gebhart/patrepeval huggingface dataset:
Connectedness, regularity and the success of local search in evolutionary multi-objective optimization (2004)

Local search techniques have proved to be very efficient in evolutionary multi-objective optimization (MOO). However, the reasons behind the success of local search in MOO have not yet been well discussed. This paper attempts to investigate empirically the main factors that may have contributed significantly to the success of local search in MOO. It is found that for many widely used test problems, the Pareto optimal solutions are connected both in objective space and parameter space. Besides, the Pareto-optimal solutions often distribute so regularly in parameter space that they can be defined by piecewise linear functions. By constructing an approximate model using the solutions produced by an optimizer, the quality of the non-dominated solution set can be further improved. The evolutionary dynamic weighted aggregation (EDWA) method has been adopted as a local search technique in finding Pareto-optimal solutions. Its effectiveness for MOO is demonstrated on a number of two or three objective optimization problems.
Interaction of Osmotic Stress, Temperature, and Abscisic Acid in the Regulation of Gene Expression in Arabidopsis (1999)

The impact of simultaneous environmental stresses on plants and how they respond to combined stresses compared with single stresses is largely unclear. By using a transgene (RD29A-LUC) consisting of the firefly luciferase coding sequence (LUC) driven by the stress-responsive RD29A promoter, we investigated the interactive effects of temperature, osmotic stress, and the phytohormone abscisic acid (ABA) in the regulation of gene expression in Arabidopsis seedlings. Results indicated that both positive and negative interactions exist among the studied stress factors in regulating gene expression. At a normal growth temperature (22 degrees C), osmotic stress and ABA act synergistically to induce the transgene expression. Low temperature inhibits the response to osmotic stress or to combined treatment of osmotic stress and ABA, whereas low temperature and ABA treatments are additive in inducing transgene expression. Although high temperature alone does not activate the transgene, it significantly amplifies the effects of ABA and osmotic stress. The effect of multiple stresses in the regulation of RD29A-LUC expression in signal transduction mutants was also studied. The results are discussed in the context of cold and osmotic stress signal transduction pathways.
Structural Basis for the Autoinhibition and STI-571 Inhibition of c-Kit Tyrosine Kinase (2004)

The activity of the c-Kit receptor protein-tyrosine kinase is tightly regulated in normal cells, whereas deregulated c-Kit kinase activity is implicated in the pathogenesis of human cancers. The c-Kit juxtamembrane region is known to have an autoinhibitory function; however the precise mechanism by which c-Kit is maintained in an autoinhibited state is not known. We report the 1.9-A resolution crystal structure of native c-Kit kinase in an autoinhibited conformation and compare it with active c-Kit kinase. Autoinhibited c-Kit is stabilized by the juxtamembrane domain, which inserts into the kinase-active site and disrupts formation of the activated structure. A 1.6-A crystal structure of c-Kit in complex with STI-571 (Imatinib or Gleevec) demonstrates that inhibitor binding disrupts this natural mechanism for maintaining c-Kit in an autoinhibited state. Together, these results provide a structural basis for understanding c-Kit kinase autoinhibition and will facilitate the structure-guided design of specific inhibitors that target the activated and autoinhibited conformations of c-Kit kinase.
A second prepilin peptidase gene in Escherichia coli K‐12 (1998)

Escherichia coli K-12 strains grown at 37 degrees C or 42 degrees C, but not at 30 degrees C, process the precursors of the Neisseria gonorrhoeae type IV pilin PilE and the Klebsiella oxytoca type IV pseudopilin PulG in a manner reminiscent of the prepilin peptidase-dependent processing of these proteins that occurs in these bacteria. Processing of prePulG in Escherichia coli requires a glycine at position -1, as does processing by the cognate prepilin peptidase (PulO), and is unaffected by mutations that inactivate several non-specific proteases. These data suggested that E. coli K-12 has a functional prepilin peptidase, despite the fact that it does not itself appear to express either type IV pilin or pseudopilin genes under the conditions that allow prePilE and prePulG processing. The E. coli K-12 genome contains two genes encoding proteins with significant sequence similarity to prepilin peptidases: gspO at minute 74.5 and pppA (f310c) at minute 67 on the genetic map. We have previously obtained evidence that gspO encodes an active enzyme but is not transcribed. pppA was cloned and shown to code for a functional prepilin peptidase capable of processing typical prepilin peptidase substrates. Inactivation of pppA eliminated the endogenous, thermoinducible prepilin peptidase activity. PppA was able to replace PulO prepilin peptidase in a pullulanase secretion system reconstituted in E. coli when expressed from high-copy-number plasmids but not when present in a single chromosomal copy. The analysis of pppA-lacZ fusions indicated that pppA expression was very low and regulated by the growth temperature at the level of translation, in agreement with the observed temperature dependence of PppA activity. Polymerase chain reaction and Southern hybridization analyses revealed the presence of the pppA gene in 12 out of 15 E. coli isolates.
Exposing rats to a predator impairs spatial working memory in the radial arm water maze (1999)

