Miracle-dz/UniFAR-FTUs huggingface dataset:
Camptothecin in sterically stabilized phospholipid micelles: a novel nanomedicine.

BACKGROUND Camptothecin (CPT) is a well-established topoisomerase I inhibitor against a broad spectrum of cancers. However, poor aqueous solubility, instability, and toxic effects to normal tissues have limited CPT clinical development. Recently, sterically stabilized micelles (SSM) composed of polyethylene glycol (PEGylated) phospholipids have been introduced as safe, biocompatible nanocarriers for the delivery of poorly water-soluble drugs. It was the aim of this study to develop and evaluate in vitro camptothecin-containing SSM (CPT-SSM) as a novel nanomedicine for parenteral administration. METHODS The solubilization potential, stability, and in vitro cytotoxicity of CPT in SSM were studied. Lyophilization of CPT-SSM under controlled conditions was also studied. RESULTS The mean size of CPT-SSM was found to be approximately 14 nm with a narrow size distribution. CPT-SSM were prepared by coprecipitation reconstitution. At a concentration of 15 mmol/L of PEGylated phospholipids where no micelle-micelle interaction was observed, CPT solubilization in SSM was 25-fold higher than CPT in buffer. We determined that CPT can be solubilized in SSM up to molar ratios of CPT/lipid = 0.0063:1. Above this critical molar ratio, heterogeneous systems of CPT-SSM and CPT self-aggregated particles were formed. CPT in SSM was at least 3 times more stable and 3-fold more cytotoxic to MCF-7 cells than CPT alone. Furthermore, CPT-SSM alone was lyophilized without additional lyoprotectants and cryoprotectants and reconstituted without any significant change in properties. CONCLUSION We have shown that CPT in SSM is a promising nanomedicine with improved drug solubility, stability, freeze-drying properties, and anticancer activity. It is anticipated that, because of the nanosize and steric stability of the micelles, CPT-SSM will be passively targeted to solid cancers in vivo, resulting in high drug concentration in tumors and reduced drug toxicity to the normal tissues.
MRI magnet design: search space analysis, EDAs and a real-world problem with significant dependencies

This paper introduces the design of superconductive magnet configurations in Magnetic Resonance Imaging (MRI) systems as a challenging real-world problem for Evolutionary Algorithms (EAs). Analysis of the problem structure is conducted using a general statistical method, which could be easily applied to other problems. The results suggest that the problem is highly multimodal and likely to present a significant challenge for many algorithms. Through a series of preliminary experiments, a continuous Estimation of Distribution Algorithm (EDA) is shown to be able to generate promising designs with a small computational effort. The importance of utilizing problem-specific knowledge and the ability of an algorithm to capture dependencies in solving complex real-world problems is also highlighted.
CD44 Expressed on Cancer‐Associated Fibroblasts Is a Functional Molecule Supporting the Stemness and Drug Resistance of Malignant Cancer Cells in the Tumor Microenvironment

Cells constituting the tumor microenvironment are attractive targets for developing new cancer therapies. Here we show that cancer‐associated fibroblasts (CAFs) support tumor growth in vivo and maintain the stemness of cancer stem/initiating cells in an in vitro model using an established CAF cell line. We found that CD44 is abundantly expressed on CAFs. This molecule is a cancer stem cell marker in several tumors, but its role in tumorigenesis when expressed by CAFs has not been investigated. It is generally accepted that hypoxic and hyponutritional conditions are triggers of cancer malignancy. We found that CAFs strongly express CD44 in hypoxic and avascular areas in the tumor and that its expression on established CAFs is upregulated under hypoxic and hyponutritional conditions in vitro. In addition, CAF CD44‐positivity in tumor tissues was increased after treatment with inhibitors of angiogenesis. Using cocultures and tumor sphere formation assays, CAFs from wild‐type mice were found to sustain the stemness of cancer stem/initiating cells, while CD44‐deficient CAFs did not. Furthermore, CD44 was involved in malignant cancer cell drug resistance mechanisms. In conclusion, our study suggests that CD44 on CAFs is a functional molecule contributing to the maintenance of cancer stem cell populations in the tumor microenvironment. Stem Cells 2014;32:145–156
Normal development and fertility of Fut1, Fut2, and Sec1 triple knockout mice

