Deep Indentations Research Articles

S122: ROCK INHIBITORS TARGET SRSF2 LEUKEMIA BY DISRUPTING CELL MITOSIS AND NUCLEAR MORPHOLOGY

Background: Spliceosome machinery mutations are common early mutations in myeloid malignancies, however effective targeted therapies against them are still lacking in clinical settings. Aims: Exploring safe and efficient methods to target hematopoietic cells carrying SRSF2 mutations might be a powerful tool not just for leukemia prevention and treatment, but also to understand the mechanisms behind SRSF2 mutations. Methods: We generated five SRSF2 Mut (P95H) isogenic cell lines with CRISPR/CAS9 system and performed high throughput drug screen with 3988 compounds in a single dose. After we narrowed down our targets, dose response assay was performed on four different ROCK inhibitors (ROCKi). The leading ROCKi compound was validated in vivo with SRSF2 Mut AML xenograft models. Next, we aimed at understanding why ROCKi target SRSF2 Mut cells and used proteomics, gene expression and imaging of the cytoskeletal system to study the effect of ROCKi on Mut and WT cells. Results: In the current study, we used an in vitro high-throughput drug screen among four different isogenic cell lines and identified ROCK inhibitors (ROCKi) as selective inhibitors of SRSF2 Mut in MOLM14 and AML2 cells. To study the efficacy of RKI-1447 on human samples, we conducted six AML patient-derived xenograft (PDX) experiments, with SRSF2 Mut samples. In four out of the six primary AML samples, RKI-1447 significantly reduced engraftment compared to the untreated group and inhibited the engraftment of both leukemic blasts and pre leukemic-HSPCs (preL-HSPCS). RKI-1447 was not toxic to mice nor human cells. ROCKi induced mitotic catastrophe (G2M arrest and multipolar spindles) through their apparent effects on microtubules and nuclear organization, and leading to cell death. Confocal imaging and transmission electron microscopy (TEM) data revealed that SRSF2 mutations induce deep nuclear indentation and segmentation, which is reminiscent of the nuclear shape of Pelger–Huët anomaly (PHA). The nuclear volume and area were significantly higher in SRSF2 Mut compared with WT MOLM14 cells regardless of ROCKi. To investigate why SRSF2 Mut cause the structural changes, we looked into the cytoplasmic intrusions that segment the nuclei, and the structures that connect the lobes of the nuclei by TEM. This examination revealed enrichment of microtubule bundles inside the nuclear indentations. More importantly, these microtubules were located at the tip of the cytoplasmic intrusions suggesting that they take an active role in the nuclear segmentation process. After exposure to RKI-1447, the cytoskeletal and nuclear morphological abnormalities of SRSF2 Mut are augmented to a level which are incompatible with cell survival. Image:Summary/Conclusion: We believe it is the first report describing in high resolution the changes in the nucleus after SRSF2 mutations are introduced. The mechanisms we identified are most probably relevant to other SMMs and to the dysplastic phenotype observed in MDS and AML. Accordingly, our findings have wide implications as ROCKi might be even more useful than describe here. Altogether, we provide data from many directions that ROCKi should be tested in clinical trials.

Quantifying bond rupture during indentation fracture of soft polymer networks using molecular mechanophores

Understanding the resistance of soft materials to puncture bears relevance to many fields. However, the complex mechanics during deep indentation make it difficult to disentangle how the different dissipation processes contribute to the fracture energy and how this depends on the molecular structure of the material. To investigate this, we perform deep indentation experiments with a flat-ended cylindrical probe on polymer networks containing the covalently incorporated mechanoluminescent bond rupture sensor 1,2-dioxetane. By carrying out the experiments inside an integrating sphere, we are able to quantify the number of ruptured bonds during puncture nucleation and propagation. We find that puncture is associated with significant diffuse damage, both prior to nucleation of the main crack and during crack propagation. Moreover, in agreement with earlier results for uniaxial extension, we show that puncture of double networks leads to strongly enhanced rupture in the prestretched sacrificial network, while fracture of the matrix network is much more localized. Finally, we complement the experiments with MD simulations that allow us to link the rupture processes to the distribution of tension in the networks.

