Some results in topology optimization applied to biomechanics

This paper presents the application of a topology optimization algorithm based in homogenization theory. Three examples in structural design will be solved numerically. The first two are formulated such that analytical solutions can also be developed. To obtain this goal, the microscopic structure that we considered is formed of laminates because for this type of composite materials there is an explicit dependence of the homogenized coefficients on the design variables. The last example regards bone remodelling. Here, where it is impossible to obtain the analytical solution, the applied algorithm produces numerical results which are in good agreement with Wolffs Law.info:eu-repo/semantics/publishedVersio

Detection and identification by PCR of Clostridium chauvoei in clinical isolates, bovine faeces and substrates from biogas plant

<p>Abstract</p> <p>Background</p> <p><it>Clostridium chauvoei </it>causes blackleg, an acute disease associated with high mortality in ruminants. The apparent primary port of entry is oral, during grazing on pasture contaminated by spores. Cases of blackleg can occur year after year on contaminated pastures. A method to determine the prevalence of <it>C. chauvoei </it>spores on pasture would be useful.</p> <p>The standard method for <it>C. chauvoei </it>detection is culture and biochemical identification, which requires a pure culture. In most muscle samples from cattle dead from blackleg the amount of <it>C. chauvoei </it>in samples is high and the bacterium can easily be cultured, although some samples may be contaminated. Detection by PCR would be faster and independent of contaminating flora.</p> <p>Digested residues from biogas plants provide an excellent fertiliser, but it is known that spore-forming baeria such as <it>Clostridium </it>spp. are not reduced by pasteurisation. The use of digested residues as fertiliser may contribute to the spread of <it>C. chauvoei</it>. Soil, manure and substrate from biogas plants are contaminated with other anaerobic bacteria which outgrow <it>C. chauvoei</it>. Therefore, detection by PCR is would be useful. This study applied a PCR-based method to detect of <it>C. chauvoei </it>in 25 muscle and blood samples, 114 manure samples, 84 soil samples and 33 samples from the biogas process.</p> <p>Methods</p> <p>Muscle tissues from suspected cases of blackleg were analysed both by the standard culture method followed by biochemical identification and by PCR, with and without preculture. To investigate whether muscle tissue samples are necessary, samples taken by swabs were also investigated. Samples from a biogas plant and manure and soil from farms were analysed by culture followed by PCR. The farms had proven cases of blackleg. For detection of <it>C. chauvoei </it>in the samples, a specific PCR primer pair complementary to the spacer region of the 16S-23S rRNA gene was used.</p> <p>Results</p> <p><it>Clostridium chauvoei </it>was detected in 32% of muscle samples analysed by culture with identification by biochemical methods and in 56% of cases by culture in combination with PCR. <it>Clostridium chauvoei </it>was detected in 3 (out of 11) samples from the biogas plants collected before pasteurisation, but samples taken after pasteurisation and after digestion all tested negative. <it>Clostridium chauvoei </it>was not detected in any soil or silage samples and only one manure samples tested positive.</p> <p>Conclusion</p> <p>The diagnostic method used for <it>C. chauvoei </it>was not applicable in estimating the risk of blackleg on particular pastures from manure or soil samples, but found to be highly useful for clinical samples.</p

Isolated Limb Perfusion With Melphalan Triggers Immune Activation in Melanoma Patients

Hyperthermic isolated limb perfusion with melphalan (M-ILP) is a treatment option for melanoma patients with metastases confined to the limbs. This study aimed at defining the role of cellular immunity for the clinical response to M-ILP in melanoma patients. It was observed that patients with enhanced cytotoxic CD8+ T cell reactivity to common antigens (HCMV/EBV/influenza virus) prior to M-ILP were more likely to achieve a complete disappearance of macroscopic tumors (complete response). Following M-ILP treatment, the proportions of CD16+ intermediate and non-classical monocytes in peripheral blood were significantly enhanced along with induction of HLA-DR on CD4+ and CD8+ T cells. For further studies of the mechanism behind melphalan-induced immune activation an in vitro model, aiming at mimicking the clinical M-ILP protocol, was established, where PBMCs were co-cultured with melanoma cells, which had been pre-exposed to melphalan under mild hyperthermia. Upon exposure to melphalan, melanoma cells showed increased expression of immune-related markers including MHC class I and Hsp70. Moreover, when the melphalan-treated melanoma cells were co-cultured with PBMCs, this triggered an increased proportion of CD33+CD14+CD16++ non-classical monocytes among the PBMCs. Furthermore, the melphalan-treated melanoma cells stimulated the expansion of CD8+ T cells in the co-cultured PBMCs. These cells produced enhanced levels of IFN-γ and granzyme B and were capable of killing melanoma cells. To further verify an immunogenic role of melphalan, mice were vaccinated with melphalan-exposed murine melanoma cells. When challenged with live melanoma cells, vaccinated mice showed reduced tumor growth and enhanced infiltration of tumor-specific T cells into tumors. We conclude that melphalan-exposed melanoma cells trigger expansion of CD16+ monocytes and activate cytotoxic T cells and that these events may contribute to the antitumoral efficacy of M-ILP

Investigating dietary life histories and mobility of children buried in St Gertrude Church Cemetery, Riga, Latvia (15th– 17th centuries AD)

Carbon and nitrogen isotope profiles were obtained from incremental dentine analysis of 19 non‐adults from a cemetery in Riga, Latvia. The research compared the life histories and diet between people buried in two mass graves and the general cemetery. The δ13C profiles of several children from the mass graves were similar but did not resemble the patterns seen in children from the general cemetery, suggesting that they probably represented a different population group. The rise in δ15N values towards the end of the life of four individuals from one mass grave suggests they were victims of an historically documented famine

A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma

Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine

Carbon-based nano-electro-mechanical systems

We provide an overview of our work where carbon-based nanostructures have been applied to twodimensional (2D) planar and three-dimensional (3D) vertically-oriented nano-electro-mechanical (NEM) switches. In the first configuration, laterally oriented single-walled nanotubes (SWNTs) synthesized using thermal chemical vapor deposition (CVD) were implemented for forming bridge-type 2D NEMS switches, where switching voltages were on the order of a few volts. In the second configuration, vertically oriented carbon nanofibers (CNFs) synthesized using plasma-enhanced (PE) CVD have been explored for their potential application in 3D NEMS. We have performed nanomechanical measurements on such vertically oriented tubes using nanoindentation to determine the mechanical properties of the CNFs. Electrostatic switching was demonstrated in the CNFs synthesized on refractory metallic nitride substrates, where a nanoprobe was used as the actuating electrode inside a scanning-electron-microscope. The switching voltages were determined to be in the tens of volts range and van der Waals interactions at these length scales appeared significant, suggesting such structures are promising for nonvolatile memory applications. A finite element model was also developed to determine a theoretical pull-in voltage which was compared to experimental results

Energy distributions of field emitted electrons from carbon nanosheets: manifestation of the quantum size effect

We emphasize the importance of experiments with voltage dependent field emission energy distribution analysis in carbon nanosheets. Our analysis shows the crucial influence of the band structure on the energy distribution of field emitted electrons in few-layer graphene. In addition to the main peak we found characteristic sub-peaks in the energy distribution. Their positions strongly depend on the number of layers and the inter-layer interaction. The discovery of these peaks in field emission experiments from carbon nanosheets would be a clear manifestation of the quantum size effect in these new materials.Comment: accepted for publication in JETP Letter