High-resolution Micrographs Research Articles

Atomistic simulations of structure and motion of twin interfaces reveal the origin of twinning in NiTi shape memory alloys

Shape memory alloys (SMAs) are functional materials featuring unique shape recovery properties that make them suitable for key industrial applications. The essential process controlling this fascinating performance is microstructural twinning. Some twin systems are much more frequently observed than others, yet a fundamental mechanistic understanding of this evidence is missing, which hampers SMA design. Here, we consider the prototypical NiTi SMA to show that the emergence of twinning can be strongly affected by twin interface mobility. In this work, we adopt an integrated approach combining crystallographic theory, state-of-the-art atomistic modelling, topological model, and validation with high-resolution transmission-electron micrographs. Atomistic simulations confirm that the occurrence of twins is dictated by the driving force for twin boundary motion rather than interfacial energy. Moreover, our findings settle long-standing questions by elucidating the propagation mechanisms of twin interfaces, which the established martensite crystallography and kinetic theories could not address conclusively. The newly discovered understanding of the role of interface mobility in twin formation can be used to predict variant selection and guide the design of SMAs with improved functional performance.

A comparative analysis of crustacean exoskeletons: structural, microstructural, morphological, and UV absorption studies

This study aims to investigate the structural, thermal, and spectral characteristics, along with the ultra-violet (UV) absorption of various marine benthos exoskeletons, such as various species of crabs (Portunus sanguinolentus, Portunus pelagicus, Charybdis feriata) and mantis shrimp (Oratosquilla oratoria). Their unique properties and ability to survive in harsh oceanic environments make them interesting research subjects. This research utilized powder x-ray diffraction (XRD) analysis to determine the crystal structure of the benthic varieties. The sample surface was analyzed using high-resolution micrographs obtained from field-emission scanning electron microscopy (FESEM), which identified the presence of chitin and calcite in the marine benthos. This was further confirmed by differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). The optical characteristics were investigated using UV-visible spectroscopy. The proximate analysis revealed high protein content in the mantis shrimp exoskeleton compared to other crab species, highlighting its excellent UV absorption characteristics. Overall, this research has the potential to broaden our understanding of marine organisms, which can have potential applications in biotechnology and materials science to develop nature-inspired innovative materials sustainably.

Elucidating the structural and spectroscopic attributes of titania-iron oxide (TiO2-([formula omitted]-Fe2O3)) nanocomposites: Showcasing a pulsed laser ablation in liquid approach

Various nanomaterials with tailored photo-electrochemical and physicochemical attributes became viable for the photo-catalysis and sensors applications. Thus, some new types of TiO2-(α-Fe2O3) nanocomposites were made via the pulse laser ablation in liquid method. These nanocomposites at each value of laser fluence were obtained by mixing the colloidal TiO2 nanoparticles and colloidal (α-Fe2O3) nanoparticles at equal ratio. The stability, structures, morphologies, and optical characteristics of the produced nanocomposites (suspended in deionized water) were customized by changing the laser fluence from 3.5–17.7 J cm−2. The high-resolution transmission electron microscopy micrographs showed the existence of homogeneous dispersion of spherical nanocrystallites (mean diameter 12.4 ± 6.0 nm) in the colloidal suspension. Both X-ray diffraction and Fourier transform infrared profiles of the specimen verified their purity and good nanocrystallinity. Two optical absorption peaks were probed in the range of 240 to 380 nm convoyed by a blue-shift. The spectral edge related to UV–Vis absorption was used to estimate the optical band gap of these nanocomposites. TiO2-(α-Fe2O3) nanocomposites made at optimum laser fluence (10.6 J cm−2) exhibited strong fluorescence with the life time decay of 3.64 μs, indicating the electronic density of states modification due to quantum size effects. The presence of Fe, Ti, and O in the X-ray photoelectron spectroscopy spectra reaffirmed the samples purity. The measured strong negative zeta potential (-33.1 mV) of the optimum TiO2-(α-Fe2O3) nanocomposites confirmed their excellent stability in the colloidal suspension. In short, these nanocomposites may be advantageous as good photo-catalysts for waste water treatment and photo-electrochemical uses.