Guided acoustic waves at periodically structured edges: Linear modes and nonlinear generation of Lamb and surface waves

Acoustic waves are investigated which are guided at the edge (apex line) of a wedge-shaped elastic body or at the edge of an elastic plate. The edges contain a periodic sequence of modifications, consisting either of indentations or inclusions with a different elastic material which gives rise to high acoustic mismatch. Dispersion relations are computed with the help of the finite element method. They exhibit zero-group velocity points on the dispersion branches of edge-localized acoustic modes. These special points also occur at Bloch-Floquet wavenumbers away from the Brillouin zone boundary. Deep indentations lead to flat branches corresponding to largely non-interacting, Einstein-oscillator like vibrations of the tongues between the grooves of the periodic structure. Due to the nonlinearity of the elastic media, quantified by their third-order elastic constants, an acoustic mode localized at a periodically modified edge generates a second harmonic which partly consists of surface and plate modes propagating into the elastic medium in the direction vertical to the edge. This acoustic radiation at the second-harmonic frequency is investigated for an elastic plate and a truncated sharp-angle wedge with periodic inclusions at their edges. Unlike nonlinear bulk wave generation by surface acoustic waves in an interdigital structure, surface and plate mode radiation by edge-localized modes can be visualized directly in laser-ultrasound experiments.

К систематике водяного клеща Feltria ishikariensis Imamura (Acari, Hydrachnidia, Feltriidae)

First illustrated description of male and redescription of female of the water mite Feltria ishikariensis Imamura, 1954 from running waters of Primorye Territory of Russia is given. Dorsum of male with large shield and two narrow posterior platelets. Dorsal shield bearing four pairs of setae, posterior plates with one glandularia each. Coxal plates in four groups. The genital field with deep posteromedian indentation, 40–50 pairs of acetabula and four pairs fine medial setae. III-Leg-6 with short ventrodistal projection bearing four to five slender setae. Excretory pore in posteroventral position.

Cu (In x Ga1-x )Se2 Thin Films Mechanical and Structural Properties

Due to Cu (In x Ga1-x )Se2 (CIGS) thin films are used as an absorbing material in solar cells because their direct bandgap overlaps the red edge of the solar spectrum and they have a relatively high absorption coefficient (α~105 cm−1) [1]. The efficiency of CIGS solar cells reached 22.9% for laboratory scale devices and up to 15.7% for commercial modules [2], which is the highest conversion efficiency among all commercial polycrystalline solar cells [3]. Structural/nanomechanical properties of Cu(In x Ga1-x )Se2 films deposited on Si(100) by one-step radio frequency magnetron sputtering are discussed. The films were sputtered at different substrate temperatures (25-500 °C). X-Ray diffraction revealed dominant diffraction peak of (112). Surface morphology was examined by field emission scanning electron microscopy and atomic force microscopy. The film composition was examined by electron probe microanalysis. The Cu/(In+Ga) and Ga/(In+Ga) ratios were 0.9 and 0.3, respectively. Nanoindentation, in conjunction with the scanning electron microscopy, was conducted and revealed that the films suffered severe delamination type fracture due to poor adhesion to the Si substrate. The hardness of the films was not influenced by the substrate temperature increase except for the film grown at 500 °C. The hardness results were largely affected at depths larger than the film thickness due to poor adhesion of the film. At deep indents, the hardness results agreed closely with the Si substrate hardness.

