gebhart/patrepeval huggingface dataset:
Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. (1996)

Transcriptional regulation by nuclear hormone receptors is thought to involve interactions with putative cofactors that may potentiate receptor function. Here we show that human thyroid hormone receptor alpha purified from HeLa cells grown in the presence of thyroid hormone (T3) is associated with a group of distinct nuclear proteins termed thyroid hormone receptor-associated proteins (TRAPs). In an in vitro system reconstituted with general initiation factors and cofactors (and in the absence of added T3), the "liganded" thyroid hormone receptor (TR)/TRAP complex markedly activates transcription from a promoter template containing T3-response elements. Moreover, whereas the retinoid X receptor is not detected in the TR/TRAP complex, its presence is required for the function of the complex. In contrast, human thyroid hormone receptor alpha purified from cells grown in the absence of T3 lacks the TRAPs and effects only a low level of activation that is dependent on added ligand. These findings demonstrate the ligand-dependent in vivo formation of a transcriptionally active TR-multisubunit protein complex and suggest a role for TRAPs as positive coactivators for gene-specific transcriptional activation.
Prolonged EVLP Using OCS Lung (2016)

The use of an autologous whole donor blood perfusate allowed 24H of preservation without functional deterioration and was superior to both RBC and buffered dextran-albumin solution for extended lung preservation in a swine model using OCS Lung. This finding represents a potentially significant advance in donor lung preservation and reconditioning.
Hematoendothelial Differentiation of Human Embryonic Stem Cells (2007)

Human embryonic stem cells (hESCs) represent a unique population of cells capable of self-renewal and differentiation into all types of somatic cells, including hematopoietic and endothelial cells. Since the pattern of hematopoietic and endothelial development observed in the embryo can be reproduced using ESCs differentiated in culture, hESCs can be used as a model for studies of specification and diversification of hematoendothelial progenitors. In addition, hESCs can be seen as a scalable source of hematopoietic and endothelial cells for in vitro studies. This unit describes a method for efficient differentiation of hESCs into hematopoietic progenitors and endothelial cells through coculture with mouse OP9 bone marrow stromal cells, as well as an approach for their analysis and isolation. Support protocols are provided for culture of mouse embryonic fibroblasts, evaluation of hematopoietic and endothelial differentiation by flow cytometry and colony-forming assay, removal of OP9 cells, and propagation of hESC-derived endothelial cells. Curr. Protoc.
A Historical Overview of the Heterologous Expression of Mammalian UDP-Glucuronosyltransferase Isoforms Over the Past Twenty Years (2005)

UDP-Glucuronosyltransferases (UGTs) are actively involved in detoxification of xenobiotics and endogenous compounds and are a major source of drug inactivation and drug-drug interactions. UGTs are membrane-bound enzymes mostly localized in the endoplasmic reticulum (ER) and inner and outer nuclear membranes. UGT activities are totally dependent on the phospholipid content of the membrane and, as a result, are usually inactive when isolated from the ER in the presence of detergent. Several UGT expression systems have been described by different laboratories. They include expression in mammalian cells such as COS, V79 and HEK293. Also, baculovirus-infected insect cells systems have been developed and allow the expression of UGT isoforms with or without histidine molecule tags (His-tags). Moreover, as for CYP450, UGT isoforms have been expressed in E.coli. This review concentrates on a detailed description of all these expression systems in terms of their use for substrate specificity studies and the preparation of pure UGT proteins for active site identification and other structural studies. The effect of detergents and alamethicin on UGT catalytic activity in different expression systems will be discussed. Moreover, extensive comparative studies on the characterization of recombinant UGTs in terms of substrate specificity, evaluation of kinetic parameters, and the effect of inhibitors will be presented in this review. An overall picture of the use of different UGT expression systems will help in selecting the best one for identification of the individual UGT isoforms involved in the glucuronidation of drugs, environmental pollutants and physiologically important endogenous compounds. Especially important is an expression system where UGTs are biosynthesized with His-tags. UGTs expressed in this system can be easily purified to homogeneity, which will result in significant development of structure-function relationship studies, including the identification of substrate active sites and eventual crystallization. These are underdeveloped areas of UGT research and the availability of these recombinant UGTs will allow these gaps to be filled.
C1q Binds Phosphatidylserine and Likely Acts as a Multiligand-Bridging Molecule in Apoptotic Cell Recognition (2008)

