gebhart/patrepeval huggingface dataset:
Crystal Structures of Anaplastic Lymphoma Kinase in Complex with ATP Competitive Inhibitors (2010)

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase involved in the development of several human cancers and, as a result, is a recognized target for the development of small-molecule inhibitors for the treatment of ALK-positive malignancies. Here, we present the crystal structures of the unphosphorylated human ALK kinase domain in complex with the ATP competitive ligands PHA-E429 and NVP-TAE684. Analysis of these structures provides valuable information concerning the specific characteristics of the ALK active site as well as giving indications about how to obtain selective ALK inhibitors. In addition, the ALK-KD-PHA-E429 structure led to the identification of a potential regulatory mechanism involving a link made between a short helical segment immediately following the DFG motif and an N-terminal two-stranded beta-sheet. Finally, mapping of the activating mutations associated with neuroblastoma onto our structures may explain the roles these residues have in the activation process.
Cytologic transformation in cutaneous T cell lymphoma: a clinicopathologic entity associated with poor prognosis. (1987)

The clinical course of cutaneous T cell lymphoma (mycosis fungoides and Sezary syndrome) is generally indolent, but in occasional patients becomes fulminant. We found that biopsies from patients with accelerating disease can reveal cytologic transformation from previously observed small, convoluted lymphocytes to large cells that are similar to cells seen in large-cell lymphoma. The cerebriform nuclei characteristic of malignant T cells can only rarely be identified. Of 150 cutaneous T cell lymphoma patients we treated from 1976 to 1984, cytologic transformation was identified in 12 after review of peripheral blood smears and biopsies from skin, lymph nodes, and visceral sites. Patients who developed cytologic transformation were initially characterized by advanced stage (11 of 12), with lymph node effacement (seven of 11) and erythroderma (five of 12). The tumor cell DNA content after transformation was aneuploid (four of four), and the ability to form rosettes with sheep erythrocytes was retained in transformed cells (three of three). The median time from diagnosis of cutaneous T cell lymphoma to cytologic transformation was 21.5 months (range, 4 to 64), and the median survival from transformation was only 2 months (range, 0 to 19+). We conclude that cytologic transformation in cutaneous T cell lymphoma represents a distinct clinicopathologic entity, characterized by an aggressive clinical course.
Interaction of the DNA‐binding domain of Drosophila heat shock factor with its cognate DNA site: A thermodynamic analysis using analytical ultracentrifugation (1994)

Heat shock transcription factor (HSF) mediates the activation of heat shock genes by binding to its cognate sites with high affinity and specificity. The high-affinity binding of HSF is dependent on the formation of an HSF homotrimer, which interacts specifically with the heat shock response element (HSE), comprised of 3 inverted repeats of the 5-bp sequence NGAAN. In order to investigate the thermodynamic basis of the interaction between HSF and HSE, we have overexpressed and purified a polypeptide (dHSF(33-163)) encompassing only the DNA-binding domain of HSF from Drosophila and analyzed its binding to DNA by equilibrium analytical ultracentrifugation using a multiwavelength scan technique. We demonstrate that dHSF(33-163) can bind as a monomer with 1:1 stoichiometry to a synthetic 13-bp DNA containing a single NGAAN sequence. The values of the thermodynamic parameters obtained from the temperature dependence of the equilibrium binding constants indicate that the changes of free energy for the binding of dHSF(33-163) to the wild-type site and a mutant DNA site are predominantly characterized by substantial negative changes of enthalpy. Binding to the wild-type DNA is characterized by a significant positive change of entropy, whereas binding to the mutant DNA is distinguished by a negative change of entropy of comparable magnitude. The binding to the mutant DNA was also highly sensitive to increasing salt concentrations, indicating a dominance of ionic interactions. The sequence-specific, 1:1 binding of dHSF(33-163) to the NGAAN sequence provides a basis for the analysis of higher order interactions between HSF trimers and the HSE.
Basic Fibroblast Growth Factor Modulates the Aminophospholipid Translocase Activity Present in the Plasma Membrane of Bovine Aortic Endothelial Cells (1995)

