gebhart/patrepeval huggingface dataset:
Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1 (1999)

Although genetic analysis has demonstrated that members of the winged helix, or forkhead, family of transcription factors play pivotal roles in the regulation of cellular differentiation and proliferation, both during development and in the adult, little is known of the mechanisms underlying their regulation. Here we show that the activation of phosphatidylinositol 3 (PI3) kinase by extracellular growth factors induces phosphorylation, nuclear export, and transcriptional inactivation of FKHR1, a member of the FKHR subclass of the forkhead family of transcription factors. Protein kinase B (PKB)/Akt, a key mediator of PI3 kinase signal transduction, phosphorylated recombinant FKHR1 in vitro at threonine-24 and serine-253. Mutants FKHR1(T24A), FKHR1(S253A), and FKHR1(T24A/S253A) were resistant to both PKB/Akt-mediated phosphorylation and PI3 kinase-stimulated nuclear export. These results indicate that phosphorylation by PKB/Akt negatively regulates FKHR1 by promoting export from the nucleus.
Toxicity and immunogenicity of Neisseria meningitidis lipopolysaccharide incorporated into liposomes (1992)

To obtain nontoxic and highly immunogenic lipopolysaccharide (LPS) for immunization, we incorporated Neisseria meningitidis LPS into liposomes. Native LPS and its salts were incorporated by the method of dehydration-rehydration of vesicles or prolonged cosonication. The most complete incorporation of LPS into liposomes and a decrease in toxicity were achieved by the method of dehydration-rehydration of vesicles. Three forms of LPS (H+ form, Mg2+ salt, and triethanolamine salt) showed different solubilities in water, the acidic form of LPS, with the most pronounced hydrophobic properties, being capable of practically complete association with liposomal membranes. An evaluation of the activity of liposomal LPS in vitro (by the Limulus amoebocyte test) and in vivo (by monitoring the pyrogenic reaction in rabbits) revealed a decrease in endotoxin activity of up to 1,000-fold. In addition, the pyrogenic activity of liposomal LPS was comparable to that of a meningococcal polysaccharide vaccine. Liposomes had a pronounced adjuvant effect on the immune response to LPS. Thus, the level of anti-LPS plaque-forming cells in the spleens of mice immunized with liposomal LPS was 1 order of magnitude higher and could be observed for a longer time (until day 21, i.e., the term of observation) than in mice immunized with free LPS. The same regularity was revealed in a study done with an enzyme-linked immunosorbent assay. This study also established that antibodies induced by immunization belonged to the immunoglobulin M and G classes, which are capable of prolonged circulation. Moreover, liposomal LPS induced a pronounced immune response in CBA/N mice (defective in B lymphocytes of the LyB-5+ subpopulation). The latter results indicate that the immunogenic action of liposomal LPS occurs at an early age.
Structural DNA Nanotechnology: From Design to Applications (2012)

The exploitation of DNA for the production of nanoscale architectures presents a young yet paradigm breaking approach, which addresses many of the barriers to the self-assembly of small molecules into highly-ordered nanostructures via construct addressability. There are two major methods to construct DNA nanostructures, and in the current review we will discuss the principles and some examples of applications of both the tile-based and DNA origami methods. The tile-based approach is an older method that provides a good tool to construct small and simple structures, usually with multiply repeated domains. In contrast, the origami method, at this time, would appear to be more appropriate for the construction of bigger, more sophisticated and exactly defined structures.
Asymptotic Dental Score and Prevalent Coronary Heart Disease (2004)

ADS may be useful as a prescreening tool to promote proactive cardiac evaluation among individuals without overt symptoms of CHD. However, additional prospective study is needed to validate the use of an oral health score as a predictor of incident CHD.
Magnitude and Breadth of the Neutralizing Antibody Response in the RV144 and Vax003 HIV-1 Vaccine Efficacy Trials (2012)

The results suggest either that weak neutralizing antibody responses can be partially protective against HIV-1 in low-risk heterosexual populations or that the modest efficacy seen in RV144 was mediated by other immune responses, either alone or in combination with neutralizing antibodies.
Optimisation of refractive index profile for high gain fibre amplifiers (1990)

