gebhart/patrepeval huggingface dataset:
Molecular Evidence on the Origin and Evolution of Glutinous Rice (2002)

Glutinous rice is a major type of cultivated rice with long-standing cultural importance in Asia. A mutation in an intron 1 splice donor site of the Waxy gene is responsible for the change in endosperm starch leading to the glutinous phenotype. Here we examine an allele genealogy of the Waxy locus to trace the evolutionary and geographical origins of this phenotype. On the basis of 105 glutinous and nonglutinous landraces from across Asia, we find evidence that the splice donor mutation has a single evolutionary origin and that it probably arose in Southeast Asia. Nucleotide diversity measures indicate that the origin of glutinous rice is associated with reduced genetic variation characteristic of selection at the Waxy locus; comparison with an unlinked locus, RGRC2, confirms that this pattern is specific to Waxy. In addition, we find that many nonglutinous varieties in Northeast Asia also carry the splice donor site mutation, suggesting that partial suppression of this mutation may have played an important role in the development of Northeast Asian nonglutinous rice. This study demonstrates the utility of phylogeographic approaches for understanding trait diversification in crops, and it contributes to growing evidence on the importance of modifier loci in the evolution of domestication traits.
Use of a protein-blotting procedure and a specific DNA probe to identify nuclear proteins that recognize the promoter region of the transferrin receptor gene. (1985)

We describe a procedure for detecting high-affinity, sequence-specific DNA-binding proteins from crude nuclear extracts. The technique utilizes electrophoretic transfer of NaDodSO4/PAGE-fractionated proteins onto nitrocellulose filters. Incubation of the filters with a 5% (wt/vol) solution of nonfat dry milk effectively blocks nonspecific and low-affinity DNA-binding sites. Incubation of the blocked filters with radiolabeled DNA under optimal binding conditions and subsequent autoradiography reveals high-affinity DNA-protein interactions. We have used this procedure to identify proteins that bind specifically to the promoter region of the transferrin receptor gene.
Analysis of a thin AlN interfacial layer in Ti/Al and Pd/Al ohmic contacts to n-type GaN (1997)

Using high resolution transmission electron microscopy, a thin pseudomorphic AlN layer (2–3 nm) has been observed at the metal/GaN interfaces of Ti/Al (35/115 nm) and Pd/Al (25/125 nm) ohmic contacts to n-type GaN annealed in Ar at 600 °C for 15 and 30 s, respectively. The interfacial layer has a c-plane (002) lattice spacing of 2.48±.03 Å and an a-plane (100) spacing matching that of GaN (2.76 Å), and the identification of this layer as AlN is consistent with chemical analysis by energy dispersive x-ray spectroscopy. The formation of this interfacial AlN layer coincides with the onset of ohmic behavior in Ti/Al and Pd/Al contacts annealed at 600 °C and may be the cause.
Prereplicative complexes of components of DNA polymerase III holoenzyme of Escherichia coli. (1992)

Stepwise reconstitution of the subunits of DNA polymerase III holoenzyme of Escherichia coli offers insights into the organization and function of this multisubunit assembly. A highly processive, holoenzyme-like activity can be generated when the gamma complex, in the presence of ATP and a primed template, activates the beta subunit to form a preinitiation complex, and this is then followed by addition of the core polymerase. Further analysis of early replicative complexes has now revealed: 1) that the gamma complex can stably bind a single-stranded DNA binding protein (SSB)-coated template, 2) that neither SSB coating of the template nor a proper primer terminus is required to form the preinitiation complex, and 3) that the gamma complex stabilizes the preinitiation complex in the presence of ATP and destabilizes it in the presence of adenosine 5'-O-(thiotriphosphate). Based on these findings, a sequence of stages can be formulated for an activation of the beta subunit that enables it to bind the template-primer and thereby interact with the core to create a processive polymerase.
Novel DNA-directed alkylating agents consisting of naphthalimide, nitrogen mustard and lexitropsin moieties: synthesis, DNA sequence specificity and biological evaluation. (1996)

