gebhart/patrepeval huggingface dataset:
Addressing the PEG Mucoadhesivity Paradox to Engineer Nanoparticles that “Slip” through the Human Mucus Barrier (2008)

Outsmarting the barrier: Conventional poly(ethylene glycol) (PEG) coated particles (green with light purple border) are immobilized in human mucus networks by adhesive interactions (red) with the mucus mesh (black lines). A dense, low molecular weight PEG coating (blue) uniquely endows nanoparticles with a mucoinert surface that enables their rapid mucus penetration (trajectory indicated by grey line). Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. 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.
ONYX-015. Onyx Pharmaceuticals. (2001)

ONYX-015 (CI-1042), an adenovirus modified selectively to replicate in and kill cells that harbor p53 mutations, is under development by Onyx Pharmaceuticals for the potential treatment of various solid tumors, including head and neck, gastrointestinal and pancreatic tumors. It is a recombinant adenovirus that carries a loss-of-function mutation at the E1B locus, the product of which is a 55 kDa protein that binds to and inactivates the p53 tumor suppressor protein. Wild-type adenoviruses must disable this gene before viral replication can occur. This, the ONYX-015 adenovirus will leave normal cells unaffected. Mutations in the p53 tumor suppressor gene are the most common type of genetic abnormality in cancer, occurring in more than half of all major cancer types. Thus, these cells are susceptible to the virus, which will readily replicate and cause cell death. ONYX-015 is in ongoing phase III trials for the treatment of recurrent head and neck cancer, phase II trials for colorectal, ovary, pancreas and mouth tumors, and phase I trials for digestive disease, esophagus and liver tumors. Onyx Pharmaceuticals was granted US-05677178 covering methods for the treatment of p53-related cancers in October 1997. The patent specifically covers the use of modified adenoviruses and other DNA viruses, which lack viral proteins that bind to p53, for the treatment of cancer patients whose tumors lack p53 function. The USPTO awarded Onyx Pharmaceuticals US-05846945 in December 1998, covering methods for treating cancer using replicating adenoviral therapy in combination with chemotherapy. In April 1999, the company also received EP-094910177.8 covering the technology in Europe.
Expression of eukaryotic recombinant proteins and deriving them from the milk of transgenic animals (2013)

Expression in milk of transgenic farm animals is one of the most effective ways to produce eukaryotic recombinant proteins. In this review, we discuss the problems of the appropriateness of selecting this expression system for the production of proteins and the development characteristics of appropriate production processes.
Transplantation of enriched CD34-positive autologous marrow into breast cancer patients following high-dose chemotherapy: influence of CD34-positive peripheral-blood progenitors and growth factors on engraftment. (1994)

CD34+ marrow and/or PBPCs provide reliable and timely hematopoietic reconstitution in breast cancer patients receiving high-dose chemotherapy. Contamination of both marrow and PBPCs with breast cancer cells was reduced using this positive selection technique.
Synthesis of Collagen-like Peptide Polymers by Native Chemical Ligation (2005)

We report on the synthesis of high molecular weight collagen-like peptide polymers prepared by a combination of solid phase peptide synthesis, polymerization, and self-assembly. The final product is a mesh of nanofibers that maintains the characteristic circular dichroism signal for collagen triple helices and the nanofiber diameter is 10−20 nm, similar to natural collagen fibrils. This method utilizes an N-terminal cysteine and C-terminal thioester to achieve selective head to tail polymerization of peptides without the need for protecting groups and under neutral aqueous conditions in which the peptide may adopt a folded conformation. The synthesized peptide polymers were characterized by size-exclusion chromatography, circular dichroism spectroscopy, and transmission electron microscopy.
Ferroelectric polymer tactile sensors with anthropomorphic features (2005)

This paper describes a composite transducer for tactile sensing, whose skin-like structure makes it potentially useful in prosthetics as well as in robotics. Such transducer comprises an "epidermal", thin film, polyvinylidene fluoride (PVF <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> ) sensor and two inner layers consisting of a conductive rubber sheet and of an array of 128 PVF <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> sensors, which are intended to reproduce in part some mechanical features and sensing capabilities of the human dermis. The proposed transducer has been tested and its ability to detect, by touch, hardness, thermal conductivity and surface texture of objects, as well as contact pressure has been assessed. Although much work is still needed to obtain a really usable device, sensitivity, linearity and bandwidth of the present tactile transducer, along with its wide range of sensorial capabilities, strongly encourage further development.
Use Of Artificial Neural Networks In Prostate Cancer (2001)

Artificial neural networks (ANNs) are a type of artificial intelligence software inspired by biological neuronal systems that can be used for nonlinear statistical modeling. In recent years, these applications have played an increasing role in predictive and classification modeling in medical research. We review the basic concepts behind ANNs and examine the role of this technology in selected applications in prostate cancer research.
Prognostic significance of genetic alterations detected by high‐density single nucleotide polymorphism array in gastric cancer (2010)