The fucose alpha(1,2) galactose structure (H antigen) is synthesized by α1,2 fucosyltransferases Fut1, Fut2 and Sec1. H antigen has been reported to be involved in cancer progression, neurite migration, synaptic plasticity, host-microbe interaction, blastocyst implantation, and the maintenance of gut microbiome. Genetic depletion of Fut1 or Fut2 only cause defects of alpha1,2 fucosylation in limited tissues because of enzyme redundancy. In this study, we generated mice with deficiencies in Fut1, Fut2, and Sec1 genes to deplete H antigen through BAC Engineering for the generation of ES Cell-Targeting construct. The homogenous triple knockout mice showed no significant decrease of viability or development. Mass spectrometry and Western blot analysis confirmed the absence of H blood group antigen in multiple organs. These results indicate normal development and fertility of mice devoid of blood group H. The fine pathophysiological alterations in these mice remain to be carefully studied, and they may serve as valuable tools to study gut microbiome and host-microbe interactions.
Treating cattle with antibiotics affects greenhouse gas emissions, and microbiota in dung and dung beetles

Antibiotics are routinely used to improve livestock health and growth. However, this practice may have unintended environmental impacts mediated by interactions among the wide range of micro- and macroorganisms found in agroecosystems. For example, antibiotics may alter microbial emissions of greenhouse gases by affecting livestock gut microbiota. Furthermore, antibiotics may affect the microbiota of non-target animals that rely on dung, such as dung beetles, and the ecosystem services they provide. To examine these interactions, we treated cattle with a commonly used broad-spectrum antibiotic and assessed downstream effects on microbiota in dung and dung beetles, greenhouse gas fluxes from dung, and beetle size, survival and reproduction. We found that antibiotic treatment restructured microbiota in dung beetles, which harboured a microbial community distinct from those in the dung they were consuming. The antibiotic effect on beetle microbiota was not associated with smaller size or lower numbers. Unexpectedly, antibiotic treatment raised methane fluxes from dung, possibly by altering the interactions between methanogenic archaea and bacteria in rumen and dung environments. Our findings that antibiotics restructure dung beetle microbiota and modify greenhouse gas emissions from dung indicate that antibiotic treatment may have unintended, cascading ecological effects that extend beyond the target animal.
The morphology of H II galaxies

We present CCD images of a sample of 39 HII galaxies taken at the Danish 1.54m telescope on La Silla. The images are used to analyse the morphology of these emission line dwarfs, and the structural properties of the knots of star formation and of the underlying galaxy. The sizes of the starbursts are measured. We propose a morphological classification based on the presence or absence of signs of tails, extensions, or distorted outer isophotes. This criterion segregates the objects into two broad morphological types with different physical properties: the more disturbed and extended (type I) HII galaxies having larger luminosities and velocity dispersions than the more compact and regular (type II) objects. The relative position of HII galaxies and of a sample of dwarf elliptical galaxies in the [R -- sigma] diagram support the hypothesis of a possible evolutionary link between the two types of galaxy.
Shortest Paths of Bounded Curvature for the Dubins Interval Problem

The Dubins interval problem aims to find the shortest path of bounded curvature between two targets such that the departure angle from the first target and the arrival angle at the second target are constrained to two respective intervals. We propose a new and a simple algorithm to this problem based on the minimum principle of Pontryagin.
Noise-Induced Min Phenotypes in E. coli