Shape optimization of studs in double-leaf plasterboard walls for maximal broadband sound insulation and minimal material use

The cross-sectional shape of the metal studs in a double-leaf wall has a significant influence on its sound insulation. In a recent study, a numerical optimization of the stud shape resulted in designs that offer a significant increase in broadband airborne sound insulation, both when compared to conventional C-shaped studs and commercially available acoustic studs, but at the expense of a much higher material use. In the present work, a multi-objective optimization of the stud shape is aimed at, so as to find an optimized trade-off between the stud material cost and the sound insulation of the overall system across the entire building acoustics frequency range. This is achieved by combining a computationally efficient, iterative multi-objective optimization scheme with a computationally efficient numerical sound insulation prediction model of sufficient accuracy. Pareto fronts, which represent the set of optimal combinations of sound insulation and stud material use, are computed for a range of plasterboard wall systems that differ in cavity depth, number of sheets of plasterboard and stud type (symmetric or point-symmetric). For nearly all walls with symmetric studs, the Pareto fronts show that the introduction of a single deep indentation in the stud results in a high increase in sound insulation at a limited increase in material cost compared to simple C-shaped studs while two or three deep indentations result in a higher material cost with a performance close to that of a wall with decoupled leafs. For nearly all walls with point-symmetric studs, the Pareto fronts show that the introduction of two deep indentations results in a high increase in sound insulation at a limited increase in material cost compared to Z-shaped studs while four deep indentations result in a higher material cost with a performance close to that of a wall with decoupled leafs. It is shown that often, the acoustic performance of commercially available acoustic stud shapes can be further improved with less material used to produce the stud and sometimes even a shallower cavity.

Flat-Top Cylinder Indenter for Mechanical Characterization: A Report of Industrial Applications.

FIMEC (flat-top cylinder indenter for mechanical characterisation) is an instrumented indentation test employing a cylindrical punch. It has been used to determine the mechanical properties of metallic materials in several applications of industrial interest. This work briefly describes the technique and the theory of indentation with a flat-ended punch. The flat indentation of metals has been investigated through experimental tests, and an equation has been derived to calculate the yield stress from the experimental data in deep indentation. The approach is supported by many data on various metals and alloys. Some selected case studies are presented in the paper: (i) crank manufacturing through pin squeeze casting; (ii) the evaluation of the local mechanical properties in a carter of complex geometry; (iii) the qualification of Al billets for extrusion; (iv) stress–relaxation tests on CuCrZr heat sinks; (v) the characterization of thick W coatings on CuCrZr alloy; (vi) the measure of the local mechanical properties of the molten-zone (MZ) and the heat-affected zone (HAZ) in welded joints. The case studies demonstrate the great versatility of the FIMEC test which provides information not available by employing conventional experimental techniques such as tensile, bending, and hardness tests. On the basis of theoretical knowledge and large amount of experimental data, FIMEC has become a mature technique for application on a large scale in industrial practice.

Effect of Two-Dimensional Short Rectangular Indentations on Hypersonic Boundary-Layer Transition

The objective of the present paper is to reveal the intrinsic mechanisms by which two-dimensional surface indentations influence the laminar–turbulent transition of natural route in hypersonic boundary layers. For an oncoming Mach number of 6 and a rectangular indentation, two relevant scattering mechanisms, namely, the local scattering of oncoming Mack modes and the local receptivity to freestream acoustic waves, are studied by direct numerical simulations. A transmission coefficient and a receptivity coefficient are introduced to quantify the two mechanisms, and their dependence on the indentation depths and the oncoming-perturbation frequencies is investigated systematically. Numerical results reveal that both the local scattering and receptivity effects increase with the indentation depth when the latter is shallow, but the opposite is true for deep indentations. Such a phenomenon is found to be related to the topological structure of the base flow inside the indentations, namely, two independent separation bubbles for shallow configurations and one large-scale separation bubble occupying the whole indentation for deep configurations.

