gebhart/patrepeval huggingface dataset:
Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics (2017)

Nucleic acid therapeutics are limited by inefficient delivery to target tissues and cells and by an incomplete understanding of how nanoparticle structure affects biodistribution to off-target organs. Although thousands of nanoparticle formulations have been designed to deliver nucleic acids, most nanoparticles have been tested in cell culture contexts that do not recapitulate systemic in vivo delivery. To increase the number of nanoparticles that could be tested in vivo, we developed a method to simultaneously measure the biodistribution of many chemically distinct nanoparticles. We formulated nanoparticles to carry specific nucleic acid barcodes, administered the pool of particles, and quantified particle biodistribution by deep sequencing the barcodes. This method distinguished previously characterized lung- and liver- targeting nanoparticles and accurately reported relative quantities of nucleic acid delivered to tissues. Barcode sequences did not affect delivery, and no evidence of particle mixing was observed for tested particles. By measuring the biodistribution of 30 nanoparticles to eight tissues simultaneously, we identified chemical properties promoting delivery to some tissues relative to others. Finally, particles that distributed to the liver also silenced gene expression in hepatocytes when formulated with siRNA. This system can facilitate discovery of nanoparticles targeting specific tissues and cells and accelerate the study of relationships between chemical structure and delivery in vivo.
Ureaplasma-eukaryotic cell interactions in vitro (1986)

Ureaplasmas from six animal species were inoculated into cell cultures derived from human, simian and murine hosts. All ureaplasmas infected at least two of the cell cultures tested. Supplemental medium urea was not a requirement for cell culture infection, and Ureaplasma growth in cell cultures occurred in as little urea as 4 micrograms/ml, similar to findings in broth-propagated organisms. These findings are of potential significance due to an observation (HM Jernigan, Jr: Exp Eye Res 37:551, 1983) that certain tissues produce urea locally. This may explain why ureaplasmas can be isolated from tissues outside the urinary tract where large amounts of urea are not routinely encountered. Ureaplasmas generally increased from titers of approximately 10(2) to 10(4) to ones of 10(5) to 10(6), but occasionally 10(7), color changing-units/ml within 2 days. Apparently a cell culture product is required for Ureaplasma growth. In several systems, Ureaplasma infection persisted and Ureaplasma-infected cell cultures could be passaged.
Structure of the human activating natural cytotoxicity receptor NKp30 bound to its tumor cell ligand B7-H6 (2011)

Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumor cells. In humans, the activating natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 play a major role in NK cell-mediated tumor cell lysis. NKp30 recognizes B7-H6, a member of the B7 family which is expressed on tumor, but not healthy, cells. To understand the basis for tumor surveillance by NCRs, we determined the structure of NKp30, a member of the CD28 family which includes CTLA-4 and PD-1, in complex with B7-H6. The overall organization of the NKp30-B7-H6-activating complex differs considerably from those of the CTLA-4-B7 and PD-1-PD-L T cell inhibitory complexes. Whereas CTLA-4 and PD-1 use only the front β-sheet of their Ig-like domain to bind ligands, NKp30 uses both front and back β-sheets, resulting in engagement of B7-H6 via the side, as well as face, of the β-sandwich. Moreover, B7-H6 contacts NKp30 through the complementarity-determining region (CDR)-like loops of its V-like domain in an antibody-like interaction that is not observed for B7 or PD-L. This first structure of an NCR bound to ligand provides a template for designing molecules to stimulate NKp30-mediated cytolytic activity for tumor immunotherapy.
Towards Scalable Speech Act Recognition in Twitter: Tackling Insufficient Training Data (2012)

Recognizing speech act types in Twitter is of much theoretical interest and practical use. Our previous research did not adequately address the deficiency of training data for this multi-class learning task. In this work, we set out by assuming only a small seed training set and experiment with two semi-supervised learning schemes, transductive SVM and graph-based label propagation, which can leverage the knowledge about unlabeled data. The efficacy of semi-supervised learning is established by our extensive experiments, which also show that transductive SVM is more suitable than graph-based label propagation for our task. The empirical findings and detailed evidences can contribute to scalable speech act recognition in Twitter. 1.
Detection of anti-ESA antibodies in human samples from PRCA and non-PRCA patients: an immunoassay platform comparison (2011)

