The Chick Chorioallantoic Membrane Model: A New In Vivo Tool to Evaluate Breast Cancer Stem Cell Activity

The high plasticity of cancer stem-like cells (CSCs) allows them to differentiate and proliferate, specifically when xenotransplanted subcutaneously into immunocompromised mice. CSCs are highly tumorigenic, even when inoculated in small numbers. Thus, in vivo limiting dilution assays (LDA) in mice are the current gold standard method to evaluate CSC enrichment and activity. The chick embryo chorioallantoic membrane (CAM) is a low cost, naturally immune-incompetent and reproducible model widely used to evaluate the spontaneous growth of human tumor cells. Here, we established a CAM-LDA assay able to rapidly reproduce tumor specificities—in particular, the ability of the small population of CSCs to form tumors. We used a panel of organotropic metastatic breast cancer cells, which show an enrichment in a stem cell gene signature, enhanced CD44⁺/CD24^−/low cell surface expression and increased mammosphere-forming efficiency (MFE). The size of CAM-xenografted tumors correlate with the number of inoculated cancer cells, following mice xenograft growth pattern. CAM and mice tumors are histologically comparable, displaying both breast CSC markers CD44 and CD49f. Therefore, we propose a new tool for studying CSC prevalence and function—the chick CAM-LDA—a model with easy handling, accessibility, rapid growth and the absence of ethical and regulatory constraints.     

Peptides to Tackle Leishmaniasis: Current Status and Future Directions

Peptide-based drugs are an attractive class of therapeutic agents, recently recognized by the pharmaceutical industry. These molecules are currently being used in the development of innovative therapies for diverse health conditions, including tropical diseases such as leishmaniasis. Despite its socioeconomic influence on public health, leishmaniasis remains long-neglected and categorized as a poverty-related disease, with limited treatment options. Peptides with antileishmanial effects encountered to date are a structurally heterogeneous group, which can be found in different natural sources—amphibians, reptiles, insects, bacteria, marine organisms, mammals, plants, and others—or inspired by natural toxins or proteins. This review details the biochemical and structural characteristics of over one hundred peptides and their potential use as molecular frameworks for the design of antileishmanial drug leads. Additionally, we detail the main chemical modifications or substitutions of amino acid residues carried out in the peptide sequence, and their implications in the development of antileishmanial candidates for clinical trials. Our bibliographic research highlights that the action of leishmanicidal peptides has been evaluated mainly using in vitro assays, with a special emphasis on the promastigote stage. In light of these findings, and considering the advances in the successful application of peptides in leishmaniasis chemotherapy, possible approaches and future directions are discussed here.     

Syndecan-1 Depletion Has a Differential Impact on Hyaluronic Acid Metabolism and Tumor Cell Behavior in Luminal and Triple-Negative Breast Cancer Cells

Glycosaminoglycans (GAGs) and proteoglycans (PGs) are major components of the glycocalyx. The secreted GAG and CD44 ligand hyaluronic acid (HA), and the cell surface PG syndecan-1 (Sdc-1) modulate the expression and activity of cytokines, chemokines, growth factors, and adhesion molecules, acting as critical regulators of tumor cell behavior. Here, we studied the effect of Sdc-1 siRNA depletion and HA treatment on hallmark processes of cancer in breast cancer cell lines of different levels of aggressiveness. We analyzed HA synthesis, and parameters relevant to tumor progression, including the stem cell phenotype, Wnt signaling constituents, cell cycle progression and apoptosis, and angiogenic markers in luminal MCF-7 and triple-negative MDA-MB-231 cells. Sdc-1 knockdown enhanced HAS-2 synthesis and HA binding in MCF-7, but not in MDA-MB-231 cells. Sdc-1-depleted MDA-MB-231 cells showed a reduced CD24-/CD44+ population. Furthermore, Sdc-1 depletion was associated with survival signals in both cell lines, affecting cell cycle progression and apoptosis evasion. These changes were linked to the altered expression of KLF4, MSI2, and miR-10b and differential changes in Erk, Akt, and PTEN signaling. We conclude that Sdc-1 knockdown differentially affects HA metabolism in luminal and triple-negative breast cancer model cell lines and impacts the stem phenotype, cell survival, and angiogenic factors.     

A Methionine Chemical Shift Based Order Parameter Characterizing Global Protein Dynamics

Coupling of side chain dynamics over long distances is an important component of allostery. Methionine side chains show the largest intrinsic flexibility among methyl-containing residues but the actual degree of conformational averaging depends on the proximity and mobility of neighboring residues. The ¹³C NMR chemical shifts of the methyl groups of methionine residues located at long distances in the same protein show a similar scaling with respect to the values predicted from the static X-ray structure by quantum methods. This results in a good linear correlation between calculated and observed chemical shifts. The slope is protein dependent and ranges from zero for the highly flexible calmodulin to 0.7 for the much more rigid calcineurin catalytic domain. The linear correlation is indicative of a similar level of side-chain conformational averaging over long distances, and the slope of the correlation line can be interpreted as an order parameter of the global side-chain flexibility.     

