gebhart/patrepeval huggingface dataset:
Small Ubiquitin-like Modifier (SUMO) Recognition of a SUMO Binding Motif (2005)

Sumoylation has recently been identified as an important mechanism that regulates protein interactions and localization in essential cellular functions, such as gene transcription, subnuclear structure formation, viral infection, and cell cycle progression. A SUMO binding amino acid sequence motif (SBM), which recognizes the SUMO moiety of modified proteins in sumoylation-dependent cellular functions, has been consistently identified by several recent studies. To understand the mechanism of SUMO recognition by the SBM, we have solved the solution structure of SUMO-1 in complex with a peptide containing the SBM derived from the protein PIASX (KVDVIDLTIESSSDEEEDPPAKR). Surprisingly, the structure reveals that the bound orientation of the SBM can reverse depending on the sequence context. The structure also reveals a novel mechanism of recognizing target sequences by a ubiquitin-like module. Unlike ubiquitin binding motifs, which all form helices and bind to the main beta-sheet of ubiquitin, the SBM forms an extended structure that binds between the alpha-helix and a beta-strand of SUMO-1. This study provides a clear mechanism of the SBM sequence variations and its recognition of the SUMO moiety in sumoylated proteins.
Replacement of a Metabolic Pathway for Large-Scale Production of Lactic Acid from Engineered Yeasts (1999)

Interest in the production of L-(+)-lactic acid is presently growing in relation to its applications in the synthesis of biodegradable polymer materials. With the aim of obtaining efficient production and high productivity, we introduced the bovine L-lactate dehydrogenase gene (LDH) into a wild-type Kluyveromyces lactis yeast strain. The observed lactic acid production was not satisfactory due to the continued coproduction of ethanol. A further restructuring of the cellular metabolism was obtained by introducing the LDH gene into a K. lactis strain in which the unique pyruvate decarboxylase gene had been deleted. With this modified strain, in which lactic fermentation substituted completely for the pathway leading to the production of ethanol, we obtained concentrations, productivities, and yields of lactic acid as high as 109 g liter(-1), 0.91 g liter(-1) h(-1), and 1.19 mol per mole of glucose consumed, respectively. The organic acid was also produced at pH levels lower than those usual for bacterial processes.
Quantization based Fast Inner Product Search (2015)

We propose a quantization based approach for fast approximate Maximum Inner Product Search (MIPS). Each database vector is quantized in multiple subspaces via a set of codebooks, learned directly by minimizing the inner product quantization error. Then, the inner product of a query to a database vector is approximated as the sum of inner products with the subspace quantizers. Different from recently proposed LSH approaches to MIPS, the database vectors and queries do not need to be augmented in a higher dimensional feature space. We also provide a theoretical analysis of the proposed approach, consisting of the concentration results under mild assumptions. Furthermore, if a small sample of example queries is given at the training time, we propose a modified codebook learning procedure which further improves the accuracy. Experimental results on a variety of datasets including those arising from deep neural networks show that the proposed approach significantly outperforms the existing state-of-the-art.
The plant ribosome inactivating proteins luffin and saporin are potent inhibitors of HIV‐1 integrase (2000)

The ribosome inactivating proteins (RIPs) are a group of proteins that are able to inactivate eukaryotic protein synthesis by attacking the 28S ribosomal RNA. Recent studies have shown that some RIPs possess strong anti-human immunodeficiency virus (HIV) activity. In this study, several common plant RIPs including agrostin, gelonin, luffin, alpha-momorcharin, beta-momorcharin, saporin and trichosanthin were examined for the ability to interfere with HIV-1 replication in a variety of mechanistic assays in vitro. These assays included the CD4/gp120 interaction assay, HIV-1 reverse transcriptase (RT) assay, HIV-1 protease assay and HIV-1 integrase assay. At the concentration of 100 nM, all RIPs appeared to enhance the CD4/gp120 interaction by about 50%. These RIPs exhibited a very weak suppressive effect on HIV-1 RT and on HIV-1 protease. In contrast, with the exception of agrostin, all the RIPs tested could strongly inhibit HIV-1 integrase, the extent of inhibition ranging from 26.1 to 96.3% in an ELISA-based assay. Two RIPs, saporin and luffin, which licited over 90% inhibition in the ELISA-based assay, were further characterized in a radiometric assay. Both of these two RIPs evoked a strong dose-dependent inhibition in the 3'-end processing and strand-transfer activities of integrase. The results from this study suggest that the anti-HIV property of RIPs may be due to inhibition of HIV-1 integrase.
Tau‐targeting passive immunization modulates aspects of pathology in tau transgenic mice (2014)

