gebhart/patrepeval huggingface dataset:
Natural antibodies to the human T cell lymphoma virus in patients with cutaneous T cell lymphomas. (1981)

Sera from patients with cutaneous T cell lymphoma and leukemia were screened for the presence of natural antibody to the human T cell lymphoma (leukemia) virus, HTLVCR, using a solid-phase radioimmunoassay. Sera from two patients, including patient CR, from whose cultured T lymphoblastic cell line (HUT102), the retrovirus HTLVCR was isolated, reacted specifically with proteins of HTLVCR. Serum from patient CR also reacted specifically with proteins of HTLVMB, an independent but highly related retroviral isolate from a patient with Sezary T cell leukemia. The specificity for HTLVCR proteins was demonstrated by solid-phase immunocompetition assays and competition radioimmunoprecipitation assays. Analysis of radioimmunoprecipitates indicated that the natural antibodies were directed against HTLVCR core proteins with molecular weights of 24,000 and 19,000 (p24 and p19). Whereas the serum reactivities for HTLVCR proteins were shown to be highly specific, additional reactivities seen against proteins of animal retroviruses including GaLV, SSV, FeLV, and BaEV were clearly shown not to be viral specific but rather were due to reactivity with cellular antigens contaminating the viral preparations or with related antigens present in fetal calf serum. These results demonstrating natural antibodies to HTLVCR provide the first evidence for a specific antibody response to a retrovirus in humans.
Oculopharyngeal Muscular Dystrophy in Hispanic New Mexicans (2001)

Individuals in this cohort had clinical and genetic characteristics of classic OPMD. Longevity was not affected, but patients experienced considerable morbidity. The origin of the PABP2 mutation in New Mexican OPMD patients is unclear, although the geographic and genetic isolation of northern New Mexicans with a long ancestry in this region may have contributed to the development of this cohort. This disease cohort represents a large and previously unrecognized health care issue in the state of New Mexico and should serve to raise the awareness of this disorder among clinicians who treat Hispanics in the Southwest and throughout the United States.
Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-α (2001)

The binding of tumor necrosis factor alpha (TNF-alpha) to the type-1 TNF receptor (TNFRc1) plays an important role in inflammation. Despite the clinical success of biologics (antibodies, soluble receptors) for treating TNF-based autoimmune conditions, no potent small molecule antagonists have been developed. Our screening of chemical libraries revealed that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones were antagonists of this protein-protein interaction. After chemical optimization, we discovered IW927, which potently disrupted the binding of TNF-alpha to TNFRc1 (IC(50) = 50 nM) and also blocked TNF-stimulated phosphorylation of Ikappa-B in Ramos cells (IC(50) = 600 nM). This compound did not bind detectably to the related cytokine receptors TNFRc2 or CD40, and did not display any cytotoxicity at concentrations as high as 100 microM. Detailed evaluation of this and related molecules revealed that compounds in this class are "photochemically enhanced" inhibitors, in that they bind reversibly to the TNFRc1 with weak affinity (ca. 40-100 microM) and then covalently modify the receptor via a photochemical reaction. We obtained a crystal structure of IV703 (a close analog of IW927) bound to the TNFRc1. This structure clearly revealed that one of the aromatic rings of the inhibitor was covalently linked to the receptor through the main-chain nitrogen of Ala-62, a residue that has already been implicated in the binding of TNF-alpha to the TNFRc1. When combined with the fact that our inhibitors are reversible binders in light-excluded conditions, the results of the crystallography provide the basis for the rational design of nonphotoreactive inhibitors of the TNF-alpha-TNFRc1 interaction.
Zero-Forcing Methods for Downlink Spatial Multiplexing in Multiuser MIMO Channels (2004)