Description of two new species of Bassozetus (Ophidiiformes: Ophidiidae) and a redescription of Bassozetus robustus Smith and Radcliffe 1913

Two new deepwater assfish species, Bassozetus trachibranchus and Bassozetus squamosus, are described from the 29 western Atlantic and four western Indian and western South Pacific specimens, respectively. In addition, a redescription of Bassozetus robustus Smith and Radcliffe in Radcliffe 1913, with which both of the above two new species have been previously confused, is provided on the basis of 14 specimens and its distributional range is revised to the western Pacific Ocean. The three species are separable from the 13 known congeners by the following combination of characters: dorsal-fin rays (116–126), anal-fin rays (95–103), oblique scale rows (30–47), pelvic-fin length (14.3–21.7% SL), a single well-developed median bashibranchial tooth patch, and one or two deep indentations on the sagitta dorsal margin, plus long gill rakers (10–14 in B. robustus) and head, predorsal and prepelvic lengths (20.5–22.8% SL, 19.4–21.1% SL and 15.3–18.1% SL, respectively, in B. robustus). Additionally, B. trachibranchus, B. squamosus and B. robustus are distinguishable from each other as follows: oblique scale rows (39–45 in B. trachibranchus, 44–47 in B. squamosus, and 30–36 in B. robustus), eye diameter to head length ratio (greater in B. squamosus than in similarly sized specimens of the other species), pelvic fin length/distance between pelvic and anal fins ratio (smaller in B. robustus than in similarly sized specimens of the other species), and 2nd to 4th lower limb morphology (many small tooth patches arranged along the outer ridges in B. trachibranchus, absent or a few only in the other species).

The Effect of Residual Stresses on Stress–Strain Curves Obtained via Profilometry‐Based Inverse Finite Element Method Indentation Plastometry

This paper concerns, the effect of (unknown) residual stresses in the near‐surface region of a sample on outcomes of an indentation plastometry technique for obtaining stress–strain relationships, using relatively large spherical indenters. The technique is based on the iterative finite element method (FEM) simulation of indentation, so as to infer the true stress–strain curve of the material (with the target outcome being the profile of the residual indent). It is expected that residual stress levels (if significant compared with the yield stress) are likely to influence the outcome, and indeed this forms the basis of many attempts to measure residual stresses in this way (using a known stress–strain curve). However, there are important issues of sensitivity here, which affect the reliability of such procedures and are also relevant to the accuracy of stress–strain curves inferred from measurements made on samples containing unknown levels of residual stress. Herein, both experimental work on samples with (equal‐biaxial) residual stresses created by the application of external loads and extensive FEM modeling to explore various scenarios are covered. The main conclusion is that the sensitivities involved are in general very low, particularly with relatively deep indentation. Inferred stress–strain curves are thus likely to be quite accurate, even in the presence of relatively high levels of residual stress. Conversely, the measurement of residual stress levels via this procedure is likely to be rather inaccurate, although the reliability is improved using shallow penetration (low ratio of depth‐to‐indenter radius). It is also noted that tensile residual stresses tend to influence outcomes more strongly than compressive ones.

Deep indentation and puncture of a rigid cylinder inserted into a soft solid.

Deep indentation and puncture can be used to characterize the large strain elastic and fracture properties of soft solids and biological tissues. While this characterization method is growing in application there are still open questions about deep indentation and puncture, including how the distribution of strains and stresses in the surrounding material relate to the resultant force exerted on the indenter. Direct quantification of the deformation field around a rigid indenter during penetration of a soft solid is necessary to substantiate the current qualitative understanding of these strains and increase the impact and usefulness of puncture tests. Here, the deformation field of a rigid cylinder inserted into a soft solid is quantified using digital image correlation (DIC). DIC measurements are validated by reconstituting the measured nominal force on the cylinder during deep indentation and puncture. The deformation field is used to map the strain field around the indenter during deep indentation and puncture. These measurements provide direct insight into the puncture process and show that while the resultant force mainly arises from the sheared region on the sides of the indenter, the compressed region below the tip is responsible for initiating failure.