It is shown that appropriately designed depressed cladding fibres offer the potential for erbium doped, Raman and Brillouin fibre amplifiers which combine high gain with low scattering losses.
Conversion of aluminum chlorohydrate to aluminum hydroxide (1982)

aluminum hydroxide. X-ray, IR, and 27A1 NMR spectroscopic data indicate that aluminum chlorohydrate is composed of a central aluminum in tetrahedral configuration surrounded by 12 aluminums each in octahedral configuration. This highly .charged complex is neutralized by 7 chloride counterions. In contrast, aluminum hydroxide has a polymer-like structure whose basic unit is a ring of six aluminums in octahedral configuration joined by double hydroxide bridges. Bayerite, an aluminum hydroxide polymorph, readily forms when the hydroxyl to aluminum ratio of aluminum chlorohydrate is raised to 3 by titration with sodium hydroxide. Dilution of aluminum chlorohydrate solutions with water or 0.9% NaCI leads to the formation of gibbsite, another aluminum hydroxide polymorph. Conversion of aluminum chlorohydrate occurs rapidly enough under simulated conditions of antiperspirant use to just!fy the conclusion that one mechanism of aluminum chlorohydrate's antiperspirant action is the formation of an obstructive aluminum hydroxide gel within the sweat duct.
High-resolution mapping of the 11q13 amplicon and identification of a gene, TAOS1 , that is amplified and overexpressed in oral cancer cells (2002)

Amplification of chromosomal band 11q13 is a common event in human cancer. It has been reported in about 45% of head and neck carcinomas and in other cancers including esophageal, breast, liver, lung, and bladder cancer. To understand the mechanism of 11q13 amplification and to identify the potential oncogene(s) driving it, we have fine-mapped the structure of the amplicon in oral squamous cell carcinoma cell lines and localized the proximal and distal breakpoints. A 5-Mb physical map of the region has been prepared from which sequence is available. We quantified copy number of sequence-tagged site markers at 42-550 kb intervals along the length of the amplicon and defined the amplicon core and breakpoints by using TaqMan-based quantitative microsatellite analysis. The core of the amplicon maps to a 1.5-Mb region. The proximal breakpoint localizes to two intervals between sequence-tagged site markers, 550 kb and 160 kb in size, and the distal breakpoint maps to a 250 kb interval. The cyclin D1 gene maps to the amplicon core, as do two new expressed sequence tag clusters. We have analyzed one of these expressed sequence tag clusters and now report that it contains a previously uncharacterized gene, TAOS1 (tumor amplified and overexpressed sequence 1), which is both amplified and overexpressed in oral cancer cells. The data suggest that TAOS1 may be an amplification-dependent candidate oncogene with a role in the development and/or progression of human tumors, including oral squamous cell carcinomas. The approach described here should be useful for characterizing amplified genomic regions in a wide variety of tumors.
The Disruption of a Gene Encoding a Putative Arylesterase Impairs Pyruvate Dehydrogenase Complex Activity and Nitrogen Fixation in Sinorhizobium meliloti (2001)

Nitrogen-fixing Sinorhizobium meliloti cells depend upon dicarboxylic acids as carbon and energy sources. The metabolism of these intermediate compounds of the trichloroacetic acid cycle is dependent upon the availability of acetyl-coenzyme A (CoA). In bacteroids, the combined activities of malic enzymes and pyruvate dehydrogenase (PDH) have been proposed to be responsible for the anaplerotic synthesis of acetyl-CoA. We obtained a S. meliloti mutant strain, PD3, in which a Tn5 insertion led to a significant decrease in the overall PDH activity. The genetic characterization of this mutant revealed that the transposon is located at the 3' end of a gene (ada) encoding a putative arylesterase. The mutant PD3 is deficient in nitrogen fixation, which strengthens the physiological importance of PDH activity in the symbiosis of S. meliloti with alfalfa plants.
Overexpression of a Nuclear Protein, TIEG, Mimics Transforming Growth Factor-β Action in Human Osteoblast Cells (2000)

