gebhart/patrepeval huggingface dataset:
The proliferative and morphologic responses of a colon carcinoma cell line (LIM 1215) require the production of two autocrine factors. (1991)

The role of autocrine growth factors in tumor cell growth has been difficult to prove. Our results indicate that more than one autocrine factor is required for the autonomous growth of the LIM 1215 colonic carcinoma cell line. Furthermore, the morphologic changes induced by epidermal growth factor (EGF) are also density dependent and appear to require a synergistic autocrine factor. The serum-free proliferation of the colonic carcinoma cell line LIM 1215 depends on cell density and the presence of EGF (A. Sizeland, S. Bol, and A.W. Burgess, Growth Factors 4:129-143, 1991). At cell densities below 10(4)/cm2, conditioned medium (from cells at a density of 10(5)/cm2) was required for the cells to elicit a mitogenic response to exogenous EGF. At higher cell densities (10(5)/cm2), the cells were independent of both exogenous EGF and conditioned medium. In addition, the EGF receptor was found to be phosphorylated on tyrosine in LIM 1215 cells proliferating at high density, suggesting that the autocrine production of transforming growth factor alpha (TGF alpha) and subsequent ligation to the EGF receptor was occurring. The proliferation of cells at high density was partly inhibited by TGF alpha antibodies but was almost completely inhibited by an antisense oligonucleotide to TGF alpha. The antisense inhibition could be overcome by the addition of EGF, indicating that the effect of the antisense TGF alpha oligonucleotide was on the production of autocrine TGF alpha. LIM 1215 cells were also observed to undergo morphologic changes (spreading and actin cable organization) in response to EGF. These changes were density dependent, but they occurred with a cell density dependence different from that of the proliferative response. These results suggest two possibilities: that the morphologic changes and proliferative responses have different sensitivities to the autocrine factors or that the actions of the autocrine factors are mediated through different signal transduction pathways.
A novel zwitterionic copolymer with a short poly(methyl acrylic acid) block for improving both conjugation and separation efficiency of a protein without losing its bioactivity (2013)

PEGylation of protein drugs has thus far been the most important method used in improving the stability and the circulation time, while lowering the immunogenicity of protein drugs. However, the loss of bioactivity of PEGylated protein drugs and the low recovery through the complicated separation process are the most challenging issues. To overcome these problems, a zwitterionic block copolymer poly(methyl acrylic acid-b-sulfobetaine methacrylate) (PMAA-b-PSBMA or abbreviated to PMS) has been chosen to modify a protein drug (uricase) since zwitterionic materials are superior to polyethylene glycol (PEG) in resistance to nonspecific protein adsorption, chemical stability and also low cytotoxicity. As indicated by the results, the conjugation between PMS and uricase could be achieved under 0.03 mg mL<sup>-1</sup> of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) and 0.018 mg mL<sup>-1</sup>N-hydroxysuccinimide (NHS) through weak charge-induced adsorption of PMS on uricase, which is about 0.3% of the concentration for conventional protein-polymer conjugation. The conjugates, efficiently separated from the reaction solution and re-suspended in physiological solution through pH adjustment from pH 5.35 to 7.4, show about 133% of the original activity and better anti-trypsin digestion than the native uricase. These results demonstrate that the conjugation of a zwitterionic copolymer with a short poly(methyl acrylic acid) block could improve the stability of an enzyme without destructively affecting its bioactivity. This may open a new way for the delivery of therapeutic protein drugs.
Solution NMR Techniques for Large Molecular and Supramolecular Structures (2002)

