gebhart/patrepeval huggingface dataset:
A Single Amino Acid Determines the Immunostimulatory Activity of Interleukin 10 (2000)

Cellular interleukin 10s (cIL-10s) of human and murine origin have extensive sequence and structural homology to the Epstein-Barr virus BCRF-I gene product, known as viral IL-10 (vIL-10). Although these cytokines share many immunosuppressive properties, vIL-10 lacks several of the immunostimulatory activities of cIL-10 on certain cell types. The molecular and cellular bases for this dichotomy are not currently defined. Here, we show that the single amino acid isoleucine at position 87 of cIL-10 is required for its immunostimulatory function. Substitution of isoleucine in cIL-10 with alanine, which corresponds to the vIL-10 residue, abrogates immunostimulatory activity for thymocytes, mast cells, and alloantigenic responses while preserving immunosuppressive activity for inhibition of interferon gamma production and prolongation of cardiac allograft survival. Conversely, substitution of alanine with isoleucine in vIL-10 converts it to a cIL-10-like molecule with immunostimulatory activity. This single conservative residue alteration significantly affects ligand affinity for receptor; however, affinity changes do not necessarily alter specific activities for biologic responses in a predictable fashion. These results suggest complex regulation of IL-10 receptor-ligand interactions and subsequent biological responses. These results demonstrate that vIL-10 may represent a captured and selectively mutated cIL-10 gene that benefits viral pathogenesis by leading to ineffective host immune responses. The ability to manipulate the activity of IL-10 in either a stimulatory or suppressive direction may be of practical value for regulating immune responses for disease therapy, and of theoretical value for determining what aspects of IL-10 activity are important for normal T cell responses.
Negative modulation of sodium channels in cultured chick muscle cells by the channel activator batrachotoxin. (1985)

We have investigated the possibility that cellular control of membrane excitability involves feedback mechanisms in which the degree of activity of voltage-sensitive Na+ channels regulates the number of these channels. Using two independent assays, channel-mediated Na+ uptake and the specific binding of [3H] saxitoxin, we have studied the effects of pharmacological activation of Na+ channels with batrachotoxin (BTX) on the number and properties of these channels. Upon exposure of cultured muscle cells to BTX (1 microM), the number of surface Na+ channels decreases by approximately 75%, with a half-time of 3-6 h. This decrease is prevented by pharmacological blockade of these channels and does not reflect changes in the apparent affinities towards either BTX or saxitoxin. This reduction is reversible: a gradual increase in surface Na+ channels that is dependent on protein synthesis is observed upon removal of the activator. The BTX-induced decrease in Na+ channels is associated with an enhanced rate of disappearance of surface Na+ channels. These findings point to the existence of a down-regulation mechanism for the modulation of membrane excitability under conditions of elevated Na+ channel activity.
cis-hydroxyproline stimulates the growth of rat mammary carcinoma cells. (2000)

With the ever-increasing evidence that the extracellular matrix (ECM) can stimulate tumor growth, it follows that inhibiting the synthesis of tumor-derived stroma may be a potential therapeutic target of cancer progression. The proline analog cis-hydroxyproline (CHP), an inhibitor of collagen deposition, was examined for its effects on the growth of clonal tumor cells that differentially produce type IV collagen and laminin. Two separate clones derived from rat mammary carcinoma cells that produce high and low amounts of type IV collagen and laminin were injected into the flanks of nude mice. Tumors in animals receiving CHP treatment grew faster than tumors in control animals receiving saline, although statistically not significant. Furthermore, upon administration of CHP to these clones in culture, increased proliferation rates of both cell types were observed. These results show that CHP is not useful in preventing stromal development and growth of rat mammary tumor xenografts.
Sensitivity of cervical carcinoma cells to vesicular stomatitis virus‐induced oncolysis: Potential role of human papilloma virus infection (2011)