Background. The immunological methods for detecting antibodies to erythropoiesis-stimulating agents (ESAs) differ in assay sensitivity. However, this parameter, routinely determined in clinical assays using a high-affinity nonhuman polyclonal antibody, gives a one-dimensional assessment of antibody detection. We compare three widely used immunological methods and evaluate the ability of each to detect mature human antibodies and human antibodies characteristic of an early immune response. Methods. The detection of anti-ESA antibodies was compared between a radioimmunoprecipitation (RIP) assay, an electrochemiluminescence (ECL) bridging enzyme-linked immunosorbent assay and a surface plasmon resonance (SPR)-based immunoassay. All three methods were validated for sensitivity, specificity and precision. Specimens from clinical studies or post market testing were categorized as pure red cell aplasia (PRCA) or non-PRCA and then analyzed in each method. Results. Among the antibody-mediated PRCA samples, which contain high affinity neutralizing antibodies, there was strong correlation between all methods. The results from non-PRCA sample analysis show high correlation between RIP and ECL methods; however, differences between the SPR immunoassay and the ECL and RIP were demonstrated. The samples that scored positive in the SPR immunoassay and negative by RIP and ECL were characterized to be of low antibody concentration, contained a high percentage of rapidly dissociating antibodies, or were antibodies of the IgM isotype. Conclusions. All three immunological methods are appropriate for detection of antibodies associated with antibodymediated PRCA. However, the SPR immunoassay platform detected an early, low affinity IgG and IgM antibody response as well as detected and characterized a pathogenic antibody response associated with antibody-mediated PRCA.
A Neural Stimulator Frontend With High-Voltage Compliance and Programmable Pulse Shape for Epiretinal Implants (2011)

This paper presents an integrated neural stimulator with highly efficient and flexible frontend which is intended for an epiretinal implant with 1024 electrodes. It features programmable stimulation pulse shapes, a high-voltage (HV) output driver with compliance monitor for supply voltage adaptation, active and passive charge balancers, and electrode impedance measurement. Area and power efficiency is achieved by global timing assignment and local amplitude control over a bus at the local stimulation units. Major power savings in the distributed digital control units are realized by implementing global and local clock gating. Two stimulator frontends have been fabricated in a 0.35 μm HVCMOS process. Each frontend features four demultiplexed outputs and consumes 0.2 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> core area. A maximum voltage compliance of 20 V is achieved and up to 1 mA of output current can be adjusted with up to 50 dB dynamic range. In vitro experimental results performed on a platinum black electrode in 0.9% saline solution are given.
Embedded Linux as a Platform for Dynamically Self-Reconfiguring Systems-On-Chip (2004)

We have previously argued the benefits of embedded Linux as an operating system platform for reconfigurable system-on-chip design. In this paper we describe our approach to building tools for the implementation of dynamically and self-reconfigurable systems, and show that embedded Linux is a natural and powerful platform on which to build these tools. We present examples and demonstrations that show how complex operations such as obtaining partial bit streams from remote servers and initiating reconfiguration are achieved with a single line of Linux shell script.
Maternal urine for prenatal diagnosis—an analysis of cell‐free fetal DNA in maternal urine and plasma in the third trimester (2007)

Our data confirm that cff-DNA is cleared by the kidneys in detectable amounts, but due to its low concentration or problematic detection in maternal urine this source seems inappropriate for noninvasive prenatal diagnosis.
Intrinsic apodisation of Bragg gratings writtenusing UV-pulse interferometry (1998)

