gebhart/patrepeval huggingface dataset:
IL-15 administered by continuous infusion to rhesus macaques induces massive expansion of CD8+ T effector memory population in peripheral blood (2011)

IL-15 promotes activation and maintenance of natural killer (NK) and CD8(+) T effector memory (T(EM)) cells, making it a potential immunotherapeutic agent for the treatment of cancer and immunodeficiency states. Here we report the immunologic effects of 3 different IL-15 dosing strategies in Rhesus macaques. IL-15 at a dose of 20 μg/kg/d administered by continuous intravenous infusion for 10 days resulted in a massive (100-fold) expansion of CD8(+) T(EM) cells in the peripheral blood. In contrast, the administration of 20-40 μg/kg/d of IL-15 by subcutaneous injection resulted in a more modest (10-fold) expansion of CD8(+) T(EM) cells. NK expansion was similar in both the continuous intravenous and daily subcutaneous treatment groups. The observation that IL-15 administered by continuous intravenous infusion is able to induce markedly greater expansions of CD8(+) T(EM) cells than the same dose administered by other routes may have important implications for clinical development of this cytokine.
EPIDEMIOLOGY, OBESITY, AND NON-INSULIN-DEPENDENT DIABETES MELLITUS (1989)

Journal Article EPIDEMIOLOGY, OBESITY, AND NON-INSULIN-DEPENDENT DIABETES MELLITUS Get access ELIZABETH BARRETT-CONNOR ELIZABETH BARRETT-CONNOR Department of Community and Family Medicine, Division of Epidemiology M-007, School of Medicine, University of CaliforniaSan Diego, La Jolla, CA 92093 Dr. Elizabeth Barrett-Connor Search for other works by this author on: Oxford Academic PubMed Google Scholar Epidemiologic Reviews, Volume 11, Issue 1, 1989, Pages 172–181, https://doi.org/10.1093/oxfordjournals.epirev.a036035 Published: 01 March 1989
Optisch aktive Lycopin‐epoxide und Lycopin‐glycole: Synthesen und chiroptische Eigenschaften (1986)

Optically Active Lycopene Epoxides and Lycopene Glycols: Synthesis and Chiroptical Properties We present extensive spectral and chiroptical data on the pure and crystalline lycopene diepoxides 1–3 and glycols 4–9 . A first synthetic approach to 1–9 with (+)‐malic acid as starting material afforded 30 as a complex mixture of isomers ( Scheme 1 ). Pure stereoisomers 1–9 were obtained using the enantiomerically pure epoxygeraniol 31 as starting material ( Scheme 2 ). Differentiation of the (5 Z )‐from the (all‐ E )‐isomers by 1 H‐NMR and UV/VIS alone is very difficult.
Three-dimensional synchrotron x-ray particle image velocimetry (2007)

There is great potential to vastly improve biological flow measurement by using a combination of synchrotron imaging and the latest experimental flow measurement techniques. In the current paper, the three-dimensional velocity field within a cylindrical tube is measured using a combination of phase-contrast x-ray imaging and particle image velocimetry (PIV). We greatly refine the techniques previously used to undertake velocity measurements with a synchrotron light source, substantially enhancing accuracy. Furthermore a PIV correlation peak analysis is developed to allow three-dimensional measurement of the velocity field.
Reappraising antiangiogenic therapy for breast cancer (2011)

