound at the ATP binding site of the N-terminal domain of Hsp90. The peptide makes several specific interactions with the binding site residues, which are comparable to those made by the nucleotide and geldanamycin. A modified peptide was designed based on these interactions. Inhibition of ATPase activity of Hsp90 was observed in the presence of the modified peptide. This study provides an alternative approach and a lead peptide molecule for the rational design of effective inhibitors of Hsp90 function.

High-throughput miniaturized microfluidic microscopy with radially parallelized channel geometry

In this article, we present a novel approach to throughput enhancement in miniaturized microfluidic microscopy systems. Using the presented approach, we demonstrate an inexpensive yet high-throughput analytical instrument. Using the high-throughput analytical instrument, we have been able to achieve about 125,880 cells per minute (more than one hundred and twenty five thousand cells per minute), even while employing cost-effective low frame rate cameras (120 fps). The throughput achieved here is a notable progression in the field of diagnostics as it enables rapid quantitative testing and analysis. We demonstrate the applicability of the instrument to point-of-care diagnostics, by performing blood cell counting. We report a comparative analysis between the counts (in cells per mu l) obtained from our instrument, with that of a commercially available hematology analyzer.

Advancing Edge Speeds of Epithelial Monolayers Depend on Their Initial Confining Geometry

Collective cell migrations are essential in several physiological processes and are driven by both chemical and mechanical cues. The roles of substrate stiffness and confinement on collective migrations have been investigated in recent years, however few studies have addressed how geometric shapes influence collective cell migrations. Here, we address the hypothesis that the relative position of a cell within the confinement influences its motility. Monolayers of two types of epithelial cells-MCF7, a breast epithelial cancer cell line, and MDCK, a control epithelial cell line-were confined within circular, square, and cross-shaped stencils and their migration velocities were quantified upon release of the constraint using particle image velocimetry. The choice of stencil geometry allowed us to investigate individual cell motility within convex, straight and concave boundaries. Cells located in sharp, convex boundaries migrated at slower rates than those in concave or straight edges in both cell types. The overall cluster migration occurred in three phases: an initial linear increase with time, followed by a plateau region and a subsequent decrease in cluster speeds. An acto-myosin contractile ring, present in the MDCK but absent in MCF7 monolayer, was a prominent feature in the emergence of leader cells from the MDCK clusters which occurred every similar to 125 mu m from the vertex of the cross. Further, coordinated cell movements displayed vorticity patterns in MDCK which were absent in MCF7 clusters. We also used cytoskeletal inhibitors to show the importance of acto-myosin bounding cables in collective migrations through translation of local movements to create long range coordinated movements and the creation of leader cells within ensembles. To our knowledge, this is the first demonstration of how bounding shapes influence long-term migratory behaviours of epithelial cell monolayers. These results are important for tissue engineering and may also enhance our understanding of cell movements during developmental patterning and cancer metastasis.

Control of vortex shedding at moderate Reynolds numbers

The suppression method of vortex shedding from a circular cylinder has been studied experimentally in the Reynolds number range from 300 to 1600. The test is performed in a water channel. The model cylinder is 1 cm in diameter and 38 cm in length. A row of small rods of 0.18 cm in diameter and 1.5 cm in length are perpendicularly connected to the surface of the model cylinder and distributed along the meridian, The distance between the neighboring rods and the angle of attack of the rods can be changed so that the suppression effect on vortex shedding can be adjusted. The results show that vortex shedding can be suppressed effectively if the distance between the neighboring rods is smaller than 3 times and the cylinder diameter and the angle of attack is in the range of 30degreesless than or equal tobeta<90&DEG;.

Boundary knot method for 2D and 3D Helmholtz and convection-diffusion problems under complicated geometry

The boundary knot method (BKM) of very recent origin is an inherently meshless, integration-free, boundary-type, radial basis function collocation technique for the numerical discretization of general partial differential equation systems. Unlike the method of fundamental solutions, the use of non-singular general solution in the BKM avoids the unnecessary requirement of constructing a controversial artificial boundary outside the physical domain. The purpose of this paper is to extend the BKM to solve 2D Helmholtz and convection-diffusion problems under rather complicated irregular geometry. The method is also first applied to 3D problems. Numerical experiments validate that the BKM can produce highly accurate solutions using a relatively small number of knots. For inhomogeneous cases, some inner knots are found necessary to guarantee accuracy and stability. The stability and convergence of the BKM are numerically illustrated and the completeness issue is also discussed.