Although transforming growth factor-beta (TGF-beta) is a growth factor with many known regulatory activities in many different cell types, its intracellular signaling pathway is still not fully understood. A TGF-beta-inducible early gene (TIEG) was discovered and shown by this laboratory to be a 3-zinc finger transcription factor family member; its expression is rapidly induced in cells treated with TGF-beta. To ascertain whether TIEG plays a major role in the TGF-beta pathway, human osteosarcoma MG-63 cells were stably transfected either with an expression vector containing a TIEG cDNA or with the vector alone. Clones that contain only the vector express normal levels of TIEG mRNA and protein and display the same patterns of gene expression and levels of cell proliferation as the nontransfected, non-TGF-beta-treated parental cells. However, transfected cells that overexpress TIEG mRNA and protein (TIEG-6 and TIEG-7) display changes that mimic those of MG-63 cells treated with TGF-beta, i.e. increased alkaline phosphatase activity, decreased levels of osteocalcin mRNA and protein, and decreased cell proliferation. The degree of these changes correlated with the level of TIEG expressed in the cell lines. TGF-beta treatment of the overexpressed cells showed no added effects. These findings and other published reports support a primary role of TIEG as a transcription factor in the TGF-beta signaling pathway.
Anionic Micelles and Vesicles Induce Tau Fibrillization in Vitro (2003)

Alzheimer's disease is defined in part by the intraneuronal accumulation of filaments comprised of the microtubule-associated protein tau. In vitro, fibrillization of recombinant tau can be induced by treatment with various agents, including phosphotransferases, polyanionic compounds, and fatty acids. Here we characterize the structural features required for the fatty acid class of tau fibrillization inducer using recombinant full-length tau protein, arachidonic acid, and a series of straight chain anionic, cationic, and nonionic detergents. Induction of measurable tau fibrillization required an alkyl chain length of at least 12 carbons and a negative charge consisting of carboxylate, sulfonate, or sulfate moieties. All detergents and fatty acids were micellar at active concentrations, due to a profound, taudependent depression of their critical micelle concentrations. Anionic surfaces larger than detergent micelles, such as those supplied by phosphatidylserine vesicles, also induced tau fibrillization with resultant filaments originating from their surface. These data suggest that anionic surfaces presented as micelles or vesicles can serve to nucleate tau fibrillization, that this mechanism underlies the activity of fatty acid inducers, and that anionic membranes may serve this function in vivo.
Current Studies on a Working Model of CaM Kinase II in Hippocampal Long-Term Potentiation and Memory (1999)

There have been recent advances in understanding the molecular basis of the long-term potentiation (LTP) of synaptic transmission in the hippocampus. This review documents current views on mechanisms underlying LTP induction, from activation of the NMDA receptor to stimulation of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). We will focus in particular on recent findings of how CaM kinase II encodes the frequency of synaptic usage and serves as a molecular memory switch at the synapse. Furthermore, a role for CaM kinase II in spatial learning and memory is demonstrated by recent studies using transgenic mice.
Aperture shared laser diode array beam combiner (1988)

An array of discrete semiconductor lasers utilizing graded-index rod lenses as collimators were fabricated to form a noncoherent laser beam combiner. Continuous wave output power of 600 mW and 5.25% total efficiency were achieved in a 5-mrad beam from a ten-diode laser array. A technique of dichroically combining five arrays is also described.
Handbook of Character Recognition and Document Image Analysis (1997)

Arabic character recognition, A. Amin automatic reading of braille documents, A. Antonacopoulos techniques for improving OCR results, A. Dengel offline handwritten word recognition using hidden Markov models, A. Kundu combinations of multiple classifier decisions for OCR, L. Lam and C.Y. Suen classification techniques - statistical pattern recognition, neural networks and their relations, J. Schurmann cursive handwriting recognition - contextual and context - free techniques, M. Shridhar and Kimura multilingual document recognition, L. Spitz information retrieval and OCR, K. Taghva technical drawing analysis - including vectorization, D. Dori and K. Tombre reading of music notation, N. Carter and D. Bainbridge benchmarking, T. Nartker et al automatic signature verification, S. Impedovo. (Part Contents).
Blocking Caspase Activity Prevents Transsynaptic Neuronal Apoptosis and the Loss of Inhibition in Lamina II of the Dorsal Horn after Peripheral Nerve Injury (2005)