The authors present a new interferometric technique for writing apodised Bragg gratings. Along the fibre, two UV-pulses interfere with a variable time delay, creating a Gaussian apodisation profile which strongly reduces the reflectivity sidelobes. This method allows the writing of truly apodised gratings by single exposure of a uniform phase-mask.
Spermatogonial stem cells: characteristics and experimental possibilities (2005)

The continuation of the spermatogenic process throughout life relies on a proper regulation of self-renewal and differentiation of the spermatogonial stem cells. These are single cells situated on the basal membrane of the seminiferous epithelium. Only 0.03% of all germ cells are spermatogonial stem cells. They are the only cell type that can repopulate and restore fertility to congenitally infertile recipient mice following transplantation. Although numerous expression markers have been helpful in isolating and enriching spermatogonial stem cells, such as expression of THY-1 and GFRalpha-1 and absence of c-kit, no specific marker for this cell type has yet been identified. Much effort has been put into developing a protocol for the maintenance of spermatogonial cells in vitro. Recently, coculture systems of testicular cells on various feeder cells have made it possible to culture spermatogonial stem cells for a long period of time, as was demonstrated by the transplantation assay. Even expansion of testicular cells, including the spermatogonial stem cells, has been achieved. In these culture systems, hormones and growth factors are investigated for their role in the process of proliferation of spermatogonial stem cells. At the moment the best culture system known still consists of a mixture of testicular cells with about 1.33% spermatogonial stem cells. Recently pure SV40 large T immortalized spermatogonial stem cell lines have been established. These c-kit-negative cell lines did not show any differentiation in vitro or in vivo. A telomerase immortalized c-kit-positive spermatogonial cell line has been established that was able to differentiate in vitro. Spermatocytes and even spermatids were formed. However, spermatogonial stem cell activity by means of the transplantation assay was not tested for this cell line. Both the primary long-term cultures and immortalized cell lines have represented a major step forward in investigating the regulation of spermatogonial self-renewal and differentiation, and will be useful for identifying specific molecular markers.
UC 729-6, a human lymphoblastoid B-cell line useful for generating antibody-secreting human-human hybridomas. (1983)

UC 729-6, a 6-thioguanine-resistant human lymphoblastoid B-cell line, was fused with normal and malignant human lymphocytes. Parent UC 729-6 cells were diploid with a 21p+ marker chromosome, expressed surface and cytoplasmic IgM kappa, and doubled every 17 hr. The resulting human-human hybridomas were pseudotetraploid containing the 21p+ marker, doubled every 20-30 hr, and secreted 3-9 micrograms of human Ig per ml per 10(6) hybrid cells for greater than 9 months in continuous culture. Human Ig-secreting hybridomas were generated in 88% (14/16) of the fusions carried out and were cloned by limiting dilution (one cell per three wells) without the use of feeder layers. The mean fusion frequencies (number of wells, plated at 10(5) cells per well, showing hybrid growth per 10(6) lymphocytes fused) of UC 729-6 with normal lymphocytes ranged from 0.45 to 2.9 and with malignant B lymphocytes, from 3 to 10. Analysis of the human-human hybridomas derived from lymphocytes isolated from regional draining lymph nodes of cancer patients revealed several that secreted human monoclonal antibody that reacted by an enzyme immunoassay with some carcinoma cell lines but not with normal fibroblast cell lines. These data suggest that (i) UC 729-6 can be fused with human lymphocytes to generate stable human-human hybridomas, some of which secrete antibody reactive to human cell surface antigens, and (ii) UC 729-6 can be used to rescue Ig from nonsecretory malignant B cells and thereby allow for the production of anti-idiotype antibodies.
Novel surface emitting GaAs/AlGaAs laser diodes based on surface mode emission (1993)

We present a novel concept to achieve surface emission from conventional semiconductor laser diodes. This new type of laser diode is modified to allow a coupling of the laser mode to a transverse electric polarized surface mode. As a result we achieve surface emission from GaAs/AlGaAs double heterostructure laser diodes with a beam divergence of 0.2%. This novel concept has a high potential for the realization of a beam steering device.
Metal-Capped Brownian and Magnetically Modulated Optical Nanoprobes (MOONs):  Micromechanics in Chemical and Biological Microenvironments (2004)