Transverse relaxation-optimized spectroscopy (TROSY) or generation of heteronuclear multiple quantum coherences during the frequency labeling period and TROSY during the acquisition period have been combined either with cross-correlated relaxation-induced polarization transfer (CRIPT) or cross-correlated relaxation-enhanced polarization transfer (CRINEPT) to obtain two-dimensional (2D) solution NMR correlation spectra of (15)N,(2)H-labeled homo-oligomeric macromolecules with molecular weights from 110 to 800 kDa. With the experimental conditions used, the line widths of the TROSY-components of the (1)H- and (15)N-signals were of the order of 60 Hz at 400 kDa, whereas, for structures of size 800 kDa, the line widths were about 75 Hz for (15)N and 110 Hz for (1)H. This paper describes the experimental schemes used and details of their setup for individual measurements. The performance of NMR experiments with large structures depends critically on the choice of the polarization transfer times, the relaxation delays between subsequent recordings, and the water-handling routines. Optimal transfer times for 2D [(15)N,(1)H]-CRIPT-TROSY experiments in H(2)O solutions were found to be 6 ms for a molecular weight of approximately 200 kDa, 2.8 ms for 400 kDa, and 1.4 ms for 800 kDa. These data validate theoretical predictions of inverse proportionality between optimal transfer time and size of the structure. The proton longitudinal relaxation times in H(2)O solution were found to be of the order of 0.8 s for structure sizes around 200 kDa, 0.4 s at 400 kDa, and 0.3 s at 800 kDa, which enabled the use of recycle times below 1 s. Since improper water handling results in severe signal loss, the water resonance was kept along the z-axis during the entire duration of the experiments by adjusting each water flip-back pulse individually.
Dynamic changes in connexin expression correlate with key events in the wound healing process (2003)

Wound healing is a complex process requiring communication for the precise co-ordination of different cell types. The role of extracellular communication through growth factors in the wound healing process has been extensively documented, but the role of direct intercellular communication via gap junctions has scarcely been investigated. We have examined the dynamics of gap junction protein (Connexins 26, 30, 31.1 and 43) expression in the murine epidermis and dermis during wound healing, and we show that connexin expression is extremely plastic between 6 hours and 12 days post-wounding. The immediate response (6 h) to wounding is to downregulate all connexins in the epidermis, but thereafter the expression profile of each connexin changes dramatically. Here, we correlate the changing patterns of connexin expression with key events in the wound healing process.
IQGAP1 Binds ERK2 and Modulates Its Activity (2004)

IQGAP1 binds several proteins including actin, calmodulin, E-cadherin, beta-catenin, Cdc42, Rac1, and CLIP-170. The interaction with these targets enables IQGAP1 to participate in many cellular functions varying from regulation of the cytoskeleton to gene transcription. Here we show that extracellular signal-regulated kinase (ERK) 2 binds to IQGAP1. In vitro analysis with purified proteins demonstrated a direct interaction between ERK2 and IQGAP1. Moreover, binding occurred in cells as endogenous ERK2 co-immunoprecipitated with IQGAP1 from human breast epithelial cell lysates. The association between ERK2 and IQGAP1 was independent of epidermal growth factor. The in vivo interaction has functional significance. Manipulation of intracellular IQGAP1 levels significantly reduced growth factor-stimulated ERK1 and ERK2 activity. Similarly, stimulation of ERK1 and ERK2 activity by insulin-like growth factor I was reduced when IQGAP1 levels were changed. In contrast, overexpression of an IQGAP1 construct lacking the ERK2 binding region did not interfere with activation of ERK1 and ERK2 by epidermal growth factor. Our data disclose a previously unidentified communication between IQGAP1 and the ERK pathway and imply that IQGAP1 modulates the Ras/mitogen-activated protein kinase signaling cascade.
SYNTHESIS AND NUCLEAR MAGNETIC RESONANCE SPECTRUM OF 3′,4′,6′-TRI-O-ACETYL-2-(METHYLTHIO)-D-GLUCOPYRANO[2′,1′:4,5]-2- THIAZOLINE (1966)