The use of space-division multiple access (SDMA) in the downlink of a multiuser multiple-input, multiple-output (MIMO) wireless communications network can provide a substantial gain in system throughput. The challenge in such multiuser systems is designing transmit vectors while considering the co-channel interference of other users. Typical optimization problems of interest include the capacity problem - maximizing the sum information rate subject to a power constraint-or the power control problem-minimizing transmitted power such that a certain quality-of-service metric for each user is met. Neither of these problems possess closed-form solutions for the general multiuser MIMO channel, but the imposition of certain constraints can lead to closed-form solutions. This paper presents two such constrained solutions. The first, referred to as "block-diagonalization," is a generalization of channel inversion when there are multiple antennas at each receiver. It is easily adapted to optimize for either maximum transmission rate or minimum power and approaches the optimal solution at high SNR. The second, known as "successive optimization," is an alternative method for solving the power minimization problem one user at a time, and it yields superior results in some (e.g., low SNR) situations. Both of these algorithms are limited to cases where the transmitter has more antennas than all receive antennas combined. In order to accommodate more general scenarios, we also propose a framework for coordinated transmitter-receiver processing that generalizes the two algorithms to cases involving more receive than transmit antennas. While the proposed algorithms are suboptimal, they lead to simpler transmitter and receiver structures and allow for a reasonable tradeoff between performance and complexity.
Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition (2001)

The Toll-like receptor (TLR) family consists of phylogenetically conserved transmembrane proteins, which function as mediators of innate immunity for recognition of pathogen-derived ligands and subsequent cell activation via the Toll/IL-1R signal pathway. Here, we show that human TLR9 (hTLR9) expression in human immune cells correlates with responsiveness to bacterial deoxycytidylate-phosphate-deoxyguanylate (CpG)-DNA. Notably "gain of function" to immunostimulatory CpG-DNA is achieved by expressing TLR9 in human nonresponder cells. Transfection of either human or murine TLR9 conferred responsiveness in a CD14- and MD2-independent manner, yet required species-specific CpG-DNA motifs for initiation of the Toll/IL-1R signal pathway via MyD88. The optimal CpG motif for hTLR9 was GTCGTT, whereas the optimal murine sequence was GACGTT. Overall, these data suggest that hTLR9 conveys CpG-DNA responsiveness to human cells by directly engaging immunostimulating CpG-DNA.
Antioxidative enzymes from chloroplasts, mitochondria, and peroxisomes during leaf senescence of nodulated pea plants (2006)

In this work the influence of the nodulation of pea (Pisum sativum L.) plants on the oxidative metabolism of different leaf organelles from young and senescent plants was studied. Chloroplasts, mitochondria, and peroxisomes were purified from leaves of nitrate-fed and Rhizobium leguminosarum-nodulated pea plants at two developmental stages (young and senescent plants). In these cell organelles, the activity of the ascorbate-glutathione cycle enzymes ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), and glutathione reductase (GR), and the ascorbate and glutathione contents were determined. In addition, the total superoxide dismutase (SOD) activity, the pattern of mitochondrial and peroxisomal NADPH-generating dehydrogenases, some of the peroxisomal photorespiratory enzymes, the glyoxylate cycle and oxidative metabolism enzymes were also analysed in these organelles. Results obtained on the metabolism of cell organelles indicate that nodulation with Rhizobium accelerates senescence in pea leaves. A considerable decrease of the ascorbate content of chloroplasts, mitochondria, and peroxisomes was found, and in these conditions a metabolic conversion of leaf peroxisomes into glyoxysomes, characteristic of leaf senescence, took place.
The analysis of doxorubicin resistance in human breast cancer cells using antibody microarrays (2006)

