Miracle-dz/UniFAR-FTUs huggingface dataset:
Study of Mesoporous Silica Nanoparticles' (MSNs) intracellular trafficking and their application as drug delivery vehicles

Mesoporous silica nanoparticles (MSNs) are attractive drug delivery vehicle candidates due to their biocompatibility, stability, high surface area and efficient cellular uptake. In this dissertation, I discuss three aspects of MSNs' cellular behavior. First, MSNs are targeted to primary and metastatic cancer cell lines, then their exocytosis from cancer cells is studied, and finally they are used to recover intracellular proteins. Targeting of MSNs to primary cancer cells is achieved by conjugating transferrin on the surface of the mesoporous framework, which resulted in enhancement of nanoparticle uptake and drug delivery efficacy in cells that overexpress the transferrin receptor. Similarly, RGD peptides are used to target metastatic cancer cell lines that over-express integrin &alpha&nu&beta3. A circular RGD peptide is bound to the surface of MSNs and the endocytosis and cell killing efficacy of camptothecin loaded nanoparticles is significantly improved in cells that express the target receptor. Besides targeting, I studied the ultimate fate of phosphonate coated mesoporous silica nanoparticles inside cells. I discovered that the nanoparticles are exocytosed from cells through lysosomal exocytosis. The nanoparticles are exocytosed in intact form and the time that they remain inside the cells is affected by the surface properties of the nanoparticles and the type of cells. Cells that have a high rate of lysosomal exocytosis excrete the nanoparticles rapidly, which makes them more resistant to drug loaded nanoparticles because the amount of drug that is released inside the cell is limited. When the exocytosis of MSNs is inhibited, the cell killing efficacy of nanoparticles loaded with camptothecin is enhanced. The discovery that MSNs are exocytosed by cells led to a study to determine if proteins could be recovered from the exocytosed nanoparticles. The procedure to isolate exocytosed zinc-doped iron core MSNs and identify the proteins bound to them was developed. This serves as a foundation to use MSNs as protein harvesting tools and investigate protein expression in cancer cells.
Bio‐based multilayer barrier films by extrusion, dispersion coating and atomic layer deposition

A single biopolymer film rarely has a competitive edge against synthetic films. One solution is to combine several layers with different properties into multilayer structures. In this way, for example, the barrier properties of bio-based materials can be improved. In this study, the multilayer films are produced by combining three different techniques/materials: 1) dispersion coating (cellulose nanofibrils, CNF), 2) atomic layer deposition (Al2O3; aluminum oxide), and 3) extrusion coating (polyglycolic acid, PGA). Especially the CNF and PGA-containing multilayer films show promising oxygen barrier improvements at different humidities. Thin inorganic coatings are brittle and sensitive toward stresses during converting, which may limit their use in such specific multilayer structures. The developed bio-based films largely fulfill the barrier requirements of fresh food packaging. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42260.
Antitumor effects of miconazole on human colon carcinoma xenografts in nude mice through induction of apoptosis and G0/G1 cell cycle arrest.

Miconazole (MIC), a promising oral antifungal agent, has been used worldwide in the treatment of superficial mycosis. In this study, we demonstrated that MIC dose dependently arrested various human cancer cells at the G0/G1 phase of the cell cycle. The protein levels of p53, p21/Cip1, and p27/Kip1 were significantly elevated by MIC treatment in COLO 205 cells. Electrophoretic mobility gel shift assays showed that the nuclear extracts of the MIC-treated COLO 205 cells exerted a significant binding between wild-type p53 and its consensus-binding site present in the p21/Cip1 promoter. These results suggested that the p53-associated signaling pathway is involved in the regulation of MIC-induced cancer cell growth arrest. By immunoblot analysis, we demonstrated that cyclin D3 and cyclin-dependent kinase-4 (CDK4) protein levels were inhibited by MIC treatment in the cancer cells. Significant therapeutic effect was further demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with MIC (50 mg/kg ip). The protein expression of p53 was significantly increased in MIC-treated tumor tissues by immunohistochemical staining and Western blotting analysis. DNA fragmentation and TUNEL assay were performed and demonstrated that apoptosis occurred in tumor tissues treated with MIC. Our study provides the novel mechanisms of antitumor effects of MIC and such results may have significant applications for cancer chemotherapy.
The impact of underfill properties on the thermomechanical reliability of FCOB assembly

