gebhart/patrepeval huggingface dataset:
An intracellular form of cathepsin B contributes to invasiveness in cancer. (2001)

Cathepsin B is a lysosomal cysteine proteinase whose expression and trafficking are frequently altered in cancer, and plasma membrane and secreted forms are thought to contribute to the invasive and metastatic properties of malignant tumors. We have manipulated the expression of cathepsin B in several tumor cell lines and measured their capacity to invade through a reconstituted extracellular (Matrigel) matrix. Transient expression of human cathepsin B in a poorly metastatic B16F1 murine melanoma variant produced a 3-5-fold increase in cathepsin B activity and a comparable increase in invasiveness. Stable antisense cathepsin B-expressing clones of the highly metastatic human melanoma A375M and prostate carcinoma PC3M cell lines produced 40-50% less cathepsin B than control cells and were proportionately less invasive. In contrast, manipulating cathepsin B levels had no effect on cell migration across an uncoated membrane. The anionic cathepsin B inhibitor (L-3-trans-propylcarbamoyloxirane-2-carbony)-L-isoleucyl-L-proline (CA-074), at a concentration of 1 microM, caused a nearly quantitative inhibition of extracellular cathepsin B but had no effect on Matrigel invasion. In contrast, the equally potent but less selective inhibitor, trans-epoxysuccinyl-L-leucylamino(4-guanidino)butane (E-64) inhibited invasion by 75%. Surprisingly, at a concentration of 10 microM, CA-074 slowly permeated the cells, causing an 80-95% inhibition of intracellular cathepsin B after 12 h, the duration of the invasion assay. The membrane-permeant cathepsin B inhibitor, CA-074 methyl ester, and the higher concentration of CA-074 that inhibited intracellular cathepsin B both significantly reduced Matrigel invasion. Collectively, these results identify an intracellular role for cathepsin B in matrix degradation. They also indicate that caution should be exercised in assuming that CA-074 is unable to enter cells when it is used to inhibit biological processes of long duration.
Human Cardiospheres as a Source of Multipotent Stem and Progenitor Cells (2013)

Cardiospheres (CSs) are self-assembling multicellular clusters from the cellular outgrowth from cardiac explants cultured in nonadhesive substrates. They contain a core of primitive, proliferating cells, and an outer layer of mesenchymal/stromal cells and differentiating cells that express cardiomyocyte proteins and connexin 43. Because CSs contain both primitive cells and committed progenitors for the three major cell types present in the heart, that is, cardiomyocytes, endothelial cells, and smooth muscle cells, and because they are derived from percutaneous endomyocardial biopsies, they represent an attractive cell source for cardiac regeneration. In preclinical studies, CS-derived cells (CDCs) delivered to infarcted hearts resulted in improved cardiac function. CDCs have been tested safely in an initial phase-1 clinical trial in patients after myocardial infarction. Whether or not CDCs are superior to purified populations, for example, c-kit(+) cardiac stem cells, or to gene therapy approaches for cardiac regeneration remains to be evaluated.
The adenovirus E3 14.7-kilodalton protein which inhibits cytolysis by tumor necrosis factor increases the virulence of vaccinia virus in a murine pneumonia model (1994)

The 14.7-kilodalton protein (14.7K protein) encoded by the adenovirus (Ad) E3 region inhibits tumor necrosis factor alpha (TNF-alpha)-mediated lysis of cells in tissue culture experiments, but the relevance of this effect in vivo is incompletely understood. To examine the effect of the ability of the Ad 14.7K protein to block TNF lysis upon viral pathogenesis in a murine model, we cloned the 14.7K protein-encoding gene into vaccinia virus (VV), permitting its study in isolation from other Ad E3 immunomodulatory proteins. The gene for murine TNF-alpha was inserted into the same VV containing the 14.7K gene to ensure that each cell infected with the VV recombinant would express both the agonist (TNF) and its antagonist (14.7K). VV was utilized as the vector because it accommodates large and multiple inserts of foreign DNA with faithful, high-level expression of the protein products. In addition, infection of mice with VV induces disease with quantifiable morbidity, mortality, and virus replication. The results of intranasal infections of BALB/c mice with these VV recombinants indicate that the Ad 14.7K protein increases the virulence of VV carrying the TNF-alpha gene by reversing the attenuating effect of TNF-alpha on VV pathogenicity. This was demonstrated by increased mortality, pulmonary pathology, and viral titers in lung tissue following infection with VV coexpressing the 14.7K protein and TNF-alpha, compared with the control virus expressing TNF-alpha alone. These results suggest that the 14.7K protein, which is nonessential for Ad replication in tissue culture, is an immunoregulatory protein which functions in vivo to help counteract the antiviral effects of TNF-alpha.
A Hydrocarbon‐Soluble Lithium Hydride Complex (2012)

