gebhart/patrepeval huggingface dataset:
An unusual bovine pancreatic protein exhibiting pH-dependent globule-fibril transformation and unique amino acid sequence. (1985)

An unusual hitherto unreported protein, extracted in acid from fresh bovine pancreas, has been purified and characterized biochemically. It precipitates in the neutral pH range in the form of uniform double-helical threads, each strand of which is smooth and of uniform diameter, about 7-8 nm. The threads dissolve to a nonviscous solution below pH 3.6 and above pH 9.4, and they reconstitute reversibly in the pH range in between. The monomer in acid has an apparent molecular weight of 17,800 and consists of two disulfide-linked nonidentical polypeptide chains of different lengths. It is rich in aromatic amino acids, particularly tryptophan. There is no significant content of carbohydrate, fatty acid, or bound phosphate. The amino acid sequences of the first NH2-terminal 48 residues of the A chain and 35 residues of the B chain appear to be unique, differing from all other reported animal proteins, including those of the pancreas. Thus far, a function has not been found.
Single-File Transport of Water Molecules through a Carbon Nanotube (2002)

Recent molecular dynamics simulations of water transport through the interior channel of a carbon nanotube in contact with an aqueous reservoir showed that conduction occurred in bursts with collective water motion. A continuous-time random-walk model is used to describe concerted transport through channels densely filled with molecules in a single-file arrangement, as also found in zeolites, as well as ion channels and aquaporins in biological membranes. Theoretical predictions for different collective properties of the single-file transport agree with the simulation results.
Extracorporeal perfusion of plasma over immobilized protein A in a patient with Kaposi's sarcoma and acquired immunodeficiency. (1984)

Plasma of a homosexual man with Kaposi's sarcoma and acquired immunodeficiency was perfused over a protein A column using a continuous-flow plasma-cell separator. Three liters of plasma was perfused during each procedure and returned to the patient at a plasma flow rate of 10-20 ml/min. Three treatments were performed over a 1-week period. Transient removal of IgG, immune complexes, antilymphocyte antibodies, and serum blocking factors to mitogenic lymphocyte stimulation was observed during each treatment. Although no striking regression occurred, microscopic examination of sarcomatous lesions revealed decrease of tumor cell density and collagen proliferation within the tumor. Immunohistochemical deposition of C3 was observed in the tumor lesions after treatment. Side effects from the treatment included a mild drop of systolic blood pressure, sinus tachycardia, and a decrease in platelet count.
Interferon: Cellular Executioner or White Knight? (2007)

Interferons (IFNs) are a family of pleiotropic cytokines that typically exhibit antiviral, antiproliferative, antitumor, and immunomodulatory properties. While their complex mechanisms of action remain unclear, IFNs are used clinically in the treatment of viral infections, such as hepatitis B and hepatitis C, and remain the primary treatment for a limited number of malignancies, such as melanoma, hairy cell leukemia, and non-Hodgkin's lymphoma and in autoimmune diseases such as multiple sclerosis. IFNs not only regulate somatic cell growth and division but also influence cell survival through the modulation of apoptosis. Paradoxically, IFNs are described to be both pro- and anti-apoptotic in nature. The biological effects of IFNs are primarily mediated via activation of the JAK/STAT pathway, formation of the ISGF3 and STAT1:STAT1 protein complexes, and the subsequent induction of IFN-stimulated genes. However, the activation of JAK/STAT-independent signal transduction pathways also contribute to IFN-mediated responses. To further demonstrate the complexity of the downstream events following stimulation, oligonucleotide microarray studies have shown that in excess of 300 genes are induced following treatment with IFN, some of which are crucial to the induction of apoptosis and cell growth control. In this review we describe the recent advances made in elucidating the various signaling pathways that are activated by IFNs and how these diverse signals contribute to the regulation of cell growth and apoptosis and inhibition of viral replication. Furthermore, we highlight the role of specific signaling molecules and the function(s) of particular IFN-stimulated genes that have been implicated in determining cell fate in response to IFN, as well as the clinical experience of IFN immunotherapy.
Macrophage Migration Inhibitory Factor Up-regulates Expression of Matrix Metalloproteinases in Synovial Fibroblasts of Rheumatoid Arthritis (2000)

