gebhart/patrepeval huggingface dataset:
Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells (2012)

Mesenchymal stem cells (MSCs) are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse) cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.
Measures of Functional Coupling in Design (1983)

Algebraic and geometric representations of the general design problem are presented. Quantitative measures of functional coupling in design are developed from this representation which provide valuable insight into the significance of the independence axiom of design. These theoretical measures are applied to Reaction Injection Molding machinery to illustrate the concept of functional independence and the application of quantitative measures of functional coupling
In vitro and in vivo activities of OX40 (CD134)-IgG fusion protein isoforms with different levels of immune-effector functions (2002)

Recombinant fusion proteins consisting of the extracellular domain of immunoregulatory proteins and the constant domain of immunoglobulin G (IgG) are a novel class of human therapeutics. IgG isoforms exert different levels of immune effector functions, such as complement lysis and antibody-dependent cell cytotoxicity (ADCC). Several OX40-Ig fusion proteins were generated and compared in their potency to inhibit immune reactions. OX40-IgG fusion proteins act as decoys and inhibit T cell costimulation and extravasation induced by OX40 ligand-expressing antigen-presenting cells (APC) and vascular endothelial cells, respectively. In addition, OX40-IgG1 protein induces ADCC and complement lysis in OX40 ligand-expressing cells. Replacement of the IgG1 by the IgG4 domain (OX40-IgG4) eliminated complement lysis and reduced ADCC by half. Mutation of Leu(235) to Glu in IgG4 eliminated the remaining ADCC activity and generated a protein devoid of immune effector functions (OX40-IgG4mut). In vitro, OX40-IgG1 was more potent in inhibiting proliferation and cytokine release by peripheral blood mononuclear cells than OX40-IgG4mut, as OX40-IgG1 induced cell death in APC. However, both proteins reduced T cell-mediated colitis in mice to the same extent, indicating that in vivo neutralization of OX40L is sufficient. This study also demonstrates that effector functions of antibodies are retained and can be rationally designed in receptor-IgG fusion proteins.
Cardiac Myocyte Z-Line Calmodulin Is Mainly RyR2-Bound, and Reduction Is Arrhythmogenic and Occurs in Heart Failure (2013)

CaM binds to RyR2 with high affinity in cardiac myocytes. Physiologically, CaM is bound to >70% of RyR2 monomers and inhibits sarcoplasmic reticulum Ca2+ release. RyR2 is the major binding site for CaM along the Z-line in cardiomyocytes, and dissociating CaM from RyR2 can cause severe ventricular arrhythmia. In heart failure, RyR2 shows decreased CaM affinity, but unaltered FKBP 12.6 affinity.
A colony assay for blast cell progenitors in non-B non-T (common) acute lymphoblastic leukemia (1981)

A clonal method in cell culture is described that permits the quantitation of blast precursors in common (non-T, non-B) ALL; the method also yields information about progenitor properties, based on analysis of cells in colonies. The technique is identical to that used successfully for normal and malignant B-cell progenitors except that it requires culture at below O2 tension (5%-7%); mononuclear cells from blood or marrow are depleted of T cells and cultured with media conditioned by T cells in the presence of phytohemagglutinin and irradiated T cells. Cultures are incubated for 5–7 days in a moist atmosphere at 5% CO2 and 5%-7% O2. Colonies were obtained from marrow or blood of 16 of 18 ALL patients. Cells in colonies had the same characteristics (E-, slg-, cALL+ and clgM+ or clgM-) as the cells in the patient. By replating pooled colonies, self-renewal of progenitors was shown. The findings are considered in light of a model of leukemic blasts that depicts such populations as lineages maintained by progenitors that either renew themselves or give rise to blast cells with little or no proliferative capacity.
Molecular and Biochemical Characterization of a Cold-Regulated PhosphoethanolamineN-Methyltransferase from Wheat (2002)