The impact of underfill properties on the thermomechanical reliability of flip chip on board (FCOB) assembly is addressed in this paper. FCOB assemblies using three underfill encapsulants were subjected to a thermal cycling test. The performance of the underfill encapsulants was assessed by a statistical analysis of the failure distribution of the FCOB assemblies. The failure modes in the thermal cycling test were found to be solder joint cracks, delamination at underfill/chip passivation interface, and underfill internal cracks. An attempt was made to correlate these failures with underfill properties such as the coefficient of thermal expansion (CTE), modulus, glass transition temperature (Tg), and adhesive strength to the chip. Additionally, nonlinear finite element analysis (FEA) was conducted to verify the experimental results.
Force regulated dynamics of RPA on a DNA fork

Replication protein A (RPA) is a single-stranded DNA binding protein, involved in most aspects of eukaryotic DNA metabolism. Here, we study the behavior of RPA on a DNA substrate that mimics a replication fork. Using magnetic tweezers we show that both yeast and human RPA can open forked DNA when sufficient external tension is applied. In contrast, at low force, RPA becomes rapidly displaced by the rehybridization of the DNA fork. This process appears to be governed by the binding or the release of an RPA microdomain (toehold) of only few base-pairs length. This gives rise to an extremely rapid exchange dynamics of RPA at the fork. Fork rezipping rates reach up to hundreds of base-pairs per second, being orders of magnitude faster than RPA dissociation from ssDNA alone. Additionally, we show that RPA undergoes diffusive motion on ssDNA, such that it can be pushed over long distances by a rezipping fork. Generally the behavior of both human and yeast RPA homologs is very similar. However, in contrast to yeast RPA, the dissociation of human RPA from ssDNA is greatly reduced at low Mg2+ concentrations, such that human RPA can melt DNA in absence of force.
Optimal beamforming in wireless multiuser MIMO-relay networks

This paper deals with optimal beamforming in wireless multiple-input-multiple-output (MIMO) relay networks that involves multiple concurrent source-destination pairs with imperfect channel state information (CSI) at relays. Our aim is the optimization of the MIMO relay weights that minimize the total relay transmit power subject to signal-to-interference-plus-noise ratio (SINR) of all destinations to be kept above a certain threshold. Since power minimization is a non-convex quadratically constrained quadratic program (QCQP), we use semi-definite programming (SDP) relaxation of above mentioned problem by using a randomization technique.
Exact and efficient calculation of lagrange multipliers in biological polymers with constrained bond lengths and bond angles: Proteins and nucleic acids as example cases

To accelerate molecular dynamics simulations, it is common to impose holonomic constraints on the hardest degrees of freedom. In this way, the time step used to integrate the equations of motion can be increased, thereby allowing longer total simulation times. The imposition of such constraints results in an aditional set of Nc equations (the equations of constraint) and unknowns (their associated Lagrange multipliers), whose solution is closely related to any algorithm implementing the constraints in Euclidean coordinates. In this work, it is shown that, due to the essentially linear structure of typical biological polymers the algebraic equations that need to be solved involve a matrix which is not only sparse, but also banded if the constraints are indexed in a skilful way. This allows the Lagrange multipliers to be obtained through a noniterative procedure, which can be considered exact up to machine precision, and which takes O(Nc) operations, instead of the usual O(N c3 ) for generic molecular systems. We develop the formalism, and describe the appropriate indexing for a number of model molecules. Finally, we provide a numerical example of the technique in a series of polyalanine peptides of different lengths. Although a use of the Lagrange multipliers without any modification in the solution of the underlying ordinary differential equations yields unstable integration algorithms, the central role of these quantities makes their efficient calculation useful for the improvement of methods that correctly enforce the exact satisfaction of the constraints at each time step. We provide several examples of this. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Development of a Damage Analysis Method in Laminated Composites Using Finite Fracture Toughness of Single Lamina

