Miracle-dz/UniFAR-FTUs huggingface dataset:
Modifying the size of nanopores of alginate microcapsules

Alginate hydrogels provide desirable biocompatibility and material properties for various biomedical applications, but are limited by the polymer's natural pore size. With the rise of nanotechnology, the desired crosslinked pore size range of 30 nm to 100 nm has not yet been achieved. This project aimed to develop a method to increase the pore size of alginate-based hydrogels in a reproducible manner without compromising their structural integrity. Experimental methods included altering alginate composition using carboxymethyl cellulose or gelatin and inducing conformational changes via Mach-1​TM mechanical compression. Fluorescence microscopy was used to visualize the diffusion of FITC-dextran weight markers and fluorescent polystyrene nanoparticles into the microcapsules (d = 300 ​μ​m) and macrocapsules (d = 3 ​m​m) for all experimental conditions. Based on pilot experiments, altered alginate composition did not significantly increase the pore size of alginate capsules for the modeled diffusivity range D = 1 x 10​-14​ m​2​/s to D = 1 x 10​-15​ m​2​/s. Mechanical compressions did not significantly affect the porosity or diffusivity of alginate macrocapsules (p > 0.05) under all conditions for Young’s moduli ranging from E = 76 kPa to E = 200 kPa. Based on image analysis results, it could be hypothesized that molecular weight cutoff cutoff may be increased to 500 kDa following 10 successive compressions. Additional work to optimize fluorescent microscopy methods and pore size manipulation methods is required for expanded use of alginate capsules with emerging nanotechnologies.
CRISPR/Cas9 genome editing in human pluripotent stem cells: Harnessing human genetics in a dish

Abstract: Because of their extraordinary differentiation potential, human pluripotent stem cells (hPSCs) can differentiate into virtually any cell type of the human body, providing a powerful platform not only for generating relevant cell types useful for cell replacement therapies, but also for modeling human development and disease. Expanding this potential, structures resembling human organs, termed organoids, have been recently obtained from hPSCs through tissue engineering. Organoids exhibit multiple cell types self‐organizing into structures recapitulating in part the physiology and the cellular interactions observed in the organ in vivo, offering unprecedented opportunities for human disease modeling. To fulfill this promise, tissue engineering in hPSCs needs to be supported by robust and scalable genome editing technologies. With the advent of the CRISPR/Cas9 technology, manipulating the genome of hPSCs has now become an easy task, allowing modifying their genome with superior precision, speed, and throughput. Here we review current and potential applications of the CRISPR/Cas9 technology in hPSCs and how they contribute to establish hPSCs as a model of choice for studying human genetics. Developmental Dynamics 245:788–806, 2016. © 2016 Wiley Periodicals, Inc.
Molecular bases of neuroserpin function and pathology

Abstract Serpins build a large and evolutionary widespread protein superfamily, hosting members that are mainly Ser-protease inhibitors. Typically, serpins display a conserved core domain composed of three main β-sheets and 9–10 α-helices, for a total of approximately 350 amino acids. Neuroserpin (NS) is mostly expressed in neurons and in the central and peripheral nervous systems, where it targets tissue-type plasminogen activator. NS activity is relevant for axogenesis, synaptogenesis and synaptic plasticity. Five (single amino acid) NS mutations are associated with severe neurodegenerative disease in man, leading to early onset dementia, epilepsy and neuronal death. The functional aspects of NS protease inhibition are linked to the presence of a long exposed loop (reactive center loop, RCL) that acts as bait for the incoming partner protease. Large NS conformational changes, associated with the cleavage of the RCL, trap the protease in an acyl-enzyme complex. Contrary to other serpins, this complex has a half-life of approximately 10 min. Conformational flexibility is held to be at the bases of NS polymerization leading to Collins bodies intracellular deposition and neuronal damage in the pathological NS variants. Two main general mechanisms of serpin polymerization are currently discussed. Both models require the swapping of the RCL among neighboring serpin molecules. Specific differences in the size of swapped regions, as well as differences in the folding stage at which polymerization can occur, distinguish the two models. The results provided by recent crystallographic and biophysical studies allow rationalization of the functional and pathological roles played by NS based on the analysis of four three-dimensional structures.
Maximum likelihood estimation of FRET efficiency and its implications for distortions in pixelwise calculation of FRET in microscopy