LiH-ghtweight: The title complex having a central (LiH)4 cube has been prepared and structurally characterized (see picture). The compound is stable towards LiH elimination at room temperature in solution, and can be employed for hydrolithiation reactivity as has been demonstrated by its reaction with benzophenone.
Characterization of a T-lymphocyte Epstein-Barr virus/C3d receptor (CD21) (1988)

The Epstein-Barr virus/C3d receptor (EBVR-CR2) was detected on three T-lymphoblastoid cell lines. The apparent Mrs of purified EBVR-CR2 of T-cell and B-cell origin were identical. The N-terminal amino acid sequence from the T-cell EBVR-CR2 confirmed the placement of this receptor in a multigene family of complement regulatory proteins. All EBVR-CR2-positive T-cell lines were T6 and T4-T8 antigen positive.
Mutant Superoxide Dismutase-1-Linked Familial Amyotrophic Lateral Sclerosis: Molecular Mechanisms of Neuronal Death and Protection (1997)

Mutations in human Cu/Zn superoxide dismutase-1 (SOD) cause approximately 20% of cases of familial amyotrophic lateral sclerosis (FALS). We investigated the mechanism of mutant SOD-induced neuronal degeneration by expressing wild-type and mutant SODs in neuronal cells by means of infection with replication-deficient recombinant adenoviruses. Expression of two FALS-related mutant SODs (A4V and V148G) caused death of differentiated PC12 cells, superior cervical ganglion neurons, and hippocampal pyramidal neurons. Cell death included many features typical of apoptosis. Death could be prevented by copper (Cu2+) chelators, Bcl-2, glutathione, vitamin E, and inhibitors of caspases. Mutant SOD-expressing PC12 cells had higher rates of superoxide (O2-) production under a variety of conditions. The results support the hypothesis that mutant SOD induced-neurodegeneration is associated with disturbances of neuronal free radical homeostasis.
<title>Optical assessment of tissue mechanical properties</title> (2000)

Many disease processes, such as scirrhous carcinoma of the breast and atherosclerosis physically manifest themselves as changes in the mechanical properties of the involved tissue. Optical evaluation of the mechanical properties of biological tissues offers methods that can directly provide information regarding the state of health of both hard and soft tissue. Clinically, this information may be used for diagnostic purposes. Since all biological tissues display viscoelastic behavior and therefore exhibits a time dependence of their mechanical behavior, the important quantities for evaluating the mechanics of tissue under load are those that reflect this time dependence. For example, by evaluating the retardation spectrum of the tissue, the underlying molecular processes that govern the mechanical behavior may be elucidated. Understanding these spectra may provide insight into pathological processes and also provide some guidance for the development of synthetic materials or engineered tissues to replace damaged or pathological tissue. Thus, there is a need for methods that directly assess the time rate of the mechanical response of tissue to an imposed load. Herein, a few such methods will be discussed and applications to biomaterials and medical diagnostics will be discussed.
In-Field Current Transport Properties of 600 A-Class ${\rm GdBa}_{2}{\rm Cu}_{3}{\rm O}_{7-\delta}$ Coated Conductor Utilizing IBAD Template (2011)