Phase III trials of antiangiogenic drugs for metastatic breast cancer have either had only limited success, e.g. the monoclonal anti-VEGF antibody bevacizumab when used with various conventional chemotherapy regimens, or have failed altogether, e.g. the small molecule oral tyrosine kinase inhibitor (TKI) sunitinib. No phase III trial has yet demonstrated an overall survival benefit and the progression free survival (PFS) benefits, when attained with bevacizumab are short, with perhaps one exception. Together, these results call for a reappraisal of using antiangiogenic drugs for breast cancer and possible strategies to improve their efficacy. Among the reasons to help explain the limited benefits observed thus far include the possibility that angiogenesis may not be a major driver of breast cancer growth, compared to some other types of cancer; that acquired resistance may develop rapidly to VEGF-pathway targeting antiangiogenic drugs, in part due to angiogenic growth factor redundancy; that optimal chemotherapy regimens have not been used in conjunction with an antiangiogenic drug; and that antiangiogenic drugs may secondarily aggravate biologic aggressiveness of the tumors, thereby reducing their overall efficacy after inducing an initial benefit. Several possible strategies are discussed for improving the efficacy of antiangiogenic drugs, including combination with different chemotherapy regimens, e.g. long term and less toxic metronomic chemotherapy protocols; validation of predictive biomarkers to individualize patient therapy; development of improved preclinical therapy models, e.g. involving advanced metastatic breast cancer, and combination with other types of anti-cancer agents especially biologies such as trastuzumab for Her2-positive breast cancer. Reasons for the current concern regarding use of antiangiogenic drug treatments for early stage cancers, including breast cancer, are also discussed.
Analysis of Neurocan Structures Interacting with the Neural Cell Adhesion Molecule N-CAM (1996)

Neurocan is a brain-specific chondroitin sulfate proteoglycan, which has been shown to bind to the neural cell adhesion molecule N-CAM and to inhibit its homophilic interaction. To study in more detail the structures of neurocan responsible for this interaction, various recombinant neurocan fragments were generated. The ability of these fragments to interact with N-CAM was investigated in several different in vitro assay systems, enzyme-linked immunosorbent assay-type binding assays, Covasphere-aggregation assays, and assays based on an optical biosensor (BIAcoreTM) system. The analysis of the homophilic N-CAM interaction in the BIAcore system revealed a KD of 64 nM. This homophilic interaction could be reduced by preincubation of soluble N-CAM with neurocan. Direct binding of N-CAM to immobilized neurocan core protein and recombinant neurocan fragments could also be demonstrated, and KD values between 25 and 100 nM were obtained. In addition, direct binding of N-CAM to chondroitin sulfate could be demonstrated. Binding of N-CAM to the immobilized neurocan core protein could be inhibited with all recombinant fragments containing chondroitin sulfate or major parts of the mucin-like central region of neurocan. For the inhibition of homophilic N-CAM interactions, however, a combination of globular and extended structures was required.
A Handbook for Seismic Data Acquisition in Exploration (1997)

The science of seismology began with the study of naturally occurring earthquakes. Seismologists at first were motivated by the desire to undetand the destructive nature of large earthquakes. They soon learned, however, that the seismic waves produced by an earthquake contained valuable information about the large-scale structure of the Earth’s interior.

Today, much of our understanding of the Eart’s mantle, crust, and core is based on the analysis of the seismic waves produced by earthquakes. Thus, seismology became an important branch of geophysics, the physics of the Earth.

Seismologists and geologists also discovered that similar, but much weaker, man-made seismic waves had a more practical use: They could probe the very shallow structure of the Earth to help locate its mineral, water, and hydrocarbon resources. Thus, the seismic exploration industry was born, and the seismologists working in that industry came to be called exploration geo-physicists. Today seismic exploration encompasses more than just the search for resources. Seismic technology is used in the search for waste-disposal sites, in determining the stability of the ground under proposed industrial facilities, and even in archaeological investigations. Nevertheless, since hydrocarbon exploration is still the reason for the existence of the seismic exploration industry, the methods and terminology explained in this book are those commonly used in the oil and natural gas exploration industry.

