gebhart/patrepeval huggingface dataset:
Transforming growth factor-beta-induced growth inhibition and cellular hypertrophy in cultured vascular smooth muscle cells. (1988)

We have explored the hypothesis that hypertrophy of vascular smooth muscle cells may be regulated, in part, by growth inhibitory factors that alter the pattern of the growth response to serum mitogens by characterizing the effects of the potent growth inhibitor, transforming growth factor-beta (TGF-beta), on both hyperplastic and hypertrophic growth of cultured rat aortic smooth muscle cells. TGF-beta inhibited serum-induced proliferation of rat aortic smooth muscle cells (ED50 = 2 pM); this is consistent with previously reported observations in bovine aortic smooth muscle cells (Assoian et al. 1982. J. Biol. Chem. 258:7155-7160). Growth inhibition was due in part to a greater than twofold increase in the cell cycle transit time in cells that continued to proliferate in the presence of TGF-beta. TGF-beta concurrently induced cellular hypertrophy as assessed by flow cytometric analysis of cellular protein content (47% increase) and forward angle light scatter (32-50% increase), an index of cell size. In addition to being time and concentration dependent, this hypertrophy was reversible. Simultaneous flow cytometric evaluation of forward angle light scatter and cellular DNA content demonstrated that TGF-beta-induced hypertrophy was not dependent on withdrawal of cells from the cell cycle nor was it dependent on growth arrest of cells at a particular point in the cell cycle in that both cycling cells in the G2 phase of the cell cycle and those in G1 were hypertrophied with respect to the corresponding cells in vehicle-treated controls. Chronic treatment with TGF-beta (100 pM, 9 d) was associated with accumulation of cells in the G2 phase of the cell cycle in the virtual absence of cells in S phase, whereas subsequent removal of TGF-beta from these cultures was associated with the appearance of a significant fraction of cycling cells with greater than 4c DNA content, consistent with development of tetraploidy. Results of these studies support a role for TGF-beta in the control of smooth muscle cell growth and suggest that at least one mechanism whereby hypertrophy and hyperploidy may occur in this, as well as other cell types, is by alterations in the response to serum mitogens by potent growth inhibitors such as TGF-beta.
Coencapsulation of CpG Oligodeoxynucleotides with RecombinantLeishmania majorStress-Inducible Protein 1 in Liposome Enhances Immune Response and Protection against Leishmaniasis in Immunized BALB/c Mice (2008)

CpG oligodeoxynucleotides (CpG ODN) have been shown to have potent adjuvant activity for a wide range of antigens. The purpose of this study was to determine the potential benefit of using liposomes as a delivery vehicle to enhance the adjuvant activity of CpG ODN with Leishmania major stress-inducible protein 1 (LmSTI1) antigen in induction of the Th1 response in a murine model of leishmaniasis. BALB/c mice were immunized subcutaneously three times in 3-week intervals with liposomal recombinant LmSTI1 (Lip-rLmSTI1), rLmSTI1 coencapsulated with CpG ODN in a liposome (Lip-rLmSTI1-CpG ODN), rLmSTI1 plus CpG ODN in phosphate-buffered saline (PBS), rLmSTI1 plus non-CpG ODN in PBS, rLmSTI1 in PBS, empty liposome, or PBS. The intensity of infection induced by L. major promastigote challenge was measured by footpad swelling. A significant (P < 0.001) inhibition of infection in mice immunized with Lip-rLmSTI1-CpG ODN was shown compared to the other groups, and no parasite was detected in the spleens of this group 14 weeks after challenge. The highest immunoglobulin G2a (IgG2a) titer and the highest IgG2a/IgG1 ratio were also shown in the sera of mice immunized with Lip-rLmSTI1-CpG ODN before and 14 weeks after challenge. The results indicated the superiority of CpG ODN in its liposomal form over its soluble form to induce the Th1 response when used in association with rLmSTI1 antigen. It seems that using a liposome delivery system carrying CpG ODN as an adjuvant coencapsulated with Leishmania antigen plays an important role in vaccine development strategies against leishmaniasis.
Microsurgical Anatomy of the Facial Nerve (1997)