A Numerical Study of Indentation Using Indenters of Different Geometry

Finite element simulation of the Berkovich, Vickers, Knoop, and cone indenters was carried out for the indentation of elastic-plastic material. To fix the semiapex angle of the cone, several rules of equivalence were used and examined. Despite the asymmetry and differences in the stress and strain fields, it was established that for the Berkovich and Vickers indenters, the load-displacement relation can closely be simulated by a single cone indenter having a semiapex angle equal to 70.3degrees in accordance with the rule of the volume equivalence. On the other hand, none of the rules is applicable to the Knoop indenter owing to its great asymmetry. The finite element method developed here is also applicable to layered or gradient materials with slight modifications.

Comportamiento agroindustrial de veinticinco variedades de caña de azúcar (Saccharum sp. hibrido) en comparación con la variedad L 68-90 en caña planta

En el ciclo 90-91 se llevó a cabo el presente trabajo en el Ingenio Javier Guerra Báez con el objetivo de determinar el comportamiento agroindustrial de 25 cultivares de caña de azúcar en comparación con la variedad L 68-90. El experimento se sembró el 21 de febrero de 1990 en un suelo franco de la serie Nandaime, la cosecha se realizó a los 12 meses de edad el 21 de febrero de 1991. El diseño utilizado fue látice triple (5 x 5) y las variables estudiadas fueron: Germinación. Población, altura de tallos, diámetro de tallos, peso promedio de los tallos, rendimiento agrícola. rendimiento industrial y rendimiento agroindustrial Los datos fueron sometidos a un análisis de varianza y prueba de rangos múltiples de Duncan al 5% de significancia. Los mejores comportamientos para cada variable en estudio los obtuvieron los siguientes cultivares: Germinación: RB 73-2727, Cp 70-321, RB 77-3720, RB 73-2223, RB 73-9735 y RB 76-5288; Población: Sp 70-1423, Cp 70-321 RB 73-1012. Cp 71-6180. RB 73-1714. RB 76-5288. RB 73-2727, Cp 72-1210 y C 87-51; Longitud de tallo: RB 73-429. Cp 70-1527. RB 73-9735. RB 73-1012. Q 96 MEX 69-420 y MEX 68-P23; DiáMetro de los tallos: RB 73-2223, Cp 74-383. MEX 53-473, RB 76-5288. RB 73-9735. RB 73-5220. RB 73-9953. Cp70-1527, MEX 56-476 y MEX 68-p23; Peso promedio de los tallos: MEX 68- p23. RB 73-9735. RB 73-2223. CP 70-1527, RB 73-429. MEX 53-473. Q 96. MEX 69-420 y MEX 56-476;Rendimiento agrícola: Cp 71 -6180. MEX 68- P23. X 69-420. RB 73-1012. Sp 70-1423. RB 76-5288 y RB 73-9735; Rendimiento industrial Q 96, Cp 70-321, Cp 72-1210, MEX 68 P23 y Cp71-6180; Rendimiento agroindustrial Cp 71-6180.MEX 68-P23. Cp 70-321. RB 76-5288, Cp 72-1210. MEX69-420, RB 73-1012 Y Q96. Las variedades que presentaron enfermedades fueron: C 87-51, Cp 71-6180, Cp 70-1527, RB 73-2223. RB 73-2727. L '8-90, Cp 74-383, Sp 70-1284, RB 73-1714 y RB 73-429.

Evaluación agro-industrial de veinticinco variedades de caña de azúcar (Saccharum sp. hibrido), en comparación con la variedad L 68-90, en planta y retoño 1

