gebhart/patrepeval huggingface dataset:
Interaction of Meloidogyne incognita and Water Stress in Two Cotton Cultivars. (1991)

A series of controlled-environment experiments were conducted to elucidate the effects of Meloidogyne incognita on host physiology and plant-water relations of two cotton (Gossypium hirsutum) cultivars that differed in their susceptibility to nematode infection. Inoculation of M. incognita-resistant cultivar Auburn 634 did not affect growth, stomatal resistance, or components of plant-water potential relative to uninoculated controls. However, nematode infection of the susceptible cultivar Stoneville 506 greatly suppressed water flow through intact roots. This inhibition exceeded 28% on a root-length basis and was similar to that observed as a consequence of severe water stress in a high evaporative demand environment. Nematodes did not affect the components of leaf water potential, stomatal resistance, transpiration, or leaf temperature. However, these factors were affected by the interaction of M. incognita and water stress. Our results indicate that M. incognita infection may alter host-plant water balance and may be a significant factor in early-season stress on cotton seedlings.
Suspended microchannel resonators for biomolecular detection (2003)

We present a resonant mass sensor for specific biomolecular detection in a subnanoliter fluid volume. The sensing principle is based on measuring shifts in resonance frequency of a suspended microfluidic channel upon accumulation of molecules on the inside walls of the device. Confining the fluid to the inside of a hollow cantilever enables direct integration with conventional microfluidic systems, significantly increases sensitivity by eliminating high damping and viscous drag, and allows the resonator to be actuated by electrostatic forces. Fluid density measurements reveal a mass resolution of 10−17 g/μm2 in a 4 mHz–4 Hz bandwidth. To demonstrate biomolecular detection, we present real-time measurements of the specific binding between avidin and biotinylated bovine serum albumin. Based on these measurements, we expect that changes in surface mass loading on the order of 10−19 g/μm2 can be detected in an optimized system.
Efficient generation of large-scale genome-modified mice using gRNA and CAS9 endonuclease (2013)

The generation of genome-modified animals is a powerful approach to analyze gene functions. The CAS9/guide RNA (gRNA) system is expected to become widely used for the efficient generation of genome-modified animals, but detailed studies on optimum conditions and availability are limited. In the present study, we attempted to generate large-scale genome-modified mice with an optimized CAS9/gRNA system, and confirmed the transmission of these mutations to the next generations. A comparison of different types of gRNA indicated that the target loci of almost all pups were modified successfully by the use of long-type gRNAs with CAS9. We showed that this system has much higher mutation efficiency and much lower off-target effect compared to zinc-finger nuclease. We propose that most of these off-target effects can be avoided by the careful control of CAS9 mRNA concentration and that the genome-modification efficiency depends rather on the gRNA concentration. Under optimized conditions, large-scale (~10 kb) genome-modified mice can be efficiently generated by modifying two loci on a single chromosome using two gRNAs at once in mouse zygotes. In addition, the normal transmission of these CAS9/gRNA-induced mutations to the next generation was confirmed. These results indicate that CAS9/gRNA system can become a highly effective tool for the generation of genome-modified animals.
Effective Hamiltonian models of the cross-resonance gate (2020)

Effective Hamiltonian methods are utilized to model the two-qubit cross-resonance gate for both the ideal two-qubit case and when higher levels are included. Analytic expressions are obtained in the qubit case and the higher-level model is solved both perturbatively and numerically, with the solutions agreeing well in the weak-drive limit. The methods are applied to parameters from recent experiments and, accounting for classical cross-talk effects, results in good agreement between theory and experimental results.
Canola (<i>Brassica napus</i> L.) (2006)

High-frequency Agrobacterium tumefaciens-mediated transformation can be obtained in canola by optimizing the preconditioning time of the explant and cocultivation time with A. tumefaciens. A preconditioning time of 72 h and cocultivation of 48 h synergistically increase the transformation efficiency to 25%. In addition, the recovery of transgenic plants can be facilitated by overcoming hyperhydration, which increases the rooting frequency to 100%.
Depletion of macrophages reduces axonal degeneration and hyperalgesia following nerve injury (2000)

Inflammatory mechanisms are believed to play an important role in hyperalgesia resulting from nerve injury. Hyperalgesia following nerve injury is temporally linked with Wallerian degeneration and macrophage recruitment, and is reduced in WLD mice, in which Wallerian degeneration is delayed. We sought more direct evidence that macrophages contribute to hyperalgesia and Wallerian degeneration by depleting macrophages with liposomes loaded with dichloromethylene diphosphonate (clodronate, Cl(2)MDP). Rats were subjected to partial ligation of the sciatic nerve. Intravenous injection of liposome-encapsulated clodronate reduced the number of macrophages in the injured nerve, alleviated thermal hyperalgesia and protected both myelinated and unmyelinated fibres against degeneration. The results confirm the role of circulating monocytes/macrophages in the development of neuropathic hyperalgesia and Wallerian degeneration due to partial nerve injury. Macrophage depletion immediately after nerve injury could have some clinical potential in prevention of neuropathic pain.
Identification of the endothelial cell binding site for factor IX. (1996)