Microsurgical dissection of cadaver facial nerves revealed quantifiable complexities not presented in standard description. Total branches, intraparotid connections between divisions, and extraparotid connections between divisions are more common than generally noted, and 33% of the dissections demonstrated an extraplanar buccal branch originating within the parotid gland, and innervating the perioral muscles. These details of facial nerve anatomy suggest surgical procedures such as tumor resection, facial nerve reconstruction, facial reanimation, and facelifting.
Novel perfluoroalkylation of alkenes with perfluoroalkanesulphonyl chlorides catalysed by a ruthenium(II) complex (1991)

The perfluoroalkylation of acyclic and cyclic alkenes by perfluoroalkanesulphonyl chlorides 1 has been investigated in the presence of a ruthenium(II) catalyst. The addition reactions proceeded smoothly, with extrusion of sulphur dioxide, in alkenes possessing either an electron-donating or an electron-withdrawing group, at 120 °C to give the corresponding chloroperfluoroalkylated compounds in high yield.
Selectivity, Cooperativity, and Reciprocity in the Interactions between the δ-Opioid Receptor, Its Ligands, and G-proteins (2004)

A better understanding of signal transduction mechanisms is of critical importance. Methodologies that allow studies to be done while receptors are incorporated into lipid bilayers are advantageous. One such technique is plasmon-waveguide resonance (PWR) spectroscopy, which can follow changes in conformation accompanying protein-ligand, protein-protein, and protein-lipid interactions occurring in G-protein-coupled receptors in real time with high sensitivity and without the need for molecular labeling. Here we investigated several aspects of human delta-opioid receptor (hDOR)-G-protein interactions: 1) the effect of different types of agonists on the interaction with individual G-protein subtypes; 2) the affinities of the separate G-protein alpha and betagamma subunits to different ligand-occupied states of the receptor; and 3) the effect of the presence of the G-protein on the interactions of the ligand with the receptor. To accomplish this we have incorporated the receptor into a solid supported lipid bilayer in the presence of ligand or G-protein and monitored the PWR spectral changes induced by the reciprocal G-protein or ligand interactions. We found a high degree of selectivity in the interactions of different agonist-bound states of the receptor with the different G-protein subtypes. This has important implications for agonist-directed trafficking and selective drug design. Studies with the separated alpha and betagamma subunits show that cooperativity exists in these interactions. The high affinities of the separated subunits to the receptor point to the possibility of independent promotion of specific signaling events. The presence of G-proteins increased the affinity of agonists to the hDOR, and caused faster binding kinetics and different ligand-induced conformational changes. Because ligand also influences G-protein binding, reciprocity exists between these two binding processes.
Data compression (1987)

This paper surveys a variety of data compression methods spanning almost 40 years of research, from the work of Shannon, Fano, and Huffman in the late 1940s to a technique developed in 1986. The aim of data compression is to reduce redundancy in stored or communicated data, thus increasing effective data density. Data compression has important application in the areas of file storage and distributed systems. Concepts from information theory as they relate to the goals and evaluation of data compression methods are discussed briefly. A framework for evaluation and comparison of methods is constructed and applied to the algorithms presented. Comparisons of both theoretical and empirical natures are reported, and possibilities for future research are suggested.
Deubiquitylases From Genes to Organism (2013)

Ubiquitylation is a major posttranslational modification that controls most complex aspects of cell physiology. It is reversed through the action of a large family of deubiquitylating enzymes (DUBs) that are emerging as attractive therapeutic targets for a number of disease conditions. Here, we provide a comprehensive analysis of the complement of human DUBs, indicating structural motifs, typical cellular copy numbers, and tissue expression profiles. We discuss the means by which specificity is achieved and how DUB activity may be regulated. Generically DUB catalytic activity may be used to 1) maintain free ubiquitin levels, 2) rescue proteins from ubiquitin-mediated degradation, and 3) control the dynamics of ubiquitin-mediated signaling events. Functional roles of individual DUBs from each of five subfamilies in specific cellular processes are highlighted with an emphasis on those linked to pathological conditions where the association is supported by whole organism models. We then specifically consider the role of DUBs associated with protein degradative machineries and the influence of specific DUBs upon expression of receptors and channels at the plasma membrane.
Properties of Polyclonal, Monoclonal, and Recombinant Antibodies Recognizing the Organophosphorus Pesticide Chlorpyrifos-ethyl (2000)