Vascular endothelial cells form the inner nonthrombogenic lining of the large blood vessel. Through back-exchange and fluorescence recovery after photobleaching experiments and using the two fluorescent lipids 1-acyl-2-[6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino] hexanoyl]glycerophosphocholine and 1-acyl-2[6-N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino]hexanoyl]glycerophosphoethanolamine, we have recently shown that an energy-dependent and protein-dependent aminophospholipid translocase activity is present in the plasma membrane of cultured bovine aortic endothelial cells, which specifically transports phosphatidylethanolamine from the outer leaflet toward the inner leaflet of the membrane lipid bilayer. In the present study, using the same approach and 1-acyl-2-[6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]hexanoyl] glycerophosphoserine as the probe, it is shown that this conclusion is also valid for phosphatidylserine. Furthermore, evidence is presented indicating that this aminophospholipid translocase activity can be maintained, suppressed, and restored at will, depending on the conditions of cell incubation. Thus, the translocase activity is detected for cells maintained in their normal culture medium or in a serum-free incubation medium [Dulbecco's modified Eagle's medium (DMEM)] supplemented with the basic fibroblast growth factor, whereas inhibition is observed for cells exposed for at least 2 h to DMEM. The translocase activity is restored when these pretreated cells are further incubated at least for 1 h in the presence of serum or of basic fibroblast growth factor. In view of the importance of basic fibroblast growth factor as a mitogenic and differentiating agent for vascular endothelial cells, various growth factors were tested (acidic fibroblast growth factor, epidermal growth factor, platelet-derived growth factor, transforming growth factors alpha and beta, vascular endothelial growth factor, interferon gamma, tumor-necrosis factor, insulin, and interleukin 4). Only basic fibroblast growth factor was active in the maintenance and restoration of the translocase activity. With respect to the effects of serum, evidence is presented showing that high-density lipoproteins might play a role in the control of the translocase activity. However, the positive effects of basic fibroblast growth factor, serum and high-density lipoproteins on the translocase activity were suppressed when experiments were carried out in the presence of an anti-(basic fibroblast growth factor) IgG, thus indicating that in all cases, basic fibroblast growth factor was directly involved in the modulation of the aminophospholipid translocase activity present in the plasma membrane of bovine aortic endothelial cells.
Three High Mobility Group-like Sequences within a 48-Base Pair Enhancer of the Col2a1 Gene Are Required for Cartilage-specific Expression in Vivo (1998)

To understand the molecular mechanisms by which mesenchymal cells differentiate into chondrocytes, we have used the gene for an early and abundant marker of chondrocytes, the mouse pro-alpha1(II) collagen gene (Col2a1), to delineate a minimal sequence needed for chondrocyte-specific expression and to identify the DNA-binding proteins that mediate its activity. We show here that a 48-base pair (bp) Col2a1 intron 1 sequence specifically targets the activity of a heterologous promoter to chondrocytes in transgenic mice. Mutagenesis studies of this 48-bp element identified three separate sites (sites 1-3) that were essential for its chondrocyte-specific enhancer activity in both transgenic mice and transient transfections. Mutations in sites 1 and 2 also severely inhibited the chondrocyte-specific enhancer activity of a 468-bp Col2a1 intron 1 sequence in vivo. SOX9, an SRY-related high mobility group (HMG) domain transcription factor, was previously shown to bind site 3, to bend the 48-bp DNA at this site, and to strongly activate this 48-bp enhancer as well as larger Col2a1 enhancer elements. All three sites correspond to imperfect binding sites for HMG domain proteins and appear to be involved in the formation of a large chondrocyte-specific complex between the 48-bp element, Sox9, and other protein(s). Indeed, mutations in each of the three HMG-like sites of the 48-bp element, which abolished chondrocyte-specific expression of reporter genes in transgenic mice and in transiently transfected cells, inhibited formation of this complex. Overall our results suggest a model whereby both Sox9 and these other proteins bind to several HMG-like sites in the Col2a1 gene to cooperatively control its expression in cartilage.
Cloning of Murine Stat6 and Human Stat6, Stat Proteins That Are Tyrosine Phosphorylated in Responses to IL-4 and IL-3 but Are Not Required for Mitogenesis (1995)