The spatiotemporal oscillations of the Escherichia coli proteins MinD and MinE direct cell division to the region between the chromosomes. Several quantitative models of the Min system have been suggested before, but no one of them accounts for the behavior of all documented mutant phenotypes. We analyzed the stochastic reaction-diffusion kinetics of the Min proteins for several E. coli mutants and compared the results to the corresponding deterministic mean-field description. We found that wild-type (wt) and filamentous (ftsZ −) cells are well characterized by the mean-field model, but that a stochastic model is necessary to account for several of the characteristics of the spherical (rodA−) and phospathedylethanolamide-deficient (PE−) phenotypes. For spherical cells, the mean-field model is bistable, and the system can get trapped in a non-oscillatory state. However, when the intrinsic noise is considered, only the experimentally observed oscillatory behavior remains. The stochastic model also reproduces the change in oscillation directions observed in the spherical phenotype and the occasional gliding of the MinD region along the inner membrane. For the PE− mutant, the stochastic model explains the appearance of randomly localized and dense MinD clusters as a nucleation phenomenon, in which the stochastic kinetics at low copy number causes local discharges of the high MinDATP to MinDADP potential. We find that a simple five-reaction model of the Min system can explain all documented Min phenotypes, if stochastic kinetics and three-dimensional diffusion are accounted for. Our results emphasize that local copy number fluctuation may result in phenotypic differences although the total number of molecules of the relevant species is high.
Antifungal Metabolites from the Plant Endophytic Fungus Pestalotiopsis Foedan Table 1. Nmr Spectroscopic Data for Pestafolide a (1) in Cdcl 3

Pestafolide A (1), a new reduced spiro azaphilone derivative, and pestaphthalides A (2) and B (3), two new isobenzofuranones, have been isolated form solid cultures of an isolate of Pestalotiopsis foedan. The structures of these compounds were determined mainly by analysis of their NMR spectroscopic data. The relative configuration of 1-3 was assigned by analysis of 1 H NMR J-values and NOESY data, and the absolute configuration was determined by application of the CD excitation chirality and modified Mosher method. Compounds 1-3 showed modest antifungal activity. Endophytic fungi that inhabit normal tissues of the host plants without causing apparent pathogenic symptoms have been demonstrated to be rich sources of bioactive natural products. 1–3 As one class of the most widely distributed endophytic fungi, Pesta-lotiopsis spp. are prolific producers of different types of bioactive metabolites. 4–12 During our ongoing chemical investigations of endophytic fungi as sources of new bioactive natural products, a subculture of an isolate of Pestalotiopsis foedan was grown in solid-substrate fermentation culture. Its organic solvent extract displayed antifungal activity against Candida albicans (ATCC 10231), Geotrichum candidum (AS2.498), and Aspergillus fumigatus (ATCC 10894). Bioassay-guided fractionation of this extract led to the isolation of one new reduced azaphilone derivative and two new isobenzofuranones that have been named pestafolide A (1) and pestaphthalides A (2) and B (3). Details of the isolation, structure elucidation, and stereochemical assignments of these compounds are presented here. Results and Discussion Pestafolide A (1) was assigned the molecular formula C 15 H 22 O 5 (five unsaturations) on the basis of HRESI analysis [m/z 305.1363 (M + Na) + ; ∆ +0.4 mmu] and NMR data (Table 1). Analysis of the 1 H, 13 C, and HMQC NMR data for 1 revealed the presence of two methyl groups, six methylene units (one of which was oxygenated), two oxymethines, two oxygenated quaternary carbons, two olefinic carbons, and one ketone carbon (δ C 199.6). These data accounted for all 1 H and 13 C resonances except two exchangeable protons and required compound 1 to be tricyclic. Analysis of the 1 H– 1 H COSY NMR data led to the identification of two isolated proton spin-systems corresponding to the C-5–C-6 and C-10–C-14 subunits of structure 1. HMBC correlations of the isolated methyl protons H 3-15 with the oxygenated quaternary carbon C-4, the oxymethine carbon C-5, and the ketone carbon C-3 indicated that C-4 was connected to C-3, C-5, and …
Studies of the relationship between environmental forcing and the structure and dynamics of tornado-like vortices