Immunization is increasingly recognized as a suitable therapeutic avenue for the treatment of neurological diseases such as Alzheimer's disease and other tauopathies. Tau is a key molecular player in these conditions and therefore represents an attractive target for passive immunization approaches. We performed such an approach in two independent tau transgenic mouse models of tauopathy, K369I tau transgenic K3 and P301L tau transgenic pR5 mice. The antibodies we used were either specific for full-length tau or tau phosphorylated at serine 404 (pS404), a residue that forms part of the paired helical filament (PHF)-1 phosphoepitope that characterizes tau neurofibrillary tangles in tauopathies. Although both pS404 antibodies had a similar affinity, they differed in isotype, and only passive immunization with the IgG2a/κ pS404-specific antibody resulted in a lower tangle burden and reduced phosphorylation of tau at the PHF1 epitope in K3 mice. In pR5 mice, the same antibody led to a reduced phosphorylation of the pS422 and PHF1 epitopes of tau. In addition, histological sections of the hippocampal dentate gyrus of the immunized pR5 mice displayed reduced pS422 staining intensities. These results show that passive immunization targeting tau can modulate aspects of tau pathology in tau transgenic mouse models, in an antibody isotype-specific manner. We show that passive immunization targeting the pathological phosphorylation site pS404 on human tau with a monoclonal IgG2a/κ, but not a IgG1/κ antibody, reduced hyperphosphorylation of tau and tangle burden in two independent mouse models of tau pathology. This shows that both specificity and isotype of phospho-tau (p-tau)-specific antibodies are important for therapeutically ameliorating tau pathology.
Fast control in object-oriented repetitive access (1994)

In a repetitive transaction object-oriented system, a trade-off for an access control mechanism is accomplished in satisfying both the requirements of user friendliness and system performance. Since access control in object-oriented systems is applied to individual methods of individual objects, hence the overhead is extremely large because a check is done on every method invocation. To properly solve the two requirements above, we present a design with the following main features : (1) the whole environment is a central controlled, opened, object-oriented system with discretionary access control, and is trying to satisfy both hierarchical and non-hierarchical control requirements. (2) a rule-based method is provided for user to describe their access control policies (3). After a series of transformation and optimization processes, the access control policies are translated into access control list table with one to one mapping between resource object id's and user id's. (4) finally, because an ACL table is maintained in main memory for each user who repetitively use resource objects in the system, there is only zero or one disk access needed per one access authorization check. A theoretical analysis of the time complexity of this design has been made, and we have implemented it by using high speed workstation, UNIX, C++ and C-ISAM.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Assembly of Short Oligoribonucleotides from Commercially Available Building Blocks on a Tetrapodal Soluble Support (2014)

A workable method for the preparation of short oligoribonucleotides from commercially available 5´-O-(4,4´- dimethoxytrityl)-2´-O-(tert-butyldimethylsilyl)ribonucleoside 3´-(2-cyanoethyl-N,N-diisopropylphosphoramidite) building blocks on a soluble tetrakis-O-[4-(1,2,3-triazol-1-yl)methylphenyl]pentaerythritol support has been developed. The 3´-terminal nucleoside was attached as a 3´-O-(4-pentynoyl) derivative to the support by Cu(I) catalyzed click reaction. The coupling cycle consisted of 4,5-dicyanoimidazole promoted coupling in MeCN with 1.5 equiv. of the monomeric building block, conventional iodine oxidation and precipitation from water followed by flash chromatographic purification. Treatment with triethylamine, followed by ammonolysis and desilylation with Et3N(HF)3 afforded the oligoribonucleotide. As a proof of concept, a pentamer 3´-UUGCA-5´ was prepared in 46% overall yield. Keywords: Nucleosides, nucleotides, oligoribonucleotides, phosphoramidites, synthesis, soluble support.
Human Osteoclast-Like Cells Are Formed from Peripheral Blood Mononuclear Cells in a Coculture with SaOS-2 Cells Transfected with the Parathyroid Hormone (PTH)/PTH-Related Protein Receptor Gene (1999)