Neutral matrix metalloproteinases (MMPs) are responsible for the pathological features of rheumatoid arthritis (RA) such as degradation of cartilage. We herein show the up-regulation of MMP-1 (interstitial collagenase) and MMP-3 (stromelysin) mRNAs of cultured synovial fibroblasts retrieved from rheumatoid arthritis (RA) patients in response to macrophage migration inhibitory factor (MIF). The elevation of MMP-1 and MMP-3 mRNA was dose-dependent and started at 6 h post-stimulation by MIF, reached the maximum level at 24 h, and was sustained at least up to 36 h. Interleukin (IL)-1beta mRNA was also up-regulated by MIF. These events were preceded by up-regulation of c-jun and c-fos mRNA. Tissue inhibitor of metalloproteinase (TIMP)-1, a common inhibitor of these proteases, was slightly up-regulated by MIF. Similarly, mRNA up-regulation of MMP-1 and MMP-3 was observed in the synovial fibroblasts of patients with osteoarthritis. However, their expression levels were much lower than those of RA synovial fibroblasts. The mRNA up-regulation by MIF was inhibited by the tyrosine kinase inhibitors genestein and herbimycin A, as well as the protein kinase C inhibitors staurosporine and H-7. On the other hand, the inhibition was not seen after the addition of the cyclic AMP-dependent kinase inhibitor, H-8. The mRNA up-regulation of MMPs was also inhibited by curcumin, an inhibitor of transcription factor AP-1, whereas interleukin-1 receptor antagonist, an IL-1 receptor antagonist, failed to inhibit the mRNA up-regulation. Considering these results, it is suggested that 1) MIF plays an important role in the tissue destruction of rheumatoid joints via induction of the proteinases, and 2) MIF up-regulates MMP-1 and MMP-3 via tyrosine kinase-, protein kinase C-, and AP-1- dependent pathways, bypassing IL-1beta signal transduction.
The immunosuppressive activity of L-leucyl-L-leucine methyl ester: selective ablation of cytotoxic lymphocytes and monocytes. (1986)

L-Leucyl-L-leucine methyl ester (Leu-Leu-OMe), a dipeptide condensation product of L-leucine methyl ester generated by human monocytes (M phi) or polymorphonuclear leukocytes, eliminates all natural killer cell (NK) function from mixed lymphocyte populations. In the present studies, the specificity of the action of Leu-Leu-OMe was examined. It was found that a variety of tissue culture cells and tumor lines of nonlymphoid origin were completely resistant to any demonstrable Leu-Leu-OMe-mediated toxicity. Furthermore, the erythroleukemia line K562, the T cell line Molt-4, the B cell lines HS-Sultan and Daudi, and EBV-transformed B cell lines were unaffected by concentrations of this compound that completely eliminated NK cells. Similarly, the vast majority of OKT4+ lymphocytes manifested no significant toxicity after Leu-Leu-OMe exposure. Furthermore, they retained the capacity to proliferate normally in response to allogeneic cells as well as the ability to provide help for the generation of immunoglobulin-secreting cells (ISC). However, Leu-Leu-OMe caused partial depletion of OKT8+ cells from mixed populations of lymphocytes. After such exposure, the remaining OKT8+ cells were still capable of proliferating in mixed lymphocyte cultures, but the suppressive effect of these cells on ISC generation was abolished. Furthermore, both precursors and activated effectors of cytotoxic T lymphocyte (CTL) and activated NK-like activity generated in mixed lymphocyte cultures were eliminated by exposure to low concentrations of Leu-Leu-OMe. Indeed, both OKT4+ and OKT8+ CTL were eliminated by Leu-Leu-OMe. In addition, both peripheral blood M phi and U937 cells, a human cell line with many M phi-like characteristics, were sensitive to Leu-Leu-OMe-mediated toxicity, although only at two- to fivefold higher concentrations than those completely eliminating NK cells. These findings indicate that Leu-Leu-OMe has selective toxicity for NK cells, CTL, and M phi without adverse effects on a variety of other lymphoid or nonlymphoid cell types.
Faster sequential genetic linkage computations. (1993)