In the present study, the strong physical meaning of the micromechanics approach and capability of the mesomechanics approach for analysis of structures with complex loadings are employed to develop a new micro-meso approach. For this purpose, a new micromechanics model is developed to predict the matrix cracking initiation and evolution in an orthotropic composite lamina. In the meso-scale damage analyses, the traditional damage evolution and constitutive laws are substituted with the progress of damage in micro-scale. The major advantage of the proposed approach is using well-known finite fracture toughness of a lamina only to predict the damage behavior of composite laminates. It is shown that the predicted stress-strain behaviors using the developed procedure are in good agreement with the available experimental results for various laminates with a different lay-up configuration.
Semantic-based distributed i/o with the paramedic framework

Many large-scale applications simultaneously rely on multiple resources for efficient execution. For example, such applications may require both large compute and storage resources; however, very few supercomputing centers can provide large quantities of both. Thus, data generated at the compute site oftentimes has to be moved to a remote storage site for either storage or visualization and analysis. Clearly, this is not an efficient model, especially when the two sites are distributed over a wide-area network. Thus, we present a framework called "ParaMEDIC: Parallel Metadata Environment for Distributed I/O and Computing" which uses application-specific semantic information to convert the generated data to orders-of-magnitude smaller metadata at the compute site, transfer the metadata to the storage site, and re-process the metadata at the storage site to regenerate the output. Specifically, ParaMEDIC trades a small amount of additional computation (in the form of data post-processing) for a potentially significant reduction in data that needs to be transferred in distributed environments.
An Adeno-Associated Virus-Based Intracellular Sensor of Pathological Nuclear Factor-κB Activation for Disease-Inducible Gene Transfer

Stimulation of resident cells by NF-κB activating cytokines is a central element of inflammatory and degenerative disorders of the central nervous system (CNS). This disease-mediated NF-κB activation could be used to drive transgene expression selectively in affected cells, using adeno-associated virus (AAV)-mediated gene transfer. We have constructed a series of AAV vectors expressing GFP under the control of different promoters including NF-κB -responsive elements. As an initial screen, the vectors were tested in vitro in HEK-293T cells treated with TNF-α. The best profile of GFP induction was obtained with a promoter containing two blocks of four NF-κB -responsive sequences from the human JCV neurotropic polyoma virus promoter, fused to a new tight minimal CMV promoter, optimally distant from each other. A therapeutical gene, glial cell line-derived neurotrophic factor (GDNF) cDNA under the control of serotype 1-encapsidated NF-κB -responsive AAV vector (AAV-NF) was protective in senescent cultures of mouse cortical neurons. AAV-NF was then evaluated in vivo in the kainic acid (KA)-induced status epilepticus rat model for temporal lobe epilepsy, a major neurological disorder with a central pathophysiological role for NF-κB activation. We demonstrate that AAV-NF, injected in the hippocampus, responded to disease induction by mediating GFP expression, preferentially in CA1 and CA3 neurons and astrocytes, specifically in regions where inflammatory markers were also induced. Altogether, these data demonstrate the feasibility to use disease-activated transcription factor-responsive elements in order to drive transgene expression specifically in affected cells in inflammatory CNS disorders using AAV-mediated gene transfer.
Optical Detection of Synaptically Induced Glutamate Transport in Hippocampal Slices

Although it has long been believed that glial cells play a major role in transmitter uptake at synapses in the CNS, the relative contribution of glial and neuronal cells to reuptake of synaptically released glutamate has been unclear. Recent identification of the diverse glutamate transporter subtypes provides an opportunity to examine this issue. To monitor glutamate transporter activity, we optically detected synaptically induced changes of membrane potential from hippocampal CA1 field in slice preparations using a voltage-sensitive dye, RH155. In the presence of ionotropic glutamate-receptor blockers, synaptic inputs gave rise to a slow depolarizing response (SDR) in the dendritic field. The amplitude of SDR correlated well with presynaptic activities, suggesting that it was related to transmitter release. The SDR was found to be caused by the activities of glutamate transporters because it was not affected by blockers for GABAA, nACh, 5-HT3, P2X, or metabotropic glutamate receptors but was greatly reduced by dihydrokainate (DHK), a specific blocker for GLT-1 transporter, and by d,l-threo-β-hydroxyaspartate (THA), a blocker for EAAC, GLAST, and GLT-1 transporters. When SDR was detected with RH482 dye, which stains both glial and neuronal cells, 1 mm DHK and 1 mm THA were equally effective in suppressing SDR. The SDR was very small in GLT-1 knockout mice but was maintained in gerbil hippocampi in which postsynaptic neurons were absent because of ischemia. Because GLT-1 transporters are exclusively expressed in astrocytes, our results provide direct evidence that astrocytes play the dominant role in sequestering synaptically released glutamate.
Isolation and characterization Shiga toxin-producing Escherichia coli from sheep and goats in Jordan with evidence of multiresistant serotype O 157 : H 7

