One-fourth of Plasmodium falciparum proteins have asparagine repeats that increase the propensity for aggregation, especially at elevated temperatures that occur routinely in malaria-infected patients. We report that a Plasmodium Asn repeat-containing protein (PFI1155w) formed aggregates in mammalian cells at febrile temperatures, as did a yeast Asn/Gln-rich protein (Sup35). Co-expression of the cytoplasmic P. falciparum heat shock protein 110 (PfHsp110c) prevented aggregation. Human or yeast orthologs were much less effective. All-Asn and all-Gln versions of Sup35 were protected from aggregation by PfHsp110c, suggesting that this chaperone is not limited to handling runs of Asn. PfHsp110c gene knockout parasites were not viable and conditional knockdown parasites died slowly in the absence of protein-stabilizing ligand. When exposed to brief heat shock, these knockdowns were unable to prevent aggregation of PFI1155w or Sup35 and died rapidly. We conclude that PfHsp110c protects the parasite from harmful effects of its asparagine repeat-rich proteome during febrile episodes.
Silicon bulk micromachining using the wet anisotropic etching process is widely employed for the development of commercial products such as an inkjet printer head, a pressure sensor, accelerometers, infrared sensors, etc using (1 0 0) silicon wafers. In wet anisotropic etching, the resultant shape and size of the microstructures are restricted by crystallographic properties of silicon. If structures such as seismic mass in an accelerometer are required to be created, convex corners will emerge in the etching process. Considerable deformation occurs at convex corners resulting in poor control on the shape and size of the microstructure. Various methods/techniques are developed to overcome the problem of undercutting at convex corners in a (1 0 0) silicon wafer. Here, we have reviewed the fabrication techniques for the realization of convex corners in silicon bulk micromachining technology. The review is restricted to the wet anisotropic etching process which is usually performed in potassium hydroxide solution, ethylenediamine pyrocatechol solution, tetramethylammonium hydroxide, etc. The corner compensation method is the most widely used technique for the fabrication of convex corners. Various types of corner compensating design have been proposed by different research groups. The corner compensation method gives nearly sharp corners. Recently developed techniques, which do not use any compensating design, give perfect convex corners. The limitations and advantages of all the techniques have been discussed.
In this paper, we have studied the undercutting at rounded concave and sharp convex corners in (1 0 0)-silicon wafers using a complementary metal-oxide semiconductor (CMOS) compatible tetramethyl ammonium hydroxide (TMAH) solution with and without surfactant. In order to minimize the undercutting at both corner types while keeping reasonable etch rates, smooth etched-surfaces and CMOS compatibility, the non-ionic surfactant NC-200 that contains 100% polyoxyethylene-alkyl-phenyl-ether is considered. The effect of concentration and etching temperature is studied using 10, 20 and 25 wt% TMAH solutions at 60, 70 and 80 °C. When NC-200 at 0.1% of the total volume of the etchant is used, the undercutting ratio at both rounded concave and sharp convex corners is beneficially reduced as the etchant concentration is increased while, simultaneously, the etch rate increases. This is the opposite trend to the etch characteristics of pure TMAH. In addition, the rough etched surface morphology at low concentration is also improved by using NC-200.
Cerebral malaria (CM) is a disease of the vascular endothelium caused by Plasmodium falciparum. It is characterized by parasite sequestration, inflammatory cytokine production, and vascular leakage. A distinguishing feature of P. falciparum infection is parasite production and secretion of histidine-rich protein II (HRPII). Plasma HRPII is a diagnostic and prognostic marker for falciparum malaria. We demonstrate that disruption of a human cerebral microvascular endothelial barrier by P. falciparum-infected erythrocytes depends on expression of HRPII. Purified recombinant or native HRPII can recapitulate these effects. HRPII action occurs via activation of the inflammasome, resulting in decreased integrity of tight junctions and increased endothelial permeability. We propose that HRPII is a virulence factor that may contribute to cerebral malaria by compromising endothelial barrier integrity within the central nervous system.
We combine spectroscopic ellipsometry (SE), Fourier transform infrared spectroscopy (FT-IR), kinetic Monte Carlo simulations (KMC) and convex corner undercutting analysis in order to characterize and explain the effect of the addition of small amounts of surfactant in alkaline aqueous solutions, such as Triton X-100 in tetra methyl ammonium hydroxide (TMAH). We propose that the surfactant is adsorbed at the silicon-etchant interface as a thin layer, acting as a filter that moderates the surface reactivity by reducing the amount of reactant molecules that reach the surface. According to the SE and FT-IR measurements, the thickness of the adsorbed layer is an orientation-and concentration-dependent quantity, mostly due to the orientation dependence of the surface density of H-terminations and the concentration dependence of the relative rates of the underlying oxidation and etching reactions, which have a direct impact on the number of OH terminations. For partial OH coverage of the surface, the hydration of the OH group effectively acts as an anchoring location for the hydration shell of a surfactant molecule, thus enabling the formation of hydration bridges that amplify the adsorption density of the surfactant. At high concentration, the model explains the large reduction in the etch rate of the exact and vicinal Si{1 1 0} surfaces, and the small changes in the etch rates for the exact and vicinal Si{1 0 0} surfaces. At low concentration, it explains how the etch rate for both families is significantly reduced. The orientation and concentration dependence of the surfactant adsorption explains the dramatic differences in the micron-scale wet-etched patterns obtained using TMAH and TMAH+Triton for microelectromechanical systems applications.
In this research, we have developed and demonstrated a fabrication method for the formation of various shapes of silicon freestanding microfluidic channels and microstructures in one-step photolithography. The fabrication process utilizes the silicon direct wafer bonding with silicon nitride as an intermediate layer, local oxidation of the silicon (LOCOS) process and wet anisotropic etching. Two different types of etchants (non-ionic surfactant (Triton-X-100) added and pure 25 wt% TMAH solutions) are used in series to perform silicon anisotropic etching. Surfactant-added tetramethyl ammonium hydroxide (TMAH) is employed to define the shapes of the structures, while pure TMAH is used to get high undercutting for their fast releasing. The non-ionic surfactant is preferred considering the complementary metal-oxide semiconductor (CMOS) post process issue of wet anisotropic etching. The undercutting at sharp and rounded concave corners, edges aligned along ⟨1 0 0⟩ directions, is measured and analyzed in both pure and surfactant-added TMAH solutions. Mask design issues that must be taken into consideration for the fabrication of desired shape and size structures are also presented.
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