We have investigated critical current I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> properties of 600 A/cm-class GdBa <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> Cu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">7-δ</sub> (GdBCO) coated conductor (CC) deposited on IBAD template. 2.5 μm thick GdBCO layer has been obtained by pulse laser deposition without degradation of critical current density by an improved heating condition in reel-to-reel deposition process. This enables stable production of long length CC with I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> (77 K, self-field) of 600 A/cm-w. In-filed I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> has also shown high value e.g., I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> @77 K, 3 T=33 A/cm-w, I <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> @20 K, 27 T=107 A/cm-w. These experimental results obtained in a wide range of bias conditions of temperature T, magnetic field B and field angle θ are useful as a fundamental data for design of superconducting devices such as coil winding and magnet. Furthermore, we have also shown that our proposed analytical expression of electric field vs. current density (E-J) characteristics agrees well with the experimental results. This analytical expression allows us to predictI <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> -B-T property as well as E-J characteristics at arbitrary conditions of B and T.
Use of Virkon as a disinfectant for clinical samples carrying a high risk of infection in inductively coupled plasma mass spectrometry (1999)

The addition of 1% Virkon, a virucidal disinfectant, to clinical samples carrying a high risk of infection can reduce the likelihood of infection, particularly when samples are nebulised, as in ICP-MS. Semiquantitative analysis of Virkon by ICP-MS showed the major elements present in Virkon (Na, Ca, Mg, Al and Zr), which would preclude their determination in samples to which Virkon had been added, and those elements present at intermediate levels (Br, B, Zn, Sc, Mo and Cr) where accurate determination by ICP-MS would be difficult. With suitable blank subtraction, it would be possible to add Virkon to high risk biological samples for the determination of many elements by ICP-MS and AAS.
Inhibitory Effect of Tannic Acid Sulfate and Related Sulfates on Infectivity, Cytopathic Effect, and Giant Cell Formation of Human Immunodeficiency Virus (1992)

The acquired immune deficiency syndrome (AIDS) is thought to result from infection of T cells by a pathogenic human retrovirus, human immunodeficiency virus [HIV (HTLV-III/LAV)]. In this report, we synthesized sulfated plant polyphenols such as tannic acid sulfate, rutin sulfate, ellagic acid sulfate, (-)-epicatechin sulfate, and (-)-epigallocatechin 3-gallate sulfate, and examined the in vitro inhibitory effect on HIV infection using human T-cell lymphotropic virus type-I-carrying MT-4 cells, which are extremely susceptible to HIV infection. Of the compounds tested, tannic acid sulfate was the most effective and had low cytotoxicity. Tannic acid sulfate completely inhibited the cytopathic effect of HIV and the HIV-specific antigen expression in MT-4 cells at the concentration of 6 micrograms/ml. In addition, this sulfate inhibited giant cell formation in coculture at the concentration of 5 micrograms/ml.
Non-RGD domains of osteopontin promote cell adhesion without involving αv integrins (1996)

Osteopontin (OPN) is an integrin-binding secreted protein that contains an Arg-Gly-Asp (RGD) amino acid sequence and binds to various cell types via RGD-mediated interaction with the alpha v beta 3 integrin. We have identified a cell line whose binding to OPN does not require RGD or alpha v interactions. We compared the ability of two murine cell lines, L929 fibroblastic cells and B16-BL6 melanoma cells, to interact with OPN (from human milk, and recombinant human and mouse OPN) as well as recombinant OPN prepared to include either the N-terminal or C-terminal halves but lacking the RGD sequence. Both cell lines adhered to GRGDS peptides coupled to BSA, and these interactions were inhibited by addition of GRGDS (but not GRGES) peptides or a monoclonal antibody specific to the alpha v integrin subunit. Adhesion of L929 cells to OPN was also dependent on the RGD sequence and the alpha v integrin subunit. However, the binding of B16-BL6 cells was not inhibited by either GRGDS peptides or the anti-alpha v antibody. B16-BL6 (but not L929) cells were also able to adhere to and spread on both N-terminal and C-terminal OPN proteins that lack the RGD sequence, and these interactions were not inhibited by either GRGDS peptides or anti-alpha v antibody. Together these results indicate that B16-BL6 cells can adhere to OPN by interactions that are independent of either the RGD sequence or the alpha v integrin subunit, and suggest that some cells can interact with additional, non-RGD binding sites in OPN.
Adhesion of Arg-Gly-Asp (RGD) Peptide Vesicles onto an Integrin Surface:  Visualization of the Segregation of RGD Ligands into the Adhesion Plaques by Fluorescence (2002)