Doxorubicin is considered to be the most effective agent in the treatment of breast cancer patients. Unfortunately, resistance to this agent is common, representing a major obstacle to successful treatment. The identification of novel biomarkers that are able to predict treatment response may allow therapy to be tailored to individual patients. Antibody microarrays provide a powerful new technique, enabling the global comparative analysis of many proteins simultaneously. This technology may identify a panel of proteins to discriminate between drug-resistant and drug-sensitive samples. The Panorama Cell Signaling Antibody Microarray was exploited to analyze the MDA-MB-231 breast cancer cell line and a novel derivative, which displays significant resistance to doxorubicin at clinically relevant concentrations. The microarray comprised 224 antibodies selected from a variety of pathways, including apoptotic and cell signaling pathways. A standard >/=2.0-fold cutoff value was used to determine differentially expressed proteins. A decrease in the expression of mitogen-activated protein kinase-activated monophosphotyrosine (phosphorylated extracellular signal-regulated kinase; 2.8-fold decrease), cyclin D2 (2.5-fold decrease), cytokeratin 18 (2.5-fold decrease), cyclin B1 (2.4-fold decrease), and heterogeneous nuclear ribonucleoprotein m3-m4 (2.0-fold decrease) was associated with doxorubicin resistance. Western blotting was exploited to confirm results from the antibody microarray experiment. These results suggest that antibody microarrays can be used to identify novel biomarkers and further validation may reveal mechanisms of chemotherapy resistance and identify potential therapeutic targets. [Mol Cancer Ther 2006;5(8):2115-20].
Hybrid Monte Carlo with multidimensional replica exchanges: Conformational equilibria of the hypervariable regions of a llama VHH antibody domain (2002)

Since the structural repertoire of the hypervariable regions of human antibodies is known to be more restricted than what is implied by sequence variability, a common approach to structural prediction is to use a knowledge-based (KB) method, such as the canonical structure model (C. Chothia and A. M. Lesk, Journal of Molecular Biology, 1987, Vol. 196, pp. 901-917). However, this model is less successful when applied to camelid heavy chain antibodies. In this study, molecular simulations were used to examine the conformational equilibria of the hypervariable regions (H1, H2, and H3) of a llama heavy chain variable domain, for which KB predictions are poor. Simulations were carried out using both conventional molecular dynamics (MD) and hybrid Monte Carlo with multidimensional replica exchanges (HYMREX). The advantage of the latter method is its ability to selectively target parts of the Hamiltonian that can most readily improve sampling. A novel variant of HYMREX was implemented in which, besides the temperature, torsional interactions and the range of nonbonded interactions were varied. To compare the sampling abilities of MD and this HYMREX scheme, simulations were started from a misfolded conformational state. Overall, MD yielded final conformations more similar to the initial state, implying quasi-ergodic sampling. In contrast, HYMREX achieved more ergodic sampling, and the majority of conformations that it sampled agreed well with the known crystal structure. The HYMREX simulation results were used to help identify the chief interactions governing the conformational equilibria and to reexamine the key assumptions underlying the KB predictions. The data show that the H1 region exhibited significant conformational freedom, in support of the hypothesis that main-chain structural variability in this region could play a greater role in antigen binding in camelid antibodies than it does in normal antibodies. Key H1 residues and associated inter-loop interactions are conjectured to account for the poor KB predictions.
Kinetics and Jamming Coverage in a Random Sequential Adsorption of Polymer Chains (1996)

Using a highly efficient Monte Carlo algorithm, we are able to study the growth of coverage in a random sequential adsorption of self-avoiding walk chains for up to \ensuremath{\sim}${10}^{12}$ time steps on a square lattice. For the first time, the true jamming coverage ${\ensuremath{\theta}}_{J}$ is found to decay with the chain length $N$ with a power law ${\ensuremath{\theta}}_{J}\ensuremath{\propto}{N}^{\ensuremath{-}0.1}$. The growth of the coverage to its jamming limit can be described by a power law $\ensuremath{\theta}(t)\ensuremath{\approx}{\ensuremath{\theta}}_{J}\ensuremath{-}\frac{c}{{t}^{y}}$ with an effective exponent $y$ which depends on the chain length, i.e., $y\ensuremath{\simeq}0.50$ for $N=4$ to $y\ensuremath{\simeq}0.07$ for $N=30$ with $y\ensuremath{\rightarrow}0$ in the asymptotic $\mathrm{limit} N\ensuremath{\rightarrow}\ensuremath{\infty}$.
Unambiguous HLA Typing for Studies of Human Immunity (35.18) (2007)