The underlying concept of seismic exploration is simple. Man-made seismic waves are just sound waves (also called acoustic waves) with frequencies typically ranging from about 5 Hz to just over 100 Hz. (The lowest sound frequency audible to the human ear is about 30 Hz.) As these sound waves leave the seismic source and travel downward into the Earth, they encounter changes in the Earth’s geological layering, which cause echoes (or reflections) to travel upward to the surface. Electromechanical transducers (geophones or hydrophones) detect the echoes arriving at the surface and convert them into electrical signals, which are then amplified, filtered, digitized, and recorded. The recorded seismic data usually undergo elaborate processing by digital computers to produce images of the earth’s shallow structure. An experienced geologist or geophysicist can interpret those images to determine what type of rocks they represent and whether those rocks might contain valuable resources.
Effect on substrate binding of an alteration at the conserved aspartic acid-162 in herpes simplex virus type 1 thymidine kinase (1996)

Despite the extensive use of antiviral drugs for the treatment of herpesvirus infections and as pro-drugs for ablative gene therapy of cancer, little structural information about the drug activating enzyme, herpes simplex virus type 1 thymidine kinase (TK), was available until recently. In the absence of the three-dimensional structure we sought to elucidate the function of the key aspartic acid residue (Dl62) present within a highly conserved tri-peptide motif that is thought to function in nucleoside binding. In this study we generated a mutant, D162Q, by site-directed mutagenesis, purified both the wild-type and mutant TKs to near homogeneity by single-step affinity chromatography and determined the kinetic parameters for thymidine, ATP, dTMP and dTTP interactions. A 12-fold increase in Km for thymidine by D162Q TK (Km = 6.67 microM) relative to wild-type enzyme (Km = 0.56 microM) was observed and the absence of any alteration in Km for ATP suggests that D162 participates in nucleoside binding. Furthermore, the Ki for dTMP is significantly higher for D162Q TK than for HSV-1 TK which is indicative of a shared or overlapping binding site with thymidine. This assessment is further supported by the different inhibition patterns of D162Q and wild-type TKs observed using [alpha-32P]5-N3dUMP photoaffinity labelling in the presence of thymidine, ganciclovir or dTMP. Interestingly, the Ki for dTTP was 30-fold lower for D162Q TK (Ki = 2.2 microM) than for the wild-type enzyme (Ki = 65.8 microM) which provides further evidence of the importance of D162 in TK function.
COLD ACCLIMATION OF TWO STRAINS OF THE CYANOBACTERIUM, SPIRULINA PLATENSIS (2000)

The changes in the antioxidant enzymes and photosynthetic activities during cold acclimation in two strains of the cyanobacterium, Spirulina platensis , marked as Kenya and M2, were investigated. Cells were cultured at 33° C then transferred to either 20° C or 15° C. Growth rate of both strains ceased when the temperature shifted from 33 to 20° C and resumed to a slower rate after the first 24 h. Similarly when the temperature was shifted from 33 to 15° C, a complete cessation of growth took place but this time the growth resumed only after 5 to 6 days. The activities of ascorbate perooxidaseperoxides were immediately decreased to about 40–60% in Kenya and 20–40% in M2 when the temperature was shifted to 20 or 15° C and remained about the same level during further cold cultivation. The activity of glutathione reductase was not modified immediately after the transfer to 20 or 15° C; however, it trended to increase gradually in M2 during cultivation at 15° C. The changes in the maximal efficiency of PS II photochemistry (Fv/Fm) were followed in order to study the effect of low temperature acclimation on the photosynthetic apparatus of the two strains.
MicroRNAs in colorectal cancer: translation of molecular biology into clinical application (2009)

MicroRNAs (miRNAs) are small non-coding RNAs 18-25 nucleotides in length that downregulate gene expression during various crucial cell processes such as apoptosis, differentiation and development. Changes in the expression profiles of miRNAs have been observed in a variety of human tumors, including colorectal cancer (CRC). Functional studies indicate that miRNAs act as tumor suppressors and oncogenes. These findings significantly extend Vogelstein's model of CRC pathogenesis and have shown great potential for miRNAs as a novel class of therapeutic targets. Several investigations have also described the ability of miRNA expression profiles to predict prognosis and response to selected treatments in CRC patients, and support diagnosis of CRC among cancer of unknown primary site. miRNAs' occurrence has been repeatedly observed also in serum and plasma, and miRNAs as novel minimally invasive biomarkers have indicated reasonable sensitivity for CRC detection and compare favorably with the fecal occult blood test. In this review, we summarize the knowledge regarding miRNAs' functioning in CRC while emphasizing their significance in pathogenetic signaling pathways and their potential to serve as disease biomarkers and novel therapeutic targets.
Expression in Escherichia coli, purification and characterization of heparinase I from Flavobacterium heparinum (1996)