We show that transsynaptic apoptosis is induced in the superficial dorsal horn (laminas I-III) of the spinal cord by three distinct partial peripheral nerve lesions: spared nerve injury, chronic constriction, and spinal nerve ligation. Ongoing activity in primary afferents of the injured nerve and glutamatergic transmission cause a caspase-dependent degeneration of dorsal horn neurons that is slow in onset and persists for several weeks. Four weeks after spared nerve injury, the cumulative loss of dorsal horn neurons, determined by stereological analysis, is >20%. GABAergic inhibitory interneurons are among the neurons lost, and a marked decrease in inhibitory postsynaptic currents of lamina II neurons coincides with the induction of apoptosis. Blocking apoptosis with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) prevents the loss of GABAergic interneurons and the reduction of inhibitory currents. Partial peripheral nerve injury results in pain-like behavioral changes characterized by hypersensitivity to tactile or cold stimuli. Treatment with zVAD, which has no intrinsic analgesic properties, attenuates this neuropathic pain-like syndrome. Preventing nerve injury-induced apoptosis of dorsal horn neurons by blocking caspase activity maintains inhibitory transmission in lamina II and reduces pain hypersensitivity.
Liquid crystal contact thermography of deep venous thrombosis (1982)

A new thermographic technique for the diagnosis of deep venous thrombosis, liquid crystal contact color thermography using naturally occurring cholesteric crystals is described. Cholesteric crystals have the property of changing colors in consistent, predictable patterns in response to local temperature changes. The technique is reliable and reproducible. It has also been rendered simple by embedding the liquid crystals in elastic, flexible sheets. The sheets are inflated and readily adapt and contour to extremities of various sizes and shapes. Preliminary results have shown excellent correlation with ascending phlebography. The two methods were in agreement in 90% of cases with no false-negative liquid crystal thermograms. The technique shows promise as a noninvasive screening study for the diagnosis of deep venous thrombosis in high risk patients.
Discovery and characterization of olokizumab (2014)

Interleukin-6 (IL-6) is a critical regulator of the immune system and has been widely implicated in autoimmune disease. Here, we describe the discovery and characterization of olokizumab, a humanized antibody to IL-6. Data from structural biology, cell biology and primate pharmacology demonstrate the therapeutic potential of targeting IL-6 at "Site 3", blocking the interaction with the signaling co-receptor gp130.
Identification and reactivity of the major metabolite (ß-1-glucuronide) of the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in humans (2001)

1. The novel anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is extensively metabolized by glucuronidation and 6-methylhydroxylation, resulting in DMXAA acyl glucuronide (DMXAA-G) and 6-hydroxymethyl-5-methylxanthenone-4-acetic acid (6-OH-MXAA). 2. The major human urinary metabolite of DMXAA was isolated and purified by a solid-phase extraction (SPE) method. The isolated metabolite was hydrolysed to free DMXAA by strong base, and by beta-glucuronidase. Liquid chromatography-mass spectrometry (LC-MS) and spectral data indicated the presence of a molecular ion [M + 1]+ at m/z 459, which was consistent with the molecular weight of protonated DMXAA-G. 3. The glucuronide was unstable in buffer at physiological pH, plasma and blood with species variability in half-life. Hydrolysis and intramolecular migration were major degradation pathways. 4. In vitro and in vivo formation of DMXAA-protein adducts was observed. The formation of DMXAA-protein adducts in cancer patients receiving DMXAA was significantly correlated with plasma DMXAA-G concentration and maximum plasma DMXAA concentration. 5. At least five metabolites of DMXAA were observed in patient urine, with up to 60% of the total dose excreted as DMXAA-G, 5.5% as 6-OH-MXAA and 4.5% as the glucuronide of 6-OH-MXAA. 6. These data suggest that the major metabolite in patients' urine is DMXAA beta-1-glucuronide, which may undergo hydrolysis, molecular rearrangement and covalent binding to plasma protein. The reactive properties of DMXAA-G may have important implications for the pharmacokinetics, pharmacodynamics and toxicity of DMXAA.
Statistical timing analysis using bounds and selective enumeration (2002)

The growing impact of within-die process variation has created the need for statistical timing analysis, where gate delays are modeled as random variables. Statistical timing analysis has traditionally suffered from exponential run time complexity with circuit size, due to the dependencies created by reconverging paths in the circuit. In this paper, we propose a new approach to statistical timing analysis which uses statistical bounds and selective enumeration to refine these bounds. First, we provide a formal definition of the statistical delay of a circuit and derive a statistical timing analysis method from this definition. Since this method for finding the exact statistical delay has exponential run time complexity with circuit size, we also propose a new method for computing statistical bounds which has linear run time complexity. We prove the correctness of the proposed bounds. Since we provide both a lower and upper bound on the true statistical delay, we can determine the quality of the bounds. If the computed bounds are not sufficiently close to each other, we propose the use of a heuristic to iteratively improve the bounds using selective enumeration of the sample space with additional run time. The proposed methods were implemented and tested on benchmark circuits. The results demonstrate that the proposed bounds have only a small error, which could be further reduced using selective enumeration with modest additional run time.
The receptor for advanced glycation end products (RAGE) is a central mediator of the interaction of AGE-beta2microglobulin with human mononuclear phagocytes via an oxidant-sensitive pathway. Implications for the pathogenesis of dialysis-related amyloidosis. (1996)

