gebhart/patrepeval huggingface dataset:
Abstract 2034: Development of 3D bioprinted human breast cancer for in vitro drug screening (2014)

Abstract As breast cancer is a disease of multiple cell types in which the growth, invasion, and metastasis of epithelial carcinomas is heavily influenced by the surrounding cell types, screening of anti-cancer compounds using cancer cell lines grown in 2D often overestimates drug potency. Regulatory agencies are currently seeking improved preclinical oncology models to overcome hurdles to efficient drug development, including bridging the gap between the use of 2D cell lines and 3D animal models. One way to more accurately determine the effects of anti-cancer compounds is through the use of cancer tissue models that incorporate stromal cells of the tumor microenvironment. Breast stroma, composed of fibroblasts, endothelial cells, and adipocytes, plays a key role in the process of carcinogenesis and metastasis. These cell types secrete extracellular matrix, growth factors, and hormones that affect how therapeutic agents access and target cancer cells. We have used Organovo's NovoGen BioprintingTM Platform to develop a model of human breast cancer in which a core of breast cancer cells is surrounded by a physiologically-relevant stromal milieu consisting of adipocytes, mammary fibroblasts, and endothelial cells. This system has several advantages over current screening tools, including the ability to simultaneously measure the effects of small molecules on cancer cells as well as different cell types in the breast microenvironment. Histological analyses of bioprinted neotissues demonstrated that they were stable and viable for at least 14 days in culture and characterized by interaction between stroma and carcinoma compartments. Incorporation of endothelial cells into the 3D neotissue led to the formation of robust microvascular networks. Breast cancer neotissues were fabricated directly into multi-well plates and used to establish biological response profiles to the standard chemotherapeutic agents cisplatin, paclitaxel, methotrexate, and tamoxifen. The cytotoxic effects of chemotherapeutic drugs on specific cell types within the neotissues were assessed biochemically and histologically. he response of the 3D breast cancer neotissues to chemotherapeutic gents was compared to the response of 2D breast cancer cell lines to determine he relative efficacy of compounds in 2D versus 3D. This model can be used to screen new anti-cancer therapeutics in the context of the in vivo-like microenvironment, leading to enhanced efficiency and accuracy of the drug development process. Citation Format: Shelby M. King, Sharon C. Presnell, Deborah G. Nguyen. Development of 3D bioprinted human breast cancer for in vitro drug screening. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2034. doi:10.1158/1538-7445.AM2014-2034
Endocytosis of HIV-1 activates plasmacytoid dendritic cells via Toll-like receptor- viral RNA interactions (2005)

HIV-1 directly activates human plasmacytoid DCs (pDCs) by upregulating the expression of costimulatory and MHC molecules and maturation markers, increasing T cell stimulatory activity, and inducing the production of type I interferons and TNF-alpha. A consequence of this activation is the bystander maturation of myeloid DCs and overall enhancement of antigen-presenting function. However, little is known about the mechanism(s) of pDC activation by HIV-1. Here we demonstrate by in vitro studies that IFN-alpha production by pDC in response to HIV-1 requires at least 2 interactions between the cell and virus. Initially, envelope-CD4 interactions mediate endocytosis of HIV-1, as demonstrated through the use of inhibitors of binding, fusion, endocytosis, and endosomal acidification. Subsequently, endosomally delivered viral nucleic acids, particularly RNA, stimulate pDCs through TLRs, as activation is reproduced with purified genomic RNA but not viral RNA packaging-deficient HIV-1 and blocked with different inhibitory TLR ligands. Finally, by using genetic complementation, we show that TLR7 is the likely primary target. Viral RNA rather than DNA in early retrotranscripts appears to be the active factor in HIV-1 that induces IFN-alpha secretion by pDCs. Since the decline in pDCs in chronic HIV-1 infection is associated with high viral loads and opportunistic infections, exploiting this natural adjuvant activity of HIV-1 RNA might be useful in the development of vaccines for the prevention of AIDS.
Controlled electrocoalescence in microfluidics: Targeting a single lamella (2006)