We Go to the Water

We Go to the Water Sarah Twombly (bio) We go to the water, the children and I—the children and I, who have been lashed together like a beleaguered life raft, each of us the other's only hope for survival. We go to the water, offer ourselves to the waterfall. We climb into its thunder. We forget the sky. We forget each other. We toss our hearts into the maelstrom, where they are battered and broken and something is knocked loose, and suddenly we can breathe. Without masks, without fear, we can breathe. We go to the water on days we cannot go elsewhere. Elsewhere has been closed for the season. Elsewhere has disappeared, is a place we see from the corners of our eyes as we drive down empty roads, past shuttered stores, on our way out of town. Elsewhere is there, but also it isn't. The week George Floyd was murdered, the week we, yet again, roared Black Lives Matter, the week a wave of anger and death and hope swept in—an overdue reap tide of devotion rising between brothers and sisters, neighbors and neighborhoods—we went to the pond and identified five species of frogs, and the children shrieked as the frogs jumped, unseen and unexpected, from the reed-ridden edge where our toes left deep indentations in the mud. We threw stones and sadness and bore witness as both sunk into the murk. We go to the water, but we dry out so quickly. We desiccate. We whither. We come undone. So we return, again and again, praying the current will salve us whole. We go to the water because the water does not come to us. We find a pocket beach, a near-impossible sandy stretch caught by the rocky jaws of a cove, along an impossibly rocky coast we had driven a dozen times before but had never seen, had never noticed. And, of course, we get out of the car. And of course, although we are clothed, although we have no towels, although we wore no suits or suntan lotion, we run to the waters' edge. My [End Page 110] daughter does cartwheels in the surf. My son digs a trench in the sand. They both peel off their clothes, down to their underwear, and dance along the rising tide, making up songs they sing at the top of their lungs and toss out to sea, blessings with kite tails knitted of kelp. Four hours it holds us, that cove—our makeshift raft of bandits and mourners and dinosaurs—eroding our exhaustion, washing the sweat from our bodies, erasing the hour-long car ride it will take us to get home, during which my son will scream and my daughter will demand story after story, and during which, neither of them will sleep. My youngest refused to leave, fled from me, naked, down the beach, arms outstretched, chasing a seagull, ready, himself, to leap into the open air, a phantasm of feathers and thirst. [End Page 111] Sarah Twombly Sarah Twombly received her mfa from Vermont College of Fine Arts. Her work has appeared in the New York Times, Esquire Magazine, Scary Mommy, Hippocampus, and Atticus Review among others, and is forthcoming from Contrary Magazine and Décor Maine. She has received the Maine Literary Award for short nonfiction, the Glascock Prize in Poetry, and the Katherine McFarland Prize for fiction. She currently resides in the woods of central Maine with her wild and beloved family. You can find her on twitter @Sarahtwombly Copyright © 2021 University of Nebraska Press

Characterization of the surface degraded layer of polymers using an indentation method

In this study, we have proposed an indentation method to characterize a surface degraded layer due to UV light irradiation of polymers. Here, we assume that the degraded layer has a homogeneous and isotropic nature, and that the target material is a bilayer system (i.e., the degraded layer is formed on the substrate of the non-degraded base material). This method enables the quantitative measurement of mechanical properties (Young’s modulus E and yield strength σY) and thickness of the degraded layer. In the first step, we conducted a shallow indentation in order to ignore the effect of substrate (non-degraded base material). This method deduces the mechanical property of degraded layer itself. The second step is deep indentation (i.e. indentation depth is deeper to capture substrate effect) for measuring the thickness of the degraded layer. To establish these methods, reverse analysis with the dimensionless function was newly proposed. We conducted a parametric study using the finite element method, in which the material cases cover various polymers, degradation properties, and layer thickness. Experimental verification was finally carried out, and the degraded layer due to UV light for polycarbonate (PC) was successfully characterized. Because this method is simple, convenient, and non-destructive, it might be useful for characterization of weathering degradation in other engineering polymers.