Three-dimensional distribution of individual atoms in the channels of beryl

AbstractSingle atom detection in nanoporous materials is a significant challenge, particularly due to their sensitivity to electron irradiation. Here, natural beryl (Be3Al2Si6O18) is used as a model system to quantitatively analyse the occupancy of its atomic channels. High-angle annular dark-field imaging in a scanning transmission electron microscope is employed, revealing the presence of Cs atoms within the channels. Through statistical analysis of atomic column intensities and comparison with a series of multislice simulations, we successfully pinpoint the three-dimensional positions of individual Cs atoms. Our findings indicate a non-uniform distribution of Cs atoms in the crystal. Importantly, by extracting both the crystal thickness and atomic positions from a single high-resolution micrograph, we effectively minimize the adverse effects of beam damage. This approach offers a promising pathway for accurately determining the three-dimensional distribution of dopant atoms in various porous materials, opening new possibilities for the study and application of these technologically important materials.

Modulating hierarchical self-assembly in thermoresponsive intrinsically disordered proteins through high-temperature incubation time

The cornerstone of structural biology is the unique relationship between protein sequence and the 3D structure at equilibrium. Although intrinsically disordered proteins (IDPs) do not fold into a specific 3D structure, breaking this paradigm, some IDPs exhibit large-scale organization, such as liquid–liquid phase separation. In such cases, the structural plasticity has the potential to form numerous self-assembled structures out of thermal equilibrium. Here, we report that high-temperature incubation time is a defining parameter for micro and nanoscale self-assembly of resilin-like IDPs. Interestingly, high-resolution scanning electron microscopy micrographs reveal that an extended incubation time leads to the formation of micron-size rods and ellipsoids that depend on the amino acid sequence. More surprisingly, a prolonged incubation time also induces amino acid composition-dependent formation of short-range nanoscale order, such as periodic lamellar nanostructures. We, therefore, suggest that regulating the period of high-temperature incubation, in the one-phase regime, can serve as a unique method of controlling the hierarchical self-assembly mechanism of structurally disordered proteins.

Enfermedades que afectan el cultivo de café: Elucidando el ciclo de vida de Roya, Mal de Hilachas y Cercosporiosis

Coffee (Coffea spp.) is the second most significant commodity worldwide, with C. arabica being its most representative species. The coffee crop is affected by different fungal diseases that reduce the photosynthetically active area of its leaves and the production of grains. In order of agronomic importance, the rust caused by the biotrophic pathogen Hemileia vastatrix is a disease difficult to manage due to its type of reproduction. Another no less important, Thread Blight, caused by the basidiomycetes Ceratobasidium noxium (Syn. Corticium koleroga) and C. chavesanum, affects all aerial tissues of plants. The third disease, Cercospora leaf spot caused by Cercospora coffeicola, affects both leaves and grains, making it difficult to manage. Although there is enough scientific information on Rust, very little is known about the etiology, symptomatology, life cycle, and management of Thread Blight and Cercospora leaf spot. High-resolution photographs and micrographs were used and related with available scientific information. In addition, current scientific information on each disease was compiled, and with that, the life cycles were developed. Likewise, this manuscript describes the management of the three diseases based mainly on the use of genetic, cultural, physical, biological, and chemical measures and their integration as a sustainable alternative in the coffee agroecosystem. Current and future challenges in coffee include the evaluation of cultivars, genetic diversity of Ceratobasidium spp. and C. coffeicola, plant-pathogen interactions, and agroecological management practices.