Electrocoalescence of aqueous droplets is investigated as a tool for microfluidic processing. Where droplets are separated by only thin lamellae, coalescence can be induced on demand within a fraction of a millisecond at low potentials (few volts). The authors show that in their approach electrocoalescence proceeds through an electric-field-induced dynamic instability of the oil/water interface. When the electrode geometry and applied potential are optimized, individual lamellae can be targeted for rupture within highly ordered droplet arrangements.
Fuzzy Nanoassemblies: Toward Layered Polymeric Multicomposites (1997)

Multilayer films of organic compounds on solid surfaces have been studied for more than 60 years because they allow fabrication of multicomposite molecular assemblies of tailored architecture. However, both the Langmuir-Blodgett technique and chemisorption from solution can be used only with certain classes of molecules. An alternative approach—fabrication of multilayers by consecutive adsorption of polyanions and polycations—is far more general and has been extended to other materials such as proteins or colloids. Because polymers are typically flexible molecules, the resulting superlattice architectures are somewhat fuzzy structures, but the absence of crystallinity in these films is expected to be beneficial for many potential applications.
Adenovirus-Mediated Gene Transfer of Heparin-Binding Epidermal Growth Factor-Like Growth Factor Enhances Neurogenesis and Angiogenesis After Focal Cerebral Ischemia in Rats (2005)

Our data suggest that gene therapy using Ad-HB-EGF contributes to functional recovery after ischemic stroke by promoting neurogenesis and angiogenesis.
Relative bioavailability of sodium cromoglycate to the lung following inhalation, using urinary excretion (1999)

The urinary excretion of sodium cromoglycate in the first 0.5 h post inhalation can be used to compare the relative lung deposition of two inhaled products or of the same product using different inhalation techniques. This represents the relative bioavailability of sodium cromoglycate to the lung following inhalation. Similar 24 h urinary excretion of sodium cromoglycate can be use to compare the total dose delivered to the body from two different inhalation products/inhalation methods. This represents the relative bioavailability of sodium cromoglycate to the body following inhalation. Because of the lack of difference between the INH and INHC in the first 0.5 h, the use of activated charcoal is not necessary when this method is used to compare the relative lung bioavailability of different products or techniques.
Dextran Nanoparticle Synthesis and Properties (2016)

Dextran is widely exploited in medical products and as a component of drug-delivering nanoparticles (NPs). Here, we tested whether dextran can serve as the main substrate of NPs and form a stable backbone. We tested dextrans with several molecular masses under several synthesis conditions to optimize NP stability. The analysis of the obtained nanoparticles showed that dextran NPs that were synthesized from 70 kDa dextran with a 5% degree of oxidation of the polysaccharide chain and 50% substitution with dodecylamine formed a NP backbone composed of modified dextran subunits, the mean diameter of which in an aqueous environment was around 100 nm. Dextran NPs could be stored in a dry state and reassembled in water. Moreover, we found that different chemical moieties (e.g., drugs such as doxorubicin) can be attached to the dextran NPs via a pH-dependent bond that allows release of the drug with lowering pH. We conclude that dextran NPs are a promising nano drug carrier.
Immunization with Herpes Simplex Virus 2 (HSV-2) Genes plus Inactivated HSV-2 Is Highly Protective against Acute and Recurrent HSV-2 Disease (2011)