This series of studies investigated the effects of predator exposure on working memory in rats trained on the radial arm water maze (RAWM). The RAWM is a modified Morris water maze that contains four or six swim paths (arms) radiating out of an open central area, with a hidden platform located at the end of one of the arms. The hidden platform was located in the same arm on each trial within a day and was in a different arm across days. Each day rats learned the location of the hidden platform during acquisition trials, and then the rats were removed from the maze for a 30-min delay period. During the delay period, the rats were placed either in their home cage (nonstress condition) or in close proximity to a cat (stress condition). At the end of the delay period, the rats were run on a retention trial, which tested their ability to remember which arm contained the platform that day. The first experiment confirmed that the RAWM is a hippocampal-dependent task. Rats with hippocampal damage were impaired at learning the location of the hidden platform in the easiest RAWM under control (non-stress) conditions. The next three experiments showed that stress had no effect on memory in the easiest RAWM, but stress did impair memory in more difficult versions of the RAWM. These findings indicate that the capacity for stress to impair memory is influenced not only by the brain memory system involved in solving the task (hippocampal versus nonhippocampal), but also by the difficulty of the task. This work should help to resolve some of the confusion in the literature regarding the heterogeneous effects of stress on hippocampal-dependent learning and memory.
Prediction of the Coding Sequences of Unidentified Human Genes. V. The Coding Sequences of 40 New Genes (KIAA0161-KIAA0200) Deduced by Analysis of cDNA Clones from Human Cell Line KG-1 (1996)

As part of our continuing efforts to accumulate information on the coding region of unidentified human genes, we newly determined the sequences of 40 cDNA clones of human cell line KG-1 which correspond to relatively long and nearly full-length transcripts, and predicted the coding sequences of the corresponding genes, named KIAA0161 to 0200. The average size of the cDNA clones analyzed was approximately 5.0 kb. A computer search of the sequences in public databases indicated that the sequences of 20 genes were unrelated to any reported genes, while the remaining 20 genes carried sequences which show some similarities to known genes. Among the genes in the latter category, KIAA0167 contained a Zn-finger motif with significant structural similarity to that of the yeast transcription factor GCS1, and KIAA0189 was classified into the RhoGAP gene family. Stretches of typical CAG (Gln) repeats, which were often correlated with genetic disorders, were found in KIAA0181 and KIAA0192. Another novel repeat composed of alternating Arg and Glu was identified in KIAA0182. Northern hybridization analysis demonstrated that 10 genes are expressed in a cell- or tissue-specific manner.
CXC Chemokine Receptor 4 Expression and Function in Human Astroglioma Cells (2001)

Chemokines constitute a superfamily of proteins that function as chemoattractants and activators of leukocytes. Astrocytes, the major glial cell type in the CNS, are a source of chemokines within the diseased brain. Specifically, we have shown that primary human astrocytes and human astroglioma cell lines produce the CXC chemokines IFN-gamma-inducible protein-10 and IL-8 and the CC chemokines monocyte chemoattractant protein-1 and RANTES in response to stimuli such as TNF-alpha, IL-1beta, and IFN-gamma. In this study, we investigated chemokine receptor expression and function on human astroglioma cells. Enhancement of CXC chemokine receptor 4 (CXCR4) mRNA expression was observed upon treatment with the cytokines TNF-alpha and IL-1beta. The peak of CXCR4 expression in response to TNF-alpha and IL-1beta was 8 and 4 h, respectively. CXCR4 protein expression was also enhanced upon treatment with TNF-alpha and IL-1beta (2- to 3-fold). To study the functional relevance of CXCR4 expression, stable astroglioma transfectants expressing high levels of CXCR4 were generated. Stimulation of cells with the ligand for CXCR4, stromal cell-derived factor-1alpha (SDF-1alpha), resulted in an elevation in intracellular Ca(2+) concentration and activation of the mitogen-activated protein kinase cascade, specifically, extracellular signal-regulated kinase 2 (ERK2) mitogen-activated protein kinase. Of most interest, SDF-1alpha treatment induced expression of the chemokines monocyte chemoattractant protein-1, IL-8, and IFN-gamma-inducible protein-10. SDF-1alpha-induced chemokine expression was abrogated upon inclusion of U0126, a pharmacological inhibitor of ERK1/2, indicating that the ERK signaling cascade is involved in this response. Collectively, these data suggest that CXCR4-mediated signaling pathways in astroglioma cells may be another mechanism for these cells to express chemokines involved in angiogenesis and inflammation.
Mutation of the miaA gene of Agrobacterium tumefaciens results in reduced vir gene expression (1992)

