gebhart/patrepeval huggingface dataset:
Cloning of rabbit interleukin-1β: differential evolution of IL-1α and IL-1β proteins (1989)

We have cloned the rabbit IL-1 beta cDNA, which encodes a 268 amino acid precursor similar in length to other sequenced IL-1 precursors. Comparison of all published IL-1 alpha and IL-1 beta sequences respectively indicates that the IL-1 alpha gene family is evolving faster than the IL-1 beta family, and that the two genes diverged approximately 270 million years ago. Surprisingly, there are differences in the regions preferentially conserved within the two families. The IL-1 alpha family is most conserved at the amino terminus whereas the IL-1 beta family is most conserved in the carboxy-terminal half. This is despite the fact that the carboxy-terminal half encodes the active portion of both molecules and would be expected to adopt a similar beta-sheet structure in IL-1 alpha as in the published X-ray structure of mature IL-1 beta. These findings suggest that differences in the function and properties of the IL-1 alpha and IL-1 beta precursor molecules may have been conserved. These differences may therefore provide an explanation for the existence of two IL-1 molecules.
Consensus Decisionmaking in NATO: French Unilateralism and the Decision to Defend Turkey (2003)

On January 15, 2003, the United States formally requested that the North Atlantic Treaty Organization ("NATO") begin planning to defend one of its members, Turkey, from any counterstrikes launched by Iraq in the event of a war with Iraq. France, Germany, and Belgium, concerned that such a move by NATO would send a message that war with Iraq was inevitable, resisted the request. In response, Turkey, the only member of NATO that shares a border with Iraq, pressed the issue by invoking Article 4 of the North Atlantic Treaty, which provides that "[t]he Parties will consult together whenever, in the opinion of any of them, the territorial integrity, political independence or security of any of the Parties is threatened." Despite Turkey's plea for collective defense, which is the purpose of NATO, France and the others continued to block any planning for almost a month. Because NATO operates under consensus decisionmaking, the votes of these three nations barred defensive preparation by NATO in support of Turkey. NATO finally resolved the issue by moving the decision into its Defense Planning Committee ("DPC"), thereby circumventing France's veto. With France excluded, Germany and Belgium compromised and agreed to support the measure. As a result, NATO committed to provide some assets for the defense of Turkey without the full consensus of its members. NATO's decision highlights a conflict between NATO's requirement of unanimity in decisionmaking and its obligation to provide collective defense. This development examines the decision and attempts to answer the following questions: Did NATO's decision without France's consent violate the North Atlantic Treaty? Did France violate the treaty by refusing to fulfill its obligation to defend a fellow NATO member? What does NATO's decision imply for the future of NATO?
Up-regulation of WRN and DNA ligase IIIα in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks (2008)

Expression of oncogenic BCR-ABL in chronic myeloid leukemia (CML) results in increased reactive oxygen species (ROS) that in turn cause increased DNA damage, including DNA double-strand breaks (DSBs). We have previously shown increased error-prone repair of DSBs by nonhomologous end-joining (NHEJ) in CML cells. Recent reports have identified alternative NHEJ pathways that are highly error prone, prompting us to examine the role of the alternative NHEJ pathways in BCR-ABL-positive CML. Importantly, we show that key proteins in the major NHEJ pathway, Artemis and DNA ligase IV, are down-regulated, whereas DNA ligase IIIalpha, and the protein deleted in Werner syndrome, WRN, are up-regulated. DNA ligase IIIalpha and WRN form a complex that is recruited to DSBs in CML cells. Furthermore, "knockdown" of either DNA ligase IIIalpha or WRN leads to increased accumulation of unrepaired DSBs, demonstrating that they contribute to the repair of DSBs. These results indicate that altered DSB repair in CML cells is caused by the increased activity of an alternative NHEJ repair pathway, involving DNA ligase IIIalpha and WRN. We suggest that, although the repair of ROS-induced DSBs by this pathway contributes to the survival of CML cells, the resultant genomic instability drives disease progression.
Batch Bayesian Optimization via Local Penalization (2015)