To date, no vaccine that is safe and effective against herpes simplex virus 2 (HSV-2) disease has been licensed. In this study, we evaluated a DNA prime-formalin-inactivated-HSV-2 (FI-HSV2) boost vaccine approach in the guinea pig model of acute and recurrent HSV-2 genital disease. Five groups of guinea pigs were immunized and intravaginally challenged with HSV-2. Two groups were primed with plasmid DNAs encoding the secreted form of glycoprotein D2 (gD2t) together with two genes required for viral replication, either the helicase (UL5) and DNA polymerase (UL30) genes or the single-stranded DNA binding protein (UL29) and primase (UL52) genes. Both DNA-primed groups were boosted with FI-HSV2 formulated with monophosphoryl lipid A (MPL) and alum adjuvants. Two additional groups were primed with the empty backbone plasmid DNA (pVAX). These two groups were boosted with MPL and alum (MPL-alum) together with either formalin-inactivated mock HSV-2 (FI-Mock) or with FI-HSV2. The final group was immunized with gD2t protein in MPL-alum. After challenge, 0/9 animals in the group primed with UL5, UL30, and gD2t DNAs and all 10 animals in the mock-immunized control group (pVAX-FI-Mock) developed primary lesions. All mock controls developed recurrent lesions through day 100 postchallenge. Only 1 guinea pig in the group primed with pVAX DNA and boosted with FI-HSV2 (pVAX-FI-HSV2 group) and 2 guinea pigs in the group primed with UL5, UL30, and gD2t DNAs and boosted with FI-HSV2 (UL5, UL30, gD2t DNA-FI-HSV2 group) developed recurrent lesions. Strikingly, the UL5, UL30, gD2t DNA-FI-HSV2 group showed a 97% reduction in recurrent lesion days compared with the mock controls, had the highest reduction in days with recurrent disease, and contained the lowest mean HSV-2 DNA load in the dorsal root ganglia.
Three‐dimensional receiver deghosting of seismic streamer data using L1 inversion and redundant extended radon dictionary (2018)

ABSTRACT In this paper, we propose a novel three‐dimensional receiver deghosting algorithm that is capable of deghosting both horizontal and slanted streamer data in a theoretically consistent manner. Our algorithm honours wave propagation phenomena in a true three‐dimensional sense and frames the three‐dimensional receiver deghosting problem as a Lasso problem. The ultimate goal is to minimise the mismatch between the actual measurements and the simulated wavefield with an L1 constraint applied in the extended Radon space to handle the underdetermined nature of this problem. We successfully demonstrate our algorithm on a modified three‐dimensional EAGE/SEG Overthrust model and a Red Sea marine dataset.
Optimized Surface Markers for the Prospective Isolation of High-Quality hiPSCs using Flow Cytometry Selection (2013)

hiPSC derivation and selection remains inefficient; with selection of high quality clones dependent on extensive characterization which is not amenable to high-throughput (HTP) approaches. We recently described the use of a cocktail of small molecules to enhance hiPSC survival and stability in single cell culture and the use of flow cytometry cell sorting in the HTP-derivation of hiPSCs. Here we report an enhanced protocol for the isolation of bona fide hiPSCs in FACS-based selection using an optimized combination of cell surface markers including CD30. Depletion of CD30(+) cells from reprogramming cultures almost completely abolished the NANOG and OCT4 positive sub-population, suggesting it is a pivotal marker of pluripotent cells. Combining CD30 to SSEA4 and TRA-1-81 in FACS greatly enhanced specificity and efficiency of hiPSC selection and derivation. The current method allows for the efficient and automated, prospective isolation of high-quality hiPSC from the reprogramming cell milieu.
The oxidant stress hypothesis in Parkinson's disease: Evidence supporting it (1992)

Oxidant stress, due to the formation of hydrogen peroxide and oxygen-derived free radicals, can cause cell damage due to chain reactions of membrane lipid peroxidation. Because the substantia nigra is rich in dopamine, which can undergo both enzymatic oxidation via monoamine oxidase and nonenzymatic autoxidation, hydrogen peroxide and oxyradicals (superoxide anion radical and hydroxyl radical) are generated in this midbrain nucleus. Although proof that oxidant stress actually causes the loss of monoaminergic neurons in patients with Parkinson's disease is lacking, there is a considerable body of evidence from studies in both animals and humans that support the concept. (1) Neurotoxins that selectively destroy the dopaminergic neurons in the nigra, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), appear to act via oxidant stress. (2) The substantia nigra of patients with Parkinson's disease reveals evidence of oxidant stress by the findings of increased lipid peroxidation and decreased reduced glutathione. (3) Total iron is increased and ferritin is reduced in the substantia nigra pars compacta in patients with Parkinson's disease. This combination suggests that this transition metal is in a low molecular weight form, capable of catalyzing nonenzymatic oxidative reactions, especially the conversion of hydrogen peroxide to hydroxyl radical, which is the most reactive of the oxygen radicals. (4) Neuromelanin, a product of dopamine autoxidation, can serve as a reservoir for iron, promoting the generation of oxyradicals. (5) Antioxidant defense mechanisms appear to be reduced in the parkinsonian substantia nigra with the findings of decreased activities of glutathione peroxidase and catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
Rilonacept pharmacokinetics in children with systemic juvenile idiopathic arthritis (2014)