Modulated optical nanoprobes (MOONs) are microscopic (spherical and aspherical) fluorescent particles designed to emit varying intensities of light in a manner that depends on particle orientation. MOONs can be prepared over a broad size range, allowing them to be tailored to applications including intracellular sensors, using submicrometer MOONs, and immunoassays, using 1−10 μm MOONs. When particle orientation is controlled remotely, using magnetic fields (MagMOONs), it allows modulation of fluorescence intensity in a selected temporal pattern. In the absence of external fields, or material that responds to external fields, the particles tumble erratically due to Brownian thermal forces (Brownian MOONs). These erratic changes in orientation cause the MOONs to blink. The temporal pattern of blinking reveals information about the local rheological environment and any forces and torques acting on the MOONs, including biomechanical forces as observed in macrophages. The rotational diffusion rate of Brownian MOONs is inversely proportional to the particle volume and hydrodynamic shape factor, for constant temperature and viscosity. Changes in the particle volume and shape due to binding, deformation, or aggregation can be studied using the temporal time pattern from the probes. The small size and the large number of MOONs that can be viewed simultaneously provide local measurements of physical properties, in both homogeneous and inhomogeneous media, as well as global statistical ensemble properties.
Analysis of an artificial zinc finger epigenetic modulator: widespread binding but limited regulation (2014)

Artificial transcription factors (ATFs) and genomic nucleases based on a DNA binding platform consisting of multiple zinc finger domains are currently being developed for clinical applications. However, no genome-wide investigations into their binding specificity have been performed. We have created six-finger ATFs to target two different 18 nt regions of the human SOX2 promoter; each ATF is constructed such that it contains or lacks a super KRAB domain (SKD) that interacts with a complex containing repressive histone methyltransferases. ChIP-seq analysis of the effector-free ATFs in MCF7 breast cancer cells identified thousands of binding sites, mostly in promoter regions; the addition of an SKD domain increased the number of binding sites ∼ 5-fold, with a majority of the new sites located outside of promoters. De novo motif analyses suggest that the lack of binding specificity is due to subsets of the finger domains being used for genomic interactions. Although the ATFs display widespread binding, few genes showed expression differences; genes repressed by the ATF-SKD have stronger binding sites and are more enriched for a 12 nt motif. Interestingly, epigenetic analyses indicate that the transcriptional repression caused by the ATF-SKD is not due to changes in active histone modifications.
Negative Regulation of Neural Stem/Progenitor Cell Proliferation by the Pten Tumor Suppressor Gene in Vivo (2001)

The mechanisms controlling neural stem cell proliferation are poorly understood. Here we demonstrate that the PTEN tumor suppressor plays an important role in regulating neural stem/progenitor cells in vivo and in vitro. Mice lacking PTEN exhibited enlarged, histoarchitecturally abnormal brains, which resulted from increased cell proliferation, decreased cell death, and enlarged cell size. Neurosphere cultures revealed a greater proliferation capacity for tripotent Pten-/- central nervous system stem/progenitor cells, which can be attributed, at least in part, to a shortened cell cycle. However, cell fate commitments of the progenitors were largely undisturbed. Our results suggest that PTEN negatively regulates neural stem cell proliferation.
Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse (2000)