The popularity of Bayesian optimization methods for efficient exploration of parameter spaces has lead to a series of papers applying Gaussian processes as surrogates in the optimization of functions. However, most proposed approaches only allow the exploration of the parameter space to occur sequentially. Often, it is desirable to simultaneously propose batches of parameter values to explore. This is particularly the case when large parallel processing facilities are available. These facilities could be computational or physical facets of the process being optimized. E.g. in biological experiments many experimental set ups allow several samples to be simultaneously processed. Batch methods, however, require modeling of the interaction between the evaluations in the batch, which can be expensive in complex scenarios. We investigate a simple heuristic based on an estimate of the Lipschitz constant that captures the most important aspect of this interaction (i.e. local repulsion) at negligible computational overhead. The resulting algorithm compares well, in running time, with much more elaborate alternatives. The approach assumes that the function of interest, $f$, is a Lipschitz continuous function. A wrap-loop around the acquisition function is used to collect batches of points of certain size minimizing the non-parallelizable computational effort. The speed-up of our method with respect to previous approaches is significant in a set of computationally expensive experiments.
Experimental Realization of Quantum Illumination (2013)

We present the first experimental realization of the quantum illumination protocol proposed by Lloyd [Science 321, 1463 (2008)] and S. Tan et al. [Phys. Rev. Lett. 101, 253601 (2008)], achieved in a simple feasible experimental scheme based on photon-number correlations. A main achievement of our result is the demonstration of a strong robustness of the quantum protocol to noise and losses that challenges some widespread wisdom about quantum technologies.
真理与后果——怎样理解J.德里达 (1989)

1966年,在一个打算用来标志美国结构主义时代到来的会议上,J.德里达声称这已经太迟了,因为结构主义事实上已经新潮衰落,从而使听众大为震惊,此后他一直成为激烈争论的焦点。在以后的这些年里,德里达由于其自身的努力而成为知名人士,他的讲演吸引了大量的听众,他的著作至少有13部被译成英语,其中包括一些新近译出、但并非新近写出的著作,评论他的书籍也是随处可见。许多德里达式的词汇,如“书写语言学”、“逻各斯中心
Germline transformation of Drosophila melanogaster with the piggyBac transposon vector (1999)

Germline transformation of Drosophila melanogaster was attempted with the piggyBac gene-transfer system from the cabbage looper moth, Trichoplusia ni. Using a self-regulated transposase helper and a white marked vector, a transformation frequency of 1-3% per fertile G0 was obtained, similar to that previously achieved in the medfly. Use of an hsp70-regulated helper increased this frequency more than eight-fold. Transformation with a vector marked with white and green fluorescent protein (GFP) under polyubiquitin-nuclear localizing sequence regulation yielded seventy G1 transformants which all expressed GFP, but only twenty-seven of these expressed eye pigmentation that would have allowed their selection based on white+ expression. PiggyBac transformation in two distantly related dipteran species and efficient expression of the gfp marker supports the potential use of this system in other dipterans, and perhaps insects in general.
Identification of Immunodominant and Conformational Epitopes in the Capsid Protein of Hepatitis E Virus by Using Monoclonal Antibodies (2000)

Antibody to the capsid (PORF2) protein of hepatitis E virus (HEV) is sufficient to confer immunity, but knowledge of B-cell epitopes in the intact capsid is limited. A panel of murine monoclonal antibodies (MAbs) was generated following immunization with recombinant ORF2.1 protein, representing the C-terminal 267 amino acids (aa) of the 660-aa capsid protein. Two MAbs reacted exclusively with the conformational ORF2.1 epitope (F. Li, J. Torresi, S. A. Locarnini, H. Zhuang, W. Zhu, X. Guo, and D. A. Anderson, J. Med. Virol. 52:289-300, 1997), while the remaining five demonstrated reactivity with epitopes in the regions aa 394 to 414, 414 to 434, and 434 to 457. The antigenic structures of both the ORF2.1 protein expressed in Escherichia coli and the virus-like particles (VLPs) expressed using the baculovirus system were examined by competitive enzyme-linked immunosorbent assays (ELISAs) using five of these MAbs and HEV patient sera. Despite the wide separation of epitopes within the primary sequence, all the MAbs demonstrated some degree of cross-inhibition with each other in ORF2. 1 and/or VLP ELISAs, suggesting a complex antigenic structure. MAbs specific for the conformational ORF2.1 epitope and a linear epitope within aa 434 to 457 blocked convalescent patient antibody reactivity against VLPs by approximately 60 and 35%, respectively, while MAbs against epitopes within aa 394 to 414 and 414 to 434 were unable to block patient serum reactivity. These results suggest that sequences spanning aa 394 to 457 of the capsid protein participate in the formation of strongly immunodominant epitopes on the surface of HEV particles which may be important in immunity to HEV infection.
Matrix metalloproteinases MMP‐2 and MMP‐9 in denervated muscle and injured nerve (1998)