Novel DNA-directed alkylating agents comprising naphthalimide, nitrogen mustard and lexitropsin moieties have been designed, synthesized and characterized. Their properties have been evaluated with respect to DNA binding ability, sequence preference, influence of flanking sequences on alkylation efficiency and cytotoxic potency against KB human nasopharangeal tumour cells. The results indicate that, in contrast to distamycin and bis-benzimidazole-bearing nitrogen mustard moieties where DNA alkylation is directed to adenine N3 sites in the minor groove, the naphthalimide nitrogen mustards alkylate DNA at accessible guanine N7 sites within the major groove. Structural factors that may affect cytotoxic efficacy are discussed.
Realistic phase distributions derived from the Wigner function (1993)

The authors present the radius integrated Wigner function for a general pure state and discuss the coefficients of the different Fourier components. A fast converging expansion of these coefficients is given and its usefulness is shown for coherent light. Remarkable and measurable differences to the Pegg-Barnett formalism appear for weakly excited coherent states while for large excitations both dispersions agree in their leading terms. Large deviations are expected for specially designed two-photon coherent states.
4.2: Integrated Scan Driver with Oxide TFTs Using Floating Gate Method (2011)

Abstract An on‐glass integrated scan driver is proposed for oxide thin film transistors TFTs with negative threshold voltage. A coupling capacitor and a TFT for setting the initial voltage to the gate of a TFT were added to minimize the off‐state current. Simulated and measured results indicate that the proposed scan driver shows no ripple and fast rise time/fall time of scan outputs. Circuit operation was verified with a 14‐inch AMOLED panel.
Fast spheres, shadows, textures, transparencies, and imgage enhancements in pixel-planes (1985)

Pixel-planes is a logic-enhanced memory system for raster graphics and imaging. Although each pixel-memory is enhanced with a one-bit ALU, the system's real power comes from a tree of one-bit adders that can evaluate linear expressions Ax+By+C for every pixel (x,y) simultaneously, as fast as the ALUs and the memory circuits can accept the results. We and others have begun to develop a variety of algorithms that exploit this fast linear expression evaluation capability. In this paper we report some of those results. Illustrated in this paper is a sample image from a small working prototype of the Pixel-planes hardware and a variety of images from simulations of a full-scale system. Timing estimates indicate that 30,000 smooth shaded triangles can be generated per second, or 21,000 smooth-shaded and shadowed triangles can be generated per second, or over 25,000 shaded spheres can be generated per second. Image-enhancement by adaptive histogram equalization can be performed within 4 seconds on a 512x512 image.
Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8 (2009)

Dendritic cell (DC) responses to extracellular self-DNA and self-RNA are prevented by the endosomal seclusion of nucleic acid-recognizing Toll-like receptors (TLRs). In psoriasis, however, plasmacytoid DCs (pDCs) sense self-DNA that is transported to endosomal TLR9 upon forming a complex with the antimicrobial peptide LL37. Whether LL37 also interacts with extracellular self-RNA and how this may contribute to DC activation in psoriasis is not known. Here, we report that LL37 can bind self-RNA released by dying cells, protect it from extracellular degradation, and transport it into endosomal compartments of DCs. In pDC, self-RNA-LL37 complexes activate TLR7 and, like self-DNA-LL37 complexes, trigger the secretion of IFN-alpha without inducing maturation or the production of IL-6 and TNF-alpha. In contrast to self-DNA-LL37 complexes, self-RNA-LL37 complexes also trigger the activation of classical myeloid DCs (mDCs). This occurs through TLR8 and leads to the production of TNF-alpha and IL-6, and the differentiation of mDCs into mature DCs. We also found that self-RNA-LL37 complexes are present in psoriatic skin lesions and are associated with mature mDCs in vivo. Our results demonstrate that the cationic antimicrobial peptide LL37 converts self-RNA into a trigger of TLR7 and TLR8 in human DCs, and provide new insights into the mechanism that drives the auto-inflammatory responses in psoriasis.
Composition and lipid spatial distribution of HDL particles in subjects with low and high HDL-cholesterol (2010)