We previously demonstrated that the primary region of factor IX and IXa responsible for saturable specific binding to bovine aortic endothelial cells resides in residues 3-11 at the amino terminus of factor IX. We also demonstrated that mutations of lysine to alanine at residue 5, factor IX K5A, or valine to lysine at residue 10, factor IX V10K, resulted in a molecule unable to bind to endothelial cells. Moreover, a mutation with lysine to arginine at residue 5, factor IX K5R, resulted in a factor IX molecule with increased affinity for the endothelial cell binding site. In this paper we report that collagen IV is a strong candidate for the factor IX binding site on endothelial cells. Factor IX and factor IX K5R compete with 125I-labeled factor IX for binding to tetrameric collagen IV immobilized on microtiter plates, while factor X, factor VII, and factor IX K5A or V10K fail to compete. The Kd for wild-type factor IX binding to collagen IV in the presence of heparin was 6.8 +/- 2 nM, and the Kd for factor IX K5R was 1.1 +/- 0.2 nM, which agrees well with our previously published Kd values of 7.4 and 2.4 nM for binding of the same proteins to endothelial cells. Our working assumption is that we have identified the endothelial cell binding site and that it is collagen IV. Its physiological relevance remains to be determined.
Thermodynamic Characterization of Mutants of Human Fibroblast Growth Factor 1 with an Increased Physiological Half-Life (2000)

Human acidic fibroblast growth factor (FGF-1) is a potent mitogen and angiogenic factor, with reportedly poor thermal stability and a relatively short in vivo half-life. However, certain mutants of FGF-1 have been described that exhibit a significant increase in half-life in tissue culture-based assays. FGF-1 contains three cysteine residues, two of which are highly conserved and buried within the protein core. Mutant forms of FGF-1 that substitute a serine residue at these cysteine positions have been reported to increase the protein's half-life and specific activity as well as decrease the dependence upon heparin for full activity. However, the underlying physical basis for this increase in half-life has not been determined. Possible effects include stabilization of protein structure and elimination of sulfhydryl chemistry at these positions. Here we have used differential scanning calorimetry and isothermal equilibrium denaturation to characterize thermodynamic parameters of unfolding for individual, and combination, cysteine to serine mutations in human FGF-1. The results show that substitution by serine is destabilizing at each cysteine position in wild-type FGF-1. Thus, the increased half-life previously reported for these mutations does not correlate with thermal stability and is most likely due to elimination of sulfhydryl chemistry. The results also suggest a method by which protein half-life may be modulated by rational design.
Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening (2009)

Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs.
Spike Timing–Dependent Plasticity: A Hebbian Learning Rule (2008)

Spike timing-dependent plasticity (STDP) as a Hebbian synaptic learning rule has been demonstrated in various neural circuits over a wide spectrum of species, from insects to humans. The dependence of synaptic modification on the order of pre- and postsynaptic spiking within a critical window of tens of milliseconds has profound functional implications. Over the past decade, significant progress has been made in understanding the cellular mechanisms of STDP at both excitatory and inhibitory synapses and of the associated changes in neuronal excitability and synaptic integration. Beyond the basic asymmetric window, recent studies have also revealed several layers of complexity in STDP, including its dependence on dendritic location, the nonlinear integration of synaptic modification induced by complex spike trains, and the modulation of STDP by inhibitory and neuromodulatory inputs. Finally, the functional consequences of STDP have been examined directly in an increasing number of neural circuits in vivo.
Electroless Plating of Metals onto Carbon Nanotubes Activated by a Single-Step Activation Method (1999)

In this work, carbon nanotubes were activated with Pd−Sn catalytic nuclei via a single-step activation approach. These activated nanotubes were used as precursors for obtaining nickel- and palladium-decorated nanotubes via electroless plating. Activation of the nanotube surfaces promoted specific deposition of metal on the catalytic tube surfaces. As a result, carbon nanotubes densely coated with metal nanoparticles were obtained with reduced metal deposition in the reaction solution.
Risk-Sensitive Optimal Feedback Control for Haptic Assistance (2012)

While human behavior prediction can increase the capability of a robotic partner to generate anticipatory behavior during physical human robot interaction (pHRI), predictions in uncertain situations can lead to large disturbances for the human if they do not match the human intentions. In this paper we present a novel control concept in which the assistive control parameters are adapted to the uncertainty in the sense that a the robot takes a more or less active role depending on its confidence in the human behavior prediction. The approach is based on risk-sensitive optimal feedback control. The human behavior is modeled using probabilistic learning methods and any unexpected disturbance is considered as a source of noise. The proposed approach is validated in situations with different uncertainties, process noise and risk-sensitivities in a tow- Degree-of-Freedom virtual reality experiment.
Synthesis, cellular evaluation, and mechanism of action of piperlongumine analogs (2012)