Efficient apoptotic cell clearance is critical for maintenance of tissue homeostasis, and to control the immune responses mediated by phagocytes. Little is known about the molecules that contribute "eat me" signals on the apoptotic cell surface. C1q, the recognition unit of the C1 complex of complement, also senses altered structures from self and is a major actor of immune tolerance. HeLa cells were rendered apoptotic by UV-B treatment and a variety of cellular and molecular approaches were used to investigate the nature of the target(s) recognized by C1q. Using surface plasmon resonance, C1q binding was shown to occur at early stages of apoptosis and to involve recognition of a cell membrane component. C1q binding and phosphatidylserine (PS) exposure, as measured by annexin V labeling, proceeded concomitantly, and annexin V inhibited C1q binding in a dose-dependent manner. As shown by cosedimentation, surface plasmon resonance, and x-ray crystallographic analyses, C1q recognized PS specifically and avidly (K(D) = 3.7-7 x 10(-8) M), through multiple interactions between its globular domain and the phosphoserine group of PS. Confocal microscopy revealed that the majority of the C1q molecules were distributed in membrane patches where they colocalized with PS. In summary, PS is one of the C1q ligands on apoptotic cells, and C1q-PS interaction takes place at early stages of apoptosis, in newly organized membrane patches. Given its versatile recognition properties, these data suggest that C1q has the unique ability to sense different markers which collectively would provide strong eat me signals, thereby allowing efficient apoptotic cell removal.
Dendritic Cell Cancer Therapy: Vaccinating the Right Patient at the Right Time (2018)

Immune checkpoint inhibitors propelled the field of oncology with clinical responses in many different tumor types. Superior overall survival over chemotherapy has been reported in various metastatic cancers. Furthermore, prolonged disease-free and overall survival have been reported in the adjuvant treatment of stage III melanoma. Unfortunately, a substantial portion of patients do not obtain a durable response. Therefore, additional strategies for the treatment of cancer are still warranted. One of the numerous options is dendritic cell vaccination, which employs the central role of dendritic cells in activating the innate and adaptive immune system. Over the years, dendritic cell vaccination was shown to be able to induce an immunologic response, to increase the number of tumor infiltrating lymphocytes and to provide overall survival benefit for at least a selection of patients in phase II studies. However, with the success of immune checkpoint inhibition in several malignancies and considering the plethora of other treatment modalities being developed, it is of utmost importance to delineate the position of dendritic cell therapy in the treatment landscape of cancer. In this review, we address some key questions regarding the integration of dendritic cell vaccination in future cancer treatment paradigms.
Concepts and performance of solid state RGB laser sources for large frame laser projection displays. (2000)

We report on concepts and the performance of diode pumped solid state laser systems which generate simultaneously red (R), green (G) and blue (B) laser light with output powers of up to 7.1 W at 629 nm, 6.9 W at 532 nm and 5.0 W at 446 nm. The superposition of this RGB radiation provides white light with a power of 19 W. In respect to the diode pump power of 110 W the RGB output corresponds to an optical efficiency of 17%.
Safety and Immunogenicity of Live Oral Cholera and Typhoid Vaccines Administered Alone or in Combination with Antimalarial Drugs, Oral Polio Vaccine, or Yellow Fever Vaccine (1997)