Additional Supporting Information may be found in the online version of this article at the publisher's web-site. Figure S1. Visual predictive check (n = 1000 simulations). Supporting Information. Table S1. Population PK Model Building Steps Summary Table S2. Final Population Pharmacokinetic Model Parameter Estimates Table S3. Individual Empirical Bayesian Estimates Using the Final popPK Model Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Artifact reduction in truncated CT using sinogram completion (2005)

Truncation of projection data in CT produces significant artifacts in the reconstruction process due to non-locality of the Radon transform. In this paper, we present a method for reducing these truncation artifacts by estimating features that lie outside the region of interest (ROI) and using these features to complete the truncated sinogram.Projection images of an object are obtained. A sinogram is obtained by stacking profile data from all projection angles. A simulated truncated sinogram is generated by setting pixel values outside an ROI to zero. The truncated sinogram is then transformed into a (radius, phase) image, with pixel values in what we term as the Polar representation (PR) image corresponding to the minimum value along sine curves given by x = r*cos(projection angle + phase). The PR image contains data for radii greater than the ROI radius. Pixel values outside the ROI in the completed sinogram are determined as follows. For each pixel in the PR image, a sine curve is generated in the completed sinogram image outside the ROI, having the same pixel value as that of the PR image for that radius and phase. Successive sine curves are laid and the values of each are summed. The intensity outside is then equalized to the intensity inside the ROI. The completed sinogram is then reconstructed, to obtain completed reconstruction.The percentage error in the difference image between the full FOV reconstruction and the corresponding completed reconstruction and the extrapolated-average reconstruction are 1.1% and 3.3% respectively. This indicates that the completed reconstruction is closer to full FOV reconstruction. Thus, the sinogram completion can be used to improve reconstructions from truncated data.
Enzymatic Properties of Rat Myelencephalon-Specific Protease (2001)

Myelencephalon-specific protease (MSP), first identified in the rat and now known to have a human homologue (human kallikrein 6), is preferentially expressed in the central nervous system (CNS), compared with nonneural tissues. MSP has been postulated to have trypsin-like activity, is upregulated in response to glutamate receptor-mediated excitotoxic injury in the CNS, and is downregulated in the brain of Alzheimer's patients. The preferential expression of this enzyme by oligodendrocytes in CNS white matter points to a role in myelin homeostasis. To further characterize the activity and substrate specificity of this newly identified enzyme, we have heterologously expressed MSP in a baculovirus/insect cell line system. We demonstrate that recombinant MSP exhibits a broad specificity for cleavage after arginine but not lysine residues, with kinetic characteristics intermediate between trypsin and pancreatic kallikrein. We show that the pro form of MSP does not self-activate but, rather, requires cleavage after lysine, indicating that mature active MSP is regulated by a distinct protease. MSP may be regulated in part by autolysis, since the active protein is readily inactivated through autolysis at specific internal arginine positions. Additionally, we show that MSP is abundantly expressed in inflammatory cells at sites of demyelination in the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis (MS). In conjunction with data demonstrating the ability of MSP to degrade myelin-associated as well as several extracellular matrix proteins, these findings delineate MSP as a broad-specificity arginine-specific protease with the potential to play a key role in immune-mediated demyelination.
Allelic Exclusion in Transgenic Mice That Express the Membrane form of Immunoglobulin μ (1987)