The use of heparin for extracorporeal therapies has been problematical due to haemorrhagic complications; as a consequence, heparinase I from Flavobacterium heparinum is used for the determination of plasma heparin and for elimination of heparin from circulation. Here we report the expression of recombinant heparinase I in Escherichia coli, purification to homogeneity and characterization of the purified enzyme. Heparinase I was expressed with an N-terminal histidine tag. The enzyme was insoluble and inactive, but could be refolded, and was purified to homogeneity by nickel-chelate chromatography. The cumulative yield was 43%, and the recovery of purified heparinase I was 14.4 mg/l of culture. The N-terminal sequence and the molecular mass as analysed by matrix-assisted laser desorption MS were consistent with predictions from the heparinase I gene structure. The reverse-phase HPLC profile of the tryptic digest, the Michaelis-Menten constant Km (47 micrograms/ml) and the specific activity (117 units/mg) of purified recombinant heparinase I were similar to those of the native enzyme. Degradation of heparin by heparinase I results in a characteristic product distribution, which is different from those obtained by degradation with heparinase II or III from F. heparinum. We developed a rapid anion-exchange HPLC method to separate the products of enzymic heparin degradation, using POROS perfusion chromatography media. Separation of characteristic di-, tetra- and hexa-saccharide products is performed in 10 min. These methods for the expression, purification and analysis of recombinant heparinase I may facilitate further development of heparinase I-based medical therapies as well as further investigation of the structures of heparin and heparan sulphate and their role in the extracellular matrix.
Development of a fiber optic gradient hydrophone (2008)

Fiber optic hydrophones have been under development since 1970s, and have been proven to have many advantages over their traditional counterparts, such as PZT hydrophones. Efforts have been made in increasing its sensitivity and dynamic range and in sensor packaging. Some attempts have also been made in the construction of pressure gradient sensors, however this area has not been intensively investigated so far.
Synthetic, site-specific biotinylated analogs of human MCP-1 (2005)

Human monocyte chemoattractant protein 1 (MCP-1, CCL2) is a 8.6-kDa protein that has been implicated in a number of diseases including atherosclerosis, rheumatoid arthritis, chronic obstructive pulmonary disease and cancer. As part of a program to identify antibodies against MCP-1, we synthesized site-specific, biotinylated human MCP-1 analogs to be used for panning of an antibody phage display library. In contrast to material obtained from random biotinylation, the site-specific biotinylated analogs were homogeneous and retained full activity.
Specific Targeting of Gene Expression to a Subset of Human Trabecular Meshwork Cells Using the Chitinase 3-Like 1 Promoter (2004)

Comparative analysis of gene expression between SC and TM primary cultures identified several genes with promoters potentially capable of targeting gene expression to specific cells within the outflow pathway. Results with the Ch3L1 promoter indicated that two different cell subtypes may be present in the TM. This study provides a new potential tool to investigate the role of these different cell types in both normal and pathophysiological function of the outflow pathway, with implications for possible future glaucoma gene therapy.
T Cell Telomere Length in HIV-1 Infection: No Evidence for Increased CD4 + T Cell Turnover (1996)