High-risk carcinogenic subtypes of human papilloma virus (HPV) are associated with the development of squamous cell carcinomas of the cervix (CC) and a subset of head and neck (HNSCC). Recurrent metastatic diseases of these sites display a dismal prognosis. Therefore, there is an urgent need to uncover innovative therapeutic strategies in this clinical setting. Oncolytic viruses, including vesicular stomatitis virus (VSV), were identified due to their ability to specifically target tumor cells that generally display defects in interferon (IFN) signaling. HPV expressed proteins can inhibit IFN signaling; therefore, HPV-infected cells may be particularly sensitive to VSV oncolysis. In this study, we evaluated the sensitivity of four CC (HPV+) and four HNSCC (HPV-) derived cell lines to VSV oncolysis. Interestingly, the CC cell lines were consistently more sensitive to VSV cytotoxicity than the HNSCC cell lines tested. Exogenous IFN addition or infection with two attenuated VSV variants that are more susceptible to IFN inhibition failed to attenuate VSV oncolysis in hypersensitive CC cell lines. Furthermore, the expression of HPV-E6, that inhibits IFN receptor signaling, in the VSV-resistant HNSCC cell line SCC25 attenuated VSV-induced IFN response and significantly enhanced VSV cytotoxicity. Finally, differential VSV infection and replication was confirmed in xenograft murine tumor models and explant tumor tissues from two patients with CC. Taken together, these results demonstrate that HPV-infected cells are susceptible to oncolytic virus therapy and that this approach may represent a novel therapeutic approach in HPV positive CC and HNSCC patients.
Expanding Recognizable Distorted Characters Using Self-Corrective Recognition (2012)

Large datasets are always demanded for better recognition performance. However, it is not easy to produce them because costly and slow human operators have been necessary for labeling. In the current paper, in order to resolve the problem on yielding large datasets, we propose a scenario for automatic labeling based on the self-corrective recognition algorithm. The strong point of the proposed method is the capability of expanding recognizable distorted characters unlike existing methods. In the experiments, we show a possibility to realize automatic labeling by the method.
Visualizing gene expression by whole-body fluorescence imaging (2000)

Transgene expression in intact animals now can be visualized by noninvasive techniques. However, the instruments and protocols developed so far have been formidable and expensive. We describe here a system for rapidly visualizing transgene expression in major organs of intact live mice that is simple, rapid, and eminently affordable. Green fluorescent protein (GFP) is expressed in the cells of brain, liver, pancreas, prostate, and bone, and its fluorescence is encoded in whole-body optical images. For low-magnification images, animals are illuminated atop a fluorescence light box and directly viewed with a thermoelectrically cooled color charge-coupled device camera. Higher-magnification images are made with the camera focused through an epi-fluorescence dissecting microscope. Both nude and normal mice were labeled by directly injecting 8 x 10(10) plaque-forming units/ml of adenoviral GFP in 20-100 microl PBS and 10% glycerol into either the brain, liver, pancreas, prostate, or bone marrow. Within 5-8 h after adenoviral GFP injection, the fluorescence of the expressed GFP in brain and liver became visible, and whole-body images were recorded at video rates. The GFP fluorescence continued to increase for at least 12 h and remained detectable in liver for up to 4 months. The system's rapidity of image acquisition makes it capable of real-time recording. It requires neither exogenous contrast agents, radioactive substrates, nor long processing times. The method requires only that the expressed gene or promoter be fused or operatively linked to GFP. A comparatively modest investment allows the study of the therapeutic and diagnostic potential of suitably tagged genes in relatively opaque organisms.
Proside A Phage-Based Method for Selecting Thermostable Proteins (2003)