Piperlongumine is a naturally occurring small molecule recently identified to be toxic selectively to cancer cells in vitro and in vivo. This compound was found to elevate cellular levels of reactive oxygen species (ROS) selectively in cancer cell lines. The synthesis of 80 piperlongumine analogs has revealed structural modifications that retain, enhance, and ablate key piperlongumine-associated effects on cells, including elevation of ROS, cancer cell death, and selectivity for cancer cells over nontransformed cell types. Structure/activity relationships suggest that the electrophilicity of the C2-C3 olefin is critical for the observed effects on cells. Furthermore, we show that analogs lacking a reactive C7-C8 olefin can elevate ROS to levels observed with piperlongumine but show markedly reduced cell death, suggesting that ROS-independent mechanisms, including cellular cross-linking events, may also contribute to piperlongumine's induction of apoptosis. In particular, we have identified irreversible protein glutathionylation as a process associated with cellular toxicity. We propose a mechanism of action for piperlongumine that may be relevant to other small molecules having two sites of reactivity, one with greater and the other with lesser electrophilicity.
Influenza A Viruses with Mutations in the M1 Helix Six Domain Display a Wide Variety of Morphological Phenotypes (2004)

Several functions required for the replication of influenza A viruses have been attributed to the viral matrix protein (M1), and a number of studies have focused on a region of the M1 protein designated "helix six." This region contains an exposed positively charged stretch of amino acids, including the motif 101-RKLKR-105, which has been identified as a nuclear localization signal, but several studies suggest that this domain is also involved in functions such as binding to the ribonucleoprotein genome segments (RNPs), membrane association, interaction with the viral nuclear export protein, and virus assembly. In order to define M1 functions in more detail, a series of mutants containing alanine substitutions in the helix six region were generated in A/WSN/33 virus. These were analyzed for RNP-binding function, their capacity to incorporate into infectious viruses by using reverse genetics, the replication properties of rescued viruses, and the morphological phenotypes of the mutant virus particles. The most notable effect that was identified concerned single amino acid substitution mutants that caused significant alterations to the morphology of budded viruses. Whereas A/WSN/33 virus generally forms particles that are predominantly spherical, observations made by negative stain electron microscopy showed that several of the mutant virions, such as K95A, K98A, R101A, and K102A, display a wide range of shapes and sizes that varied in a temperature-dependent manner. The K102A mutant is particularly interesting in that it can form extended filamentous particles. These results support the proposition that the helix six domain is involved in the process of virus assembly.
Glucagon-Like Peptide 21 (2001)

Glucagon-like peptide 2 (GLP-2) is a 33 amino acid peptide-encoded carboxyterminal to the sequence of GLP-1 in the proglucagon gene. Both GLP-1 and GLP-2 are secreted from gut endocrine cells and promote nutrient absorption through distinct mechanisms of action. GLP-2 regulates gastric motility, gastric acid secretion, intestinal hexose transport, and increases the barrier function of the gut epithelium. GLP-2 significantly enhances the surface area of the mucosal epithelium via stimulation of crypt cell proliferation and inhibition of apoptosis in the enterocyte and crypt compartments. The cytoprotective and reparative effects of GLP-2 are evident in rodent models of experimental intestinal injury. GLP-2 reduces mortality and decreases mucosal injury, cytokine expression, and bacterial septicemia in the setting of small and large bowel inflammation. GLP-2 also enhances nutrient absorption and gut adaptation in rodents or humans with short bowel syndrome. The actions of GLP-2 are transduced by the GLP-2 receptor, a G protein-coupled receptor expressed in gut endocrine cells of the stomach, small bowel, and colon. Activation of GLP-2 receptor signaling in heterologous cells promotes resistance to apoptotic injury in vitro. The cytoprotective, reparative, and energy-retentive properties of GLP-2 suggests that GLP-2 may potentially be useful for the treatment of human disorders characterized by injury and/or dysfunction of the intestinal mucosal epithelium.
Channels active in the excitability of nerves and skeletal muscles across the neuromuscular junction: basic function and pathophysiology (2008)

Ion channels are essential for the basic physiological function of excitable cells such as nerve, skeletal, cardiac, and smooth muscle cells. Mutations in genes that encode ion channels have been identified to cause various diseases and disorders known as channelopathies. An understanding of how individual ion channels are involved in the activation of motoneurons and their corresponding muscle cells is essential for interpreting basic neurophysiology in nerves, the heart, and skeletal and smooth muscle. This review article is intended to clarify how channels work in nerves, neuromuscular junctions, and muscle function and what happens when these channels are defective. Highlighting the human diseases that result from defective ion channels is likely to be interesting to students in helping them choose to learn about channel physiology.
A two-step, two-signal model for the primary activation of precursor helper T cells (1999)