Ratiometric determination of the efficiency of fluorescence or Förster resonance energy transfer (FRET) is one of the most widespread methods for the characterization of protein clustering and conformation. Low photon numbers, often present in pixel‐by‐pixel determination of FRET efficiency in digital microscopy, result in large uncertainties in the derived FRET parameter. Here, we propose a method based on maximum likelihood estimation (MLE) of FRET efficiency using photon counting detectors to overcome this limitation. Intensities measured in the donor, FRET, and acceptor channels were all assumed to follow Poisson statistics as a result of detector shot noise. The joint probability of photon numbers detected in the donor, FRET, and acceptor channels was derived using an equation describing the relationship between the three measured intensities. The FRET efficiency generating the measured photon numbers with the largest likelihood was determined iteratively providing a single FRET value for all pixels in the calculation. Since as few as 100 pixels are sufficient to provide a maximum likelihood estimate for FRET, biological variability in FRET values can be revealed by performing the analysis for regions of interests in an image. Since the algorithm provides the probability of a combination of donor, FRET, and acceptor intensities observed in each individual pixel given a certain FRET efficiency, outlier pixels with low probabilities could be excluded from the analysis. Simulations carried out with low photon numbers in the presence and absence of outlier pixels revealed that the proposed approach can reliably and reproducibly estimate FRET efficiency. In addition, systematic evaluation of the simulation results showed that the distribution of pixel‐by‐pixel FRET efficiencies is skewed, and the mean of these FRET values is a biased and unreliable estimate of the FRET efficiency. In the absence of outlier pixels, FRET calculated from summed donor, FRET, and acceptor intensities proved to be as reliable as MLE. We conclude that MLE of FRET outperforms calculations using summed and pixel‐by‐pixel intensities in biologically relevant situations involving low photon numbers and outlier pixels. © 2014 International Society for Advancement of Cytometry
Huffman-based code compression techniques for embedded systems

Increasing embedded systems functionality causes a steep increase in code size. For instance, more than 60MB of software is installed in current state-of-the-art cars [9]. It is often challenging and cumbersome to host vast amount of software in an efficient way within a given hardware resource budget of an embedded system. This may be done by using code compression techniques, which compress the program code off-line (i.e. at design time) and decompress it on-line (i.e. at run time). Among all statistical compression algorithms, Huffman Coding is one of the best compression techniques since it provably provides the shortest average codeword length [36]. When Huffman Coding is used as a compression technique, Look-up Table(s) are generated to store the original instructions. As the size of the tables becomes large, it may negatively affect the final compression ratio (defined as the ratio of compressed code to uncompressed code). Thus, the Look-up Tables diminish the advantages that could be obtained by compressing the code. This thesis presents different Huffman-based hardware supported code compression techniques, which can efficiently solve this problem and improve the compression ratio. In addition to that, this the presents a new technique to improve the performance of the hardware decoder. The code compression techniques are targeted two processor architectures, namely RISC and VLIW. In this thesis, the Look-up Table size is reduced by using the “Look-up Table Compression Technique” for RISC processors. This is done by sorting the entries of the table to decrease the number of bit toggles between each two successive entries. To show the efficiency of the “Look-up Table Compression Technique”, we apply it to two compression schemes, i.e. Dictionary-based Compression Scheme and Statistical Compression Scheme. Using the “Look-up Table Compression Technique” reduces the table size by up to 45% and improves the compression ratio on average by more than 25%. The evaluations are conducted using a representative set of applications from MiBench [20] and are built for three major embedded processor architectures, namely ARM, MIPS viii
Fast kilovoltage/megavoltage (kVMV) breathhold cone-beam CT for image-guided radiotherapy of lung cancer

Long image acquisition times of 60–120 s for cone-beam CT (CBCT) limit the number of patients with lung cancer who can undergo volume image guidance under breathhold. We developed a low-dose dual-energy kilovoltage–megavoltage-cone-beam CT (kVMV-CBCT) based on a clinical treatment unit reducing imaging time to ⩽15 s. Simultaneous kVMV-imaging was achieved by dedicated synchronization hardware controlling the output of the linear accelerator (linac) based on detector panel readout signals, preventing imaging artifacts from interference of the linac's MV-irradiation and panel readouts. Optimization was performed to minimize the imaging dose. Single MV-projections, reconstructed MV-CBCT images and images of simultaneous 90° kV- and 90° MV-CBCT (180° kVMV-CBCT) were acquired with different parameters. Image quality and imaging dose were evaluated and compared to kV-imaging. Hardware-based kVMV synchronization resulted in artifact-free projections. A combined 180° kVMV-CBCT scan with a total MV-dose of 5 monitor units was acquired in 15 s and with sufficient image quality. The resolution was 5–6 line pairs cm−1 (Catphan phantom). The combined kVMV-scan dose was equivalent to a kV-radiation scan dose of ∼33 mGy. kVMV-CBCT based on a standard linac is promising and can provide ultra-fast online volume image guidance with low imaging dose and sufficient image quality for fast and accurate patient positioning for patients with lung cancer under breathhold.
Supporting multi-example image queries in image databases