Linkage analysis using maximum-likelihood estimation is a powerful tool for locating genes. As available data sets have grown, the computation required for analysis has grown exponentially and become a significant impediment. Others have previously shown that parallel computation is applicable to linkage analysis and can yield order-of-magnitude improvements in speed. In this paper, we demonstrate that algorithmic modifications can also yield order-of-magnitude improvements, and sometimes much more. Using the software package LINKAGE, we describe a variety of algorithmic improvements that we have implemented, demonstrating both how these techniques are applied and their power. Experiments show that these improvements speed up the programs by an order of magnitude, on problems of moderate and large size. All improvements were made only in the combinatorial part of the code, without restoring to parallel computers. These improvements synthesize biological principles with computer science techniques, to effectively restructure the time-consuming computations in genetic linkage analysis.
Thin-film sensing with planar terahertz metamaterials: sensitivity and limitations (2008)

The limiting effects of varying the thickness of a dielectric overlayer on planar double split-ring resonator (SRR) arrays are studied by terahertz time-domain spectroscopy. Uniform dielectric overlayers from 100 nm to 16 mum thick are deposited onto fixed SRR arrays in order to shift the resonance frequency of the electric response. We discuss the bounds of resonance shifting and emphasize the resulting limitations for SRR-based sensing. These results are presented in the context of typical biosensing situations and are compared to previous work and other existing sensing platforms.
Placing microalgae on the biofuels priority list: a review of the technological challenges (2009)

Microalgae provide various potential advantages for biofuel production when compared with 'traditional' crops. Specifically, large-scale microalgal culture need not compete for arable land, while in theory their productivity is greater. In consequence, there has been resurgence in interest and a proliferation of algae fuel projects. However, while on a theoretical basis, microalgae may produce between 10- and 100-fold more oil per acre, such capacities have not been validated on a commercial scale. We critically review current designs of algal culture facilities, including photobioreactors and open ponds, with regards to photosynthetic productivity and associated biomass and oil production and include an analysis of alternative approaches using models, balancing space needs, productivity and biomass concentrations, together with nutrient requirements. In the light of the current interest in synthetic genomics and genetic modifications, we also evaluate the options for potential metabolic engineering of the lipid biosynthesis pathways of microalgae. We conclude that although significant literature exists on microalgal growth and biochemistry, significantly more work needs to be undertaken to understand and potentially manipulate algal lipid metabolism. Furthermore, with regards to chemical upgrading of algal lipids and biomass, we describe alternative fuel synthesis routes, and discuss and evaluate the application of catalysts traditionally used for plant oils. Simulations that incorporate financial elements, along with fluid dynamics and algae growth models, are likely to be increasingly useful for predicting reactor design efficiency and life cycle analysis to determine the viability of the various options for large-scale culture. The greatest potential for cost reduction and increased yields most probably lies within closed or hybrid closed-open production systems.
Immunological characterization of cell‐surface and soluble forms of membrane type 1 matrix metalloproteinase in human breast cancer cells and in fibroblasts (1998)

Membrane type (MT) 1 matrix metalloproteinase (MMP) activates progelatinase A (pro–MMP-2), a type IV collagenase, on the cell surface of tumors; however, its function in breast cancer progression and metastasis is not fully understood. To examine the expression of MT1-MMP in breast cancer cells and fibroblasts, a specific rabbit antibody (Ab) directed against a unique synthetic peptide derived from the human MT1-MMP catalytic domain was produced, purified, and characterized. This Ab is not likely to cross-react with MT2-, MT3-, or MT4-MMP or any other MMPs. MT1-MMP expression and pro–MMP-2 activation were stimulated by concanavalin A in two human breast carcinoma cell lines (BT549 and MDA-MB-231) and in normal human fetal-lung fibroblasts (HFL-1) and were slightly upregulated by breast cancer cell–fibroblast interactions. Both pro-MT1-MMP in plasma membrane (63.4 kDa) and the soluble forms of the enzyme in culture medium (57.6 and 25–30 kDa) were detected by immunoblot analysis, suggesting that cell-surface MT1-MMP exhibits an active conformation without the removal of its propeptide domain and that the mature enzyme is shed into the medium. In breast cancer cells, MT1-MMP and a recombinant catalytic domain of MT1-MMP were unable to activate pro-matrilysin, indicating that MT1-MMP is not a universal activator of all MMPs. MT1-MMP may play an important role in the invasive growth and spread of breast cancer cells by specifically activating pro–MMP-2 to cleave the connective-tissue barrier. Furthermore, use of the specific Ab may aid in the investigation of the role of MT1-MMP in human tumors. Mol. Carcinog. 22:84–94, 1998. © 1998 Wiley-Liss, Inc.
The Renal Clearance of Dextran of Different Molecular Sizes in Normal Humans (1964)