Abstract A cDNA that encodes a methyltransferase (MT) was cloned from a cold-acclimated wheat (Triticum aestivum) cDNA library. Molecular analysis indicated that the enzyme WPEAMT (wheat phosphoethanolamine [P-EA] MT) is a bipartite protein with two separate sets ofS-adenosyl-l-Met-binding domains, one close to the N-terminal end and the second close to the C-terminal end. The recombinant protein was found to catalyze the three sequential methylations of P-EA to form phosphocholine, a key precursor for the synthesis of phosphatidylcholine and glycine betaine in plants. Deletion and mutation analyses of the twoS-adenosyl-l-Met-binding domains indicated that the N-terminal domain could perform the threeN-methylation steps transforming P-EA to phosphocholine. This is in contrast to the MT from spinach (Spinacia oleracea), suggesting a different functional evolution for the monocot enzyme. The truncated C-terminal and the N-terminal mutated enzyme were only able to methylate phosphomonomethylethanolamine and phosphodimethylethanolamine, but not P-EA. This may suggest that the C-terminal part is involved in regulating the rate and the equilibrium of the three methylation steps. Northern and western analyses demonstrated that both Wpeamt transcript and the corresponding protein are up-regulated during cold acclimation. This accumulation was associated with an increase in enzyme activity, suggesting that the higher activity is due to de novo protein synthesis. The role of this enzyme during cold acclimation and the development of freezing tolerance are discussed.
Translational readthrough of an amber termination codon during synthesis of feline leukemia virus protease (1985)

Feline leukemia virus contains a protease which apparently has the same specificity as murine leukemia virus protease. It cleaves in vitro the Pr65gag of Gazdar-mouse sarcoma virus into the constituent p15, p12, p30, and p10 proteins. We purified the protease and determined its NH2-terminal amino acid sequence (the first 15 residues). Alignment of this amino acid sequence with the nucleotide sequence (I. Laprevotte, A. Hampe, C. H. Sherr, and F. Galibert, J. Virol. 50:884-894, 1984) reveals that the protease is a viral-coded enzyme and is located at the 5' end of the pol gene. As previously found for murine leukemia virus (Y. Yoshinaka, I. Katoh, T. D. Copeland, and S. Oroszlan, Proc. Natl. Acad. Sci. U.S.A. 82:1618-1622, 1985), feline leukemia virus protease is synthesized through in-frame suppression of the gag amber termination codon by insertion of a glutamine in the fifth position, and the first four amino acids are derived from the gag gene.
High-efficiency electroplated heterojunction solar cell (1984)

Over 9% efficiency is demonstrated in electroplated CdS/CdTe thin film solar cells. Processing of the devices is described. A brief heat treatment step first anneals out the deep lifetime killer centers in the material then converts the originally n-type film into solar cell grade p-CdTe.
Receptor engagement by viral interleukin-6 encoded by Kaposi sarcoma–associated herpesvirus (2001)

Receptor usage by viral interleukin-6 (vIL-6), a virokine encoded by Kaposi sarcoma- associated herpesvirus, is an issue of controversy. Recently, the crystal structure of vIL-6 identified vIL-6 sites II and III as directly binding to glycoprotein (gp)130, the common signal transducer for the IL-6 family of cytokines. Site I of vIL-6, however, comprising the outward helical face of vIL-6, where human IL-6 (hIL-6) would interact with the specific alpha-chain IL-6 receptor (IL-6R), is accessible and not occupied by gp130. This study examined whether this unused vIL-6 surface is available for IL-6R binding. By enzyme-linked immunosorbent assay, vIL-6 bound to soluble gp130 (sgp130) but not to soluble IL-6R (sIL-6R). Using plasmon surface resonance, vIL-6 bound to sgp130 with a dissociation constant of 2.5 microM, corresponding to 1000-fold lower affinity than that of hIL-6/sIL-6R complex for gp130. sIL-6R neither bound to vIL-6 nor affected vIL-6 binding to gp130. In bioassays, vIL-6 activity was neutralized by 4 monoclonal antibodies (mAbs) recognizing a domain within vIL-6 site I, mapped to the C-terminal part of the AB-loop and the beginning of helix B. The homologous region in hIL-6 participates in site I binding to IL-6R. In addition, binding of vIL-6 to sgp130 was interfered with specifically by the 4 neutralizing anti-vIL-6 mAbs. Based on the vIL-6 crystal structure, the vIL-6 neutralizing mAbs map outside the binding interface to gp130, suggesting that they either produce allosteric changes or block necessary conformational changes in vIL-6 preceding its binding to gp130. These results document that vIL-6 does not bind IL-6R and suggest that conformational change may be critical to vIL-6 function.
The Herpes Simplex Virus 1 IgG Fc Receptor Blocks Antibody-Mediated Complement Activation and Antibody-Dependent Cellular CytotoxicityIn Vivo (2011)