El presente estudio corresponde a la evaluación de dos años de producción (90-91;91-92), de 25 variedades de caña de azúcar en comparación con la variedad L 68-90, establecido en el ingenio " Julio Buitrago Urroz ", para determinar su comportamiento agro­ industrial y seleccionar las mejores variedades para una segunda fase de selección. El ensayo se sembró 24 de marzo de 1990, la cosecha de planta se realizó el 21 de marzo de 1991, y el retoño 1 se cosecho el 21 de febrero de 1992. El diseño utilizado fue el de látice triple (5 x 5) parcialmente equilibrado y los parámetros estudiados fueron: Germinación, Población, Altura, Diámetro de los tallos, Peso promedio de los tallos, Rendimiento agrícola, Rendimiento industrial, y Rendimiento agro-industrial. Cada una de las variables fueron evaluadas mediante un análisis de varianza y a la prueba de rango múltiple de Duncan a un 5% de significación. Los resultados obtenidos fueron los siguientes: Germinación; Se obtuvieron diferencias altamente significativas, las mejores variedades son: Cp 70-321, Cp 70-1527, RB 73-9735, Mex 68-P23, RB 73-1012, Mex 53-473. Población; Se presentaron diferencias altamente significativas, resultando los mejores genotipos: Rb 73-2727, Cp 70-321, Sp 70-1423. Altura; Se determinó una alta diferencia significativa entre los cultivares destacándose: Sp 72-4790, RB 76-5288, RB 73-429. Diámetro de tallo; Se obtuvo una alta diferencia significativa siendo las mejores: RB 73-2223, Mex 56-476, Mex 69-420, RB 73-9735, Mex 53- 473, RB 73-9953, Cp 74-383. Peso promedio de los tallos; Se observó una alta diferencia significativa resultando los mejores genotipos: Mex 56-476, RB 73-2223, Mex 69-420, RB 73-429, Q 96, Mex 68-P23, RB 76-5288, RB 73-9735. Rendimiento agrícola; Estadísticamente se determinó una alta diferencia significativa, las variedades que superan al testigo son: Sp 72-4790, Sp 70- 1284, RB 73-9735. Rendimiento industrial; Se obtuvo diferencia significativa, siendo el mejor genotipo: La Q-96. Rendimiento agro-industrial; No se observaron diferencias significativas entre los cultivares en estudio, de acuerdo a la separación de medias las variedades más destacadas fueron: Sp 72-4790, RB 73- 5220. Respecto a las observaciones fitosanitarias la única variedad que no presento síntomas de las enfermedades señaladas en este estudio es: Sp 72-4790, las variedades más afectadas por el carbón son: RB 74-5672, Cp 72-1210, Cp 70-1527, RB 76-5288, RB 77-320, RB 73-1012, RB 73-9735, L 68-90.

Efecto de diferentes dosis de N.P.K. sobre el rendimiento agroindustrial de la variedad L-68-90 (Saccharum sp hibrido); en caña planta

El presente estudio se realizó de junio de 1992 a marzo de 1993 en El Ingenio Victoria de Julio. Se evaluó el efecto de 13 dosis de N-P-K (0-60-60, 40-60-60, 80-60-60, 120-60-60, 40-0-60, 40-30-60, 80-0-60, 80-30-60, 40-9Ó-60, 120-0-60, 120-30-60, 120-60-0 y 120-60-30), sobre el cultivo de la caña de azúcar (Saccharum sp. híbrido), las cuales se compararon con e1 testigo (0-0-0). Se plantó la variedad L 68-90. El diseño experimental utilizado fue de Bloques Completos al Azar modificado, las variables analizadas fueron: brotación, diámetro, altura, población, rendimiento agrícola, rendimiento industrial y rendimiento agro industrial. Los datos que se obtuvieron se sometieron al análisis de varianza y separación de medías según Tukey a un 5 % de margen de error. En ninguna de las variables evaluadas se observó diferencia estadística significativa. Con respecto a la Germinación el mayor porcentaje fue de 75.33 porciento y correspondió a los tratamientos 120-60-0 y 40-30-60. El mayor diámetro fue de 2.73 cm habiéndose obtenido con el tratamiento 120-60-30. La mayor altura se obtuvo con el tratamiento 40-30-60 y fue de 2.94 cm. La población mayor fue de 231 750 tallos/ha correspondiendo al tratamiento 40-30-60. El mayor rendimiento agrícola se logró con el tratamiento 80-0-60 y fue de 86.23 t/ha. El mayor rendimiento industrial fue de 93.80 kg/t correspondiendo éste al tratamiento 120-0-60. El mayor rendimiento agro-industrial se obtuvo con el tratamiento 80-0-60 siendo éste valor de 7.675 t/ha.

Using internal fibre geometry to improve the performance of pin-loaded holes in composite materials

The anisotropic nature of fibre reinforced composites leads to large stress concentrations around pin-loaded holes through standard weave cloths. Proper understanding of how this anisotropic nature affects the load distribution around holes can be utilised to reduce these con-centrations if sufficient thought is given to the internal fibre geometry near to the hole. Such local reinforcements need not be highly complex and can be readily produced without excessive effort, producing significant improvements in performance. © 1996 Kluwer Academic Publishers.

A geometry model for tortuosity of flow path in porous media

A simple geometry model for tortuosity of flow path in porous media is proposed based on the assumption that some particles in a porous medium are unrestrictedly overlapped and the others are not. The proposed model is expressed as a function of porosity and there is no empirical constant in this model. The model predictions are compared with those from available correlations obtained numerically and experimentally, both of which are in agreement with each other. The present model can also give the tortuosity with a good approximation near the percolation threshold. The validity of the present tortuosity model is thus verified.