(1964). The Renal Clearance of Dextran of Different Molecular Sizes in Normal Humans. Scandinavian Journal of Clinical and Laboratory Investigation: Vol. 16, No. 1, pp. 81-86.
Tetrahydrocannabinol Stability in Whole Blood: Plastic Versus Glass Containers (1986)

The stability of tetrahydrocannabinol (THC) in whole blood during storage was investigated. Two types of containers were used: plastic tubes (polystyrene) and glass vials. Freshly drawn blood was spiked with 10 pmol THC/mL and stored for four days at room temperature (20 degrees to 25 degrees C). The material was kept for four weeks at -20 degrees C. Blood samples from 16 persons apprehended by the police on suspicion of cannabis smoking were collected into the two types of containers and stored frozen (-20 degrees C) until analysis. THC was quantified by capillary column gas chromatography/electron impact mass spectrometry (GC/EI-MS) combined with selected ion monitoring (SIM). Deuterium-labeled THC (THC-d3) was used as internal standard (IS) and was added to the samples immediately prior to extraction. The THC level remained unchanged in glass vials. Samples from the plastic containers had lost 60 to 100% of their THC during storage. In 13 authentic samples, the THC level in blood from the plastic containers varied 0 to 87% from the level in the same blood stored in glass vials. The IS was undetectable in some of these samples.
Anti-Tumor Immunity Provided by a Synthetic Multiple Antigenic Glycopeptide Displaying a Tri-Tn Glycotope (2001)

In many cancer cells the alteration of glycosylation processes leads to the expression of cryptic carbohydrate moieties, which make them good targets for immune intervention. Identification of cancer-associated glycotopes as well as progress in chemical synthesis have opened up the way for the development of fully synthetic immunogens that can induce anti-saccharide immune responses. Here, we synthesized a dendrimeric multiple antigenic glycopeptide (MAG) containing the Tn Ag O:-linked to a CD4(+) T cell epitope. This MAG is based on three consecutive Tn moieties (tri-Tn) corresponding to the glycotope recognized by an mAb (MLS 128) produced against the LS180 colon carcinoma cell line. The Abs induced by this MAG recognized murine and human tumor cell lines expressing the Tn Ag. Prophylactic vaccination using MAG provided protection of mice against tumor challenge. When used in active specific immunotherapy, the MAG carrying the tri-Tn glycotope was much more efficient than the mono-Tn analogue in promoting the survival of tumor-bearing mice. Furthermore, in active specific immunotherapy, a linear glycopeptide carrying two copies of the tri-Tn glycotope was shown to be poorly efficient compared with the dendrimeric MAG. Therefore, both the clustering of carbohydrate Ags and the way they are displayed seem to be important parameters for stimulating efficient anti-saccharide immune responses.
The Inducibly Expressed GTPase Localizes to the Endoplasmic Reticulum, Independently of GTP Binding (1997)

The inducibly expressed GTPase (IGTP) is representative of a newly identified group of interferon gamma-inducible GTPases, whose functions are currently unknown. We have begun to address the cellular function of IGTP by examining its subcellular distribution and its guanine nucleotide binding status. Using immunofluorescence, electron microscopy, and subcellular fractionation, IGTP was localized predominantly to the endoplasmic reticulum of both RAW 264. 7 macrophages and C127 fibroblasts. In the immunostaining experiments, staining of discrete cytoplasmic structures on the periphery of the endoplasmic reticulum was also evident. Using polyethyleneimine-cellulose thin layer chromatography, the guanine nucleotides that complexed to immunoprecipitated IGTP, in both control and interferon gamma-stimulated cells, were 90-95% GTP and 5-10% GDP, suggesting that the protein was in an active state. A mutant IGTP protein was created that had no detectable complexed GTP, and in both subcellular fractionation and IGTP-green fluorescent protein fusion studies, this mutant also localized to the endoplasmic reticulum. These results suggested that the GTP binding status of IGTP is independent of its capacity to localize to the endoplasmic reticulum. Given these results, we propose that IGTP is representative of a new family of endoplasmic reticulum GTPases that may be involved in protein processing or trafficking.
Loss of the Forkhead Transcription Factor FoxM1 Causes Centrosome Amplification and Mitotic Catastrophe (2005)