Measurement of Residual Stresses Using Indentation Plastometry

This study concerns the potential use of the indentation plastometry technique to obtain information about residual stresses. This is a logical extension of the technique, which is based on iterative FEM simulation of the indentation procedure so as to infer the true stress-strain curve of the material, with the target outcome being the profile of the residual indent. Once this has been obtained (in the form of parameter values in a constitutive law), a logical extension of the procedure is to create an initial (residual) stress in the model and then converge on the value that gives the best agreement with experiment. In the present work, this has been done for some copper sheet samples, with different levels of residual stress created experimentally via the application of external loads. This has been done for a series of equal biaxial stress levels. The inferring of residual stress levels in this way, and comparison with expected levels, has not been reported previously. The main conclusion is that the sensitivity of the measured indent profile to the residual stress level is low. This is particularly the case for compressive stresses and for relatively deep indents, but it is also true for tensile stresses and shallower indents. The prospects for accurately inferring residual stress levels via this procedure are therefore poor. A positive aspect to this rather negative conclusion is that, when obtaining plasticity characteristics in this way, there need be little concern about the outcome being influenced by the presence of (unknown) residual stresses.

Continuous multi-cycle nanoindentation behavior of a gradient nanostructured metastable β titanium alloy fabricated by rotationally accelerated shot peening

A novel gradient nanostructured structure fabricated by rotationally accelerated shot peening (RASP) has been proven useful in the enhancement of strength and ductility. In this study, a series of nanoindentation tests using continuous multi-cycle (CMC) mode are first used to characterize the nanoindentation behavior of the RASP-processed metastable β titanium alloy with a gradient nanostructured structure. The experimental results indicate that indentation depth and grain size paly a dominant role in the nanoindentation behavior. Inverse indentation size effect (ISE) on the hardness occurs at shallow indentation depth (<50 nm), which is due to the hardening behavior caused by the effect of grain boundaries. While ISE occurs at the indentation depth ranging from 50 nm to 225 nm, then ISE disappears in deep indentation depth (>225 nm), which is dominated by the known strain gradient mechanism. The hardness, reduced module and back stress decrease from the treated surface with a nanostructured grain size of 20 nm to the center zone with a coarse grain size of 216 μm. For the RASP-processed sample, the fine grain zone exhibits a more pronounced inverse and normal ISEs than these of the coarse grain zone. In addition, the Bauschinger effect and back stress strengthening mechanism are also firstly used to explain the variation of gradient micro-mechanical properties.

Do Carotid Plaque Ulcers Heal? Potential Detection of Carotid Artery Plaque Healing by Carotid Ultrasound Imaging.

Carotid plaque ulcers confer an increased risk for stroke/ transient ischemic attacks in both symptomatic and asymptomatic carotid artery stenosis. Little is known about the healing rates of ulcers or the development of new ulcers. Carotid Duplex studies are noninvasive and easily repeatable tests to monitor progression of carotid stenosis and plaque morphology. Our aim was to determine the prevalence and healing rates of ultrasound-detected carotid plaque ulcers. We retrospectively reviewed 5837 carotid Duplex studies performed in an outpatient ultrasound laboratory affiliated with the neurological department of an academic center. A total of 3215 patients underwent a first carotid ultrasound Duplex study, and 2622 follow-up studies were done. Carotid ulcer was defined as a 2 mm deep surface indentation in a carotid plaque with a well-defined back wall, as determined by multimodal ultrasound imaging techniques. The prevalence of carotid plaque ulcers among the 3215 patients with a first ultrasound study was 3% (82/3215). The mean follow-up was 42 ± 30 months, and the median number of follow-up studies was 6. Among patients with ulcers, follow-up studies were available in 65/82 patients. During the follow-up period, 28/65 (43%) ulcers healed. Among all 2622 follow-up studies, 45 patients developed a new ulcer. Duplex-detected carotid plaque ulcer prevalence is low. The carotid ulcers healed in approximately half of patients during follow-up. Factors associated with ulcer healing and development remain poorly understood.