Ninety-three rectal swabs of lambs and young goats from two extensively and two intensively managed herds in Jordan were taken and examined for Shiga toxin-producing Escherichia coli (STEC). The bacteriological examination included the preenrichment of rectal swabs in EC broth with novobiocin, and a subsequent parallel isolation on enterohemolysin agar and immunomagnetic separation with cultivation on CT-SMAC. The STEC O157:H7 strains were demonstrated in 8 of 32 diarrheic lambs 1to 3-weeks old in one sheep herd with intensive milk production. In the remaining three herds, serogroups O128, O78, O15 and serotype O128:K85 of STEC strains were the most frequent findings. The presence of stx2, ehlyA and eaeA genes in all STEC O157:H7 isolates was confirmed by PCR. In two untypable STEC isolates, stx2 and ehlyA genes were detected. In other STEC non-O157 isolates, only stx1 a ehlyA genes were found. All STEC O157:H7 isolates were resistant against sulphonamides and chloramphenicol, five were also resistant against ampicillin and streptomycin, one against co-trimoxazole. One isolate was resistant against ampicillin, ampicillin-sulbactam, cephalosporins (cefazolin, cefuroxime), monobactams (aztreonam), sulphonamides, co-trimoxazole, aminoglycosides, tetracycline and chloramphenicol. Compared the resistant STEC O157:H7 isolates, the multiresistant isolate had a different RAPD pattern. Of 36 STEC non-O157 isolates, one isolate was resistant against sulphonamides and co-trimoxazole, and another one against ampicillin, streptomycin, sulphonamides and co-trimoxazole. STEC isolates resistant against antimicrobial agents were demonstrated only in herds with intensive management.
Taxonomy-superimposed graph mining

New graph structures where node labels are members of hierarchically organized ontologies or taxonomies have become commonplace in different domains, e.g., life sciences. It is a challenging task to mine for frequent patterns in this new graph model which we call taxonomy-superimposed graphs, as there may be many patterns that are implied by the generalization/specialization hierarchy of the associated node label taxonomy. Hence, 'standard' graph mining techniques are not directly applicable. In this paper, we present Taxogram, a taxonomy-superimposed graph mining algorithm that can efficiently discover frequent graph structures in a database of taxonomy-superimposed graphs. Taxogram has two advantages: (i) It performs a subgraph isomorphism test once per class of patterns which are structurally isomorphic, but have different labels, and (ii) it reconciles standard graph mining methods with taxonomy-based graph mining and takes advantage of well-studied methods in the literature. Taxogram has three stages: (a) relabeling nodes in the input database, (b) mining pattern classes/families and constructing associated occurrence indices, and (c) computing patterns and eliminating useless (i.e., over-generalized) patterns by post-processing occurrence indices. Experimental results show that Taxogram is significantly more efficient and more scalable compared to other alternative approaches.
Emulation of Operational Amplifiers and Diodes in Audio Distortion Circuits

This brief presents a generic model to emulate distortion circuits using operational amplifiers and diodes. Distortion circuits are widely used for enhancing the sound of guitars and other musical instruments. This brief introduces a new model for an ideal operational amplifier that does not include implicit equations and is thus suitable for implementation using wave digital filters (WDFs). Furthermore, a novel WDF model for a diode is proposed using the Lambert W function. A comparison of output signals of the proposed models to those obtained from a reference simulation using SPICE shows that the distortion characteristics are accurately reproduced over a wide frequency range. Additionally, the proposed model enables real-time emulation of distortion circuits using ten multiplications, 22 additions, and two interpolations from a lookup table per output sample.
Anti-Angiogenesis Therapy in the Vx2 Rabbit Cancer Model with a Lipase-cleavable Sn 2 Taxane Phospholipid Prodrug using αvβ3-Targeted Theranostic Nanoparticles