An important component of amyloid fibrils in dialysis-related amyloidosis is a form of beta2microglobulin modified with advanced glycation end products (AGEs) of the Maillard reaction, known as AGE-beta2M. We demonstrate here that the interaction of AGE-beta2M with mononuclear phagocytes (MPs), cells important in the pathogenesis of the inflammatory arthropathy of dialysis-related amyloidosis, is mediated by the receptor for AGEs, or RAGE. 125I-AGE-beta2M bound to immobilized RAGE or to MPs in a specific, dose-dependent manner (Kd approximately 53.5 and approximately 81.6 nM, respectively), a process inhibited in the presence of RAGE blockade. AGE-beta2M-mediated monocyte chemotaxis was prevented by excess sRAGE or anti-RAGE IgG. Induction of tumor necrosis factor-alpha (TNF) expression by MPs exposed to AGE-beta2M resulted from engagement of RAGE, as appearances of TNF transcripts and TNF antigen release into culture supernatants were prevented by addition of sRAGE, a process mediated, at least in part, by oxidant stress. AGE-beta2M reduced cytochrome c and the elaboration of TNF by MPs was inhibited by N-acetylcysteine. Consistent with these data, immunohistochemical studies of AGE-laden amyloid deposits of a long-term hemodialysis patient revealed positive staining for RAGE in the MPs infiltrating these lesions. These data indicate that RAGE is a central binding site for AGEs formed in vivo and suggest that AGE-beta2M-MP-RAGE interaction likely contributes to the initiation of an inflammatory response in amyloid deposits of long-term hemodialysis patients, a process which may ultimately lead to bone and joint destruction.
Characterization of Ex Vivo Expanded Oral Mucosal Epithelium Cells on Acellular Porcine Corneal Stroma for Ocular Surface Reconstruction (2017)

OMECs can be successfully cultured on APCS without using xenobiotic feeder cells and serum. Characterization showed that these sheets retain the morphologic and phenotypic characteristics of OMECs within differentiated cells and stem cells. The optimal transplantable sheets can prove to be particularly beneficial to both bilateral limbal stem cell deficiency and deep corneal lesions.
Establishment of an in vitro Assay to Characterize Hepatitis C Virus NS3-4A Protease <i>Trans</i>-Processing Activity (1996)

An in vitro cleavage system was established to measure HCV NS3 protease trans-processing activity. This system utilizes purified NS3-4A protein from baculovirus, purified substrates expressed by in vitro transcription and translation and defined buffer components. The 41-residue substrates, 5A/5B and 4A/4B, were processed efficiently in trans by wild-type NS3 but not by a catalytically inactive mutant protease; radiolabel sequencing confirmed that NS3-mediated cleavage occurred at the correct cysteine/serine sites, thereby authenticating this system. Two striking features of this in vitro assay are: (1) analogous 4B/5A and 3/4A substrates cannot be processed in trans under the same conditions, and (2) in vitro cleavage of the 5A/5B and 4A/4B sites is highly dependent on the presence of NS4A, which we show is not the case in vivo.
Scheme to measure relative clock skew of two internet hosts based on end-link capacity (2012)

Proposed is a scheme to measure the relative clock skew between two network nodes. The scheme is based on measuring the intra-packet gaps of probes sent between the two network nodes. The proposed scheme is evaluated through simulation under a heavy cross-traffic load scenario. The obtained results show that the scheme measures the clock skew with high accuracy despite the presence of cross-traffic.
EFFECTS OF ION BEAM IRRADIATION ON MUTATION INDUCTION IN ARABIDOPSIS THALIANA (2007)

We evaluated the effects of the conditions of heavyion beam irradiation on effective mutation induction in Arabidopsis thaliana. First, mutation rates were compared between nuclides. Dry seeds were irradiated with 12 C 6+ , 14 N 7+ , 20 Ne 10+ (135MeV/u), 40 Ar 17+ (95