By searching a database of expressed sequences, we identified a member of the signal transducers and activators of transcription (Stat) family of proteins. Human and murine full-length cDNA clones were obtained and sequenced. The sequence of the human cDNA was identical to the recently published sequence for interleukin-4 (IL-4)-Stat (J. Hou, U. Schindler, W.J. Henzel, T.C. Ho, M. Brasseur, and S. L. McKnight, Science 265:1701-1706, 1994), while the murine Stat6 amino acid and nucleotide sequences were 83 and 84% identical to the human sequences, respectively. Using Stat6-specific antiserum, we demonstrated that Stat6 is rapidly tyrosine phosphorylated following stimulation of appropriate cell lines with IL-4 or IL-3 but is not detectably phosphorylated following stimulation with IL-2, IL-12, or erythropoietin. In contrast, IL-2, IL-3, and erythropoietin induce the tyrosine phosphorylation of Stat5 while IL-12 uniquely induces the tyrosine phosphorylation of Stat4. Inducible tyrosine phosphorylation of Stat6 requires the membrane-distal region of the IL-4 receptor alpha chain. This region of the receptor is not required for cell growth, demonstrating that Stat6 tyrosine phosphorylation does not contribute to mitogenesis.
Excitatory Amino Acid Neurotransmission: NMDA Receptors and Hebb-Type Synaptic Plasticity (1988)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
NPR1 Differentially Interacts with Members of the TGA/OBF Family of Transcription Factors That Bind an Element of the PR-1 Gene Required for Induction by Salicylic Acid (2000)

NPR1 is a critical component of the salicylic acid (SA)-mediated signal transduction pathway leading to the induction of defense genes, such as the pathogenesis-related (PR)-1 gene, and enhanced disease resistance. Using a yeast two-hybrid screen, we identified several NPR1-interacting proteins (NIPs). Two of these NIPs are members of the TGA/OBF family of basic leucine zipper (bZIP) transcription factors; this family has been implicated in the activation of SA-responsive genes, including PR-1. Six TGA family members were tested and shown to differentially interact with NPR1: TGA2 and TGA3 showed strong affinity for NPR1; TGA5 and TGA6 exhibited weaker affinity; and TGA1 and TGA4 displayed little or no detectable interaction with NPR1, respectively. Interestingly, the amino-termini of these factors were found to decrease their stability in yeast and differentially affect their apparent affinity toward NPR1. The interacting regions on NPR1 and the TGA factors were also defined. Each of four point mutations in NPR1 that disrupt SA signaling in Arabidopsis completely blocked interaction of NPR1 with TGA2 and TGA3. TGA2 and TGA3 were also found to bind the SA-responsive element of the Arabidopsis PR-1 promoter. These results directly link NPR1 to SA-induced PR-1 expression through members of the TGA family of transcription factors.
SummaRuNNer: A Recurrent Neural Network based Sequence Model for Extractive Summarization of Documents (2016)

We present SummaRuNNer, a Recurrent Neural Network (RNN) based sequence model for extractive summarization of documents and show that it achieves performance better than or comparable to state-of-the-art. Our model has the additional advantage of being very interpretable, since it allows visualization of its predictions broken up by abstract features such as information content, salience and novelty. Another novel contribution of our work is abstractive training of our extractive model that can train on human generated reference summaries alone, eliminating the need for sentence-level extractive labels.
Common problems in wound care: overgranulation (1995)

Overgranulation in wounds causes a delay in wound healing and often produces an increase in wound exudate and is therefore difficult to dress. This article suggests non-traumatic methods of removal in order to preserve the granulation of tissue required for healing.
Voltage-Enhancement Mechanisms of an Organic Dye in High Open-Circuit Voltage Solid-State Dye-Sensitized Solar Cells (2011)