We sought to identify genomic changes that could be useful for clinical application, focusing on chromosomal instability and using a high-density single nucleotide polymorphism (SNP) array. We analyzed 34 gastric cancer cell lines for areas of DNA that exhibited copy number changes using the Affymetrix GeneChip Human Mapping 50 K Arrays. The results obtained with the cell lines were verified in 42 gastric cancer tissues using genomic PCR, quantitative real-time PCR, and loss of heterozygosity (LOH) analyses. Twenty-six local homozygous deletion regions, including 13 novel loci, and 31 recurrent high-grade gain regions, encompassing 14 novel loci, were found in the gastric cancer cell lines. Among the genes detected for high-grade gain in the cell lines, MYC, PAK1, and ITGB4BP showed copy number gain in more than 40% of gastric cancer tissues. LOH of AB051467, PTPRD, A2BP1, and C20orf133 was detected in more than 35% of gastric cancer tissues. The number of LOH was significantly greater in tumors with lymph node metastasis. In the early stage, the prognosis of patients with LOH of less than two genes was significantly better than that of those with LOH of two genes or more. Using high-density SNP arrays, we identified several novel and minute genomic alterations. LOH of four genes could be useful for prediction of lymph node metastasis and prognosis in early stage gastric cancers.
RELEASE OF GLUCAGON, INDUCED BY STRESS (1973)

When conscious, lightly restrained primates were startled by noise, the level of glucagon in the plasma rose rapidly and this rise was followed by an elevation of blood glucose but not of plasma insulin. In anaesthetized animals similar effects were produced by unpleasant stimuli (rectal distension, drilling a burr hole in the skull or the passage of an electric current through the head). These experiments show that glucagon is rapidly released in response to various types of stress.
Automatic Classification and Segmentation of Teeth on 3D Dental Model Using Hierarchical Deep Learning Networks (2019)

To solve the problem of low efficiency, the complexity of the interactive operation, and the high degree of manual intervention in existing methods, we propose a novel approach based on the sparse voxel octree and 3D convolution neural networks (CNNs) for segmenting and classifying tooth types on the 3D dental models. First, the tooth classification method capitalized on the two-level hierarchical feature learning is proposed to solve the misclassification problem in highly similar tooth categories. Second, we exploit an improved three-level hierarchical segmentation method based on the deep convolution features to conduct segmentation of teeth-gingiva and inter-teeth, respectively, and the conditional random field model is used to refine the boundary of the gingival margin and the inter-teeth fusion region. The experimental results show that the classification accuracy in Level_1 network is 95.96%, the average classification accuracy in Level_2 network is 88.06%, and the accuracy of tooth segmentation is 89.81%. Compared with the existing state-of-the-art methods, the proposed method has higher accuracy and universality, and it has great application potential in the computer-assisted orthodontic treatment diagnosis.
Protective effects of reduced dynamin-related protein 1 against amyloid beta-induced mitochondrial dysfunction and synaptic damage in Alzheimer’s disease (2016)

The purpose of our study was to understand the protective effects of reduced expression of dynamin-related protein (Drp1) against amyloid beta (Aβ) induced mitochondrial and synaptic toxicities in Alzheimer's disease (AD) progression and pathogenesis. Our recent molecular and biochemical studies revealed that impaired mitochondrial dynamics-increased mitochondrial fragmentation and decreased fusion-in neurons from autopsy brains of AD patients and from transgenic AD mice and neurons expressing Aβ, suggesting that Aβ causes mitochondrial fragmentation in AD. Further, our recent co-immunoprecipitation and immunostaining analysis revealed that the mitochondrial fission protein Drp1 interacted with Aβ, and this interaction increased as AD progressed. Based on these findings, we hypothesize that a partial deficiency of Drp1 inhibits Drp1-Aβ interactions and protects Aβ-induced mitochondrial and synaptic toxicities, and maintains mitochondrial dynamics and neuronal function in AD neurons. We crossed Drp1+/- mice with APP transgenic mice (Tg2576 line) and created double mutant (APPXDrp1+/-) mice. Using real-time RT-PCR and immunoblotting analyses, we measured mRNA expressions and protein levels of genes related to the mitochondrial dynamics, mitochondrial biogenesis and synapses from 6-month-old Drp1+/-, APP, APPXDrp1+/- and wild-type (WT) mice. Using biochemical methods, we also studied mitochondrial function and measured soluble Aβ in brain tissues from all lines of mice in our study. Decreased mRNA expressions and protein levels of Drp1 and Fis1 (fission) and CypD (matrix) genes, and increased levels of Mfn1, Mfn2 and Opa1 (fusion), Nrf1, Nrf2, PGC1α, TFAM (biogenesis) and synaptophysin, PSD95, synapsin 1, synaptobrevin 1, neurogranin, GAP43 and synaptopodin (synaptic) were found in 6-month-old APPXDrp1+/- mice relative to APP mice. Mitochondrial functional assays revealed that mitochondrial dysfunction is reduced in APPXDrp1+/- mice relative to APP mice, suggesting that reduced Drp1enhances mitochondrial function in AD neurons. Sandwich ELISA assay revealed that soluble Aβ levels were significantly reduced in APPXDrp1+/- mice relative to APP mice, indicating that reduced Drp1 decreases soluble Aβ production in AD progression. These findings suggest that a partial reduction of Drp1 reduces Aβ production, reduces mitochondrial dysfunction, and maintains mitochondrial dynamics, enhances mitochondrial biogenesis and synaptic activity in APP mice. These findings may have implications for the development of Drp1 based therapeutics for AD patients.
Neuropilin-1 Expression Is Induced on Tolerant Self-Reactive CD8+ T Cells but Is Dispensable for the Tolerant Phenotype (2014)