For many applications proteins must retain their function for a long time and under a wide range of conditions, sometimes at elevated temperatures. However, the stability of natural proteins is often very low, just sufficient to ensure proper functioning under cellular conditions (). It is still largely unknown how the stability of a protein is encoded in its sequence, and theoretical approaches to calculate the contributions of individual amino acids to stability are still in their infancy. Therefore, evolutionary methods for increasing protein stability are of great interest. In such approaches, large protein libraries are searched for stabilized variants by a screening or, ideally, a selection technique.
The Evolution of Our Understanding on Glioma (2008)

The description of neuroglia by Virchow in 1848 may be considered the starting point of our understanding of primary brain tumors. At the beginning of the 20th century, surgical removal of primary brain tumors became possible, and therefore, tissue for microscopic analysis and clinical data on survival became available. During this time, research on gliomas beyond improving surgical procedures focused on their classification. The classification schemes developed emphasized parameters for sorting tumors with regard to (i) cytological aspects; (ii) presumed tumor cell origin; (iii) histological appearance of the tissue; or (iv) clinical outcome. Over the years, experimental studies have greatly improved our knowledge on gliomas. Gliomas induced by viruses, chemicals, radiation, transgenes and knock-out technology contributed to the understanding of their pathogenesis and still serve as preclinical models for the testing of novel therapies. Recent advances in developmental neurobiology and the identification of stem cells provided new insights into the origin of brain tumors and the molecular mechanisms of tumor formation. This review briefly compiles the evolution of our concepts on gliomas, focusing on the latest developments.
Stereoselective Synthesis of β‐Amino Alcohols from Optically Active α‐Amino Acids (1987)

Effective use of the “chiral pool” of natural L-amino acids is achieved by means of the easily accessible derivatives 1. Depending on the reagent, 1 reacts stereoselectively under either chelate or non-chelate control to give 2 or 3, respectively. Three examples for R = Me: the ratio 2 : 3 is 3 : 97 with PhMgBr, 4 : 96 with allylTi(NEt2)3, and 94 : 6 with CH3TiCl3.
Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues. (1987)

To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase (BtChoEase; EC 3.1.1.8) and Torpedo electric organ "true" acetylcholinesterase (AcChoEase; EC 3.1.1.7). Using these probes, we isolated several cDNA clones from lambda gt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. In RNA blots of poly(A)+ RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These findings demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species.
GENES AND ENZYMES OF CAROTENOID BIOSYNTHESIS IN PLANTS (1998)

Carotenoids are integral and essential components of the photosynthetic membranes in all plants. Within the past few years, genes encoding nearly all of the enzymes required for the biosynthesis of these indispensable pigments have been identified. This review focuses on recent findings as to the structure and function of these genes and the enzymes they encode. Three topics of current interest are also discussed: the source of isopentenyl pyrophosphate for carotenoid biosynthesis, the progress and possibilities of metabolic engineering of plants to alter carotenoid content and composition, and the compartmentation and association of the carotenogenic enzymes. A speculative schematic model of carotenogenic enzyme complexes is presented to help frame and provoke insightful questions leading to future experimentation.
Fast free-of-acrylamide clearing tissue (FACT)—an optimized new protocol for rapid, high-resolution imaging of three-dimensional brain tissue (2017)

Fast Free-of-Acrylamide Clearing Tissue (FACT) is a new sodium dodecyl sulfate (SDS)-based clearing protocol for the chemical clearing and imaging of brain tissue containing transgenic or immunolabeled fluorescent proteins. In the present study, we have developed this new method and optimized multiple dimensions of the workflow, including reduced clearing time, improved efficiency of fluorescent signals without the need for electrophoretic or complex instrumentations, preservation of cytoarchitectural details, optimized confocal microscopy, and accelerated data collection. We systematically compared seven clearing protocols with the FACT protocol, using transgenic mouse brains with fluorochrome expression in microglia. Only six days were required for detecting transgene-labeled markers in a 1-mm thick brain slice from adult mice, and 14 days were required for detecting antibody-labeled markers in the same-sized tissue. Preservation of fluorescent signal was achieved by decreasing clearing time, adjusting the pH of the SDS solution, and using the appropriate temperature for tissue clearing, all of which contributed to the superiority of our method. We conclude that the FACT protocol can be successfully applied to the fluorescent imaging of mouse brain tissue, and will facilitate structural analyses and connectomics of large assemblies of cells and their networks in the context of three-dimensional organ systems.
Distributed Joint Source-Channel Coding of Video Using Raptor Codes (2005)