A large expert-curated cryo-EM image dataset for machine learning protein particle picking

Cryo-electron microscopy (cryo-EM) is a powerful technique for determining the structures of biological macromolecular complexes. Picking single-protein particles from cryo-EM micrographs is a crucial step in reconstructing protein structures. However, the widely used template-based particle picking process is labor-intensive and time-consuming. Though machine learning and artificial intelligence (AI) based particle picking can potentially automate the process, its development is hindered by lack of large, high-quality labelled training data. To address this bottleneck, we present CryoPPP, a large, diverse, expert-curated cryo-EM image dataset for protein particle picking and analysis. It consists of labelled cryo-EM micrographs (images) of 34 representative protein datasets selected from the Electron Microscopy Public Image Archive (EMPIAR). The dataset is 2.6 terabytes and includes 9,893 high-resolution micrographs with labelled protein particle coordinates. The labelling process was rigorously validated through 2D particle class validation and 3D density map validation with the gold standard. The dataset is expected to greatly facilitate the development of both AI and classical methods for automated cryo-EM protein particle picking.

Correlative light-electron microscopy: integrating dynamics to structure

A challenge of classical electron microscopy (EM) modalities is the static and limited view they present of dynamic biological processes. Correlative light and EM (CLEM) pairs the precise imaging of the cellular location in light microscopy (LM) and EM, taking advantage of both methods. Recent advances in protein labeling, fluorescent markers, super-resolution microscopy, and EM technologies have allowed widespread application in modern biological research. Because of the wide versatility of CLEM, it is difficult to describe a single workflow. In general, samples are prepared and imaged by LM before EM preparation and imaging, with software utilized for the correlation of the two images. Fluorescent tags can help to select and localize structures for EM or add dynamics through live-cell imaging. Future developments in multimodal probes showing electron density and fluorescence activity will allow greater integration of the modalities and high-throughput workflows. Can be paired with focused ion beam-scanning EM (FIB-SEM), cryo-EM, transmission EM (TEM), and serial block-face SEM (SBF-SEM), as well as structured illumination microscopy (SIM), stimulated emission depletion (STED), and total internal reflection fluorescence (TIRF). Amenable to live-cell imaging, in part due to advances that can quickly freeze a sample for cryo-EM. Systems to pair with microscopic X-ray computed tomography to provide non-destructive forms of 3D imaging alongside high-resolution micrographs obtained by TEM and fluorescence. Sensitive enough for applications such as virus–host cell membrane interactions. Alongside other techniques, can localize the distribution of specific proteins or structures within a sample and correlate this information with the ultrastructural details provided by EM. Finding the appropriate FM and EM microscopes may be difficult and expensive. Preparing samples for both modalities requires careful planning and optimization so they are properly preserved, labeled, and processed for the chosen application. The growth of cells on the grid during the LM phase can make correlational positioning difficult. Aligning LM and EM micrographs can be challenging and time-consuming due to differences in resolution and sample shrinkage. Lower throughput and smaller region-of-interest size than traditional FM techniques due to being reliant on EM acquisition and additional sample preparation times. We thank Kit Neikirk for his thoughtful suggestions and edits to the manuscript. Funding by the UNCF/Bristol-Myers Squibb E.E. Just Faculty Fund, BWF Career Awards at the Scientific Interface Award, BWF Ad-hoc Award, National Institutes of Health (NIH) Small Research Pilot Subaward to 5R25HL106365-12 from the NIH PRIDE Program, DK020593, Vanderbilt Diabetes and Research Training Center for DRTC Alzheimer’s Disease Pilot & Feasibility Program. CZI Science Diversity Leadership grant number 2022- 253529 from the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (to A.H.). The images were arranged using BioRender and all representative images are original. The authors have no interests to declare.

Novel high-entropy microwave dielectric ceramics Sr(La0.2Nd0.2Sm0.2Eu0.2Gd0.2)AlO4 with excellent temperature stability and mechanical properties