Herpes simplex virus 1 (HSV-1) glycoprotein E (gE) mediates cell-to-cell spread and functions as an IgG Fc receptor (FcγR) that blocks the Fc domain of antibody targeting the virus or infected cell. Efforts to assess the functions of the HSV-1 FcγR in vivo have been hampered by difficulties in preparing an FcγR-negative strain that is relatively intact for spread. Here we report the FcγR and spread phenotypes of NS-gE264, which is a mutant strain that has four amino acids inserted after gE residue 264. The virus is defective in IgG Fc binding yet causes zosteriform disease in the mouse flank model that is only minimally reduced compared with wild-type and the rescue strains. The presence of zosteriform disease suggests that NS-gE264 spread functions are well maintained. The HSV-1 FcγR binds the Fc domain of human, but not murine IgG; therefore, to assess FcγR functions in vivo, mice were passively immunized with human IgG antibody to HSV. When antibody was inoculated intraperitoneally 20 h prior to infection or shortly after virus reached the dorsal root ganglia, disease severity was significantly reduced in mice infected with NS-gE264, but not in mice infected with wild-type or rescue virus. Studies of C3 knockout mice and natural killer cell-depleted mice demonstrated that the HSV-1 FcγR blocked both IgG Fc-mediated complement activation and antibody-dependent cellular cytotoxicity. Therefore, the HSV-1 FcγR promotes immune evasion from IgG Fc-mediated activities and likely contributes to virulence at times when antibody is present, such as during recurrent infections.
Approach to chronic cough: the neuropathic basis for cough hypersensitivity syndrome. (2014)

Chronic cough is a common symptom that can be difficult to manage because associated causes may remain elusive and treatment of any associated cause may not provide relief. Current antitussives have limited efficacy and undesirable side-effects. Patients with chronic cough describe sensory symptoms suggestive of upper airway and laryngeal neural dysfunction, and report cough triggered by low-level physical and chemical stimuli supporting the concept of cough reflex hypersensitivity. Mechanisms underlying peripheral and central augmentation of the afferent cough pathways have been identified. Chronic cough is a neuropathic condition that could be secondary to sensory nerve damage caused by inflammatory, infective and allergic factors. Recent success in the treatment of chronic cough with agents used for treating neuropathic pain such as gabapentin and amitryptiline would also support this concept. Research into neuropathic cough may lead to the discovery of more effective antitussives.
Stability, Compatibility, and Safety of Intrathecal Bupivacaine Administered Chronically via an Implantable Delivery System (2001)

Bupivacaine is stable and compatible with a commonly used implantable drug infusion system. In this study, chronic supplementation of intrathecal opioids with bupivacaine was a safe method for providing continued management of chronic pain of cancer or noncancer origin.
Hypervisor-based fault tolerance (1995)

Protocols to implement a fault-tolerant computing system are described. These protocols augment the hypervisor of a virtttalmachine manager and coordinate a primary virtual machine with its backup. The result is a fault-tolerant computing system. No modification to hardware, operating system, or application programs is required. A prototype system was constructed for HP's PA-RISC instruction-set architecture. The prototype was able to run programs about a factor of 2 slower than a bare machine would.
Immunohistochemical localization of Ih channel subunits, HCN1–4, in the rat brain (2004)