Progression to acquired immunodeficiency syndrome (AIDS) has been related to exhaustion of the regenerative capacity of the immune system resulting from high T cell turnover. Analysis of telomeric terminal restriction fragment (TRF) length, a marker for cellular replicative history, showed that CD8(+) T cell TRF length decreased but CD4(+) T cell TRF length was stable during the course of human immunodeficiency virus type-1 (HIV-1) infection, which was not explained by differential telomerase activity. This observation provides evidence that turnover in the course of HIV-1 infection can be increased considerably in CD8(+) T cells, but not in CD4(+) T cells. These results are compatible with CD4(+) T cell decline in HIV-1 infection caused by interference with cell renewal.
The mechanism regulating the dissociation of the centrosomal protein C-Nap1 from mitotic spindle poles (2002)

The centrosomal protein C-Nap1 is thought to play an important role in centrosome cohesion during interphase of the cell cycle. At the onset of mitosis, when centrosomes separate for bipolar spindle formation, C-Nap1 dissociates from centrosomes. Here we report the results of experiments aimed at determining whether the dissociation of C-Nap1 from mitotic centrosomes is triggered by proteolysis or phosphorylation. Specifically, we analyzed both the cell cycle regulation of endogenous C-Nap1 and the fate of exogenously expressed full-length C-Nap1. Western blot analyses suggested a reduction in the endogenous C-Nap1 level during M phase, but studies using proteasome inhibitors and destruction assays performed in Xenopus extracts argue against ubiquitin-dependent degradation of C-Nap1. Instead, our data indicate that the mitotic C-Nap1 signal is reduced as a consequence of M-phase-specific phosphorylation. Overexpression of full-length C-Nap1 in human U2OS cells caused the formation of large structures that embedded the centrosome and impaired its microtubule nucleation activity. Remarkably, however, these centrosome-associated structures did not interfere with cell division. Instead, centrosomes were found to separate from these structures at the onset of mitosis, indicating that a localized and cell-cycle-regulated activity can dissociate C-Nap1 from centrosomes. A prime candidate for this activity is the centrosomal protein kinase Nek2, as the formation of large C-Nap1 structures was substantially reduced upon co-expression of active Nek2. We conclude that the dissociation of C-Nap1 from mitotic centrosomes is regulated by localized phosphorylation rather than generalized proteolysis.
Metabolic products of Aspergillus terreus. IV. Metabolites of the Strain IFO 8835. (2). The isolation and chemical structure of indolyl benzoquinone pigments. (1981)

Eleven kinds of bisindolyl-dimethoxyl-p-benzoquinones, "asterriquinones A-1, A-2, A-3, A-4, B-1, B-2, B-3, B-4, C-1, C-2, and D"were isolated from Aspergillus terreus IFO 8835, and their structures were determined. Asterriquinone D had the basic structure, and the others were substituted with dimethylallyl group (s) in the indole ring.
Human Traumatic Brain Injury Induces Autoantibody Response against Glial Fibrillary Acidic Protein and Its Breakdown Products (2014)

The role of systemic autoimmunity in human traumatic brain injury (TBI) and other forms of brain injuries is recognized but not well understood. In this study, a systematic investigation was performed to identify serum autoantibody responses to brain-specific proteins after TBI in humans. TBI autoantibodies showed predominant immunoreactivity against a cluster of bands from 38-50 kDa on human brain immunoblots, which were identified as GFAP and GFAP breakdown products. GFAP autoantibody levels increased by 7 days after injury, and were of the IgG subtype predominantly. Results from in vitro tests and rat TBI experiments also indicated that calpain was responsible for removing the amino and carboxyl termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody staining co-localized with GFAP in injured rat brain and in primary rat astrocytes. These results suggest that GFAP breakdown products persist within degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter living astroglia cells in culture and its presence appears to compromise glial cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP autoantibody levels from early (0-1 days) to late (7-10 days) times post injury. Changes in autoantibody levels were negatively correlated with outcome as measured by GOS-E score at 6 months, suggesting that TBI patients with greater anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients.
Creatine kinase release and clearance using MM variants following repeated bouts of eccentric exercise (1998)

Accelerated clearance of CK seems to be one factor contributing to the blunted response of this enzyme following a repeated bout of exercise.