1,3,4,6-Tetra-O-acetyl-2-deoxy-2-(dithiocarbomethoxy)-2-amino-β-D-glucopyranose, when it was treated with trifluoroacetic acid, gave 3′,4′,6′-tri-O-acetyl-2-(methylthio)-D-glucopyrano-[2′,1′:4,5]-2-thiazoline (III). Compound III showed a nuclear magnetic resonance spectrum capable of full interpretation. Long-range coupling between H 2 and H 4 was observed. The conformation of this compound in solution was discussed on the basis of the coupling constants for ring hydrogens.
Synergism between corticosteroids and Rapamycin for the treatment of intraocular inflammation (1995)

The authors studied the combination effect of corticosteroids with the new immunosuppressant Rapamycin for the treatment of intraocular inflammation. A median-effect analysis, of the combined effect of Rapamycin and dexamethasone, was performed on the inhibition of lymphocyte proliferation in culture. The mathematical formulas allowed for the calculation of combination indices and dose-reduction factors. On the basis of these in-vitro results, treatment with reduced doses of drugs in combination was evaluated in the rat model of experimental autoimmune uveoretinitis. The results showed that Rapamycin and dexamethasone were synergistic over a wide concentration range. The calculated dose reduction factors indicated that an equivalent inhibition of lymphocyte proliferation was achieved with a combination of Rapamycin and dexamethasone reduced by 5-7 and 3-6 fold respectively, compared to the concentration required when each drug was used alone. In animals, there was a significant reduction of the incidence and severity of ocular inflammation with low doses of the drugs in combination. The authors conclude that the observed synergistic effect between Rapamycin and dexamethasone suggests that the use of this drug combination might be advantageous in the treatment of patients with severe uveitis.
Nanoparticle-based delivery of small interfering RNA: challenges for cancer therapy (2012)

During recent decades there have been remarkable advances and profound changes in cancer therapy. Many therapeutic strategies learned at the bench, including monoclonal antibodies and small molecule inhibitors, have been used at the bedside, leading to important successes. One of the most important advances in biology has been the discovery that small interfering RNA (siRNA) is able to regulate the expression of genes, by a phenomenon known as RNA interference (RNAi). RNAi is one of the most rapidly growing fields of research in biology and therapeutics. Much research effort has gone into the application of this new discovery in the treatment of various diseases, including cancer. However, even though these molecules may have potential and strong utility, some limitations make their clinical application difficult, including delivery problems, side effects due to off-target actions, disturbance of physiological functions of the cellular machinery involved in gene silencing, and induction of the innate immune response. Many researchers have attempted to overcome these limitations and to improve the safety of potential RNAi-based therapeutics. Nanoparticles, which are nanostructured entities with tunable size, shape, and surface, as well as biological behavior, provide an ideal opportunity to modify current treatment regimens in a substantial way. These nanoparticles could be designed to surmount one or more of the barriers encountered by siRNA. Nanoparticle drug formulations afford the chance to improve drug bioavailability, exploiting superior tissue permeability, payload protection, and the "stealth" features of these entities. The main aims of this review are: to explain the siRNA mechanism with regard to potential applications in siRNA-based cancer therapy; to discuss the possible usefulness of nanoparticle-based delivery of certain molecules for overcoming present therapeutic limitations; to review the ongoing relevant clinical research with its pitfalls and promises; and to evaluate critically future perspectives and challenges in siRNA-based cancer therapy.
An automated method to build a corpus of rhetorically-classified sentences in biomedical texts (2014)

The rhetorical classification of sentences in biomedical texts is an important task in the recognition of the components of a scientific argument. Generating supervised machine learned models to do this recognition requires corpora annotated for the rhetorical categories Introduction (or Background), Method, Result, Discussion (or Conclusion). Currently, a few, small annotated corpora exist. We use a straightforward feature of co-referring text using the word "this" to build a selfannotating corpus extracted from a large biomedical research paper dataset. The corpus is annotated for all of the rhetorical categories except Introduction without involving domain experts. In a 10-fold cross-validation, we report an overall Fscore of 97% with Nave Bayes and 98.7% with SVM, far above those previously reported.
Paper-Based Augmented Reality (2007)