The Eyelid Crease Height, Depth, and Shape: A Scoring System for Revisional Asian Blepharoplasty.

Data on 64 revisional cases were collected between January 1, 2006, and June 30, 2019, with 126 upper eyelids. These were cases with little skin remaining after previous surgeries, and each eyelid was scored based on a height, depth, shape scoring method. A composite score (H + D + S) is then summed up, which ranged from 1 to 10, with the higher number being the most challenging. The logic and rules behind this scoring scale are explained. Data regarding age, gender, and eyelid crease characteristics of the cases were collected; photographs, notes, and diagrams in the medical records were used to complete each eyelid's scoring. The age of the patients (57 women and 7 men) ranged from 21 to 74 years. The revision score distribution, age distribution, and averaged scores within each age group were investigated for those starting at 24 years or younger, and for each added decade until over 65 years. Patients with revisional effort scores of 5-8 were found in all age groups surveyed. In this study, the author presents a practical scoring scale that recognizes the factors responsible for the suboptimal results in double eyelid plasty and helps clinicians in management, patient-counseling, and planning of surgical solutions.

Terminal ballistic and static impactive loading on thick concrete target

The rigid projectile penetration into thick concrete targets was studied through static deep indentation and terminal ballistic tests with small-diameter projectiles. This work aims to investigate the correlation between indentation and penetration for concrete. First, ballistic penetration tests were conducted to obtain the dynamic impact test data including depth of penetration (DOP) and crater dimensions. Second, a sequent static deep indentation test on the concrete target was also carried out. The net axial resisting force was calculated from the recorded force-displacement history considering the effect of friction on static indentation. The resistance measurement was in good agreement with the ones from the ballistic tests suggesting that the static deep indentation tests can be used to estimate the target strength parameter R (Forrestal et al. 2003) of penetration resistance. Third, both the penetration and indentation tests were numerically studied by using the recently developed Lattice Discrete Particles Model (LDPM). LDPM is a discrete model built upon the internal structure of materials at mesoscale with inter-particle constitutive laws accounting for tensile cohesive fracture between aggregates, strain hardening in compression and compaction due to pore collapse. Numerical simulations of the penetration tests were validated by comparing the numerical results with the experimentally recorded DOP and crater damage contour. Moreover, the indentation simulation well captured the force-displacement curve with friction subtracted. Finally, the correlation between the penetration resisting force and static indentation load was further validated by extensive numerical simulations.

Interaction of 5-substituted pyrimidine nucleoside analogues and M.Tuberculosis: A view through an electron microscope

The data of transmission electron microscopy (TEM) on morphology of M. tuberculosis H37Rv bacterial cells treated with four analogues of pyrimidine nucleosides with different substituents at 5 position of base are presented. We showed that the growth of M. tuberculosis H37Rv cells effectively inhibited by each of these compounds. This process is accompanied with the accumulation of lipid intracellular vacuole-like inclusions in the cells, appearance of deep protrusions and indentations on the surface, partial and/or complete destruction of the three-layered cell envelope. The exact molecular mechanism of action of 5-substituted pyrimidine nucleosides on M. tuberculosis cells remains to be proved. However, one can suggest that mechanism of action for these compounds is related either to their direct interactions with bacteria cell walls or to interactions with enzymes participating in the process of cell wall formation.

Modeling of deep indentation in brittle materials

We modelled deep indentation in brittle materials via a tensorial approach in three dimensions. Experimentally, we performed deep indentation in base catalyzed aerogels. When deep indentation is performed in these materials, it appears a Hertzian cone crack for both experimental and numerical results. The cone angle (angle between the surface and the boundaries of the Hertzian cone) depends on the material in which indentation is performed. The Young moduli of the materials has no effect on these angles. The tendency is that materials with increasing Poisson ratios have a decreasing value of the Hertzian cone angle.