A low level of high density lipoprotein cholesterol (HDL-C) is a powerful risk factor for cardiovascular disease. However, despite the reported key role of apolipo-proteins, specifically, apoA-I, in HDL metabolism, lipid molecular composition of HDL particles in subjects with high and low HDL-C levels is currently unknown. Here lipidomics was used to study HDL derived from well-characterized high and low HDL-C subjects. Low HDL-C subjects had elevated triacylglycerols and diminished lysophosphatidylcholines and sphingomyelins. Using information about the lipid composition of HDL particles in these two groups, we reconstituted HDL particles in silico by performing large-scale molecular dynamics simulations. In addition to confirming the measured change in particle size, we found that the changes in lipid composition also induced specific spatial distributions of lipids within the HDL particles, including a higher amount of triacylglycerols at the surface of HDL particles in low HDL-C subjects. Our findings have important implications for understanding HDL metabolism and function. For the first time we demonstrate the power of combining molecular profiling of lipoproteins with dynamic modeling of lipoprotein structure.
Chemical synthesis and characterization of branched oligodeoxyribonucleotides (bDNA) for use as signal amplifiers in nucleic acid quantification assays (1997)

The divergent synthesis of bDNA structures is described. This new type of branched DNA contains one unique oligonucleotide, the primary sequence, covalently attached through a comb-like branching network to many identical copies of a different oligonucleotide, the secondary sequence. The bDNA comb molecules were assembled on a solid support using parameters optimized for bDNA synthesis. The chemistry was used to synthesize bDNA comb molecules containing 15 secondary sequences. The bDNA comb molecules were elaborated by enzymatic ligation into branched amplification multimers, large bDNA molecules (a total of 1068 nt) containing an average of 36 repeated DNA oligomer sequences, each capable of hybridizing specifically to an alkaline phosphatase-labeled oligonucleotide. The bDNA comb molecules were characterized by electrophoretic methods and by controlled cleavage at periodate-cleavable moieties incorporated during synthesis. The branched amplification multimers have been used as signal amplifiers in nucleic acid quantification assays for detection of viral infection. It is possible to detect as few as 50 molecules with bDNA technology.
Visualising student tracking data to support instructors in web-based distance education (2004)

This paper presents a novel approach of using web log data generated by course management systems (CMS) to help instructors become aware of what is happening in distance learning classes. Specifically, techniques from Information Visualization are used to graphically render complex, multidimensional student tracking data collected by CMS. A system, called CourseVis, illustrates the proposed approach. Graphical representations from the use of CourseVis to visualise data from a java on-line distance course ran with WebCT are presented. Findings from the evaluation of CourseVis are presented, and it is argued that CourseVis can help teachers become aware of some social, behavioural, and cognitive aspects related to distance learners. Using graphical representations of student tracking data, instructors can identify tendencies in their classes, or quickly discover individuals that need special attention.
Cloning, Isolation, and IgE-Binding Properties of <i>Helix aspersa</i> (Brown Garden Snail) Tropomyosin (2002)

Tropomyosin represents a minor allergen in snail extracts, but it is clearly involved in invertebrate cross-reactivity.
The Evolution of Obstruction Induced Overactive Bladder Symptoms Following Urethrolysis for Female Bladder Outlet Obstruction (2008)

Following urethrolysis overactive bladder symptoms may remain refractory in 50% or greater of patients, which has a negative impact on quality of life and the impression of improvement after surgery. Detrusor overactivity demonstrated preoperatively may be useful for predicting who may have persistent overactive bladder symptoms despite an effective urethrolysis procedure.
Interleukin-22 (IL-22) Activates the JAK/STAT, ERK, JNK, and p38 MAP Kinase Pathways in a Rat Hepatoma Cell Line (2002)

IL (interleukin)-22 is an IL-10-related cytokine; its main biological activity known thus far is the induction of acute phase reactants in liver and pancreas. IL-22 signals through a receptor that is composed of two chains from the class II cytokine receptor family: IL-22R (also called ZcytoR11/CRF2-9) and IL-10Rbeta (CRF2-4), which is also involved in IL-10 signaling. In this report, we analyzed the signal transduction pathways activated in response to IL-22 in a rat hepatoma cell line, H4IIE. We found that IL-22 induces activation of JAK1 and Tyk2 but not JAK2, as well as phosphorylation of STAT1, STAT3, and STAT5 on tyrosine residues, extending the similarities between IL-22 and IL-10. However our results unraveled some differences between IL-22 and IL-10 signaling. Using antibodies specific for the phosphorylated form of MEK1/2, ERK1/2, p90RSK, JNK, and p38 kinase, we showed that IL-22 activates the three major MAPK pathways. IL-22 also induced serine phosphorylation of STAT3 on Ser(727). This effect, which is not shared with IL-10, was only marginally affected by MEK1/2 inhibitors, indicating that other pathways might be involved. Finally, by overexpressing a STAT3 S727A mutant, we showed that serine phosphorylation is required to achieve maximum transactivation of a STAT responsive promoter upon IL-22 stimulation.
Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain (2016)