Nerve crush or axotomy results in a transient or longterm denervation accompanied by remodelling in nerve, muscle and neuromuscular junctions. These changes include an increased turnover of several extracellular matrix molecules and proliferation of Schwann cells in injured nerves. Given the role of matrix degrading metalloproteinases MMP-2 and MMP-9 (gelatinases-type IV collagenases) in extracellular matrix remodelling, we investigated their regulation and activation in denervated muscles and injured nerves in mice. For this, immunofluorescence using MMP-2 and MMP-9 antibodies was carried concomitantly with gelatin zymography and quantification of gelatinase activity using [3H]-gelatin substrate. Results show that in normal mouse muscles MMP-2 and MMP-9 are localized at the neuromuscular junctions, in Schwann cells and the perineurium of the intramuscular nerves. In denervated mouse muscles, MMP-2 immunolabelling persists at the neuromuscular junctions but decreases in the nerves whereas MMP-9 immunolabelling persists at the neuromuscular junctions but is enhanced in degenerated intramuscular nerves. Denervated muscles did not show any significant change of gelatinolytic activity or expression pattern, while injured nerves exhibited a transient increase of MMP-9 and activation of MMP-2. In conclusion, this study demonstrates that MMP-2 and MMP-9 are expressed at mouse neuromuscular junctions and that their localization and expression pattern appear not to be modified by denervation. Their modulation in injured nerves suggests they are involved in axonal degeneration and regeneration.
Efficacy and Safety of Aripiprazole and Haloperidol Versus Placebo in Patients With Schizophrenia and Schizoaffective Disorder (2002)

Aripiprazole, effective against positive and negative symptoms, is a safe and well-tolerated potential treatment for schizophrenia and schizoaffective disorder.
Morphine Mimics the Cardioprotective Effect of Ischemic Preconditioning via a Glibenclamide-Sensitive Mechanism in the Rat Heart (1996)

Previous results from our laboratory have suggested that opioid receptors are involved in ischemic preconditioning (PC) in rat heart. Furthermore, other investigators have suggested that mu- and delta-opioid receptors mediate analgesia and hypoxic cerebral vasodilatation via opening of ATP-sensitive K+ (KATP) channels. Thus, the purpose of the present study was to test the hypothesis that activation of opioid receptors mimics the cardioprotective effect of ischemic PC and that this effect is produced by activation of KATP channels in the rat heart. Anesthetized open-chest Wistar rats were subjected to six different protocols. All groups were subjected to 30 minutes of occlusion and 2 hours of reperfusion. Ischemic PC was elicited by three 5-minute occlusion periods interspersed with 5 minutes of reperfusion. Similarly, morphine-induced PC was elicited by three 5-minute drug infusions (100 micrograms/kg i.v. ) interspersed with 5-minute drug-free periods before the prolonged 30-minute occlusion. Infarct size (IS) as a percentage of the area at risk (AAR) was determined by triphenyltetrazolium staining. Ischemic PC and morphine infusions resulted in similar reductions in IS/AAR from 56 +/- 5% to 11 +/- 3% and 12 +/- 5%, respectively (P < .05). Administration of glibenclamide (0.3 mg/kg i.v.), a KATP channel antagonist, or naloxone (3 mg/kg i.v.), a nonselective opioid receptor antagonist, both blocked the cardioprotective effects of morphine. These results indicate that opioid receptor stimulation results in a reduction in infarct size similar to that produced by ischemic PC. The effect of morphine is most likely mediated via an opioid receptor-KATP channel-linked mechanism in the rat heart, since glibenclamide abolished its protection.
Mounting evidence against the role of ICC in neurotransmission to smooth muscle in the gut (2009)