Sensitization of solid-state dye-sensitized solar cells (SSDSSCs) with a new, organic donor-π-acceptor dye with a large molar absorption coefficient led to an open-circuit voltage of over 1 V at AM1.5 solar irradiance (100 mW/cm(2)). Recombination of electrons in the TiO(2) film with the oxidized species in the hole-transfer material (HTM) was significantly slower with the organic dye than with a standard ruthenium complex dye. Density functional theory indicated that steric shielding of the electrons in the TiO(2) by the organic dye was important in reducing recombination. Preventing the loss of photoelectrons resulted in a significant voltage gain. There was no evidence that the organic dye contributed to the high voltage by shifting the band edges to more negative electrode potentials. Compared with an iodide-based liquid electrolyte, however, the more positive redox potential of the solid-state HTM used in the SSDSSCs favored higher voltages.
ICAM‐3 and E‐selectin endothelial cell expression differentiate two phases of angiogenesis in infantile hemangiomas (1999)

Cellular adhesion molecules are newly identified mediators of angiogenesis. Infantile hemangiomas, characterized in the early stages by a proliferation of poorly differentiated vessels followed in the late stages by a vascular differentiation and regression of the tumor, represent an interesting model to study angiogenesis. We studied by immunohistochemistry the distribution of HLA-DR and three adhesion molecules ICAM-3, E-selectin and VCAM-1 on endothelial cells in different stages of vessel differentiation in infantile hemangiomas. We found high levels of ICAM-3 expression on proliferating vessels, while its expression was low or undetectable on well differentiated vessels. A different set of E-selectin antibodies showed a more heterogenous pattern of distribution and VCAM-1 antigens were found in both proliferating and differentiated vessels. HLA-DR expression on endothelial cells was inversely correlated to the vascular differentiation. Our results are consistent with the hypothesis that ICAM-3 plays a role in the early stages of vessel formation. Our results also suggest that variation of E-selectin and HLA-DR expression may be related either to vessel differentiation or may reflect the acquisition of an activated endothelial cell status.
Fabrication technology for wafer through-hole interconnections and three-dimensional stacks of chips and wafers (2002)

This paper presents an approach to build electronic systems with very high chip count. Instead of packing the chips laterally as it is done in multichip-modules (MCMs), individual dies, blocks of dies and ultimately entire wafers are stacked on top of each other. Electrical interconnection is accomplished using plated through-hole contacts through the silicon substrate. Proper thermal management is obtained using dedicated heat distribution contacts, which can be fabricated by a judiciously designed mask layout and without additional processing effort. Thermally induced stress in the interconnections between the stacked layers is limited both by means of design and process variations.
IκB kinase (IKK)β, but not IKKα, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss (2005)

Transcription factor, nuclear factor kappaB (NF-kappaB), is required for osteoclast formation in vivo and mice lacking both of the NF-kappaB p50 and p52 proteins are osteopetrotic. Here we address the relative roles of the two catalytic subunits of the IkappaB kinase (IKK) complex that mediate NF-kappaB activation, IKKalpha and IKKbeta, in osteoclast formation and inflammation-induced bone loss. Our findings point out the importance of the IKKbeta subunit as a transducer of signals from receptor activator of NF-kappaB (RANK) to NF-kappaB. Although IKKalpha is required for RANK ligand-induced osteoclast formation in vitro, it is not needed in vivo. However, IKKbeta is required for osteoclastogenesis in vitro and in vivo. IKKbeta also protects osteoclasts and their progenitors from tumor necrosis factor alpha-induced apoptosis, and its loss in hematopoietic cells prevents inflammation-induced bone loss.
Intravitreal Anti–Vascular Endothelial Growth Factor Therapy and Retinal Nerve Fiber Layer Loss in Eyes With Age-Related Macular Degeneration: A Meta-Analysis (2016)

There was no association between anti-VEGF injections and RNFL thickness changes when all studies were examined together. However, when two low-biased, controlled clinical trials were separately examined, repeated anti-VEGF injection was associated with RNFL loss. Large-scale, prospective studies are needed to determine long-term effects of anti-VEGF treatments on the RNFL in AMD patients.
泰国和柬埔寨:“贸易市场”和内战之间 (1991)