Adeno-associated viruses (AAV) are currently being evaluated in clinical trials for gene therapy of CNS disorders. However, host factors that influence the spread, clearance, and transduction efficiency of AAV vectors in the brain are not well understood. Recent studies have demonstrated that fluid flow mediated by aquaporin-4 (AQP4) channels located on astroglial end feet is essential for exchange of solutes between interstitial and cerebrospinal fluid. This phenomenon, which is essential for interstitial clearance of solutes from the CNS, has been termed glial-associated lymphatic transport or glymphatic transport. In the current study, we demonstrate that glymphatic transport profoundly affects various aspects of AAV gene transfer in the CNS. Altered localization of AQP4 in aged mouse brains correlated with significantly increased retention of AAV vectors in the parenchyma and reduced systemic leakage following ventricular administration. We observed a similar increase in AAV retention and transgene expression upon i.c.v. administration in AQP4<sup>-/-</sup> mice. Consistent with this observation, fluorophore-labeled AAV vectors showed markedly reduced flux from the ventricles of AQP4<sup>-/-</sup> mice compared with WT mice. These results were further corroborated by reduced AAV clearance from the AQP4-null brain, as demonstrated by reduced transgene expression and vector genome accumulation in systemic organs. We postulate that deregulation of glymphatic transport in aged and diseased brains could markedly affect the parenchymal spread, clearance, and gene transfer efficiency of AAV vectors. Assessment of biomarkers that report the kinetics of CSF flux in prospective gene therapy patients might inform variable treatment outcomes and guide future clinical trial design.
PD-1 Is a Regulator of NY-ESO-1-Specific CD8+ T Cell Expansion in Melanoma Patients (2009)

The programmed death 1 (PD-1) receptor is a negative regulator of activated T cells and is up-regulated on exhausted virus-specific CD8(+) T cells in chronically infected mice and humans. Programmed death ligand 1 (PD-L1) is expressed by multiple tumors, and its interaction with PD-1 resulted in tumor escape in experimental models. To investigate the role of PD-1 in impairing spontaneous tumor Ag-specific CD8(+) T cells in melanoma patients, we have examined the effect of PD-1 expression on ex vivo detectable CD8(+) T cells specific to the tumor Ag NY-ESO-1. In contrast to EBV, influenza, or Melan-A/MART-1-specific CD8(+) T cells, NY-ESO-1-specific CD8(+) T cells up-regulated PD-1 expression. PD-1 up-regulation on spontaneous NY-ESO-1-specific CD8(+) T cells occurs along with T cell activation and is not directly associated with an inability to produce cytokines. Importantly, blockade of the PD-1/PD-L1 pathway in combination with prolonged Ag stimulation with PD-L1(+) APCs or melanoma cells augmented the number of cytokine-producing, proliferating, and total NY-ESO-1-specific CD8(+) T cells. Collectively, our findings support the role of PD-1 as a regulator of NY-ESO-1-specific CD8(+) T cell expansion in the context of chronic Ag stimulation. They further support the use of PD-1/PD-L1 pathway blockade in cancer patients to partially restore NY-ESO-1-specific CD8(+) T cell numbers and functions, increasing the likelihood of tumor regression.
Cytokine Requirements for Acute and Basal Homeostatic Proliferation of Naive and Memory CD8+ T Cells (2002)