Establishing peripheral CD8(+) T cell tolerance is vital to avoid immune mediated destruction of healthy self-tissues. However, it also poses a major impediment to tumor immunity since tumors are derived from self-tissue and often induce T cell tolerance and dysfunction. Thus, understanding the mechanisms that regulate T cell tolerance versus immunity has important implications for human health. Signals received from the tissue environment largely dictate whether responding T cells become activated or tolerant. For example, induced expression and subsequent ligation of negative regulatory receptors on the surface of self-reactive CD8(+) T cells are integral in the induction of tolerance. We utilized a murine model of T cell tolerance to more completely define the molecules involved in this process. We discovered that, in addition to other known regulatory receptors, tolerant self-reactive CD8(+) T cells distinctly expressed the surface receptor neuropilin-1 (Nrp1). Nrp1 was highly induced in response to self-antigen, but only modestly when the same antigen was encountered under immune conditions, suggesting a possible mechanistic link to T cell tolerance. We also observed a similar Nrp1 expression profile on human tumor infiltrating CD4(+) and CD8(+) T cells. Despite high expression on tolerant CD8(+) T cells, our studies revealed that Nrp1 had no detectable role in the tolerant phenotype. Specifically, Nrp1-deficient T cells displayed the same functional defects as wild-type self-reactive T cells, lacking in vivo cytolytic potential, IFNγ production, and antitumor responses. While reporting mostly negative data, our findings have therapeutic implications, as Nrp1 is now being targeted for human cancer therapy in clinical trials, but the precise molecular pathways and immune cells being engaged during treatment remain incompletely defined.
Observational constraints on a cosmological model with Lagrange multipliers (2012)

Cosmological models with Lagrange multipliers are appealing because they could explain the behaviour of the dark sector in a unified way. In this work we analyse extensions to the “Dust of Dark Energy model” proposed in Lim et al. (2010) [10] by including spatial curvature and more general potentials of the scalar field. We perform dynamical system analysis and we determine the evolution of the equation of state parameter as a function of the scale factor. We present observational constraints on this model by using Union2.1 dataset and H(z) data.
Ganging up on information overload (1998)

When information is abundant, the knowledge of which information is useful and valuable matters most. We all use our network of family, friends, and colleagues to recommend movies, books, cars, and news articles. Collaborative filtering technology automates the process of sharing opinions on the relevance and duality of information. Collaborative filtering is one technique among many information filtering techniques that range from unfiltered to personalized and from effortless to laborious. Libraries or the Web are good examples of unfiltered information sources. E-mail directed to one recipient is a good example of a filtered information source. A best-seller list requires little effort fur the user, but provides the same recommendations to all users. Filters based on demographics, such as age, sex, or marital status, require some effort from the user in providing the demographics, and provide some level of personal filtering, so they are near the middle of the chart. Collaborative filtering requires relatively little effort from the user, and provides individually targeted recommendations, so it is in the upper right of the chart. Effort, of course, can be reduced via automation. While collaborative filtering is not necessarily effortless, it requires a relatively small amount of effort on the part of the user and provides very individualized recommendations. The collaborative filtering systems that we discuss here each offer a high degree of personalization, but each system takes a different approach to automation, attempting to find the best trade-off between the amount of work the users must put into the system and the perceived value and benefits they receive in return.
Antagonist activities of mecamylamine and nicotine show reciprocal dependence on beta subunit sequence in the second transmembrane domain (1999)