A new method for augmenting paper documents with electronic information is described that does not modify the format of the paper document in any way. Applicable to both commercially printed documents as well as documents that are output from PC's, the technique we call paper-based augmented reality substantially improves the utility of paper. We describe the recognition technology that makes this possible as well as several applications. An implementation on a camera phone is discussed that lets users retrieve data and access links from paper documents to electronic data. Recognition is performed at 4 frames per second on a Treo 700 w and support is provided for several user applications, including "clickable paper" - printed Web pages whose appearance is unchanged but that can be navigated with a camera phone.
A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. (1993)

This report describes a new method for simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. The method is based on the use of a reagent containing phenol and guanidine thiocyanate. A biological sample is homogenized in the reagent and the simultaneous isolation of RNA, DNA and proteins is accomplished in a single step by a liquid-phase separation. The isolation of RNA can be completed in about 1 h, and DNA and proteins in about 3 h. The simultaneously isolated RNA, DNA and proteins are ready for Northern, Southern and Western blotting. The complete recovery of DNA from samples used for the RNA and protein isolation makes it possible to normalize the results of gene expression studies based on DNA content instead of on the more variable total RNA, protein content or tissue weight.
Conditionally reprogrammed cells represent a stem-like state of adult epithelial cells (2012)

The combination of irradiated fibroblast feeder cells and Rho kinase inhibitor, Y-27632, conditionally induces an indefinite proliferative state in primary mammalian epithelial cells. These conditionally reprogrammed cells (CRCs) are karyotype-stable and nontumorigenic. Because self-renewal is a recognized property of stem cells, we investigated whether Y-27632 and feeder cells induced a stem-like phenotype. We found that CRCs share characteristics of adult stem cells and exhibit up-regulated expression of α6 and β1 integrins, ΔNp63α, CD44, and telomerase reverse transcriptase, as well as decreased Notch signaling and an increased level of nuclear β-catenin. The induction of CRCs is rapid (occurs within 2 d) and results from reprogramming of the entire cell population rather than the selection of a minor subpopulation. CRCs do not overexpress the transcription factor sets characteristic of embryonic or induced pluripotent stem cells (e.g., Sox2, Oct4, Nanog, or Klf4). The induction of CRCs is also reversible, and removal of Y-27632 and feeders allows the cells to differentiate normally. Thus, when CRCs from ectocervical epithelium or tracheal epithelium are placed in an air-liquid interface culture system, the cervical cells form a well differentiated stratified squamous epithelium, whereas the tracheal cells form a ciliated airway epithelium. We discuss the diagnostic and therapeutic opportunities afforded by a method that can generate adult stem-like cells in vitro without genetic manipulation.
Oligomeric States of the HIV-1 Integrase As Measured by Time-Resolved Fluorescence Anisotropy (2000)

Self-assembly properties of HIV-1 integrase were investigated by time-resolved fluorescence anisotropy using tryptophanyl residues as a probe. From simulation analyses, we show that suitable photon counting leads to an accurate determination of long rotational correlation times in the range of 20-80 ns, permitting the distinction of the monomer, dimer, and tetramer from higher oligomeric forms of integrase. The accuracy of correlation times higher than 100 ns is too low to distinguish the octamer from other larger species. The oligomeric states of the widely used detergent-solubilized integrase were then studied in solution under varying parameters known to influence the activity. In the micromolar range, integrase exists as high-order multimers such as an octamer and/or aggregates and a well-defined tetramer, at 25 and 35 degrees C, respectively. However, integrase is monomeric at catalytically active concentrations (in the sub-micromolar range). Detergents (NP-40 and CHAPS) and divalent cation cofactors (Mg(2+) and Mn(2+)) have a clear dissociative effect on the high multimeric forms of integrase. In addition, we observed that Mg(2+) and Mn(2+) have different effects on both the oligomeric state and the conformation of the monomer. This could explain in part why these two metal cations are not equivalent in terms of catalytic activity in vitro. In contrast, addition of Zn(2+) stimulates dimerization. Interestingly, this role of Zn(2+) in the multimerization process was evident only in the presence of Mg(2+) which by itself does not induce oligomerization. Finally, it is highly suggested that the presence of detergent during the purification procedure plays a negative role in the proper self-assembly of integrase. Accordingly, the accompanying paper [Leh, H., et al. (2000) Biochemistry 39, 9285-9294] shows that a detergent-free integrase preparation has self-assembly and catalytic properties different from those of the detergent-solubilized enzyme.
Person re-identification by symmetry-driven accumulation of local features (2010)