1989年7月11日老挝人民民主共和国官方万象电台强烈谴责泰国政府企图用它的新经济政策“损害”老挝。万象电台指责说:“敌人(指泰国)未能用武力摧毁我们的国家,现在竟使用所谓的把战场变市场的新战略来进攻我们。”这里指的就是1988年8月初泰国总理差猜上任后不久提出的政策原则。差猜的这一政策是要他的政府设法把长期充满冲突的印支半岛变成“一个贸易市场”,即曼谷把扩大其经济关系摆在最优先地位的地区。
New Developments in Nucleation Theory and Their Impact on Natural Gas Separation (2007)

Abstract Conventional separators in the oil industry use a feed of oil and gas in two-phase multi-component equilibrium. Recently a new concept of separators has been introduced which can be fed with a single-phase gaseous mixture. The separator combines a quasi-isentropic expansion of the gas during which liquid droplets are formed by the nucleation process and a gas-liquid cyclonic separator. The performance predictions of such a separator depend critically on an adequate description of nucleation phenomena. For a large number of practical cases the Classical Nucleation Theory is very inaccurate. The recently proposed Mean-field Kinetic Nucleation Theory yields quantitatively accurate predictions of nucleation behavior of various microscopically diverse substances. An important advantage of non-equilibrium separation is the minimal use of chemicals and absence of regeneration systems, as opposed to conventional separation methods such as glycol contactors or silica gel towers.
Frequency agility MIMO-SAR imaging and anti-deception jamming performance (2014)

Imaging proceduce for frequency agility multiple-input multiple-output synthetic aperture radar (MIMO-SAR) in presence of deception jamming is proposed, where the radar, at each pulse repetition interval (PRI), emits a waveform by one antenna, and the transmitted baseband signals are modulated with step carrier frequencies in successive PRIs. System model and signal model of both target echo and jamming were analyzed. Imaging procedure flow of frequency agility MIMO-SAR was expounded, a signal recombination technique was presented, enables the MIMO-SAR to achieve high resolution imagery. Frequency agility MIMO-SAR imaging in deception jamming scenarios was simulated at the end. Experiment results are used to show the validity of the introduced concepts.
Laser Vascular Welding (1988)

Vascular tissue fusion by lasers is performed by directing a low energy beam at the apposed edges of the repair. The tissues are approximated with stay sutures or non-reflective instruments and laser energy is passed back-and-forth over the anastomotic site until fusion is achieved. Vessel welding is apparent to the trained eye, as is nonunion caused by inadequate energy delivery. Conversely, excessive energy delivery results in obvious tissue coagulation or vaporization. Fiberoptic laser transmission and hand-eye coordination are adequate for repair or anastomosis of vessels with diameters greater than 3 mm, whereas magnification and precise mechanical control of the laser beam are necessary for microanastomoses of smaller vessels. The laser power (watts, W), and the amount of energy and time required (energy fluence or power density) vary according to the type of laser and the size of the vessels. Although laser repairs can be fashioned in time intervals equal to or slightly longer than those required for suture repairs, the optimum wavelengths and laser parameters for different types of seals are not yet established.
Ribosomal synthesis of nonstandard peptidesThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Systems and Chemical Biology, and has undergone the Journal's usual peer review process. (2008)

It is well known that standard peptides, which comprise proteinogenic amino acids, can act as specific chemical probes to target proteins with high affinity. Despite this fact, a number of peptide drug leads have been abandoned because of their poor cell permeability and protease instability. On the other hand, nonstandard peptides isolated as natural products often exhibit remarkable pharmaco-behavior and stability in vivo. Although it is likely that numerous nonstandard therapeutic peptides capable of recognizing various targets could have been synthesized, enzymes for nonribosomal peptide syntheses are complex; therefore, it is difficult to engineer such modular enzymes to build nonstandard peptide libraries. Here we describe an emerging technology for the synthesis of nonstandard peptides that employs an integrated system of reconstituted cell-free translation and flexizymes. We summarize the historical background of this technology and discuss its current and future applications to the synthesis of nonstandard peptides and drug discovery.