Query by example (or image) is commonly supported in image databases. However, it is also desirable for a content-based image retrieval system to support multi-example queries. A multi-example query refers to a query which contains one or more example images. Although multi-example query problem can be solved by dividing it to several single-example queries, merging these single-example queries' results to find the top n relevant images is a non-trivial problem. The Netview system, which is a geographic data retrieval system developed at the State University of New York at Buffalo, provides users with flexible choices to adjust query parameters such as importance of each example image and result combination strategies to generate satisfiable retrieval output. In this paper, we formally define the multi-example image query problem. We then present a variety of result combination strategies, including linear distance combination and non-linear result combination. We finally discuss the experimental performance of these strategies.
Unigram Backoff vs . TnT Evaluating Part of Speech Taggers Introduction to Computational Linguistics

Automated statistical part-of-speech (POS) tagging has been a very active research area for many years and is the foundation of natural language processing systems. This paper introduces and analyzes the performance of two part-of-speech taggers, namely the NLTK unigram backoff tagger and the TnT tagger, a trigram tagger. Experimental results show that the TnT tagger outperforms the NLTK unigram backoff tagger. However, the tagging accuracy of both taggers decreases almost by the same number when the taggers are tested on a corpus which differs from the one they were trained on.
Design and optimization of the silver nanograting structure utilizing surface plasmon-polariton for increase of SERS sensor response

This paper reports on the design of the surface enhanced Raman spectroscopy (SERS) structures that were optimized through computation and simulation to obtain the best enhancement of the surface plasmon-polariton (SPP) response on these structures. The structure of the silver nano-grating was designed, fabricated, optimized and measured. The enhancement factor and the increase in the absorption capabilities associated with SPP were evaluated. The rigorous coupled wave analysis (RCWA) and finite-difference time-domain (FDTD) computational/simulation methods were utilized. The comparison between the computation simulation outputs and the measured outputs of the fabricated samples was performed.
Identifying environmental sounds: a multimodal mapping study

Our environment is full of auditory events such as warnings or hazards, and their correct recognition is essential. We explored environmental sounds (ES) recognition in a series of studies. In study 1 we performed an Activation Likelihood Estimation (ALE) meta-analysis of neuroimaging experiments addressing ES processing to delineate the network of areas consistently involved in ES processing. Areas consistently activated in the ALE meta-analysis were the STG/MTG, insula/rolandic operculum, parahippocampal gyrus and inferior frontal gyrus bilaterally. Some of these areas truly reflect ES processing, whereas others are related to design choices, e.g., type of task, type of control condition, type of stimulus. In study 2 we report on 7 neurosurgical patients with lesions involving the areas which were found to be activated by the ALE meta-analysis. We tested their ES recognition abilities and found an impairment of ES recognition. These results indicate that deficits of ES recognition do not exclusively reflect lesions to the right or to the left hemisphere but both hemispheres are involved. The most frequently lesioned area is the hippocampus/insula/STG. We made sure that any impairment in ES recognition would not be related to language problems, but reflect impaired ES processing. In study 3 we carried out an fMRI study on patients (vs. healthy controls) to investigate how the areas involved in ES might be functionally deregulated because of a lesion. The fMRI evidenced that controls activated the right IFG, the STG bilaterally and the left insula. We applied a multimodal mapping approach and found that, although the meta-analysis showed that part of the left and right STG/MTG activation during ES processing might in part be related to design choices, this area was one of the most frequently lesioned areas in our patients, thus highlighting its causal role in ES processing. We found that the ROIs we drew on the two clusters of activation found in the left and in the right STG overlapped with the lesions of at least 4 out of the 7 patients' lesions, indicating that the lack of STG activation found for patients is related to brain damage and is crucial for explaining the ES deficit.
Filling the dead‐time gap in zero echo time MRI: Principles compared

MRI of tissues with short coherence lifetimes T2 or T2* can be performed efficiently using zero echo time (ZTE) techniques such as algebraic ZTE, pointwise encoding time reduction with radial acquisition (PETRA), and water‐ and fat‐suppressed proton projection MRI (WASPI). They share the principal challenge of recovering data in central k‐space missed due to an initial radiofrequency dead time. The purpose of this study was to compare the three techniques directly, with a particular focus on their behavior in the presence of ultra–short‐lived spins.
Measurement Error Impact on Node Localization of Large Scale Underwater Sensor Networks