We show that a portion of the TM2 domain regulates the sensitivity of beta subunit-containing rat neuronal nicotinic AChR to the ganglionic blocker mecamylamine, such that the substitution of 4 amino acids of the muscle beta subunit sequence into the neuronal beta4 sequence decreases the potency of mecamylamine by a factor of 200 and eliminates any long-term effects of this drug on receptor function. The same exchange of sequence that decreases inhibition by mecamylamine produces a comparable potentiation of long-term inhibition by nicotine. Inhibition by mecamylamine is voltage-dependent, suggesting a direct interaction of mecamylamine with sequence elements within the membrane field. We have previously shown that sensitivity to TMP (tetramethylpiperidine) inhibitors is controlled by the same sequence elements that determine mecamylamine sensitivity. However, inhibition by bis-TMP compounds is independent of voltage. Our experiments did not show any influence of voltage on the inhibition of chimeric receptors by nicotine, suggesting that the inhibitory effects of nicotine are mediated by binding to a site outside the membrane's electric field. An analysis of point mutations indicates that the residues at the 6' position within the beta subunit TM2 domain may be important for determining the effects of both mecamylamine and nicotine in a reciprocal manner. Single mutations at the 10' position are not sufficient to produce effects, but 6' 10' double mutants show more effect than do the 6' single mutants.
Reservoir Connectivity Analysis – Defining Reservoir Connections and Plumbing (2005)

Abstract Gas, oil, and water fluids in channelized or faulted reservoirscan create complex reservoir plumbing relationships. Variable hydrocarbon contacts can develop when some, but not all, fluids are in pressure communication. Reservoir Connectivity Analyis (RCA) is a series of analyses and approaches to integrate structural, stratigraphic, and fluid pressure and composition data into permissible but non-unique scenarios offluid contacts and pressures. RCA provides the basis for fluid contact and pressure scenarios at all business stages, allowing the creation of fluid contact and segmentation scenarios earlier in an exploration or development setting, and the identification of by-passed pays or new exploration opportunities in aproduction setting. Combining conventional structural and fault juxtaposition spill concepts with a renewed appreciation of fluid breakover (contacts controlled by spill of pressure-driven, denser fluid, like water over a dam) and capillary leak (to define the ratio of gas and oil where capillary gas leak determines the GOC), we define permissible but non-unique scenarios of the full fluid fill/displacement/spill pathways of ahydrocarbon accumulation comprised of single or multiple reservoir intervals. This new analytical approach has been used in a wide range of reservoirs, including clastic (from fluvial to shoreface to deepwater) and carbonate reservoirs, in fields around the world.RCA models have been used to predict fluid contacts in faulted reservoirs where other approaches failed, to locateby-passed pay opportunities for in fill drilling in mature fields,and to condition connections in reservoir simulation models. RCA is an integrated technology that challenges the interpreter to evaluate and incorporate fluid property, composition, and pressure data with stratigraphic and structural interpretations of a reservoir to achieve a deeper, more comprehensive understanding of reservoir compartments and the connections between them.
Detergent-assisted refolding of guanidinium chloride-denatured rhodanese. The effects of the concentration and type of detergent. (1987)

We have established the generality of using detergents for facilitating the reactivation of 6 M guanidinium chloride-denatured rhodanese that was recently described for the nonionic detergent lauryl maltoside (LM) (Tandon, S., and Horowitz, P. (1986) J. Biol. Chem. 261, 15615-15618). We report here that not only LM but other nonionic as well as ionic and zwitterionic detergents also have favorable effects in reactivating the denatured enzyme. Not all detergents are useful, and the favorable effects occur over a limited concentration range. Above and below that range there is little or no effect. Zwittergents, which represent a homologous series with varying critical micelle concentrations (CMCs) are effective only above their CMCs. Induction phases occur in the progress curves of rhodanese refolded in the presence of the effective detergents, suggesting the presence of refolding intermediates that are apparently stabilized by detergent interactions. Gel filtration chromatography of rhodanese with and without LM suggests that even though the renaturation of the denatured enzyme requires detergent at concentrations above its CMC, the enzyme does not bind an amount of detergent equivalent to a micelle. It is suggested that renaturation of other proteins might also be assisted by inclusion of "nondenaturing" detergents, although the optimal conditions will have to be determined for each individual case.
In Vitro Prefabrication of Human Cartilage Shapes Using Fibrin Glue and Human Chondrocytes (1998)

We report the first generation of human cartilage from fibrin glue using a technique of molding chondrocytes in fibrin glue developed in our laboratory. Human costal chondrocytes were suspended in cryoprecipitate and polymerized into a human nasal shape with bovine thrombin. After culture in vitro for 4 weeks, this construct was implanted subcutaneously into a nude mouse. The final construct harvested after 4 weeks in vivo demonstrated some preservation of its original features. Histological analysis showed features of native cartilage, including matrix synthesis and viable chondrocytes by nuclear staining. Biochemical analysis demonstrated active matrix production. Biomechanical testing was performed. To our knowledge this is the first reported creation of human cartilage from fibrin glue, and the first creation of human cartilage in vitro. This technique may become a promising means of engineering precisely designed autogenous cartilage for human reconstruction.