vir regulon expression in Agrobacterium tumefaciens involves both chromosome- and Ti-plasmid-encoded gene products. We have isolated and characterized a new chromosomal gene that when mutated results in a 2- to 10-fold reduction in the induced expression of vir genes by acetosyringone. This reduced expression occurs in AB minimal medium (pH 5.5) containing either sucrose or glucose and containing phosphate at high or low concentrations. The locus was cloned and used to complement A. tumefaciens strains harboring Tn5 insertions in the gene. Sequence analysis of this locus revealed an open reading frame with strong homology to the miaA locus of Escherichia coli and the mod5 locus of Saccharomyces cerevisiae. These genes encode tRNA: isopentenyltransferase enzymes responsible for the specific modification of the A-37 residue in UNN codon tRNA species. The function of the homologous gene in A. tumefaciens was proven by genetic complementation of E. coli miaA mutant strains. tRNA undermodification in A. tumefaciens miaA mutant strains may reduce vir gene expression by causing a reduced translation efficiency. A slight reduction in the virulence of these mutant Agrobacterium strains on red potato plants, but not on tobacco, tomato, kalanchoe, or sunflower plants, was observed.
Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression. (1995)

Treatment of human endothelial cells with cytokines such as interleukin-1, tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma induces the expression of specific leukocyte adhesion molecules on the endothelial cell surface. Interfering with either leukocyte adhesion or adhesion protein upregulation is an important therapeutic target as evidenced by the potent anti-inflammatory actions of neutralizing antibodies to these ligands in various animal models and in patients. In the present study we report that cotreatment of human endothelial cells with certain hydroxyflavones and flavanols blocks cytokine-induced ICAM-1, VCAM-1, and E-selectin expression on human endothelial cells. One of the most potent flavones, apigenin, exhibited a dose- and time-dependent, reversible effect on adhesion protein expression as well as inhibiting adhesion protein upregulation at the transcriptional level. Apigenin also inhibited IL-1 alpha-induced prostaglandin synthesis and TNF-alpha-induced IL-6 and IL-8 production, suggesting that the hydroxyflavones may act as general inhibitors of cytokine-induced gene expression. Although apigenin did not inhibit TNF-alpha-induced nuclear translocation of NF-kappa B(p50(NFKB1)/p65(RelA)) we found this flavonoid did inhibit TNF-alpha induced beta-galactosidase activity in SW480 cells stably transfected with a beta-galactosidase reporter construct driven by four NF-kappa B elements, suggesting an action on NF-kappa B transcriptional activation. Adhesion of leukocytes to cytokine-treated endothelial cells was blocked in endothelial cells cotreated with apigenin. Finally, apigenin demonstrated potent anti-inflammatory activity in carrageenan induced rat paw edema and delayed type hypersensitivity in the mouse. We conclude that flavonoids offer important therapeutic potential for the treatment of a variety of inflammatory diseases involving an increase in leukocyte adhesion and trafficking.
Apoptotic Cells Induced Signaling for Immune Homeostasis in Macrophages and Dendritic Cells (2017)

Inefficient and abnormal clearance of apoptotic cells (efferocytosis) contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs), and contributes to maintenance of peripheral tolerance. As many as 3 × 10<sup>8</sup> cells undergo apoptosis every hour in our bodies, and one of the primary "eat me" signals expressed by apoptotic cells is phosphatidylserine (PtdSer). Apoptotic cells themselves are major contributors to the "anti-inflammatory" nature of the engulfment process, some by secreting thrombospondin-1 (TSP-1) or adenosine monophosphate and possibly other immune modulating "calm-down" signals that interact with macrophages and DCs. Apoptotic cells also produce "find me" and "tolerate me" signals to attract and immune modulate macrophages and DCs that express specific receptors for some of these signals. Neither macrophages nor DCs are uniform, and each cell type may variably express membrane proteins that function as receptors for PtdSer or for opsonins like complement or opsonins that bind to PtdSer, such as protein S and growth arrest-specific 6. Macrophages and DCs also express scavenger receptors, CD36, and integrins that function <i>via</i> bridging molecules such as TSP-1 or milk fat globule-EGF factor 8 protein and that differentially engage in various multi-ligand interactions between apoptotic cells and phagocytes. In this review, we describe the anti-inflammatory and pro-homeostatic nature of apoptotic cell interaction with the immune system. We do not review some forms of immunogenic cell death. We summarize the known apoptotic cell signaling events in macrophages and DCs that are related to toll-like receptors, nuclear factor kappa B, inflammasome, the lipid-activated nuclear receptors, Tyro3, Axl, and Mertk receptors, as well as induction of signal transducer and activator of transcription 1 and suppressor of cytokine signaling that lead to immune system silencing and DC tolerance. These properties of apoptotic cells are the mechanisms that enable their successful use as therapeutic modalities in mice and humans in various autoimmune diseases, organ transplantation, graft-versus-host disease, and sepsis.
Blood-derived angioblasts accelerate blood-flow restoration in diabetic mice (2000)