Subclones of the human osteosarcoma cell line SaOS-2 were established by transfecting with an expression vector containing the human PTH/PTH-related protein (PTHrP) receptor, and their abilities to support osteoclast-like multinucleated cell (OCL) formation were examined in coculture with mouse or human hemopoietic cells. Of four subclones examined, SaOS-2/4 and SaOS-4/3 bound high levels of [125I]-PTH and produced a significant amount of cAMP in response to PTH. OCLs were formed in response to PTH in the cocultures of mouse bone marrow cells with either SaOS-2/4 cells or SaOS-4/3 cells. Human OCLs were also formed in response to PTH in the coculture of SaOS-4/3 cells and human peripheral blood mononuclear cells. Adding dexamethasone together with PTH greatly enhanced PTH-induced human OCL formation. Like mouse OCLs, human OCLs formed in response to PTH were tartrate-resistant acid phosphatase positive, expressed abundant calcitonin receptors and vitronectin receptors, and formed resorption pits on dentine slices. Other osteotropic factors such as 1alpha,25-dihydroxyvitamin D3, prostaglandin E2, and interleukin 6 plus soluble interleukin 6 receptors failed to induce mouse and human OCLs in cocultures with SaOS-4/3 cells. Both mouse and human OCL formation supported by SaOS-4/3 cells were inhibited by either adding an antibody against macrophage-colony stimulating factor or adding granulocyte/macrophage-colony stimulating factor. Thus, it is likely that human and mouse OCL formation supported by SaOS-4/3 cells are similarly regulated. These results indicate that the target cells of PTH for inducing osteoclast formation are osteoblast/stromal cells but not osteoclast progenitor cells in the coculture. This coculture model will be useful for investigating the abnormalities ofosteoclast differentiation and function in human metabolic bone diseases.
Detecting Targeted Attacks Using Shadow Honeypots (2005)

We present Shadow Honeypots, a novel hybrid architecture that combines the best features of honeypots and anomaly detection. At a high level, we use a variety of anomaly detectors to monitor all traffic to a protected network/service. Traffic that is considered anomalous is processed by a "shadow honeypot'' to determine the accuracy of the anomaly prediction. The shadow is an instance of the protected software that shares all internal state with a regular ("production'') instance of the application, and is instrumented to detect potential attacks. Attacks against the shadow are caught, and any incurred state changes are discarded. Legitimate traffic that was misclassified will be validated by the shadow and will be handled correctly by the system transparently to the end user. The outcome of processing a request by the shadow is used to filter future attack instances and could be used to update the anomaly detector. Our architecture allows system designers to fine-tune systems for performance, since false positives will be filtered by the shadow. Contrary to regular honeypots, our architecture can be used both for server and client applications. We demonstrate the feasibility of our approach in a proof-of-concept implementation of the Shadow Honeypot architecture for the Apache web server and the Mozilla Firefox browser. We show that despite a considerable overhead in the instrumentation of the shadow honeypot (up to 20% for Apache), the overall impact on the system is diminished by the ability to minimize the rate of false-positives.
Rearrangement of chromatin domains during development inXenopus (2000)

A dynamic change in the organization of different gene domains transcribed by RNA polymerase I, II, or III occurs during the progression from quiescent [pre-midblastula transition (pre-MBT)] to active (post-MBT) embryos during Xenopus development. In the rDNA, c-myc, and somatic 5S gene domains, a transition from random to specific anchorage to the nuclear matrix occurs when chromatin domains become active. The keratin gene domain was also randomly associated to the nuclear matrix before MBT, whereas a defined attachment site was found in keratinocytes. In agreement with this specification, ligation-mediated (LM)-PCR genomic footprinting carried out on the subpopulation of 5S domains specifically attached to the matrix reveals the hallmarks of determined chromatin after the midblastula transition. In contrast, the same analysis performed on the total 5S gene population does not reveal specific chromatin organization, validating the use of nuclear matrix fractionation to unveil active chromatin domains. These data provide a means for the determination of active chromosomal territories in the embryo and emphasize the role of nuclear architecture in regulated gene expression during development.
Tibial Plafond Fractures: Changing Principles of Treatment (1994)