This paper studies the impact of distance measurement error on node localization in large scale Underwater Wireless Sensor Networks (UWSNs) where only a small percent of nodes are anchor nodes with accurate location information and a large percent of ordinary nodes are to be localized. The recursive localization algorithm is re-evaluated under realistic assumptions that low-cost underwater sensor node may experience large system errors and random errors of distance measurement. Our results show that the errors indeed cause severe performance degradation in localization coverage and normalized localization errors. The sources of distance measurement errors are also identified and their remedies are suggested.
The Distribution of Polycomb-Group Proteins During Cell Division and Development in Drosophila Embryos: Impact on Models for Silencing

The subcellular three-dimensional distribution of three polycomb-group (PcG) proteins—polycomb, polyhomeotic and posterior sex combs—in fixed whole-mount Drosophila embryos was analyzed by multicolor confocal fluorescence microscopy. All three proteins are localized in complex patterns of 100 or more loci throughout most of the interphase nuclear volume. The rather narrow distribution of the protein intensities in the vast majority of loci argues against a PcG-mediated sequestration of repressed target genes by aggregation into subnuclear domains. In contrast to the case for PEV repression (Csink, A.K., and S. Henikoff. 1996. Nature. 381:529–531), there is a lack of correlation between the occurrence of PcG proteins and high concentrations of DNA, demonstrating that the silenced genes are not targeted to heterochromatic regions within the nucleus. There is a clear distinction between sites of transcription in the nucleus and sites of PcG binding, supporting the assumption that most PcG binding loci are sites of repressive complexes. Although the PcG proteins maintain tissue-specific repression for up to 14 cell generations, the proteins studied here visibly dissociate from the chromatin during mitosis, and disperse into the cytoplasm in a differential manner. Quantitation of the fluorescence intensities in the whole mount embryos demonstrate that the dissociated proteins are present in the cytoplasm. We determined that <2% of PH remains attached to late metaphase and anaphase chromosomes. Each of the three proteins that were studied has a different rate and extent of dissociation at prophase and reassociation at telophase. These observations have important implications for models of the mechanism and maintenance of PcG- mediated gene repression.
Emx2 is a dose-dependent negative regulator of Sox2 telencephalic enhancers

The transcription factor Sox2 is essential for neural stem cells (NSC) maintenance in the hippocampus and in vitro. The transcription factor Emx2 is also critical for hippocampal development and NSC self-renewal. Searching for ‘modifier’ genes affecting the Sox2 deficiency phenotype in mouse, we observed that loss of one Emx2 allele substantially increased the telencephalic β-geo (LacZ) expression of a transgene driven by the 5′ or 3′ Sox2 enhancer. Reciprocally, Emx2 overexpression in NSC cultures inhibited the activity of the same transgene. In vivo, loss of one Emx2 allele increased Sox2 levels in the medial telencephalic wall, including the hippocampal primordium. In hypomorphic Sox2 mutants, retaining a single ‘weak’ Sox2 allele, Emx2 deficiency substantially rescued hippocampal radial glia stem cells and neurogenesis, indicating that Emx2 functionally interacts with Sox2 at the stem cell level. Electrophoresis mobility shift assays and transfection indicated that Emx2 represses the activities of both Sox2 enhancers. Emx2 bound to overlapping Emx2/POU-binding sites, preventing binding of the POU transcriptional activator Brn2. Additionally, Emx2 directly interacted with Brn2 without binding to DNA. These data imply that Emx2 may perform part of its functions by negatively modulating Sox2 in specific brain areas, thus controlling important aspects of NSC function in development.
Ontology application and use at the ENCODE DCC

The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a catalog of genomic annotations. To date, the project has generated over 4000 experiments across more than 350 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory network and transcriptional landscape of the Homo sapiens and Mus musculus genomes. All ENCODE experimental data, metadata and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage and distribution to community resources and the scientific community. As the volume of data increases, the organization of experimental details becomes increasingly complicated and demands careful curation to identify related experiments. Here, we describe the ENCODE DCC’s use of ontologies to standardize experimental metadata. We discuss how ontologies, when used to annotate metadata, provide improved searching capabilities and facilitate the ability to find connections within a set of experiments. Additionally, we provide examples of how ontologies are used to annotate ENCODE metadata and how the annotations can be identified via ontology-driven searches at the ENCODE portal. As genomic datasets grow larger and more interconnected, standardization of metadata becomes increasingly vital to allow for exploration and comparison of data between different scientific projects. Database URL: https://www.encodeproject. org/