A rabbit polyclonal antiserum and two murine monoclonal antibodies recognizing the organophosphorus pesticide chlorpyrifos-ethyl were produced. The two hybridoma cell lines were then used as sources of immunoglobulin genes for the generation of recombinant scFv antibodies in Escherichia coli. The two scFvs showed either similar or improved limits of detection in an ELISA when compared with the monoclonal antibodies. Cross-reactivity studies showed that all of the antibodies were specific toward the chlorinated aromatic ring. Furthermore, scFv gene sequences were linked directly to sequences coding for either a c-Myc tag, a His-tag, or alkaline phosphatase. The fusion products generated were functional, and their properties were determined. The problems associated with producing scFvs and scFv derivatives for detection of pesticide residues from hybridoma are addressed and discussed.
An Immortalized Cystic Fibrosis Tracheal Epithelial Cell Line Homozygous for the ΔF508 CFTR Mutation (1993)

The development of transformed human airway epithelial cell lines has been important in advancing the understanding of the biochemical and genetic mechanisms underlying the cystic fibrosis (CF) defect. Since the most common mutation associated with CF is a phenylalanine deletion at position 508 (delta F508) in the CF transmembrane conductance regulator (CFTR) gene, a transformed airway epithelial cell line homozygous for this mutation will be important for determining the biologic significance of this mutation in the airways. We report the genotypic and phenotypic characterization of a delta F508 homozygote cell line derived from luminal epithelium in the trachea. The cells were transformed with a plasmid containing an origin of replication defective SV40 genome and have progressed through crisis. Immunocytochemical characterization of the cells shows that they express keratin, indicating epithelial cell origin, and that a calcium-dependent cell adhesion molecule, cellCAM 120/80, is present at plasma membrane junctions between cells. Electrophysiologically, the cells show no cAMP-dependent Cl transport. However, after treatment with the calcium ionophore, ionomycin, cells secrete Cl, albeit at a lower level than that observed in normal cells. Genetically, the cells express CFTR mRNA as determined by polymerase chain reaction amplification and CFTR protein as determined by Western hybridization analysis. Karyotypic analysis shows that 70% of the cells contain two copies of chromosome 7.
Carbon Isotope Composition of Selected Flavoring Compounds for the Determination of Natural Origin by Gas Chromatography/Isotope Ratio Mass Spectrometer (1998)

Capillary gas chromatography coupled to an on-line Isotope Ratio Mass Spectrometer (GC/IRMS) is used to determine individual compound δ13C values for selected flavoring mixtures. These mixtures include citrus oils from geographical regions including China, Argentina, Italy, and the United States; peppermint oils from Oregon; and vanilla extracted from beans grown in geographical regions including Madagascar, Java, Indonesia, and Mexico. The resultant data can be used to generate a fingerprint pattern of the major and ancillary compounds found in these specific flavors. Comparison of these patterns to those of synthetically derived flavors or compounds can be applied to establish the authenticity or natural origin of these flavors.
Heat regulation: homeostasis of central temperature in man (1969)