Novel high-entropy Sr(La0.2Nd0.2Sm0.2Eu0.2Gd0.2)AlO4 ceramics with a layered perovskite structure have been prepared via the standard solid-state reaction method. The design of high-entropy improves the bond valence and subsequently optimizes the large negative temperature coefficient of resonant frequency (τf = −32 ppm/°C) of the simple SrLaAlO4 ceramics. Excellent temperature stability (τf = −6 ppm/°C) together with a relative permittivity (εr) of 18.6 and a quality factor (Qf = 14,509 GHz) are obtained in Sr(La0.2Nd0.2Sm0.2Eu0.2Gd0.2)AlO4 ceramics sintered at 1475 °C. It indicates that the present ceramics have great application prospects in passive microwave components such as resonators and filters. Meanwhile, significant improvements in compressive strength and strain are achieved, which are 1040 MPa and 15.7% for Sr(La0.2Nd0.2Sm0.2Eu0.2Gd0.2)AlO4 compared to 583 MPa and 12% in SrLaAlO4. The enhanced mechanical properties originate from the dislocation strengthening mechanism as the intertwining of interlayer lattices is revealed from the high-resolution transmission electronic micrographs.

Reverse transition of ball milling induced m-Y2O3 nano-crystallites during in-situ annealing

Structural transition during in-situ annealing of monoclinic-Yttria (m-Y2O3) is studied using X-Ray Diffraction (XRD) and Transmission Electron Microscopy (TEM). The m-Y2O3 has been prepared by high energy ball milling of cubic-Y2O3 (c-Y2O3). Monoclinic to cubic (m → c) phase transition with detailed crystallite size analysis from the Rietveld fit on XRD profiles and strain analysis from Geometric Phase Analysis (GPA) on High-Resolution phase contrast-TEM micrographs has been discussed. During annealing, the m- and c-phases of Y2O3 coexist up to ∼850 °C. The data has been compared with those reported earlier for the milling induced c → m transition. At 1000 °C, the phase is completely c-Y2O3. HRTEM time-lapse images have been employed to examine the growth mechanism involved as they develop into cubic crystallites. Grain rotation and defect-assisted grain alignment govern the sluggish growth of crystallites.

Toward Efficient Bactericidal and Dye Degradation Performance of Strontium- and Starch-Doped Fe2O3 Nanostructures: In Silico Molecular Docking Studies.

In this study, various concentrations of strontium (Sr) into a fixed amount of starch (St) and Fe2O3 nanostructures (NSs) were synthesized with the co-precipitation approach to evaluate the antibacterial and photocatalytic properties of the concerned NSs. The study aimed to synthesize nanorods of Fe2O3 with co-precipitation to enhance the bactericidal behavior with dopant-dependent Fe2O3. Advanced techniques were utilized to investigate the structural characteristics, morphological properties, optical absorption and emission, and elemental composition properties of synthesized samples. Measurements via X-ray diffraction confirmed the rhombohedral structure for Fe2O3. Fourier-transform infrared analysis explored the vibrational and rotational modes of the O-H functional group and the C=C and Fe-O functional groups. The energy band gap of the synthesized samples was observed in the range of 2.78-3.15 eV, which indicates that the blue shift in the absorption spectra of Fe2O3 and Sr/St-Fe2O3 was identified with UV-vis spectroscopy. The emission spectra were obtained through photoluminescence spectroscopy, and the elements in the materials were determined using energy-dispersive X-ray spectroscopy analysis. High-resolution transmission electron microscopy micrographs showed NSs that exhibit nanorods (NRs), and upon doping, agglomeration of NRs and nanoparticles was observed. Efficient degradations of methylene blue increased the photocatalytic activity in the implantation of Sr/St on Fe2O3 NRs. The antibacterial potential for Escherichia coli and Staphylococcus aureus was measured against ciprofloxacin. E. coli bacteria exhibit inhibition zones of 3.55 and 4.60 mm at low and high doses, respectively. S. aureus shows the measurement of inhibition zones for low and high doses of prepared samples at 0.47 and 2.40 mm, respectively. The prepared nanocatalyst showed remarkable antibacterial action against E. coli bacteria rather than S. aureus at high and low doses compared to ciprofloxacin. The best-docked conformation of the dihydrofolate reductase enzyme against E. coli for Sr/St-Fe2O3 showed H-bonding interactions with Ile-94, Tyr-100, Tyr-111, Trp-30, ASP-27, Thr-113, and Ala-6.