Antibody-producing cells display a special form of regulation whereby each cell produces immunoglobulin from only one of its two sets of antibody genes. This phenomenon, called allelic exclusion, is thought to be mediated by the product of one heavy chain allele restricting the expression of the other. Heavy chains are synthesized in two molecular forms, secreted and membrane bound. In order to determine whether it is specifically the membrane-bound form of the immunoglobulin M (IgM) heavy chain (mu) that mediates this regulation, transgenic mice were created that carry a human mu chain gene altered so that it can only direct the synthesis of the membrane-bound protein. The membrane-bound form of the human mu chain was made by most of the B cells in these animals as measured by assays of messenger RNA and surface immunoglobulins. Further, the many B cells that express the human gene do not express endogenous mouse IgM, and the few B cells that express endogenous mouse mu do not express the transgene. Thus, the membrane-bound form of the mu chain is sufficient to mediate allelic exclusion. In addition, the molecular structures recognized for this purpose are conserved between human and mouse systems.
Biological evaluation of Paclitaxel-peptide conjugates as a model for MMP2-targeted drug delivery (2010)

Paclitaxel (PTX) is a highly effective cytotoxic agent widely used for the treatment of several solid tumors. However, PTX shows dose-limiting cytotoxicity and in most cases induces drug resistance followed by failure in treatment. To enhance the therapeutic index of a given drug, various drug delivery methods have been explored to systemically deliver sufficient amount of the drug to the desired site. In the present study, we designed and synthesized two PTX prodrugs by conjugating PTX at different sites with an octapeptide (AcGPLGIAGQ) that can be cleaved by MMP2 at tumor sites. As a result, PTX is expected to be released at the tumor sites, absorbed by the tumor cells, and thereby inhibit the tumor growth. We evaluated the in vitro activities of the two drugs in a panel of drug-sensitive and -resistant cancer cell lines and their in vivo efficacies in a HT1080 fibrosarcoma mouse xenograft model that overexpresses MMP2. Our in vitro results showed that the PTX-AcGPLGIAGQ conjugates inhibited cancer cell proliferation with higher activity compared to that observed for free PTX, both of which were mediated by an arrest of G(2)/M-phase of the cell cycle. Consistent with the in vitro results, treatment with PTX-octapeptide conjugate resulted in extensive areas of necrosis and a lower percentage of proliferating cells in xenograft tumor sections. Together, our results indicate the potential of the tumor-targeted delivery of PTX to exploit the specific recognition of MMP2, reduce toxicity, and selectively kill tumor cells.
Molecular Engineering of Therapeutic Cytokines (2013)

Over the past three decades, a large body of work has been directed at the development of therapeutic cytokines. Despite their central role in immune modulation, only a handful of cytokine therapeutics has achieved regulatory approval. One of the major challenges associated with the therapeutic use of cytokines relates to their short serum half-life and low bioavailability. High doses are required to overcome these problems, which often result in dose-limiting toxicities. Consequently, most cytokines require protein engineering approaches to reduce toxicity and increase half-life. For this purpose, PEGylation, fusion proteins, antibody complexes and mutagenesis have been utilized. Here, we summarize past, recent and emerging strategies in this area.
Payments and banking with mobile personal devices (2003)

Mobile devices enable secure, convenient authorization of e-banking, retail payment, brokerage, and other types of transactions.
Distinction between voluntary cough sound and speech in volunteers by spectral and complexity analysis. (2008)

Objective monitoring of cough sound for extended period is an important step toward a better understanding of this symptom. Because ambulatory cough monitoring systems are not commercially available, we prepared own monitoring system, which is able to distinguish between voluntary cough sound and speech in healthy volunteers. 20-min sound records were obtained using portable digital voice recorder. Characteristics of the sound events have been calculated in time and frequency domains and by a nonlinear analysis. Based on selected parameters, classification tree was constructed for the classification of cough and non-cough sound events. We validated the usefulness of our algorithm developed against manual counts of cough obtained by a trained observer. The median sensitivity value was 100% (the interquartile range was 98-100) and the median specificity was 95% (the interquartile range was 90-97). In conclusion, we developed an algorithm to distinguish between voluntary cough sound and speech with a high degree of accuracy.