Focus is on the concept of the quantitative thermostat or setpoint as it evolved experimentally, not theoretically, from measurements of central temperature at the tympanic membrane and from measurements of physiological responses by human gradient layer calorimetry and continuous analysis of oxygen consumption. Heat-flow responses as they relate to stimuli by which they are evoked -- peripheral or central temperatures at thermoreceptive sites -- and discussed, and individual systems of reflex action are described. These systems are then correlated with what is known of their tangible components -- sensory receptors, effector organs, nervous centers, and afferent or efferent nervous pathways -- classically derived from anatomical studies, lesion experiments, recording of action currents, or electrical or thermal stimulation of pertinent structures. Such as correlation is a crucial test, and when the results are consistent, they provide independent, mutual confirmation via the 2 approaches. Doubts are then removed that lesions or interferences, which are unavoidable with most neurophysiological methods, may have produced artifacts. Conversely, calorimetry allows one to observe and analyze thermoregulation in process in a human subject without disturbing normal structures or functions other than by the stresses to which the body is made to respond. Prior to a description of experimental findings, the essential methods are reviewed. With the methods of gradient layer calorimetry, tympanic (eardrum) thermonetry, and indirect calorimetry, thermoregulatory responses -- by chemical overproduction of metabolic heat -- were observed in transient states as a result of a stimulus of cold impinging on peripheral neurons or warm-inhibition removed from central structures. With tympanic thermometry permitting for the 1st time om humans the continuous recording of central thermal stimulation, and with gradient calorimetry permitting the continuous recording (with insignificant inertial distortion) of the sweating responses in precisely controlled environments of a large variety and under conditions where complete evaporation of sweat is ensured by strong but smooth air convection, a new study of physical thermoregulation was initiated in 1958. The experimental results did not support the expection that sweating would follow the average temperature of the skin in the classical tradition, with skin warm-receptors as the hypothetical origin of exciting warm-impulses and cenral temperature as a participant prescribing the action of the "thermoregulator" in some as yet undetermined, additive, manner. Vasomotor mechanisms to human thermoregulation can be assessed in quantitative manner only by whole-body calorimetry. Mechanisms of thermal homeostasis also considered include hormonal regulation, transmitter substances, conscious sensation of warmth and coordinations of behavioral and autonomic mechanisms, setpoint and its variations, and fever.
Why does Escherichia coli recycle its cell wall peptides? (1995)

This review discusses the phenomenon of recycling of cell wall peptides. It is a major, though non-essential, pathway of the cell and is required for induction of beta-lactamase. Consequently, the recycling pathway is viewed as a possible signalling vehicle, informing the cell of the condition of the murein sacculus, an essential structure existing outside the cell itself. As the study of this phenomenon is in its infancy, several speculations are offered for a possible regulatory function.
OverFeat: Integrated Recognition, Localization and Detection using Convolutional Networks (2013)

We present an integrated framework for using Convolutional Networks for classification, localization and detection. We show how a multiscale and sliding window approach can be efficiently implemented within a ConvNet. We also introduce a novel deep learning approach to localization by learning to predict object boundaries. Bounding boxes are then accumulated rather than suppressed in order to increase detection confidence. We show that different tasks can be learned simultaneously using a single shared network. This integrated framework is the winner of the localization task of the ImageNet Large Scale Visual Recognition Challenge 2013 (ILSVRC2013) and obtained very competitive results for the detection and classifications tasks. In post-competition work, we establish a new state of the art for the detection task. Finally, we release a feature extractor from our best model called OverFeat.
Direct protein quantification in complex sample solutions by surface-engineered nanorod probes (2017)

Detecting biomarkers from complex sample solutions is the key objective of molecular diagnostics. Being able to do so in a simple approach that does not require laborious sample preparation, sophisticated equipment and trained staff is vital for point-of-care applications. Here, we report on the specific detection of the breast cancer biomarker sHER2 directly from serum and saliva samples by a nanorod-based homogeneous biosensing approach, which is easy to operate as it only requires mixing of the samples with the nanorod probes. By careful nanorod surface engineering and homogeneous assay design, we demonstrate that the formation of a protein corona around the nanoparticles does not limit the applicability of our detection method, but on the contrary enables us to conduct in-situ reference measurements, thus further strengthening the point-of-care applicability of our method. Making use of sandwich assays on top of the nanorods, we obtain a limit of detection of 110 pM and 470 pM in 10-fold diluted spiked saliva and serum samples, respectively. In conclusion, our results open up numerous applications in direct protein biomarker quantification, specifically in point-of-care settings where resources are limited and ease-of-use is of essence.
Sixty-five gene-based risk score classifier predicts overall survival in hepatocellular carcinoma (2011)