Hyperpolarization-activated cation currents (I(h)) contribute to various physiological properties and functions in the brain, including neuronal pacemaker activity, setting of resting membrane potential, and dendritic integration of synaptic input. Four subunits of the Hyperpolarization-activated and Cyclic-Nucleotide-gated nonselective cation channels (HCN1-4), which generate I(h), have been cloned recently. To better understand the functional diversity of I(h) in the brain, we examined precise immunohistochemical localization of four HCNs in the rat brain. Immunoreactivity for HCN1 showed predominantly cortical distribution, being intense in the neocortex, hippocampus, superior colliculus, and cerebellum, whereas those for HCN3 and HCN4 exhibited subcortical distribution mainly concentrated in the hypothalamus and thalamus, respectively. Immunoreactivity for HCN2 had a widespread distribution throughout the brain. Double immunofluorescence revealed colocalization of immunoreactivity for HCN1 and HCN2 in distal dendrites of pyramidal cells in the hippocampus and neocortex. At the electron microscopic level, immunogold particles for HCN1 and HCN2 had similar distribution patterns along plasma membrane of dendritic shafts in layer I of the neocortex and stratum lacunosum moleculare of the hippocampal CA1 area, suggesting that these subunits could form heteromeric channels. Our results further indicate that HCNs are localized not only in somato-dendritic compartments but also in axonal compartments of neurons. Immunoreactivity for HCNs often occurred in preterminal rather than terminal portions of axons and in specific populations of myelinated axons. We also found HCN2-immunopositive oligodendrocytes including perineuronal oligodendrocytes throughout the brain. These results support previous electrophysiological findings and further suggest unexpected roles of I(h) channels in the brain.
Targeting XBP-1 as a novel anti-cancer strategy (2006)

The survival and growth of tumor cells within the microenvironment of a solid tumor necessitates the adaptation of these cells to ER stress. Hypoxia, in the context of the tumor microenvironment, is a critical ER stress that activates the unfolded protein response (UPR). This review focuses on the role of the IRE1-XBP1 branch of the UPR and its role in mediating cell survival and tumor growth. Inhibition of this pathway will be discussed as a therapeutic strategy.
Tortuosity of bubble rise path in a liquid‐solid fluidized bed: Effect of particle shape (1995)

Abstract Effects of particle properties on the rise of single bubbles in a liquid‐solid fluidized bed ared studied by focusing on the particle‐shape effect at various bed voidages near incipient fluidization of glass beads and sand particles. Experiments, covering the bubble‐size range 6–37 mm and solids holdups as high as 0.94 times that in the packed state, are conducted in a 2‐D column to directly observe the possible relationship between the rate and tortuous path of bubble rise. The shape effect, being significant when the close‐range (surface‐to‐surface) interactions between particles are predominant, is appreciable for the relative solids holdups exceeding 0.9. Marked reduction in the bubble rise velocity is observed as the bubble size is decreased below 8 and 12 mm for the spherical glass and irregular sand particles, respectively. This anomalous reduction stems partly from the tortuousness in the rise path and partly from the “hesitation” in the net vertical movement. The former, in particular, is quantified in terms of the tortuosity of the 2–D rise path. The results support the peculiar trend in the rise velocity observed, especially for the sand particles.
Enhanced T cell receptor gene therapy for cancer (2010)

Despite technical obstacles, many advances have been made in the generation of high-avidity T cells expressing enhanced TCRs. Mouse studies and clinical trials will evaluate the effect of these improvements.
Efficient generation of blue light by doubly resonant sum-frequency mixing in a monolithic KTP resonator (1992)