Summary form only given. In this paper, we consider the case of a noisy channel in Wyner-Ziv coding (WZC) and address distributed joint source-channel coding (JSCC), while targeting at video transmission over packet erasure channels. Our idea is to use a single Raptor code, for both SWC and erasure protection. Raptor codes are the latest addition to a family of low-complexity rateless fountain codes which consist of a high-rate precode and an LT code. We use IRA codes as the precode of our Raptor code, as IRA codes are well suited for distributed JSCC. For the decoder design, due to the presence of side information, we develop a new iterative soft-decision Raptor decoder for joint decoding that combines the received packets and the side information.
Pluronic F-68 reduces the endothelial adherence and improves the rheology of liganded sickle erythrocytes. (1987)

A perfluorochemical blood substitute emulsified with Pluronic F-68 has been shown to improve the filterability of deoxygenated sickle red cells. We questioned whether some of the effect was independent of oxygen loading and studied the influence of Fluosol DA (Green Cross, Osaka, Japan) and Pluronic on the rheology and adhesion of sickle red cells saturated with oxygen and carbon monoxide. A 5-vol/vol% concentration of Fluosol or equivalent concentration of Pluronic was equally effective at improving the filtration of washed sickle cells through 5-micron-diameter pores at wall shear stresses approximating 1,000 dyne/cm2. The same concentration of Pluronic reduced the extensional static rigidity of irreversibly sickled cells (ISC) by 25% and also abolished the adherence of gravity-sedimented sickle cells to endothelial monolayers in the presence of saline or plasma. The inhibition of adherence was not reversible by washing and was accomplished with equal ease by isolated treatment of sickle cells or endothelium. Pluronic had no effect on the rheology or adhesion of normal adult red cells. Neither Fluosol nor Pluronic changed sickle or normal cell shape, mean cell volume, mean cell density, or cell density distribution. A lubricating effect of Pluronic on cell surfaces could explain all of the rheological observations and offers another direction of inquiry in the search for therapy for sickle cell disease.
Gene expression profiles with activation of the estrogen receptor alpha-selective estrogen receptor modulator complex in breast cancer cells expressing wild-type estrogen receptor. (2002)

Selective Estrogen Receptor Modulators (SERMs) are a new class of drugsthat bind to estrogen receptor (ER) and elicit agonistic or antagonistic responses, depending on the target tissue. We have developed an in vitro system in which some SERMs (4-hydroxytamoxifen and resveratrol) demonstrate estrogenic response through wild-type (wt) ER, whereas others (raloxifene and GW7604) remain antiestrogenic. This system mimics the tamoxifen-resistant phenotype in clinic, when resistant tumors contain wtER. We used Atlas cDNA arrays to study gene expression profiles after ER activation by different SERMs in MDA-MB-231 human breast cancer cells stably transfected with wtER. Cells were treated with estradiol, four different SERMs, and the pure antiestrogen ICI 182,780. The obtained expression data were analyzed using GeneSpring software. Real-time reverse transcription-PCR was used to verify the array data. Our results showed that treatment with various compounds altered the expression of a diverse group of genes, revealing sets of overlapping genes that may represent a complex network of genes of interrelated signal transduction pathways. Sets of "agonistic" and "antagonistic" genes were identified on the basis of the known response to different SERMs. Further analysis of selected sets of genes revealed functionally related group of genes in each set, encoding proteins that were related to cell proliferation, survival, and apoptosis. Flow cytometry data indicated an antiapoptotic activity in cells treated with agonists versus apoptotic activity in cells treated with antagonists. A model for estradiol-like (survival) and antiestrogen-like (apoptosis) activities of SERMs on the basis of their gene expression profiles is suggested.
Liquid Warping GAN: A Unified Framework for Human Motion Imitation, Appearance Transfer and Novel View Synthesis (2019)