Integrins are adhesion receptors that mediate cell adhesion and play an important function in many biological processes such as morphogenesis and tissue remodeling. These membrane proteins specifically interact with a short tripeptide sequence, RGD (Arg-Gly-Asp), present in numerous extracellular macromolecules. Model systems have been developed in order to understand how membrane adhesion is induced by this specific RGD peptide ligand/integrin recognition system. We have previously shown that RGD giant vesicles selectively adhere to endothelial cells by formation of pinning centers. Nevertheless, the nature of the lipids located in the adhesion contact zone is unknown. One hypothesis is that the lipidic ligands migrate to the contact zone where they are confined after binding to the receptor. To study the possible formation of ligand domains within the vesicle bilayer, we synthesized a fluorescently labeled RGD lipid that can be easily incorporated in giant vesicles. Adhesion of giant RGD vesicles onto an integrin-functionalized surface was followed simultaneously by reflection interference contrast microscopy and fluorescence microscopy. For the first time, it was possible to observe the microsegregation of RGD lipids in the contact zone during adhesion. Additionally, we observed interesting photosensitive properties of the chalcone chromophore that could lead to a new method of analyzing the lipid organization within the membrane during adhesion and to the design of new ligand lipids and vesicle vectors for cell targeting.
HybF, a Zinc-Containing Protein Involved in NiFe Hydrogenase Maturation (2004)

ABSTRACT HypA and HypB are maturation proteins required for incorporation of nickel into the hydrogenase large subunit. To examine the functions of these proteins in nickel insertion, the hybF gene, which is a homolog of hypA essential for maturation of hydrogenases 1 and 2 from Escherichia coli , was overexpressed, and the product was purified. This protein behaves like a monomer in gel filtration and contains stoichiometric amounts of zinc but insignificant or undetectable amounts of nickel and iron. In filter binding assays radioactively labeled nickel binds to HybF with a K D of 1.87 μM and in a stoichiometric ratio. To identify amino acid residues of HybF involved in nickel and/or zinc binding, variants in which conserved residues were replaced were studied. An H2Q replacement eliminated both in vivo activity and in vitro binding of nickel. The purified protein, however, contained zinc at the level characteristic of the wild-type protein. When E3 was replaced by Q, activity was retained, but an E3L exchange was detrimental. Replacement of each of the four conserved cysteine residues of a zinc finger motif reduced the cellular amount of HybF protein without a loss of in vivo activity, indicating that these residues play a purely structural role. A triple mutant deficient in the synthesis or activity of HypA, HybF, and HypB was constructed, and it exhibited the same responsiveness for phenotypic complementation by high nickel as mutants with a single lesion in one of the genes exhibited. The results are interpreted in terms of a concerted action of HypB and HybF in nickel insertion in which HybF (as well as its homolog, HypA) functions as a metallochaperone and HypB functions as a regulator that controls the interaction of HybF with the target protein.
Personalized Medicine in Ophthalmology: From Pharmacogenetic Biomarkers to Therapeutic and Dosage Optimization (2013)

Rapid progress in genomics and nanotechnology continue to advance our approach to patient care, from diagnosis and prognosis, to targeting and personalization of therapeutics. However, the clinical application of molecular diagnostics in ophthalmology has been limited even though there have been demonstrations of disease risk and pharmacogenetic associations. There is a high clinical need for therapeutic personalization and dosage optimization in ophthalmology and may be the focus of individualized medicine in this specialty. In several retinal conditions, such as age-related macular degeneration, diabetic macular edema, retinal vein occlusion and pre-threshold retinopathy of prematurity, anti-vascular endothelial growth factor therapeutics have resulted in enhanced outcomes. In glaucoma, recent advances in cytoskeletal agents and prostaglandin molecules that affect outflow and remodel the trabecular meshwork have demonstrated improved intraocular pressure control. Application of recent developments in nanoemulsion and polymeric micelle for targeted delivery and drug release are models of dosage optimization, increasing efficacy and improving outcomes in these major eye diseases.
Advances in the Treatment of Mucopolysaccharidosis Type I (2004)