The effects of concomitant administration of antimalarial drugs, oral polio vaccine, or yellow fever vaccine on the immune response elicited by the Vibrio cholerae CVD103-HgR and Salmonella typhi Ty21a live oral vaccines were investigated. Healthy adults were immunized with CVD103-HgR alone or combined with Ty21a. Subjects were randomized to simultaneously receive mefloquine, chloroquine or proguanil, or oral polio or yellow fever vaccine. The vibriocidal antibody seroconversion rate was significantly reduced (P = .008) only in the group that received chloroquine with the CVD103-HgR. The geometric mean vibriocidal antibody titer was significantly decreased in the groups that received chloroquine (P = .001) or mefloquine (P = .02) compared with titers in groups that received CVD103-HgR alone. However, similar immunosuppressive effects were not observed in the groups immunized with Ty21a and CVD103-HgR. Only the concomitant administration of proguanil effected a significant (P = .013) decline in the anti-S. typhi lipopolysaccharide antibody response. These results indicate that chloroquine and proguanil should not be simultaneously administered with the CVD103-HgR and Ty21a vaccine strains, respectively.
Synthesis and Characterization of Photo-Cross-Linkable Keratin Hydrogels for Stem Cell Encapsulation (2016)

The objective of this work was to synthesize an injectable and photopolymerizable hydrogel based on keratin extracted from poultry feather for encapsulation and delivery of stem cells in tissue regeneration. Since feather keratin is rich in cysteine residue, allylation of sulfhydryl groups was used for functionalization of keratin. Keratin was extracted from feather barbs by reducing the disulfide bonds in cysteine residues to sulfhydryl groups (-SH). Next, the free thiol groups were converted to dehydroalanine (Dha) by oxidative elimination using O-(2,4,6-trimethylbenzenesulfonyl) hydroxylamine. Then, the Dha moieties were converted to s-allyl cysteine by reaction with allyl mercaptan to produce keratin allyl thioether (KeratATE) biopolymer. Human mesenchymal stem cell (hMSCs) were suspended in the aqueous solution of KeratATE, injected into a mold, and photopolymerized to generate a KeratATE hydrogel encapsulating hMSCs. The freeze-dried photo-cross-linked KeratATE hydrogels had a porous, interconnected, honeycomb microstructure with pore sizes in the 20-60 μm range. The compressive modulus of the hydrogels ranged from 1 to 8 kPa depending on KeratATE concentration. KeratATE hydrogels had <5% mass loss in collagenase solution after 21 days of incubation, whereas the mass loss was 15% in trypsin solution. Degradation of KeratATE hydrogel was strongly dependent on trypsin concentration but independent of collagenase. hMSCs proliferated and adopted an elongated spindle-shape morphology after seeding on KeratATE hydrogel. KeratATE hydrogel supported differentiation of the encapsulated hMSCs to the osteogenic and chondrogenic lineages to the same extent as those hMSCs encapsulated in gelatin methacryloyl hydrogel. The results suggest that keratin allyl thioether hydrogel with controllable degradation is a viable matrix for encapsulation and delivery of stem cells in tissue regeneration.
Phase Inversion Membranes (1985)

The science of membrane formation via phase inversion and the technology of producing phase inversion membranes are related in this paper. The discussion begins by presenting the phase inversion mechanism and continues by distinguishing and describing in detail four membrane formation processes used to achieve phase inversion. The structure of the resulting membranes are discussed in terms of asymmetry or skinning and anisotropy. Skinned membranes are classified as integrally- and nonintegrally-skinned microgels and ultragels. Finally, structural irregularities such as wavemarks, macrovoids and blushing are discussed.
Intraclonal heterogeneity and distinct molecular mechanisms characterize the development of t(4;14) and t(11;14) myeloma (2012)

We have used whole exome sequencing to compare a group of presentation t(4;14) with t(11;14) cases of myeloma to define the mutational landscape. Each case was characterized by a median of 24.5 exonic nonsynonymous single-nucleotide variations, and there was a consistently higher number of mutations in the t(4;14) group, but this number did not reach statistical significance. We show that the transition and transversion rates in the 2 subgroups are similar, suggesting that there was no specific mechanism leading to mutation differentiating the 2 groups. Only 3% of mutations were seen in both groups, and recurrently mutated genes include NRAS, KRAS, BRAF, and DIS3 as well as DNAH5, a member of the axonemal dynein family. The pattern of mutation in each group was distinct, with the t(4;14) group being characterized by deregulation of chromatin organization, actin filament, and microfilament movement. Recurrent RAS pathway mutations identified subclonal heterogeneity at a mutational level in both groups, with mutations being present as either dominant or minor subclones. The presence of subclonal diversity was confirmed at a single-cell level using other tumor-acquired mutations. These results are consistent with a distinct molecular pathogenesis underlying each subgroup and have important impacts on targeted treatment strategies. The Medical Research Council Myeloma IX trial is registered under ISRCTN68454111.
Optical Creation of Radiophotoluminescence Centres in Dosemeter Glass By Two-Photon Absorption (1996)