Tibial plafond fractures from axial loading are high-energy injuries with significant associated soft-tissue damage. New classification methods include detailed anatomic subgroupings and highlight the soft-tissue injury. The traditional treatment of this intra-articular fracture with open reduction and internal fixation resulted in high rates of wound breakdown and infection. Treatment of these complications is lengthy and costly and not infrequently results in a poor outcome. Newer techniques using external fixation minimize disturbance of the soft-tissue envelope and have decreased these complications. Because the long-term outcome with all techniques is variable and often depends on factors beyond the surgeon's control, it is particularly important to avoid complications of initial treatment. Longer follow-up will determine whether patients treated with these techniques have a different rate of arthrosis.
Three-dimensional microscopic tomographic imaging of the cataract in a human lens in vivo (1998)

The problem of three-dimensional visualization of a human lens in vivo has been solved by a technique of volume rendering a transformed series of 60 rotated Scheimpflug (a dual slit reflected light microscope) digital images. The data set was obtained by rotating the Scheimpflug camera about the optic axis of the lens in 3 degree increments. The transformed set of optical sections were first aligned to correct for small eye movements, and then rendered into a volume reconstruction with volume rendering computer graphics techniques. To help visualize the distribution of lens opacities (cataracts) in the living, human lens the intensity of light scattering was pseudocolor coded and the cataract opacities were displayed as a movie.
A novel method for accurate collagen and biochemical assessment of pulmonary tissue utilizing one animal. (2011)

The hydroxyproline assay showed significant increases in collagen content in the lungs of asbestos-treated mice. Identical results were present between collagen content determined on dried whole lung or whole lung homogenates. The Sirius red plate assay showed a significant increase in collagen content in lung homogenates however, this assay grossly over-estimated the total amount of collagen and underestimated changes between control and fibrotic lungs, conclusions: The proposed method provides accurate quantification of collagen content in whole lungs and additional homogenate samples for biochemical analysis from a single animal. The Sirius-red colorimetric plate assay provides a complementary method for determination of the relative changes in lung collagen but the values tend to overestimate absolute values obtained by the gold standard hydroxyproline assay and underestimate the overall fibrotic injury.
Desymmetrization of Hydrazinocyclohexadienes: A New Approach for the Synthesis of Polyhydroxylated Aminocyclohexanes (2009)

Hydrazinocyclohexadienes, easily prepared by an ene-reaction between commercially available azodicarboxylate reagents and cyclohexadiene, are interesting substrates for desymmetrization reactions. Under Sharpless asymmetric dihydroxylation conditions, they can lead efficiently to several chiral building blocks as well as advanced precursors of biologically active compounds.
Synthesis and Conformational Analysis of the T-Antigen Disaccharide (β-D-Gal-(1→3)-α-D-GalNAc-OMe) (2001)

We report an improved synthesis of the T-antigen disaccharide [β-D-Gal-(1→3)-α-D-GalNAc-OMe], incorporating recycling of the undesired β-glycosyl acceptor [methyl 2-azido-4,6-benzylidene-2-deoxy-β-D-galactopyranoside (9β)] through anomerization by treatment with FeCl3. The conformational analysis of the disaccharide made use of high quality NOE data in combination with extensive Metropolis Monte-Carlo (MMC) and molecular dynamic (MD) simulations. To sample the conformational space sufficiently, 9.5·106 Monte-Carlo steps were collected for the MMC simulations, while the fully solvated MD simulations were performed for 10 ns for comparison. In general, the MMC and MD simulations agreed very well. Comparison of theoretical NOE curves from both MMC and MD simulations with the experimental curves showed that the disaccharide populates two regions of conformational space, with a population of about 95% for the global minimum energy region and about 5% for a local minimum energy region.
Sweep Strategies for a Sensory-Driven, Behavior-Based Vacuum Cleaning Agent (1993)