I present here a new model for the primary activation of precursor helper T cells. Observations demonstrate that the immune system learns not to respond to extrathymic, organ-specific self-antigens because of their early appearance in development. The immune system thus discriminates between peripheral self-antigens and foreign antigens and, when mature, usually makes an immune response against only the latter. Contemporary models for the activation and inactivation of T helper (Th) function do not account for such discrimination. The model proposed here is consistent with contemporary findings and incorporates a mechanism of peripheral self-nonself discrimination.
User interface design (2003)

This item is not the definitive copy. Please use the following citation when referencing this material: Dillon, A. (2003) User Interface Design. MacMillan Encyclopedia of Cognitive Science, Vol. 4, London:MacMillan, 453-458. Article definition: This article covers the basic issues that the field of cognitive science raises in the design and testing of new digital technologies for human use. Contents list: Introduction, Cognitive Science and design, The Basics of Human-Computer Interaction, Cognitive Design Guidelines: from psychophysics to semiotics, Beyond guidelines Cognitive theories and models in HCI, Developing user-centered design methods, Summary, Bibliography, Glossary
Functional characterization of human hepatocyte growth factor mutants obtained by deletion of structural domains (1992)

Human hepatocyte growth factor (hHGF) consists of characteristic structural domains. In this study, we prepared mutant proteins lacking each of these domains and examined their biological activities for stimulation of hepatocyte DNA synthesis, inhibition of Meth A cell growth, and induction of MDCK cell dissociation. We also examined their interactions with the c-met/HGF receptor by competition analysis and by analysis of levels of tyrosine phosphorylation. The mutant proteins lacking the N-terminal, the first kringle, or the second kringle domain were not biologically effective and could not compete with hHGF bound to the c-met/HGF receptor. The results indicate that these domains are necessary for the biological activities of hHGF mediated by binding to the c-met/HGF receptor. The mutant proteins lacking the third or fourth kringle domain moderately retained biological activities and the receptor binding. The relative levels of the tyrosine phosphorylation of the c-met/HGF receptor by these mutant proteins correlated well with the relative potencies of the biological activities when compared with that of the wild-type hHGF. The mutant protein lacking the light chain was not effective in the biological activities and tyrosine phosphorylation of the c-met/HGF receptor, but competed with hHGF bound to the c-met/HGF receptor. These results suggest that the heavy chain plays an important role in the interaction of hHGF with the c-met/HGF receptor and that the light chain is further required for the tyrosine phosphorylation of the c-met/HGF receptor.
Small Molecule Inhibitors of Wee1 Degradation and Mitotic Entry (2011)

The tyrosine kinase Wee1 is part of a key cellular sensing mechanism that signals completion of DNA replication, ensuring proper timing of entry into mitosis. Wee1 acts as an inhibitor of mitotic entry by phosphorylating cyclin-dependent kinase CDK1. Wee1 activity is mainly regulated at the protein level through its phosphorylation and subsequent degradation by the ubiquitin proteasome pathway. To facilitate identification of small molecules preventing Wee1 degradation, a homogeneous cell-based assay was developed using HeLa cells transiently transfected with a Wee1-luciferase fusion protein. To ensure ultra-high-throughput screening (uHTS) compatibility, the assay was scaled to a 1536-well plate format and cells were transfected in bulk and cryopreserved. This miniaturized homogeneous assay demonstrated robust performance, with a calculated Z′ factor of 0.65 +/− 0.05. The assay was screened against a publicly available library of approximately 218,000 compounds to identify Wee1 stabilizers. Nonselective, cytotoxic, and promiscuous compounds were rapidly triaged through the use of a similarly formatted counterscreen that measured stabilization of an N-cyclin B-luciferase fusion protein, as well as execution of viability assessment in the parental HeLa cell line. This screening campaign led to the discovery of 4 unrelated cell-permeable small molecules that showed selective Wee1-luciferase stabilization with micromolar potency. One of these compounds, SID-4243143 (ML118), was shown to inhibit cell cycle progression, underscoring the importance of Wee1 degradation to the cell cycle. This probe was found to be inactive in a whole-cell assay against its anti-target, cyclin B. In contrast, the current state-of-the-art probe, MG132, inhibits degradation of both Wee1 and cyclin B in the same assays. More importantly, flow-cytometry assays confirm that the probe is able to induce an increase in the G2/M population after cell treatment, without increasing the sub-G1 population, suggesting the probe is not toxic to cells. These results suggest that this uHTS approach is suitable for identifying selective chemical probes that prevent Wee1 degradation and generally applicable to discovering inhibitors of the ubiquitin proteasome pathway.