Molecular Bridges Link Monolayers of Hexagonal Boron Nitride during Dielectric Breakdown

We use conduction atomic force microscopy (CAFM) to examine the soft breakdown of monocrystalline hexagonal boron nitride (h-BN) and relate the observations to the defect generation and dielectric degradation in the h-BN by charge transport simulations and density functional theory (DFT) calculations. A modified CAFM approach is adopted, whereby 500 × 500 nm2 to 3 × 3 μm2 sized metal/h-BN/metal capacitors are fabricated on 7 to 19 nm-thick h-BN crystal flakes and the CAFM tip is placed on top of the capacitor as an electrical probe. Current–voltage (I-V) sweeps and time-dependent dielectric breakdown measurements indicate that defects are generated gradually over time, leading to a progressive increase in current prior to dielectric breakdown. Typical leakage currents are around 0.3 A/cm2 at a 10 MV/cm applied field. DFT calculations indicate that many types of defects could be generated and contribute to the leakage current. However, three defects created from adjacent boron and nitrogen monovacancies exhibit the lowest formation energy. These three defects form molecular bridges between two adjacent h-BN layers, which in turn “electrically shorts” the two layers at the defect location. Electrical shorting between layers is manifested in charge transport simulations, which show that the I-V data can only be correctly modeled by incorporating a decrease in effective electrical thickness of the h-BN as well as the usual increase in trap density, which, alone, cannot explain the experimental data. An alternative breakdown mechanism, namely, the physical removal of h-BN layers under soft breakdown, appears unlikely given the h-BN is mechanically confined by the electrodes and no change in AFM topography is observed after breakdown. High-resolution transmission electron microscope micrographs of the breakdown location show a highly localized (<1 nm) breakdown path extending between the two electrodes, with the h-BN layers fractured and disrupted, but not removed.

Deep Learning on Multimodal Chemical and Whole Slide Imaging Data for Predicting Prostate Cancer Directly from Tissue Images.

Prostate cancer is one of the most common cancers globally and is the second most common cancer in the male population in the US. Here we develop a study based on correlating the hematoxylin and eosin (H&E)-stained biopsy data with MALDI mass-spectrometric imaging data of the corresponding tissue to determine the cancerous regions and their unique chemical signatures and variations of the predicted regions with original pathological annotations. We obtain features from high-resolution optical micrographs of whole slide H&E stained data through deep learning and spatially register them with mass spectrometry imaging (MSI) data to correlate the chemical signature with the tissue anatomy of the data. We then use the learned correlation to predict prostate cancer from observed H&E images using trained coregistered MSI data. This multimodal approach can predict cancerous regions with ∼80% accuracy, which indicates a correlation between optical H&E features and chemical information found in MSI. We show that such paired multimodal data can be used for training feature extraction networks on H&E data which bypasses the need to acquire expensive MSI data and eliminates the need for manual annotation saving valuable time. Two chemical biomarkers were also found to be predicting the ground truth cancerous regions. This study shows promise in generating improved patient treatment trajectories by predicting prostate cancer directly from readily available H&E-stained biopsy images aided by coregistered MSI data.

NiCo2O4@V2O5 nanobelts as electrode materials for efficient electrochemical charge storage

The development of novel nanostructured composites is of current interest for applications as electrode materials. In this regard, an attempt has been made to synthesize NiCo2O4@V2O5 nanocomposite and compare its charge storage performance with pristine NiCo2O4 nanoparticles. High-resolution scanning electron microscope micrographs reveal a mesoporous nanobelt like morphology of the nanocomposite with a Brunauer–Emmett–Teller surface area of ∼65 m2 g−1 and average mesopore size centered on ∼7.55 nm. Electrochemical measurements performed on both samples anticipate capacitive behavior with quasi-reversible redox reactions. However, NiCo2O4@V2O5 is found to demonstrate a strikingly high specific capacity of 194 mAh g−1 at 1 A g−1 along with a notable capacity retention of ∼90%, even after 3000 charge–discharge cycles, and a Coulombic efficiency >97% at 5 A g−1. These features are much superior to the properties of pristine NiCo2O4 nanoparticles. The results obtained in this work ascertain the functional robustness of NiCo2O4@V2O5 nanocomposites as electrode materials in supercapacitors.