The effect of ceria content on the performance of Pt/CeO2/Al2O3 catalysts in the partial oxidation of methane

The effect of CeO₂ loading (1–20 wt.%) on the properties and catalytic behaviors of CeO₂–Al₂O₃-supported Pt catalysts on the partial oxidation of methane was studied. The catalysts were characterized by S_BET, X-ray diffraction (XRD), temperature-programmed reduction (TPR) and oxygen storage capacity (OSC). XRD and TPR results showed that the pretreatment temperature of the support influences on the amount of CeO₂ with fluorite structure. The pretreatment temperature of the support and CeO₂ loading influenced the morphology of Pt. OSC analysis showed a significant increase in the oxygen storage capacity per weight of CeO₂ for samples with high CeO₂ loading (12 and 20 wt.%). TPR analyses showed that the addition of Pt promotes the reduction of CeO₂. This effect was more significant for the catalysts with high CeO₂ loading (≥12 wt.%). The dispersion of Pt, measured by the rate of cyclohexane dehydrogenation, increases with increasing of the pretreatment temperature of the support. It was shown that the kind of the support is very important for obtaining of catalysts resistant to carbon formation. The catalysts with high CeO₂ loading (≥12 wt.%) showed the highest catalytic activity and stability in the reaction of partial oxidation of methane due to a higher Pt–CeO₂ interface.     

The Building Blocks of a PaaS

Traditional cloud computing providers enable developers to program and deploy applications in the cloud by using platform as a service (PaaS) providers. Despite the benefits of such an approach, this service model usually comes with a high level of the lock in effect into the service provider. The lock in effect occurs when a software developer needs to change its cloud provider. When this happens, it usually means a major application rewrite, specific for the new PaaS. This paper details the initial results of a project whose goal is to build a PaaS where vendor lock in does not occur. With this PaaS, developers wishing to deploy their applications into the cloud may continue to program using their usual development environments. There are no necessary changes required to make the application PaaS compatible. As a proof of concept, we developed an open source PaaS management application as a regular web application and then deployed it on the cloud.     

The Influence of the Acid Sites on the Methylamines Synthesis with Cu-HZSM-5 Zeolite

There is a high industrial demand for MMA and DMA, however, the production of TMA is favored with the commercial catalysts. This work tested the methanol amination reaction with HZSM-5 and Cu/HZSM-5 zeolites (%Cu = 1.2, 3.7 and 6.0). Regarding the MMA selectivity, light differences were observed among Cu/HZSM-5 catalysts and pure zeolite, although the catalysts containing 3.7% copper was slightly more selective to MMA than the other metallic catalysts studied. From these results it is suggested that the metal loading present in the catalysts leads to a modification in the nature of the acidic sites, in particular, the selectivity depends on ratio Brönsted/Lewis acid sites. This modifications would facilitate the amines desorption during the reaction.     

EDT Method for Multiple Labelled Objects Subject to Tied Distances

Machine Intelligence Research - The success of new scientific areas can be assessed by their potential for contributing to new theoretical approaches aligned with real-world applications. The...     

Lyapunov Design of Multivariable MRAC via Generalized Passivation

A Lyapunov design of multiple input, multiple output (MIMO) model‐reference adaptive control (MRAC) systems is proposed using new generalized passivity concepts based on WSPR and WASPR properties. The new design avoids control overparameterization and leads to the simplest unnormalized gradient algorithm by means of a passivating multiplier. To this end, a necessary and sufficient condition on the high frequency gain matrix to achieve the WASPR property is established. This condition is referred to as Positive Diagonal Jordan (PDJ) form. Based on the robustness WSPR and WASPR properties, a systematic determination of a robust passivating matrix multiplier is then presented. The advantages of the new design are illustrated by numerical simulation including a robotics adaptive visual servoing problem and a 4‐input‐4‐output dynamic system. © 2014 Chinese Automatic Control Society and Wiley Publishing Asia Pty Ltd     

One-Way Functions Using Algorithmic and Classical Information Theories

We prove several results relating injective one-way functions, time-bounded conditional Kolmogorov complexity, and time-bounded conditional entropy. First we establish a connection between injective, strong and weak one-way functions and the expected value of the polynomial time-bounded Kolmogorov complexity, denoted here by?E(K ^t (x|f(x))). These results are in both directions. More precisely, conditions on?E(K ^t (x|f(x))) that imply that?f is a weak one-way function, and properties of?E(K ^t (x|f(x))) that are implied by the fact that?f is a strong one-way function. In particular, we prove a separation result: based on the concept of time-bounded Kolmogorov complexity, we find an interval in which every function?f is a necessarily weak but not a strong one-way function. Then we propose an individual approach to injective one-way functions based on Kolmogorov complexity, defining Kolmogorov one-way functions and prove some relationships between the new proposal and the classical definition of one-way functions, showing that a Kolmogorov one-way function is also a deterministic one-way function. A relationship between Kolmogorov one-way functions and the conjecture of polynomial time symmetry of information is also proved. Finally, we relate?E(K ^t (x|f(x))) and two forms of time-bounded entropy, the unpredictable entropy?H ^unp, in which ??one-wayness?? of a function can be easily expressed, and the Yao⁺ entropy, a measure based on compression/decompression schema in which only the decompressor is restricted to be time-bounded.