Efficient generation of blue light is demonstrated by using resonantly enhanced sum-frequency mixing in a monolithic KTP resonator. Two infrared sources, a diode-pumped Nd:YAG laser and a GaAlAs laser diode, were simultaneously coupled into the monolithic cavity and tuned to resonant frequencies, so that high-intensity intracavity fields were built up at both wavelengths. A blue power of 4 mW in a TEM(00) mode was generated with 55% of the 30 mW of 809-nm power and 45% of the 33 mW of 1064-nm power coupled into the standing-wave nonlinear resonator. By using a novel monolithic ring resonator, 2 mW of power was generated in a TEM(00) mode at 462 nm. Electric-field-induced tuning of the resonant frequencies was also demonstrated.
Data-driven discourse modeling for semantic interpretation (2002)

We propose a task-independent dialog controller that is able to work with different databases and tasks just changing a configuration file. This configuration file specifies a semantic tree for each task. The tree hierarchically organizes the information of the task and database, going from general concepts, towards more specific ones. So the dialogue controller is an inference engine that just follows the strategy specified in the data configuration file. We have defined four types of nodes that imply four different strategies. Moreover all output messages for each node in the tree are defined in the configuration file. So our message generator is task independent too. We have defined six different types of messages and two recovery strategies. Using this approach a system for information retrieval and voice commands has been built at Telefonica I+D.
A Large-Scale Network Data Analysis via Sparse and Low Rank Reconstruction (2014)

With the rapid growth of data communications in size and complexity, the threat of malicious activities and computer crimes has increased accordingly as well. Thus, investigating efficient data processing techniques for network operation and management over large-scale network traffic is highly required. Some mathematical approaches on flow-level traffic data have been proposed due to the importance of analyzing the structure and situation of the network. Different from the state-of-the-art studies, we first propose a new decomposition model based on accelerated proximal gradient method for packet-level traffic data. In addition, we present the iterative scheme of the algorithm for network anomaly detection problem, which is termed as NAD-APG. Based on the approach, we carry out the intrusion detection for packet-level network traffic data no matter whether it is polluted by noise or not. Finally, we design a prototype system for network anomalies detection such as Probe and R2L attacks. The experiments have shown that our approach is effective in revealing the patterns of network traffic data and detecting attacks from large-scale network traffic. Moreover, the experiments have demonstrated the robustness of the algorithm as well even when the network traffic is polluted by the large volume anomalies and noise.
Salicylic acid prevents the adherence of bacteria and yeast to silastic catheters (1993)

Abstract During the pathogenesis of catheter‐related urinary tract infection, bacteria attach to the catheter and migrate along a biofilm into the bladder. We studied the effect of coating silastic catheters with salicylic acid on bacterial and yeast adherence. An agar roll technique, bioluminescent assay, and radiolabeling study all produced consistent results. There was a dose related inhibition of adherence with Pseudomonas aeruginosa, Enterobacter aerogenes, Klebsiella pneumoniae, Candida albicans , and Enterococcus faecalis. Inhibition of over 90% was noted with Enterobacter and Pseudomonas. Similar results were obtained in broth and synthetic urine. A dose related reduction in adherence was seen with all gram‐negative rods and yeast as measured by a radiolabeling assay. TDMAC was used to bind the salicylic acid to the catheters with &gt; 95% inhibition of the gram‐negative rods. These studies suggest the potential role of coating catheters with salicylic acid to reduce bacterial adherence and urinary tract infection. © 1993 John Wiley &amp; Sons, Inc.
Discovery of Disubstituted Cyclohexanes as a New Class of CC Chemokine Receptor 2 Antagonists (2008)

We describe the design, synthesis, and evaluation of novel disubstituted cyclohexanes as potent CCR2 antagonists. Exploratory SAR studies led to the cis-disubstituted derivative 22, which displayed excellent binding affinity for CCR2 (binding IC50 = 5.1 nM) and potent functional antagonism (calcium flux IC50 = 18 nM and chemotaxis IC 50 = 1 nM). Site-directed mutagenesis studies with 22 suggest the compound is binding near the key receptor residue Glu291, however, 22 is not reliant on Glu291 for its binding affinity.