In the Machine Intelligence Laboratory, University of Florida, we have built a small autonomous robot and programmed it to exhibit various reactive behaviors. The robot, named Gator, performs area coverage in an interior room by combining distinct behaviors. Gator has 26 sensors of which only 7 are used in the coverage algorithms examined here. Gator&amp;apos;s behaviors allow it to avoid obstacles, follow walls, seek open areas and break out of confined areas. In the limited number of experiments performed here it appears that the best coverage algorithm among those tried consisted of a random walk with a probability of 0.05 for following a wall after each encounter with an obstacle. After 20 minutes about 80% of the floor space was covered with an efficiency close to 70%.
Isolation of Exosomes for Subsequent mRNA, MicroRNA, and Protein Profiling (2011)

Exosomes are nano-sized, cell membrane surrounded structures that are released from many cell types. These exosomes are believed to transport a range of molecules, including mRNAs, miRNAs, and proteins; the contents depending on their cell of origin. The physiological and pathological relevance of exosomes has yet to be fully elucidated. Exosomes have been implicated in cell-to-cell communication. For example, in relation to the immune system, such exosomes may enable exchange of antigen or major histocompatibility complex-peptide complexes between antigen-bearing cells and antigen-presenting cells; in cancer, they may contain molecules that not only have relevance as biomarkers, but may also be taken up and cause adverse effects on secondary cells. Furthermore, exosomes have been proposed as autologous delivery systems that could be exploited for personalised delivery of therapeutics. In order to explore the contents and functional relevance of exosomes from medium conditioned by culture cells or from other biological fluids, prior to extensive molecular profiling, they must be isolated and purified. Here, we describe differential centrifugation methods suitable for isolating exosomes from conditioned medium and from other biological fluids, including serum, saliva, tumour ascites, and urine. We also detail Western blotting and transmission electron microscopy methods suitable for basic assessment of their presence, size, and purity, prior to progressing to global mRNA, miRNA, or protein profiling.
Analysis of the boundaries of Salmonella pathogenicity island 2 and the corresponding chromosomal region of Escherichia coli K-12 (1997)

We recently identified a pathogenicity island (SPI2) located at 30.7 centisomes on the Salmonella typhimurium chromosome. SPI2 contains genes encoding a type III secretion system whose function is distinct from that of the type III secretion system encoded by a pathogenicity island (SPI1) at 63 centisomes which is involved in epithelial cell entry. An analysis of the boundaries of SPI2 and comparison with the corresponding region of the Escherichia coli chromosome revealed that SPI2 inserted adjacent to the tRNA(Val) gene. The E. coli chromosome contains 9 kb of DNA at the region corresponding to the SPI2 insertion point which appears to be absent in S. typhimurium. The distribution of SPI1 and SPI2 was examined in various Salmonella isolates. In contrast to type III secretion system genes of SPI1, those of SPI2 are not present in Salmonella bongori, which diverged at the first branch point in the Salmonella lineage. These and other data indicate that SPI2 was acquired by a Salmonella strain already harboring SPI1 by horizontal transfer from an unknown source.
Gastrin mediates the gastric mucosal proliferative response to feeding (1996)

The role of endogenous gastrin in oxyntic mucosal proliferation during feeding in the rat was studied by immunoneutralization with a gastrin-specific monoclonal antibody (MAb) (CURE 051091.5). The immunochemical characteristics of this antibody were characterized by competitive radioimmunoassay, and the in vivo immunoneutralizing properties were validated by measuring effects on gastric acid and pancreatic secretion. Oxyntic mucosal proliferation in response to feeding was measured in adult male rats after a 48-h fast using bromodeoxyuridine (BrdU) immunohistochemistry. Gastrin-specific MAb inhibited gastrin-17- but not pentagastrin-stimulated gastric acid secretion and had no effect on cholecystokinin (CCK)-stimulated pancreatic secretion. In contrast, a MAb specific for the common COOH-terminal pentapeptide of gastrin and CCK inhibited gastrin-17- and pentagastrin-stimulated gastric acid secretion and CCK-stimulated pancreatic secretion. Pretreatment with gastrin-specific MAb 8 h before refeeding significantly reduced by 61% the number of BrdU-labeled cells in the oxyntic mucosal proliferative zone compared with control MAb-treated rats. These results demonstrate the importance of endogenous gastrin in the proliferative response of the oxyntic mucosa to feeding in the rat.