How nerves transmit their signals to regulate activity of smooth muscle is of fundamental importance to autonomic and enteric physiology, clinical medicine, and therapeutics. A traditional view of neurotransmission to smooth muscles has been that motor nerve varicosities release neurotransmitters that act on receptors on smooth muscles to cause their contraction or relaxation via electromechanical and pharmacomechanical signaling pathways in the smooth muscle. In recent years, an old hypothesis that certain interstitial cells of Cajal (ICC) may transduce neural signals to smooth muscle cells has been resurrected. This later hypothesis is based on indirect evidence of closer proximity and presence of synapses between the nerve varicosities and ICC, gap junctions between ICC and smooth muscles, and presence of receptors and signaling pathways for the neurotransmitters and ICC. This indirect evidence is at best circumstantial. The direct evidence is based on the reports of loss of neurotransmission in mutant animals lacking ICC due to c-Kit receptor deficiency. However, a critical analysis of the recent data show that animals lacking ICC have normal cholinergic and purinergic neurotransmission and tachykinergic neurotransmission is actually increased. The status of nitrergic neurotransmission in c-Kit deficient animals has been controversial. However, reports suggest that 1) nitrergic neurotransmission in the internal anal sphincter does not require ICC and 2) the in vivo phenotype of ICC deficiency does not resemble nNOS deficiency. 3) The most recent report, in this issue of the Journal, concludes that impaired nitrergic neurotransmission may be due to smooth muscle defects associated with c-Kit receptor deficiency.
Neutrophil activation through high-affinity Fc gamma receptor using a monomeric antibody with unique properties. (1991)

The high-affinity, type I Ig Fc receptor (Fc gamma RI) for human IgG1, human IgG3, murine IgG2a, and murine IgG3 is highly expressed on monocytes, neutrophils (PMN) in certain disease states, and phagocytes treated with interferon-gamma (IFN-gamma). We studied the activation of the human PMN oxidative burst and stimulated fluid pinocytosis induced by three monoclonal antibodies (MoAbs) directed against Fc gamma RI (CD64) to study the role of this receptor in Fc-mediated cellular activation. All three MoAbs were capable of triggering PMN activation from IFN-gamma-treated PMN when cross-linked with goat antimurine Ig reagents. However, MoAb 197 alone demonstrated a concentration-dependent activation of the oxidative burst without the use of a second cross-linking antibody. The oxidative burst and stimulated fluid pinocytosis responses induced by monomeric MoAb 197 could be elicited only after the IFN-gamma induction of approximately 8,000 Fc gamma RI receptor equivalents and did not occur in freshly isolated or control-cultured PMN. Competitive blocking of Fc binding of MoAb 197 by human IgG or purified Fc fragments inhibited cellular activation. We believe the ability of MoAb 197 to activate these oxidative burst and fluid pinocytic responses was because of its murine IgG2a subclass, which allowed it to function as a trivalent anti-Fc gamma RI antibody binding through the combination of its two FAB regions and the Fc domain. This study demonstrates that the cross-linking of CD64 can activate PMN oxidative and endocytic responses and supports a role for Fc gamma RI in the human neutrophil inflammatory response.
ANNIVERSARY ARTICLE: Option Pricing: Valuation Models and Applications (2004)

This paper surveys the literature on option pricing from its origins to the present. An extensive review of valuation methods for European- and American-style claims is provided. Applications to complex securities and numerical methods are surveyed. Emphasis is placed on recent trends and developments in methodology and modeling.
Stability of the Regulatory T Cell Lineage in Vivo (2010)

Tissue maintenance and homeostasis can be achieved through the replacement of dying cells by differentiating precursors or self-renewal of terminally differentiated cells or relies heavily on cellular longevity in poorly regenerating tissues. Regulatory T cells (T(reg) cells) represent an actively dividing cell population with critical function in suppression of lethal immune-mediated inflammation. The plasticity of T(reg) cells has been actively debated because it could factor importantly in protective immunity or autoimmunity. By using inducible labeling and tracking of T(reg) cell fate in vivo, or transfers of highly purified T(reg) cells, we have demonstrated notable stability of this cell population under physiologic and inflammatory conditions. Our results suggest that self-renewal of mature T(reg) cells serves as a major mechanism of maintenance of the T(reg) cell lineage in adult mice.
The role of cytokines in radiation oncology. (1993)