Axisymmetric numerical simulations continue to provide insight into how the structure, dynamics, and maximum wind speeds of tornadoes, and other convectively-maintained vortices, are influenced by the surrounding environment. This work is continued with a new numerical model of axisymmetric incompressible flow that incorporates adaptive mesh refinement. The model dynamically increases or decreases the resolution in regions of interest as determined by a specified refinement criterion. Here, the criterion used is based on the cell Reynolds number dx dv / nu, so that the flow is guaranteed to be laminar on the scale of the local grid spacing. The model is used to investigate how the altitude and shape of the convective forcing, the size of the domain, and the effective Reynolds number (based on the choice of the eddy viscosity nu) influence the structure and dynamics of the vortex. Over a wide variety of domain and forcing geometries,the vortex Reynolds number Gamma / nu (the ratio of the far-field circulation to the eddy viscosity) is shown to be the most important parameter for determining vortex structure and behavior. Furthermore,it is found that the vertical scale of the convective forcing only affects the vortex inasmuch as this vertical scale contributes tomore » the total strength of the convective forcing. The horizontal scale of the convective forcing, however, is found to be the fundamental length scale in the problem, in that it can determine both the circulation of the fluid that is drawn into the vortex core, and also influences the depth of the swirling boundary layer. Higher mean wind speeds are sustained as the eddy viscosity is decreased; however, it is observed that the highest wind speeds are found in the high-swirl, two-celled vortex regime rather than in the low-swirl, one-celled regime, which is in contrast with some previous results. The conclusions drawn from these results are applied to dimensional simulations with scales similar to the mesocyclone/thunderstorm environment. Tornado-like vortices are reproduced, using a constant eddy viscosity with such values as 40 m2s-1, which have maximum wind speeds, radii of maximum winds, and boundary layer depths which are quite similar to those recently observed with portable Doppler radar. Based on the results of both nondimensional and tornado-scale simulations, scaling laws are empirically derived for the internal length scales in tornado-like vortices, such as the depth of the boundary layer and the radius of maximum winds. « less
New Lipase for Biodiesel Production: Partial Purification and Characterization of LipSB 25-4

The lipolytic activities of 300 Streptomyces isolates were determined in Tributyrin and Rhodamine-B Agar. Lipase activities were also measured with p-nitrophenyl palmitate (p-NPP) as a substrate. The strain of Streptomyces bambergiensis OC 25-4 used in this study was selected among 300 strains of Streptomyces from MUCC as the best lipase producer. The incubation conditions were optimized and the inoculum amount, incubation period, effect of carbon and nitrogen sources, and rates of MgSO4 and CaCO3 were investigated. LipSB 25-4 (the lipase produced by S. bambergiensis OC 25-4 strain) was partially purified with ammonium sulphate precipitation, dialysis, and gel filtration chromatography 2.73-fold and with 92.12 U/mg specific activity. The optimal pH and temperature for LipSB 25-4 were determined as 8.0 and 50°C, respectively. The lipase has high stability in all pH and temperature values used in this study. While LipSB 25-4 was slightly activated in the presence of β-mercaptoethanol, it was slightly reduced by PMSF. The enzyme conserved approximately 75% of its activity at the end of 60 h, in the presence of methanol and ethanol. Since LipSB 25-4 displays high activity in the thermophilic conditions and stability in the presence of organic solvents, this lipase can catalyse the biodiesel production from olive oil by the transesterification reactions.
Neuromuscular Responses to Simulated Brazilian Jiu-Jitsu Fights

Abstract The aim of this study was to investigate the neuromuscular performance responses following successive Brazilian Jiu-Jitsu (BJJ) fights. Twenty-three BJJ athletes (age: 26.3 ± 6.3 years; body mass: 79.4 ± 9.7 kg; body height: 1.80 ± 0.1 m) undertook 3 simulated BJJ fights (10 min duration each separated by 15 min of rest). Neuromuscular performance was measured by the bench press throw (BPT) and vertical counter movement jump (VCMJ) tests, assessed before the 1st fight (Pre) and after the last one (Post). Blood lactate (LA) was measured at Pre, 1 min Post, and 15 min Post fights. Paired t-tests were employed in order to compare the BPT and VCMJ results. One-way ANOVA with Bonferroni post hoc tests were utilized to compare LA responses. The results revealed a significant (p < 0.05) increase in VCMJ performance (40.8 ± 5.5 cm Pre vs. 42.0 ± 5.8 cm Post), but no significant changes in the BPT (814 ± 167 W Pre vs. 835 ± 213 W Post) were observed. LA concentration increased significantly (p < 0.05) at Post, both in the 1st min and the 15th min of recovery. We concluded that successive simulated BJJ fights demanded considerable anaerobic contribution of ATP supply, reinforcing the high-intensity intermittent nature of the sport. Nevertheless, no negative impact on acute neuromuscular performance (power) was observed.
Growth Forecast Errors and Fiscal Multipliers