Compositional analysis of oxide-embedded III–V nanostructures

Nanowire growth enables creation of embedded heterostructures, where one material is completely surrounded by another. Through materials-selective post-growth oxidation it is also possible to combine amorphous oxides and crystalline, e.g. III–V materials. Such oxide-embedded structures pose a challenge for compositional characterization through transmission electron microscopy since the materials will overlap in projection. Furthermore, materials electrically isolated by an embedding oxide are more sensitive to electron beam-induced alterations. Methods that can directly isolate the embedded material, preferably at reduced electron doses, will be required in this situation. Here, we analyse the performance of two such techniques—local lattice parameter measurements from high resolution micrographs and bulk plasmon energy measurements from electron energy loss spectra—by applying them to analyse InP-AlInP segments embedded in amorphous aluminium oxide. We demonstrate the complementarity of the two methods, which show an overall excellent agreement. However, in regions with residual strain, which we analyse through molecular dynamics simulations, the two techniques diverge from the true value in opposite directions.

АРТЕФАКТЫ ФОРМЕННЫХ ЭЛЕМЕНТОВ И ПЛАЗМЫ КРОВИ ПТИЦ, ИХ ПРОИСХОЖДЕНИЕ И ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ

The work is devoted to the study of literature data (humane and veterinary medicine) and the practical analysis of artifacts formed elements and plasma in peripheral blood smears of birds in a model of broiler chickens Gallus gallus L. of early postnatal ontogenesis. The age of the studied clinically healthy chicks and young hens was: day 1, day 7, day 23 and day 42 (n = 40). We studied 158 (n = 158) high-resolution color micrographs of the fields of view, in blood smears stained according to Pappenheim. As a result, single artifacts of avian erythrocytes were identified: cytoplasmic vacuoles of various pattern character, scalloped «bitten» edges of cells. Artifacts of blood plasma were found: pericellular and adhesioned on the cell surface of colored coagulated granularity. In some cases, this granularity imitated the toxic forms of granulocytes and agranulocytes in the peripheral blood of birds. It is necessary to distinguish artifacts of cells and plasma in peripheral blood smears from adaptive changes and symptoms of infectious, invasive and non-infectious diseases.

Rebuttal of: “Reply to response to “diffraction artefacts from twins and stacking faults, and the mirage of hexagonal, polytypes or other superstructures”” by C. Cayron, Scripta Materialia 203 (2021) 114,115

Cayron. [1,2] has sought to discredit our identification of a 9R structure of copper precipitates in iron. We responded to the first of these papers with a brief rebuttal [3]. Cayron however repeated his claim and has presented new arguments [2] which attempt to explain our electron microscopy images as due to Moiré fringes. We examine Cayron's model, and find it not only physically unconvincing, but incapable of explaining our results. We also present high-resolution micrographs which show clearly the 3-layer motif of the 9R structure, and allow its unambiguous identification, and describe other observations, including fringe rotations and detwinning, which support this identification, and cannot be explained by Cayron's model. We conclude that our identification of the 9R structure in copper precipitates in iron is robust and that Cayron's interpretation is fundamentally flawed.

The evolution of slate microfabrics during progressive accretion of foreland basin sediments

Here, we study slate microfabrics from the exhumed accretionary wedge of the central European Alps and focus on the development of foliation. High-resolution micrographs from novel BIB-SEM imaging and Synchrotron X-ray Fluorescence Microscopy are analysed with 2D auto-correlation functions to quantify the geometry and spacing of slate microfabrics along a metamorphic gradient covering the outer and inner wedge (200–330 °C). The sedimentary layering primarily controls the morphology of the slate microfabrics. However, from outer to inner wedge, a fabric evolution is observed where diagenetic foliations gradually transform to secondary continuous and spaced foliations. With increasing metamorphic grade, the amount of recrystallized phyllosilicate grains and their interconnectivity increase, as does clast/microlithon elongation (aspect ratios up to 11), while foliation spacing decreases to <20 μm. This foliation evolution under non-coaxial deformation involves a combination of mechanical rotation of phyllosilicates, fracturing, and fluid-assisted pressure-dissolution-precipitation creep. The latter is the dominant deformation mechanism at T > 230 °C and accommodates background strain in the inner wedge. The evolving microstructural anisotropy is interpreted to lead to strain weakening by structural softening and may provide preferential fluid pathways parallel to the foliation, enabling the dehydration of large rock volumes in accretionary sediment wedges undergoing prograde metamorphism.