Cytokine induction following ionizing radiation exposure occurs through transcriptional activation in specific proteins studied to date. This process can be blocked by inhibition of radiation-induced signaling pathways, which may potentially modify certain deleterious effects of radiotherapy, e.g., effects related to production of TNF or TGF-beta. bFGF is another radiation-inducible protein that may participate in repair and protection of irradiated endothelial cells following a complex interaction with cellular receptors. The cytokines such as IL-6, TNF, and IL-1 may be useful to protect hematopoietic cells from radiation, while TNF may enhance the killing of tumor cells. Our understanding of cytokine/radiation interactions is only beginning to be understood, but knowledge of the biology of these interactions may prove clinically useful.
Small-fragment genomic libraries for the display of putative epitopes from clinically significant pathogens (2003)

Taking advantage of whole genome sequences of bacterial pathogens in many thriving diseases with global impact, we developed a comprehensive screening procedure for the identification of putative vaccine candidate antigens. Importantly, this procedure relies on highly representative small-fragment genomic libraries that are expressed to display frame-selected epitope-size peptides on a bacterial cell surface and to interact directly with carefully selected disease-relevant high-titer sera. Here we describe the generation of small-fragment genomic libraries of Gram-positive and Gram-negative clinically significant pathogens, including Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae, Enterococcus faecalis, Helicobacter pylori, Chlamydia pneumoniae, the enterotoxigenic Escherichia coli, and Campylobacter jejuni. Large-scale sequencing revealed that the libraries, which provide an average of 20-fold coverage, were random and, as demonstrated with two S. aureus libraries, highly representative. Consistent with the comprehensive nature of this approach is the identification of epitopes that reside in both annotated and putatively novel open reading frames. The use of these libraries therefore allows for the rapid and direct identification of immunogenic epitopes with no apparent bias or difficulty that often associate with conventional expression methods.
T Cell-Activating Mesenchymal Stem Cells as a Biotherapeutic for HCC (2017)

The outcome for advanced stage hepatocellular carcinoma (HCC) remains poor, highlighting the need for novel therapies. Genetically modified mesenchymal stem cells (MSCs) are actively being explored as cancer therapeutics due to their inherent ability to migrate to tumor sites. We reasoned that MSCs can be genetically modified to redirect T cells to Glypican-3 (GPC3)<sup>+</sup> HCC, and genetically modified these with viral vectors encoding a GPC3/CD3 bispecific T cell engager (GPC3-ENG), a bispecifc T cell engager specific for an irrelevant antigen (EGFRvIII), and/or costimulatory molecules (CD80 and 41BBL). Coculture of GPC3<sup>+</sup> cells, GPC3-ENG MSCs, and T cells resulted in T cell activation, as judged by interferon γ (IFNγ) production and killing of tumor cells by T cells. Modification of GPC3-ENG MSCs with CD80 and 41BBL was required for antigen-dependent interleukin-2 (IL-2) production by T cells and resulted in faster tumor cell killing by redirected T cells. In vivo, GPC3-ENG MSCs ± costimulatory molecules had antitumor activity in the HUH7 HCC xenograft model, resulting in a survival advantage. In conclusion, MSCs genetically modified to express GPC3-ENG ± costimulatory molecules redirect T cells to GPC3<sup>+</sup> tumor cells and have potent antitumor activity. Thus, further preclinical exploration of our modified approach to GPC3-targeted immunotherapy for HCC is warranted.
Wavelength multiplexing in single-mode fiber couplers (1983)

Theoretical and experimental studies of wavelength-division multiplexing in a single-mode fiber optic coupler fabricated by mechanical polishing are reported. The variable spacing geometry of the device allows fine tuning of the center wavelength of operation. Wavelength selectivities ranging from 200 to 35 nm have been experimentally demonstrated, with cross talk ranging from 50 to 10 dB. Selectivity control is simply achieved by proper choice of the interaction length of the coupler. The dependence of the multiplexer behavior on all relevant parameters is investigated and found to satisfy predicted results.