Both naive and memory T cells undergo antigen-independent proliferation after transfer into a T cell-depleted environment (acute homeostatic proliferation), whereas only memory T cells slowly divide in a full T cell compartment (basal proliferation). We show, first, that naive and memory CD8+ T cells have different cytokine requirements for acute homeostatic proliferation. Interleukin (IL)-7 receptor(R)alpha-mediated signals were obligatory for proliferation of naive T cells in lymphopenic hosts, whereas IL-15 did not influence their division. Memory T cells, on the other hand, could use either IL-7Ralpha- or IL-15-mediated signals for acute homeostatic proliferation: their proliferation was delayed when either IL-7Ralpha was blocked or IL-15 removed, but only when both signals were absent was proliferation ablated. Second, the cytokine requirements for basal and acute homeostatic proliferation of CD8+ memory T cells differ, as basal division of memory T cells was blocked completely in IL-15-deficient hosts. These data suggest a possible mechanism for the dearth of memory CD8+ T cells in IL-15- and IL-15Ralpha-deficient mice is their impaired basal proliferation. Our results show that naive and memory T lymphocytes differ in their cytokine dependence for acute homeostatic proliferation and that memory T lymphocytes have distinct requirements for proliferation in full versus empty compartments.
Cancer immunotherapy: co-stimulatory agonists and co-inhibitory antagonists (2009)

The generation and maintenance of immune responses are controlled by both co-stimulatory and co-inhibitory signalling through T cell co-receptors, many of which belong to the immunoglobulin-like superfamily or the tumour necrosis factor receptor superfamily. Agonistic or antagonistic monoclonal antibodies targeting these co-receptors have the potential to enhance immunity. Furthermore, their activity on the immunosuppressive regulatory T cell populations which are prevalent within many tumours provides an additional rationale for their use as anti-cancer therapies. This review summarizes the interactions between cancer and the immune system, highlighting the ways in which these new classes of immunostimulatory antibodies might enhance anti-tumour immunity and summarizing early clinical experience with their use.
Identification of inbred mouse strains harboring genetic modifiers of mammary tumor age of onset and metastatic progression (1998)

Metastasis is one of the most important and complex processes in human neoplastic disease. A large number of both positive and negative events must occur to permit a tumor cell to colonize a distant site successfully. To identify mouse strains that harbor dominant genetic modifiers of this process, a strain survey was initiated utilizing a transgenic mouse mammary tumor model that exhibits a high incidence of pulmonary metastases. The transgenic animal was bred to 27 different inbred strains of mice and scored for the metastatic organ tropism and metastatic density. Thirteen strains were identified that had a statistically significant reduction in the numbers of pulmonary metastases. In addition, 10 strains were identified that altered the kinetics of induction of the primary mammary tumor. These strains will likely provide useful model systems for the analysis of genetic interactions in the initiation and progression of mammary adenocarcinomas.
Enrichment of Hepatic Progenitor Cells From Adult Mouse Liver (2003)

Hepatic progenitor cells (HPCs) have been characterized in several drug-treated rodent models and in the fetal liver; however, their properties have not been fully clarified in the normal adult liver, presumably because of their relatively small population and the existence of mature hepatocytes. In an attempt to resolve this issue, we developed a new enrichment system for HPCs using their cell aggregate formation properties. Nonparenchymal cells (NPCs) derived from enzymatically digested liver cells in normal adult mouse liver were treated in a hypoxic 2-hour suspension culture under constant shaking. This procedure resulted in cell aggregate formation and almost complete elimination of mature hepatocytes. Cell aggregates were formed only in Ca(2+)-containing medium, suggesting cadherin-dependent cell-cell adhesion. In these cell aggregates, 95% consisted of vascular endothelial cells that expressed VE-cadherin. The remaining 5% consisted of rapidly proliferating, small epithelial cells that expressed alpha-fetoprotein (AFP), E-cadherin, and albumin but not cytokeratin 19 (CK19), alpha-smooth muscle actin, or VE-cadherin. These results are consistent with an immature hepatic cell phenotype. When these immature hepatic cells were cultured with 10(-7) mol/L dexamethasone and 1% dimethyl sulfoxide, the de novo expression of mature hepatocyte markers such as tryptophan-2,3-dioxygenase (TO) was induced concomitantly with the induction of morphologic characteristics such as mitochondria- and peroxisome-rich cytoplasm and bile canaliculi formation. In conclusion, our methodology allows the enrichment of immature hepatic cells from the normal adult mouse. These cells are capable of growth and maturation along the hepatocyte lineage, indicating that these cells are HPCs.