In this paper, we present an appearance-based method for person re-identification. It consists in the extraction of features that model three complementary aspects of the human appearance: the overall chromatic content, the spatial arrangement of colors into stable regions, and the presence of recurrent local motifs with high entropy. All this information is derived from different body parts, and weighted opportunely by exploiting symmetry and asymmetry perceptual principles. In this way, robustness against very low resolution, occlusions and pose, viewpoint and illumination changes is achieved. The approach applies to situations where the number of candidates varies continuously, considering single images or bunch of frames for each individual. It has been tested on several public benchmark datasets (ViPER, iLIDS, ETHZ), gaining new state-of-the-art performances.
Microglia-specific targeting by novel capsid-modified AAV6 vectors (2016)

Recombinant adeno-associated viruses (rAAV) have been widely used in gene therapy applications for central nervous system diseases. Though rAAV can efficiently target neurons and astrocytes in mouse brains, microglia, the immune cells of the brain, are refractile to rAAV. To identify AAV capsids with microglia-specific transduction properties, we initially screened the most commonly used serotypes, AAV1-9 and rh10, on primary mouse microglia cultures. While these capsids were not permissive, we then tested the microglial targeting properties of a newly characterized set of modified rAAV6 capsid variants with high tropism for monocytes. Indeed, these newly characterized rAAV6 capsid variants, specially a triply mutated Y731F/Y705F/T492V form, carrying a self-complementary genome and microglia-specific promoters (F4/80 or CD68) could efficiently and selectively transduce microglia in vitro. Delivery of these constructs in mice brains resulted in microglia-specific expression of green fluorescent protein, albeit at modest levels. We further show that CD68 promoter-driven expression of the inflammatory cytokine, interleukin-6, using this capsid variant leads to increased astrogliosis in the brains of wild-type mice. Our study describes the first instance of AAV-targeted microglial gene expression leading to functional modulation of the innate immune system in mice brains. This provides the rationale for utilizing these unique capsid/promoter combinations for microglia-specific gene targeting for modeling or functional studies.
Intravascular Catheter-Related Infections (2002)

Novel technologies that have been proved to aid in the diagnosis and prevention of CRBSIs should be considered in clinical practice. The management approach should be based on the type of microorganism causing the infection and on whether the infection is complicated or uncomplicated.
A cDNA coding for human sex hormone binding globulin Homology to vitamin K‐dependent protein S (1987)

Affinity purified antibodies to human sex hormone binding globulin (SHBG) were used in screening a human liver cDNA library, constructed in the expression vector lambda gt11. One clone, identified as producing recombinant SHBG, carried a cDNA insert of 1.1 kb. The nucleotide sequence of the insert had an open reading frame coding for 356 amino acid residues. The coding sequence was followed by a short 3'-region of 19 non-translated nucleotides and a poly(A) tail. Confirmation that the cDNA clone represented human SHBG was obtained by the finding of a complete agreement in amino acid sequence with several peptide fragments generated from purified SHBG by proteolytic cleavage. The primary structure of SHBG shows a considerable homology to that of protein S, a vitamin K-dependent protein with functions in the coagulation system.
Bispecific antibodies engage T cells for antitumor immunotherapy (2011)

The BiTE platform has great potential in the treatment of malignant disease. Despite burgeoning interest in bispecific antibodies and permutations thereof, the issues of stability and cost-effective production persist as obstacles.