We tackle the human motion imitation, appearance transfer, and novel view synthesis within a unified framework, which means that the model once being trained can be used to handle all these tasks. The existing task-specific methods mainly use 2D keypoints (pose) to estimate the human body structure. However, they only expresses the position information with no abilities to characterize the personalized shape of the individual person and model the limbs rotations. In this paper, we propose to use a 3D body mesh recovery module to disentangle the pose and shape, which can not only model the joint location and rotation but also characterize the personalized body shape. To preserve the source information, such as texture, style, color, and face identity, we propose a Liquid Warping GAN with Liquid Warping Block (LWB) that propagates the source information in both image and feature spaces, and synthesizes an image with respect to the reference. Specifically, the source features are extracted by a denoising convolutional auto-encoder for characterizing the source identity well. Furthermore, our proposed method is able to support a more flexible warping from multiple sources. In addition, we build a new dataset, namely Impersonator (iPER) dataset, for the evaluation of human motion imitation, appearance transfer, and novel view synthesis. Extensive experiments demonstrate the effectiveness of our method in several aspects, such as robustness in occlusion case and preserving face identity, shape consistency and clothes details. All codes and datasets are available on https://svip-lab.github.io/project/impersonator.html
Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways. (2003)

Cyclin G1 is a p53-responsive gene that is induced in alternative reading frame (ARF)-arrested cells, yet its role in growth control is unclear. We tested its effects on growth and involvement in the ARF-Mdm2-p53 tumor suppressor pathway. We show that cyclin G1 interacts with ARF, Mdm2, and p53 in vitro and in vivo. At high levels, cyclin G1 induces a G(1)-phase arrest in mammalian cells that coincides with p53 activation. Conversely, lower levels of cyclin G1 lack intrinsic growth inhibitory effects yet potentiate ARF-mediated growth arrest. Notably, cyclin G1 is down-regulated by Mdm2 through proteasome-mediated degradation. These data suggest that cyclin G1 is a positive feedback regulator of p53 whose expression is restrained by Mdm2. Interestingly, growth inhibition by cyclin G1 does not require p53 but instead exhibits partial retinoblastoma protein (pRb) dependence. These findings reveal that cyclin G1 has growth inhibitory activity that is mechanistically linked to ARF-p53 and pRb tumor suppressor pathways.
Efficient and scalable Online Game Server Architecture for Massive Users (2002)

In this paper, I tried to propose efficient online game server architecture that decrease server overload. I used replicated distributed sever type together with non-replicated distributed sever type. Replicated distributed sever type has the advantage to maintain efficient distribution of server overload and non-replicated distributed sever type has the advantage to move a game server to a different game server freely in one server group. I used these advantages suitably in this proposal, and I will show the efficiency of online game server architecture.
N-myc can functionally replace c-myc in murine development, cellular growth, and differentiation (2000)

Members of the myc family of cellular oncogenes have been implicated as transcriptional regulators in pathways that govern cellular proliferation and death. In addition, N-myc and c-myc are essential for completion of murine embryonic development. However, the basis for the evolutionary conservation of myc gene family has remained unclear. To elucidate this issue, we have generated mice in which the endogenous c-myc coding sequences have been replaced with N-myc coding sequences. Strikingly, mice homozygous for this replacement mutation can survive into adulthood and reproduce. Moreover, when expressed from the c-myc locus, N-myc is similarly regulated and functionally complementary to c-myc in the context of various cellular growth and differentiation processes. Therefore, the myc gene family must have evolved, to a large extent, to facilitate differential patterns of expression.