Abstract The Major Histocompatibility Complex (MHC) is recognized as the most polymorphic region of the human genome. Our HLA typing laboratory at the University of Oklahoma Health Sciences Center has performed more than 30,000 HLA typings in the past 10 years. We have systematically overcome various capacity and cost constraints to provide precision, DNA sequence-based, HLA typing data for studies of transplantation, vaccine development, and autoimmunity. A confounding variable in the HLA typing field is data heterogeneity; different HLA laboratories provide different levels of resolution when reporting an HLA type for autoimmune, transplant, and vaccine studies. For example, HLA-A*02, A*0201, or A*0201/09/43N/66/75/83N/89/97 might all be reported for a like sample. Such data heterogeneity hinders data integration and comparison. On the basis of our experience with HLA typing and with functional assays such as the ELISpot and tetramer staining, we propose a system of HLA typing that encompasses known functional regions of the HLA molecule. The DNA sequencing of the appropriate exons at various HLA loci, along with the resolution of known null substitutions, will provide cost efficient HLA typing data that can be integrated among different laboratories. Improved HLA data uniformity will ultimately strengthen studies of human immune responses and disease.
Hydrophobically stabilized open state for the lateral gate of the Sec translocon (2010)

The Sec translocon is a central component of cellular pathways for protein translocation and membrane integration. Using both atomistic and coarse-grained molecular simulations, we investigate the conformational landscape of the translocon and explore the role of peptide substrates in the regulation of the translocation and integration pathways. Inclusion of a hydrophobic peptide substrate in the translocon stabilizes the opening of the lateral gate for membrane integration, whereas a hydrophilic peptide substrate favors the closed lateral gate conformation. The relative orientation of the plug moiety and a peptide substrate within the translocon channel is similarly dependent on whether the substrate is hydrophobic or hydrophilic in character, and the energetics of the translocon lateral gate opening in the presence of a peptide substrate is governed by the energetics of the peptide interface with the membrane. Implications of these results for the regulation of Sec-mediated pathways for protein translocation vs. membrane integration are discussed.
Decreased cAMP Response Element-mediated Transcription (2004)

Huntington's disease (HD) is one of nine neurodegenerative diseases caused by an expanded polyglutamine (polyQ) tract within the disease protein. To characterize pathways induced early in HD, we have developed stable inducible PC12 cell lines expressing wild-type or mutant forms of huntingtin exon 1 fragments or the full-length huntingtin protein. Three cAMP response element-binding protein (CREB)-binding protein-dependent transcriptional pathways, regulated by cAMP response element (CRE), retinoic acid response element, and nuclear factor kappaB, show abnormalities in our exon 1 cell model. Of these, the CRE pathway shows the earliest disruption and is significantly down-regulated as early as 12 h following mutant htt transgene induction. This pathway is also the only one of the three that is similarly perturbed in our full-length HD model, where it is also down-regulated at an early time point, compatible with observations in HD brains. Reduced CRE-dependent transcription may contribute to polyQ disease pathogenesis because overexpression of transcriptionally active CREB, but not an inactive form of the protein, is able to protect against polyQ-induced cell death and reduce aggregation.
Horizontal Drill-in Fluid Reclamation for Re-use or Waste Minimization Field Trial (2000)

Abstract Horizontal Drill-in Fluid Reclamation for Re-use or Waste Minimization Field Trial for Shell Auger Project Due to the high cost and logistical concerns of drilling open holes in the geopressured arena, Shell began looking at ways facilitate this option. Most horizontal drill-in fluids, regardless of density, are discharged if they meet environmental regulations. In the geopressure fluid densities, these fluids have a lot of value residing in the base brine which can be comparable to, or even more valuable than the base for synthetic fluids. This practice is not only costly, but in the heavier fluids, they have environmental implications as well. Working closely with Reclamation Solutions and MI Drilling Fluids we came up with a process that would both reduce environmental impact give us back a fluid that could be reused. The new process has been developed that incorporates both conventional and new technologies to reclaim these types of fluids back to original specifications which have value to both Shell and MI. This process is known as CENTRIFLUX. Depending upon the solids content and/or characteristics of the waste fluid, a mechanical pretreatment phase involves both decanting and high speed disc centrifuges that jointly remove solids above 1-5 micron. The ultrafiltration phase removes the remaining suspended solids above 0.1 micron by circulating the fluid through a SCEPTER stainless steel membrane module. This ultrafiltration removes both polymer and starch residue which have been a problem in the past. The solids removed by the CENTRIFLUX process are transferred for disposal and the quality of the reclaimed base fluid meets or exceeds original specifications and can be used again.
Semi-automatic stereo extraction from video footage (2009)