The mucopolysaccharidoses are a group of lysosomal storage diseases caused by a deficiency of enzymes that degrade glycosaminoglycans.1 Mucopolysaccharidosis type I, an autosomal recessive disorder caused by a deficiency of the enzyme α-L-iduronidase, is characterized by multisystemic clinical disease. The α-L-iduronidase deficiency leads to the progressive accumulation of glycosaminoglycans, resulting in tissue and organ dysfunction. A wide range of clinical presentations, with variations in the severity of symptoms and the extent of central nervous system involvement, is observed in patients with iduronidase deficiency.In 1919, a German pediatrician named Gertrud Hurler provided the first description of mucopolysaccharidosis type I. Characteristics . . .
Resistance to Anticancer Drugs: Are We Ready to Use Biologic Information for the Treatment of Patients With Cancer? (1998)

Multidrug resistance (MDR) to anticancer drugs can be diagnosed in tumors by molecular biology techniques (expression of the MDR1 gene), by immunologic techniques (expression of P-glycoprotein), and by functional approaches (dye exclusion). Numerous studies have tried to correlate the MDR status of tumors to the clinical response to the treatment, but wide discrepancies prevented definitive conclusions. As a consequence, the routine use of these techniques is still not possible, and continuous efforts are needed for their standardization. The development of MDR modulators in the clinical setting is a promising approach that requires rigorous clinical trials, especially with sequential design of phase 2 protocols. Definitive results are still lacking concerning the interest of combining an MDR modulator to standard chemotherapy for resistant cancers.
Expression of Human Bone Morphogenetic Proteins-2 or -4 in Murine Mesenchymal Progenitor C3H10T½ Cells Induces Differentiation into Distinct Mesenchymal Cell Lineages (1993)

The cDNAs encoding the human bone morphogenetic proteins BMP-2 and BMP-4 in an eukaryotic expression vector were permanently transferred into the murine mesenchymal progenitor cell line C3H10T1/2. Originally, these cells are known to differentiate into myotubes, adipocytes, and chondrocytes upon the addition of azacytidine. Permanent transfection of genes encoding human BMP-2 and BMP-4 induces differentiation into the osteogenic lineage. The osteogenic differentiation potential of C3H10T1/2 cells is substantiated by histochemical and genetic analyses of marker genes typical or specific for osteogenesis, including the parathyroid hormone receptor, alkaline phosphatase, osteopontin, osteonectin, and osteocalcin. In addition to osteoblast formation, development into adipocytes and chondrocytes is also observed, suggesting that BMP-2 and BMP-4 induce differentiation into three mesenchymal lineages.
Mutational Analysis of Yeast TFIIB: A Functional Relationship Between Ssu72 and Sub1/Tsp1 Defined by Allele-Specific Interactions With TFIIB (1999)

TFIIB is an essential component of the RNA polymerase II core transcriptional machinery. Previous studies have defined TFIIB domains required for interaction with other transcription factors and for basal transcription in vitro. In the study reported here we investigated the TFIIB structural requirements for transcription initiation in vivo. A library of sua7 mutations encoding altered forms of yeast TFIIB was generated by error-prone polymerase chain reaction and screened for conditional growth defects. Twenty-two single amino acid replacements in TFIIB were defined and characterized. These replacements are distributed throughout the protein and occur primarily at phylogenetically conserved positions. Most replacements have little or no effect on the steady-state protein levels, implying that each affects TFIIB function rather than synthesis or stability. In contrast to the initial sua7 mutants, all replacements, with one exception, have no effect on start site selection, indicating that specific TFIIB structural defects affect transcriptional accuracy. This collection of sua7 alleles, including the initial sua7 alleles, was used to investigate the allele specificity of interactions between ssu72 and sub1, both of which were initially identified as either suppressors (SUB1 2mu) or enhancers (sub1Delta, ssu72-1) of sua7 mutations. We show that the interactions of ssu72-1 and sub1Delta with sua7 are allele specific; that the allele specificities of ssu72 and sub1 overlap; and that each of the sua7 alleles that interacts with ssu72 and sub1 affects the accuracy of transcription start site selection. These results demonstrate functional interactions among TFIIB, Ssu72, and Sub1 and suggest that these interactions play a role in the mechanism of start site selection by RNA polymerase II.