The risk score classifier we have developed can identify two clinically distinct HCC subtypes at early and late stages of the disease in a simple and highly reproducible manner across multiple datasets.
Direct detection of early-stage cancers using circulating tumor DNA (2017)

Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction sequencing (TEC-Seq) that allows ultrasensitive direct evaluation of sequence changes in circulating cell-free DNA using massively parallel sequencing. We have used this approach to examine 58 cancer-related genes encompassing 81 kb. Analysis of plasma from 44 healthy individuals identified genomic changes related to clonal hematopoiesis in 16% of asymptomatic individuals but no alterations in driver genes related to solid cancers. Evaluation of 200 patients with colorectal, breast, lung, or ovarian cancer detected somatic mutations in the plasma of 71, 59, 59, and 68%, respectively, of patients with stage I or II disease. Analyses of mutations in the circulation revealed high concordance with alterations in the tumors of these patients. In patients with resectable colorectal cancers, higher amounts of preoperative circulating tumor DNA were associated with disease recurrence and decreased overall survival. These analyses provide a broadly applicable approach for noninvasive detection of early-stage tumors that may be useful for screening and management of patients with cancer.
THE TAO OF STEM CELLS IN THE GERMLINE (1997)

Germline stem cells (GSCs) are the self-renewing population of germ cells that serve as the source for gametogenesis. GSCs exist in diverse forms, from those that undergo strict self-renewing asymmetric divisions in Drosophila to those that maintain their population by balancing between mitosis and differentiation in Caenorhabditis elegans. Most vertebrate spermatogonial GSCs appear to adopt an intermediate strategy. In most animals, GSCs are established during preadult gonadogenesis following the proliferation and migration of embryonic primordial germ cells. GSCs produce numerous gametes throughout the sexually active period of adult life. The establishment and self-renewing division of GSCs are controlled by extracellular signals such as hormones from the hypothalamic-pituitary axis and local interactions between GSCs and their neighboring cells. These extracellular signals may then influence differential gene expression, cell cycle machinery, and cytoskeletal organization of GSCs for their formation and/or divisional asymmetry. In addition, the GSC mechanism is related to that for germline and sex determination. Current knowledge has provided a solid framework for further study of GSCs and stem cells in general.
Target Analogue Imprinted Polymers with Affinity for Folic Acid and Related Compounds (2001)

Two approaches to synthesize molecularly imprinted polymers with affinity for folic acid and other substituted pteridines have been compared. In the first approach, the folic acid analogue methotrexate was used as template and functional monomers capable of generating selective binding sites were searched in a miniaturized screening system based on binding assessment in the batch mode. Highest selectivity was seen using 2-vinylpyridine as functional monomer, which was confirmed in the chromatographic mode for a batch synthesized on a gram scale. However, the retentivity and selectivity of this phase were insufficient for anticipated applications. In a second approach, using methacrylic acid as the functional monomer, organic soluble inhibitors for the enzyme dihydrofolate reductase were used to develop sites complementary toward the pteridine substructure. This resulted in materials showing enhanced selectivity for substituted pteridines when evaluated by HPLC. Thus, methotrexate and leucovorine were selectively retained in mobile phases of either low or high aqueous content, thus showing the typical bimodal retention behavior of previously reported MIPs. In organic mobile-phase systems, the inhibitor used as template had an influence on the retentivity and selectivity of the MIP. The polymer imprinted with trimethoprim retained all folic acid analogues strongly and showed the highest selectivity among the MIPs in an organic mobile-phase system. This was supported by Scatchard analysis resulting in biphasic plots and a quantitative yield of high-energy binding sites. All templates were shown to associate strongly with MAA in CDCl(3), the strength of association correlating roughly with the template basicity and the selectivity observed in chromatography. Nonparallel complexation-induced shifts indicated formation of 1:2 template monomer complexes at concentrations corresponding to those of the prepolymerization solutions.