This paper investigates the relation between growth forecast errors and planned fiscal consolidation during the crisis. We find that, in advanced economies, stronger planned fiscal consolidation has been associated with lower growth than expected, with the relation being particularly strong, both statistically and economically, early in the crisis. A natural interpretation is that fiscal multipliers were substantially higher than implicitly assumed by forecasters. The weaker relation in more recent years may reflect in part learning by forecasters and in part smaller multipliers than in the early years of the crisis.
Monoclonal antibodies against the M-protein and carbohydrate antigens of histoplasmin characterized by the enzyme-linked immunoelectrotransfer blot method

Monoclonal antibodies (MAbs) of two different specificities were produced by immunizing mice with the semipurified M antigen of histoplasmin. One type, from clone CB4, was an immunoglobulin M that precipitated a polysaccharide present in histoplasmin and also formed immunoprecipitates with a cross-reactive polysaccharide present in extracts of Blastomyces dermatitidis and Coccidioides immitis. The second type of MAb, from clone EC2, was an immunoglobulin G that reacted in the enzyme-linked immunoelectrotransfer blot (EITB) assay with a doublet of proteins with an apparent molecular size of 70 to 75 kilodaltons. This molecule is proposed as the authentic M protein antigen that is recognized by M antibodies in sera from mice and rabbits immunized with Histoplasma capsulatum and from persons with histoplasmosis. The M factor also occurs in an abundant disulfide-bridged dimer which has a molecular size of 150 kilodaltons and is nonimmunoreactive under the conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
Characterization of the stability range of the Hilbert transform with applications to spectral factorization

The Hilbert transform plays an important role in many different applications. Especially in the area of detection and estimation it is closely related to the calculation of the spectral factorization. Generally, it is not possible to calculate the Hilbert transform in closed form. Therefore approximation methods are applied. This paper studies the stability of a general class of approximation algorithms for the Hilbert transform which contains all traditional numerical integration methods. To this end, the paper introduces a scale of signal spaces with finite energy in which a factor (log n)β measures the concentration of the signal energy in its Fourier coefficients cn. It will be shown that if the energy concentration is too weak, i.e. if 0 ≤ β ≤ 1, then every approximation method diverges. Conversely, if the energy concentration is sufficiently good, i.e. if β > 1, convergent approximation methods do exist and we give a natural characterization of all convergent methods.
Molecular biology of histidine decarboxylase and prostaglandin receptors

Histamine and prostaglandins (PGs) play a variety of physiological roles as autacoids, which function in the vicinity of their sources and maintain local homeostasis in the body. They stimulate target cells by acting on their specific receptors, which are coupled to trimeric G proteins. For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses. We cloned the cDNAs for mouse l-histidine decarboxylase (HDC) and 6 mouse prostanoid receptors (4 PGE2 receptors, PGF receptor, and PGI receptor). We then characterized the expression patterns and functions of these genes. Furthermore, we established gene-targeted mouse strains for HDC and PG receptors to explore the novel pathophysiological roles of histamine and PGs. We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors.
Molecular mechanism of a frequent genetic form of deafness.

To the Editor: The genes encoding the two major connexins of the cochlea are contiguous on human chromosome 13 (GJB2 and GJB6) and on mouse chromosome 14 (Cx26 and Cx30, respectively). Biallelic GJB2 mutations account for a large proportion of cases of recessive deafness in many European countries,1 whereas biallelic mutations of GJB6 appear to be involved only rarely. However, del Castillo et al.2 have shown that a significant proportion of people who have severe or profound prelingual deafness carry both a deleterious point mutation in GJB2 on one chromosome and a large deletion (approximately 340 kb) in GJB6, but .