In recent years considerable progress has been achieved in the field of phosphate glass dosimetry through the evolution of improved glass material with good batch uniformity, newly designed dosemeter encapsulation and automatic readout techniques based on pulsed UV laser excitation. The peak intensity of the laser pulses exceeds the range of intensity available with conventional UV light sources. This paper reports on effects that may occur when an intense light source is used for RPL readout. In a specially designed reader unirradiated flat RPL glasses and a scanning focused laser beam for RPL readout were used. The influence of intense UV laser excitation on RPL readout intensity has been studied for dependence on the intensity and duration of excitation. The experimental arrangement, the scanning procedure for laser excitation, the dosemeter glass handling and the method of RPL readout are described. The observed RPL intensity is attributed to the optical creation of RPL centres by two-photon absorption in the focal region of the laser beam. By means of beam profile and power measurements an estimation of the lower limit of excitation intensity is given where two-photon absorption becomes important.
Review Article:1House Dust Mites (1976)

The most common mites found in the contents of vacuum cleaner sweepings are members of a family of Acaridei, the Pyroglyphidae. Techniques for collecting them effectively were first described in 1964. Since that time, systems for extracting mites from vacuumed dust using sieves and flotation or sedimentation have been improved. The species found in homes are readily cultured. Successful methods utilize high protein foods, an area-enlarging substrate, 25°C and a humidity in equilibrium with saturated NaCl (aw = 0.75, RH = 75%). Development from egg through larva, protonymph, tritonymph to adult requires about a month in cultures under optimum conditions. Pyroglyphids have the reduced setation of parasitic Acaridei but most live as nidicoles. There are 35 species now recognized and 12 of these are associated with man. Dermatophagoides pteronyssinus, D. farinae and Euroglyphus maynei most common on a world basis but other species are significant in some areas, such as Hirstia domicola in Japan. Both D. farinae and D. pteronyssinus have facultative quiescent protonymphs that can survive harsh conditions. These species have a critical equilibrium activity (CEA) below 0.75 and thus can maintain their water content as long as they have access to air as humid as 75% rh during at least part of the time. The favored site for the association of these mites with man is his bed. Populations maintain themselves in beds on a continuing basis. When temperatures and humidities are favorable, these mites also develop in other areas of the house. Their association with man is significant because they either produce or concentrate allergens that are responsible for house dust allergy, which is prevalent on a global basis. In the U. S. it is estimated that 4% of the population is involved. Both mites and house dust can be held at low levels by use of non-fibrous materials and frequent vacuuming. These measures alleviate suffering from house dust allergy. In persistent cases, extracts of house dust or house dust mites have been used in desensitizing patients. House dust mites seem to be resistant to most pesticides, but they are susceptible to low concentrations of lindane.
Nonlinear Spectroscopy on a Single Quantum System: Two-Photon Absorption of a Single Molecule (1996)

Two-photon fluorescence excitation spectra of single diphenyloctatetraene molecules trapped in an n -tetradecane matrix were measured at cryogenic temperatures. The purely electronic zero-phonon line (transition at 444 nanometers) of these single molecules with a width of about 60 megahertz was excited by a continuous-wave, single-mode laser at 888 nanometers. Even though the two-photon absorption cross section is extremely small, a high photon count rate and low background allowed nonlinear spectroscopy to be extended to the single-molecule level. This experiment also suggests the possibility of two-photon single-molecule scanning microscopy.
Hepatic and extrahepatic expression of the new iron regulatory protein hemojuvelin. (2004)