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease arising from defects in the dystrophin gene, typically nonsense or frameshift mutations, that preclude the synthesis of a functional protein. A milder, allelic version of the disease, Becker muscular dystrophy, generally arises from in-frame deletions that allow synthesis of a shorter but still semifunctional protein. Therapies to introduce functional dystrophin into dystrophic tissue through either cell or gene replacement have not been successful to date. We report an alternative approach where 2'-O-methyl antisense oligoribonucleotides have been used to modify processing of the dystrophin pre-mRNA in the mdx mouse model of DMD. By targeting 2'-O-methyl antisense oligoribonucleotides to block motifs involved in normal dystrophin pre-mRNA splicing, we induced excision of exon 23, and the mdx nonsense mutation, without disrupting the reading frame. Exon 23 skipping was first optimized in vitro in transfected H-2K(b)-tsA58 mdx myoblasts and then induced in vivo. Immunohistochemical staining demonstrated the synthesis and correct subsarcolemmal localization of dystrophin and gamma-sarcoglycan in the mdx mouse after intramuscular delivery of antisense oligoribonucleotide:liposome complexes. This approach should reduce the severity of DMD by allowing a dystrophic gene transcript to be modified, such that it can be translated into a Becker-dystrophin-like protein.
Wafer level embedding technology for 3D wafer level embedded package (2009)

This paper presents the development of wafer level embedding process for a three dimensional (3D) embedded micro wafer level package (EMWLP). Wafer level embedding process was carried out by using compression molding machine and low-cost granular epoxy molding compound (EMC). Various molding process parameters such as molding time and temperature and three EMCs of different CTEs were analyzed to achieve reliable 3D EMWLP. Several molding process issues, such as warpage, die-sweep, EMC penetration, and die-shift, were faced during embedding process development. A large warpage of more than 1 mm and die-shift of more than 600 mum were found to occur in reconstructed molded wafer. Wafer level embedding process was optimized to reduce warpage and die-shift problems. A significant reduction in warpage (~ 30 %) and die-shift (~ 88 %) were achieved after embedding process optimization. The detail of process optimization is presented in the paper. Reconstructed molded wafers were subjected to various reliability tests, such as thermal cycle (TC), moisture sensitivity test-level 3 (MST-L3), and highly accelerated stress test (HAST). Scanning acoustic microscopy (SAM) analysis of molded wafers was carried out to analyze the void formation and delamination in molded wafers. No major void or delamination was observed in reconstructed wafer after molding as well as after reliability tests.
Clinical Utility of Simultaneous Quantitation of 25-Hydroxyvitamin D and 24,25-Dihydroxyvitamin D by LC-MS/MS Involving Derivatization With DMEQ-TAD (2014)

The new method showed good utility in clinical settings involving vitamin D deficiency; supplementation with vitamin D and idiopathic infantile hypercalcemia, as well as in animal models with ablation of selected cytochrome P450-containing enzymes involved in vitamin D metabolism.
Enhancement of the Krylov Subspace Regularization for Microwave Biomedical Imaging (2009)

Although Krylov subspace methods provide fast regularization techniques for the microwave imaging problem, they cannot preserve the edges of the object being imaged and may result in an oscillatory reconstruction. To suppress these spurious oscillations and to provide an edge-preserving regularization, we use a multiplicative regularizer which improves the reconstruction results significantly while adding little computational complexity to the inversion algorithm. We show the inversion results for a real human forearm assuming the 2-D transverse magnetic illumination and a cylindrical object assuming the 2-D transverse electric illumination.
[Gynecomastia: effect of prolonged treatment with dihydrotestosterone by the percutaneous route]. (1983)

Gynaecomastia is a frequent disorder, sometimes painful or psychologically disturbing. Percutaneous dihydrotestosterone (DHT) was used to treat 30 patients with idiopathic gynaecomastia (IG) and 17 patients in whom the condition was associated with hypogonadism. All patients complaining of pain were relieved. Breast enlargement regressed or was substantially reduced in 22 of the IG patients and in all cases with hypogonadism, except those with gonadal dysgenesis. Plasma levels of testosterone and 17 beta-estradiol were significantly lowered in patients with IG as compared with controls. There was a significant increase in plasma DHT levels and in plasma androgen/estradiol ratio in all cases. The beneficial effects of the drug were manifest within 1 to 2 months in responsive patients. These effects may be due to a local and/or systemic activity. It is suggested that this medium-term treatment without side-effects should be tried in all cases of hypogonadism with gynaecomastia and in IG before considering more drastic therapeutic measures.