Improved Skin Permeability after Topical Treatment with Serine Protease: Probing the Penetration of Rapamycin by Scanning Transmission X-ray Microscopy.

Drug penetration in human skin ex vivo following a modification of skin barrier permeability is systematically investigated by scanning transmission X-ray microscopy. Element-selective excitation is used in the O 1s regime for probing quantitatively the penetration of topically applied rapamycin in different formulations with a spatial resolution reaching <75 nm. The data were analyzed by a comparison of two methods: (i) two-photon energies employing the Beer–Lambert law and (ii) a singular value decomposition approach making use of the full spectral information in each pixel of the X-ray micrographs. The latter approach yields local drug concentrations more reliably and sensitively probed than the former. The present results from both approaches indicate that rapamycin is not observed within the stratum corneum of nontreated skin ex vivo, providing evidence for the observation that this high-molecular-weight drug inefficiently penetrates intact skin. However, rapamycin is observed to penetrate more efficiently the stratum corneum when modifications of the skin barrier are induced by the topical pretreatment with the serine protease trypsin for variable time periods ranging from 2 to 16 h. After the longest exposure time to serine protease, the drug is even found in the viable epidermis. High-resolution micrographs indicate that the lipophilic drug preferably associates with corneocytes, while signals found in the intercellular lipid compartment were less pronounced. This result is discussed in comparison to previous work obtained from low-molecular-weight lipophilic drugs as well as polymer nanocarriers, which were found to penetrate the intact stratum corneum exclusively via the lipid layers between the corneocytes. Also, the role of the tight junction barrier in the stratum granulosum is briefly discussed with respect to modifications of the skin barrier induced by enhanced serine protease activity, a phenomenon of clinical relevance in a range of inflammatory skin disorders.

APPLICATION POTENTIAL OF RESPONSE SURFACE METHOD ON ELECTRO DISCHARGE MACHINING OF AA6061–CENOSPHERE AMCs PREPARED BY COMPOCASTING METHOD

Cenosphere fly ash particles are incorporated into AA6061 alloys with different concentrations ranging from 0[Formula: see text]wt.% to 10[Formula: see text]wt.% using a modified semi-solid metal processing technique. X-ray diffraction patterns were recorded to analyze the morphology of the aluminum-based metal matrix composites (AMCs). The major diffraction peaks of Al, SiO2, Al2O3 and Fe2O3 are distinctly identified which revealed the presence of cenosphere particles and their integrity within the matrix is preserved. The high-resolution optical micrograph identifies the homogeneous distribution and uniform dispersion of the particles. Machinability of the prepared AMCs was investigated by electro discharge machining (EDM) using response surface methodology (RSM). Face-centered CCD of RSM was considered to design the number of experimental runs required. ANOVA was used to explore the influence of selected process parameters and their interactions on the performance characteristics of the systems by developing a second-order quadratic mathematical model for all the responses. Pulse on-time and pulse current were observed to be the most influencing independent variables of EDM system that affect the selected performance measures during spark erosion process. Finally, desirability function approach was employed to optimize the parameters. The optimal processing condition was identified as follows: pulse current: 6 A, pulse on-time: 1010[Formula: see text][Formula: see text]s, percentage of reinforcement: 2% and flushing pressure: 0.2 MPa. Very small percentages of deviation have been observed while comparing with the experimental results obtained for MRR (8.6%), TWR (10.3%) and SR (2.18%).