Expression of the forkhead transcription factor FoxM1 correlates with proliferative status in a variety of normal and transformed cell types. Elevated expression of FoxM1 has been noted in both hepatocellular carcinoma and basal cell carcinoma. However, whether FoxM1 expression is essential for the viability of transformed cells is unknown. We report here that the expression of FoxM1 is significantly elevated in primary breast cancer. Microarray analysis shows that FoxM1 regulates genes that are essential for faithful chromosome segregation and mitosis, including Nek2, KIF20A, and CENP-A. Loss of FoxM1 expression generates mitotic spindle defects, delays cells in mitosis, and induces mitotic catastrophe. Time-lapse microscopy indicates that depletion of FoxM1 generates cells that enter mitosis but are unable to complete cell division, resulting in either mitotic catastrophe or endoreduplication. These findings indicate that FoxM1 depletion causes cell death due to mitotic catastrophe and that inhibiting FoxM1 represents a therapeutic strategy to target breast cancer.
Does L-Canavanine Ingestion Induce Murine SLE?: Paradoxical Effects on Survival of BALB/c Mice (2008)

Abstract Observations in humans and macaques suggest that ingestion of an excess of alfalfa sprouts can induce systemic lupus erythematosus (SLE). Feeding L-canavanine increased the incidence of autoimmune symptoms in several strains of mice. The presence of L-canavanine in alfalfa sprouts could result in the synthesis of proteins rich in L-canavanyl residues and subsequent recognition of these modified endogenous proteins as foreign. The original purpose of this long-term study in BALB/c mice was to determine whether ingestion of L-canavanine did induce an SLE-like disorder by such a mechanism. Analysis of mortality patterns observed during that investigation of diet-induced autoimmune disease suggests that L-canavanine increases murine longevity. Eighteen female BALB/c mice were fed a diet containing 1.56% L-canavanine sulfate (equivalent to 1% L-canavanine base). Eighteen other mice received a control diet. The animals were monitored for the presence of anti-nucleic acids and survival. There was no evi...
A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia (2012)

The interaction of acute myeloid leukemia (AML) blasts with the leukemic microenvironment is postulated to be an important mediator of resistance to chemotherapy and disease relapse. We hypothesized that inhibition of the CXCR4/CXCL12 axis by the small molecule inhibitor, plerixafor, would disrupt the interaction of leukemic blasts with the environment and increase the sensitivity of AML blasts to chemotherapy. In this phase 1/2 study, 52 patients with relapsed or refractory AML were treated with plerixafor in combination with mitoxantrone, etoposide, and cytarabine. In phase 1, plerixafor was escalated to a maximum of 0.24 mg/kg/d without any dose-limiting toxicities. In phase 2, 46 patients were treated with plerixafor 0.24 mg/kg/d in combination with chemotherapy with an overall complete remission and complete remission with incomplete blood count recovery rate (CR + CRi) of 46%. Correlative studies demonstrated a 2-fold mobilization in leukemic blasts into the peripheral circulation. No evidence of symptomatic hyperleukocytosis or delayed count recovery was observed with the addition of plerixafor. We conclude that the addition of plerixafor to cytotoxic chemotherapy is feasible in AML, and results in encouraging rates of remission with correlative studies demonstrating in vivo evidence of disruption of the CXCR4/CXCL12 axis.
Survey of nanomanipulation systems (2002)

Nanomanipulation as a new emerging area enables to change, interact and control the nano scale phenomenon precisely. Nanomanipulation systems are surveyed in this paper. Nanomanipulation approaches are grouped according to their starting point, utilized process, operation type, manipulation environment, interaction type, etc. Main components of such systems such as nanomanipulators, nano physics, sensors, actuators, and control are given in detail. Problems are defined and possible solutions are proposed. Moreover, possible applications in biotechnology, computer technology, material science and micro/nanotechnology are reported.