Hereditary hemochromatosis (HH) is a common disorder of iron overload. A rare variant of the disease, juvenile hemochromatosis, is an early-onset form which is caused by mutations in a recently identified gene, called HJV or HFE2. A previous report based on Northern blotting showed human HJV mRNA expression only in the skeletal muscle, liver and heart.In this study we analyzed the expression of HJV mRNA in a number of human and mouse tissues by a sensitive reverse transcription-polymerase chain reaction method. We also studied the expression of HJV protein in mouse tissues using Western blotting. A polyclonal rabbit antibody was raised against a synthetic peptide which was designed based on the predicted sequence of human and mouse HJV protein.Human HJV mRNA expression was detected in the liver, heart, esophagus, pancreas, descending colon, ileocecum and skeletal muscle. Mouse tissues that were positive for expression included brain, liver, heart, lung, stomach, spleen, kidney, duodenum, jejunum, ileum, colon, skeletal muscle, testis and blood. By Western blotting, HJV protein expression was detected in the mouse liver, heart, kidney, brain and muscle.The facts that HJV protein is expressed in the liver and mutations in the HJV gene induce hepatic iron accumulation point to a possibility that HJV protein may modulate iron transport in hepatocytes. The wide expression of HJV as shown in the present study suggests that its role in regulating iron allocation could be extended to other tissues beyond the liver.
Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models (2001)

Pharmaceuticals acting to stimulate 5-HT1A receptors could prove useful in the treatment of the motor response complications in parkinsonian patients.
DEAD/H BOX 3 (DDX3) helicase binds the RIG‐I adaptor IPS‐1 to up‐regulate IFN‐β‐inducing potential (2010)

Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLR) are members of the DEAD box helicases, and recognize viral RNA in the cytoplasm, leading to IFN-beta induction through the adaptor IFN-beta promoter stimulator-1 (IPS-1) (also known as Cardif, mitochondrial antiviral signaling protein or virus-induced signaling adaptor). Since uninfected cells usually harbor a trace of RIG-I, other RNA-binding proteins may participate in assembling viral RNA into the IPS-1 pathway during the initial response to infection. We searched for proteins coupling with human IPS-1 by yeast two-hybrid and identified another DEAD (Asp-Glu-Ala-Asp) box helicase, DDX3 (DEAD/H BOX 3). DDX3 can bind viral RNA to join it in the IPS-1 complex. Unlike RIG-I, DDX3 was constitutively expressed in cells, and some fraction of DDX3 is colocalized with IPS-1 around mitochondria. The 622-662 a.a DDX3 C-terminal region (DDX3-C) directly bound to the IPS-1 CARD-like domain, and the whole DDX3 protein also associated with RLR. By reporter assay, DDX3 helped IPS-1 up-regulate IFN-beta promoter activation and knockdown of DDX3 by siRNA resulted in reduced IFN-beta induction. This activity was conserved on the DDX3-C fragment. DDX3 only marginally enhanced IFN-beta promoter activation induced by transfected TANK-binding kinase 1 (TBK1) or I-kappa-B kinase-epsilon (IKKepsilon). Forced expression of DDX3 augmented virus-mediated IFN-beta induction and host cell protection against virus infection. Hence, DDX3 is an antiviral IPS-1 enhancer.
Semantics and evaluation techniques for window aggregates in data streams (2005)

A windowed query operator breaks a data stream into possibly overlapping subsets of data and computes a result over each. Many stream systems can evaluate window aggregate queries. However, current stream systems suffer from a lack of an explicit definition of window semantics. As a result, their implementations unnecessarily confuse window definition with physical stream properties. This confusion complicates the stream system, and even worse, can hurt performance both in terms of memory usage and execution time. To address this problem, we propose a framework for defining window semantics, which can be used to express almost all types of windows of which we are aware, and which is easily extensible to other types of windows that may occur in the future. Based on this definition, we explore a one-pass query evaluation strategy, the Window-ID (WID) approach, for various types of window aggregate queries. WID significantly reduces both required memory space and execution time for a large class of window definitions. In addition, WID can leverage punctuations to gracefully handle disorder. Our experimental study shows that WID has better execution-time performance than existing window aggregate query evaluation options that retain and reprocess tuples, and has better latency-accuracy tradeoffs for disordered input streams compared to using a fixed delay for handling disorder.