We present a semi-automatic system that converts conventional video shots to stereoscopic video pairs. The system requires just a few user-scribbles in a sparse set of frames. The system combines a diffusion scheme, which takes into account the local saliency and the local motion at each video location, coupled with a classification scheme that assigns depth to image patches. The system tolerates both scene motion and camera motion. In typical shots, containing hundreds of frames, even in the face of significant motion, it is enough to mark scribbles on the first and last frames of the shot. Once marked, plausible stereo results are obtained in a matter of seconds, leading to a scalable video conversion system. Finally, we validate our results with ground truth stereo video.
Bone morphogenetic protein 7 induces mesenchymal‐to‐epithelial transition in melanoma cells, leading to inhibition of metastasis (2009)

Bone morphogenetic protein (BMP) 7 counteracts physiological epithelial-to-mesenchymal transition, a process that is indicative of epithelial plasticity in developmental stages. Because epithelial-to-mesenchymal transition and its reversed process mesenchymal-to-epithelial transition (MET) are also involved in cancer progression, we investigated whether BMP7 plays a role in WM-266-4 melanoma cell growth and metastasis. An MTT assay was conducted in WM-266-4 and HEK293T cell lines to show the cell growth inhibition ability of BMP7 and cisplatin. Semiquantitative RT-PCR was used to determine MET in morphologically changed BMP7-treated melanoma cells. MET-induced cells expressed less a basic helix-loop-helix transcription factor (TWIST) in western blot analysis, and we confirm that BMP receptor (Alk2) siRNA transduction could restore TWIST protein expression via blocking of Smad 1, 5 and 8 signaling. Matrigel invasion and cell migration assays were done to investigate the BMP7-induced metastasis inhibition ability. BMP7 treatment only slightly reduced cell growth rate, but induced apparent MET. BMP7 also reduced the invasion and migration ability. Furthermore, BMP7 reduced the resistance of WM-266-4 cells to cisplatin. Collectively, our findings indicate that the metastatis inhibition ability of BMP7 is involved in MET, and that BMP7 could be used as a potential metastasis inhibitor in human melanoma cells.
Simple, efficientin vitrosynthesis of capped RNA useful for direct expression of cloned eukaryoti genes (1982)

A simple and efficient method for direct in vitro synthesis of capped transcripts of cloned eukaryotic genes is described. As an example capped transcripts were made from a plasmid containing the human fibroblast interferon gene cloned under the control of a prokaryotic promoter. These transcripts were translated in vivo in Xenopus laevis oocytes and in vitro in reticulocyte and in wheat germ cell-free protein synthesizing systems.
Effect of Metformin on Glucagon-Like Peptide 1 (GLP-1) and Leptin Levels in Obese Nondiabetic Subjects (2001)

Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation.
Block of purinergic P2X7 receptor is neuroprotective in an animal model of Alzheimer's disease (2008)

Pharmacological antagonism of the ionotropic purinergic P2X7R has been studied for effects on inflammatory reactivity and neuronal viability in amyloid-beta1-42-injected rat hippocampus. Amyloid-beta1-42-injected brains (7-day postinjection) demonstrated marked increases in P2X7R expression, gliosis, leakiness of blood-brain barrier and loss of hippocampal neurons. The P2X7R antagonist, brilliant blue G reduced levels of purinergic receptor expression, attenuated gliosis, diminished leakiness of blood-brain barrier and was neuroprotective in peptide-injected brain. Brilliant blue G also demonstrated neuroprotection and antagonism against inflammatory responses induced by the P2X7R agonist, 2',3'-(benzoyl-4-benzoyl)-ATP. The findings constitute the first report that pharmacological inhibition of P2X7R, possibly by acting to inhibit inflammatory reactivity, confers neuroprotection in an animal model of Alzheimer's disease brain.