In nanomedicine, the hydrophobic nature of paclitaxel has favored its incorporation into many nanoparticle formulations for anti-cancer chemotherapy. At lower doses taxanes are reported to elicit anti-angiogenic responses. In the present study, the facile synthesis, development and characterization of a new lipase-labile docetaxel prodrug is reported and shown to be an effective anti-angiogenic agent in vitro and in vivo. The Sn 2 phosphatidylcholine prodrug was stably incorporated into the lipid membrane of αvβ3-integrin targeted perfluorocarbon (PFC) nanoparticles (αvβ3-Dxtl-PD NP) and did not appreciably release during dissolution against PBS buffer or plasma over three days. Overnight exposure of αvβ3-Dxtl-PD NP to plasma spiked with phospholipase enzyme failed to liberate the taxane from the membrane until the nanoparticle integrity was compromised with alcohol. The bioactivity and efficacy of αvβ3-Dxtl-PD NP in endothelial cell culture was as effective as Taxol® or free docetaxel in methanol at equimolar doses over 96 hours. The anti-angiogenesis effectiveness of αvβ3-Dxtl-PD NP was demonstrated in the Vx2 rabbit model using MR imaging of angiogenesis with the same αvβ3-PFC nanoparticle platform. Nontargeted Dxtl-PD NP had a similar MR anti-angiogenesis response as the integrin-targeted agent, but microscopically measured decreases in tumor cell proliferation and increased apoptosis were detected only for the targeted drug. Equivalent dosages of Abraxane® given over the same treatment schedule had no effect on angiogenesis when compared to control rabbits receiving saline only. These data demonstrate that αvβ3-Dxtl-PD NP can reduce MR detectable angiogenesis and slow tumor progression in the Vx2 model, whereas equivalent systemic treatment with free taxane had no benefit.
Approaches and databases for online calibration of binaural sound localization for robotic heads

In this paper, we evaluate adaptive sound localization algorithms for robotic heads. To this end we built a 3 degree-of-freedom head with two microphones encased in artificial pinnae (outer ears). The geometry of the head and pinnae induce temporal differences in the sound recorded at each microphone. These differences change with the frequency of the sound, location of the sound, and orientation of the robot in a complex manner. To learn the relationship between these auditory differences and the location of a sound source, we applied machine learning methods to a database of different audio source locations and robot head orientations. Our approach achieves a mean error of 2.5 degrees for azimuth and 11 degrees for elevation for estimating the position of an audio source. The impressive results highlight the benefits of a two-stage regression model to make use of the properties of the artificial pinnae for elevation estimation. In this work, the algorithms were trained using ground truth data provided by a motion capture system. We are currently generalizing the approach so that the training signal is provided online based on a real-time face detection and speech detection system.
Built-in Potential Mapping of Silicon Field Effect Transistor Cross Sections by Multimode Scanning Probe Microscopy

Built-in potential maps of metal-oxide-semiconductor field effect transistors (MOSFETs) with gate lengths of 30 and 150 nm were measured on cross sectional Si(110) surfaces covered with ultra-thin oxide. The maps were obtained by measuring the contact potential difference (CPD) using multimode scanning probe microscopy (MSPM) with a vibrating probe in the constant force mode. The improved spatial resolution and the sensitivity to the electrostatic potential were achieved for an optimal probe-sample gap (~1 nm) and vibration amplitude of 0.2 nm. The capability and challenges of the measurement method are discussed by comparing measured CPD maps with device simulation results.
Numerical Investigation of the Upper Ocean Response to the Typhoon Winnie (1997) Using an Air-Sea Coupled Model

In order to investigate the impact of air-sea interaction on the ocean surface mixed layer, Typhoon Winnie (1997) was numerical simulated with a two-way air-sea coupled model MCM (Mesoscale Coupled Model). It shows that the Sea Surface Temperature (SST) decreases over a large area with a magnitude up to 4°C. The sea temperature at 30-50 m depth increases about 1°C corresponding to the surface cooling. Moreover, the oceanic mixed layer depth deepens by 20-30 m. It can be included that these variations in the upper ocean are mainly due to vertical mixing induced by the wind stress of the typhoon.