Endothelial cell progenitors, angioblasts, have been detected in the peripheral blood of adult humans, mice, and rabbits. These cells have been shown to incorporate into the endothelium of newly forming blood vessels in pathological and nonpathological conditions. Here we investigated the possibility that the CD34-expressing leukocytes (CD34(+) cells) that appear to be enriched for angioblasts could be used to accelerate the rate of blood-flow restoration in nondiabetic and diabetic mice undergoing neovascularization due to hindlimb ischemia. CD34(+) cells did not accelerate the restoration of flow in nondiabetic mice, but dramatically increased it in diabetic mice. Furthermore, CD34(+) cells derived from type 1 diabetics produced fewer differentiated endothelial cells in culture than did their type 2 diabetic- or nondiabetic-derived counterparts. In vitro experiments suggest that hyperglycemia per se does not alter the ability of angioblasts to differentiate or of angioblast-derived endothelial cells to proliferate. In contrast, hyperinsulinemia may enhance angioblast differentiation but impair angioblast-derived endothelial cell survival or proliferation. Our findings suggest that CD34(+) cells may be a useful tool for therapeutic angiogenesis in diabetics.
Deficient cyclic adenosine 3',5'-monophosphate control in mutants of two genes of Neurospora crassa. (1981)

Strains of Neurospora crassa mutant in either of two genes, Crisp-1 (cr1) and Frost (fr), showed no increase of cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels when subjected to several treatments which produce large increases of cyclic AMP in wild-type Neurospora. Evidently, the previously reported deficiencies of adenylate cyclase in these mutants were sufficient to block the normal increases. This fact suggests that both mutants could be used to help determine which control phenomena involve cyclic AMP and to interrupt the control of established cyclic AMP-regulated functions. Earlier studies had suggested an interdependence of the cyclic AMP level and the electric potential difference across the plasma membrane of Neurospora. Present experiments, therefore, employed several strains with the cr1 mutation to test for possible roles of cyclic AMP in recovery and oscillatory behavior of the Neurospora membrane potential. The results showed all such phenomena to be normal in the adenylate cyclase-defective strains, which demonstrates that variations of cyclic AMP are not obligatorily involved in the apparent control processes. Evidence is also presented that the induction of both glucose transport system II and the alternative oxidase do not require elevated cyclic AMP levels.
Amorphous ices: experiments and numerical simulations (2006)

Polyamorphism, i.e. the presence of more than one amorphous state, was observed for the first time in amorphous ice or glassy water. In addition to LDA (low-density amorphous ice), a second amorphous state, HDA (high-density amorphous ice), was discovered ∼20 years ago. Since then, polyamorphism has been observed in many other substances, such as SiO2, GeO2, Si, and Ge. Five years ago, experimental results suggesting the existence of a third amorphous state, VHDA (very high-density amorphous ice), were reported, opening the possibility that more than two amorphous states could also be observed in other substances. A consistent phase diagram of glassy water does not yet exist. Such a phase diagram is necessary if one also wants to understand the anomalous behaviour of supercooled liquid water. Since the discovery of HDA, a large amount of work based on experiments and computer simulations has appeared. It is the purpose of this work to review such studies with special emphasis in comparing the experimental and simulation results. In particular, we review the recent studies concerning VHDA and its nature, and discuss the main open questions relating to the phase diagram of glassy water.
Glucocorticoid Resistance in Childhood Leukemia (1994)

Glucocorticoids (GC) are being used in the treatment of childhood leukemia for several decades, most successfully in newly diagnosed acute lymphoblastic leukemia (ALL). However, GC resistance is seen in 10-30% of untreated ALL patients, and is much more frequent in relapsed ALL and in acute nonlymphoblastic leukemia (ANLL). Sensitivity or resistance to GC can be measured using a cell culture drug resistance assay. For this purpose, we use the colorimetric methyl-thiazol-tetrazolium (MTT) assay. We have shown that GC resistance in childhood leukemia is related to clinical and cell biological features, and to the clinical outcome after multi-drug chemotherapy. These results are summarized in this review. In addition, we describe the apoptotic 'cell-lysis pathway' by which GC exert their antileukemic activity. This description provides a model to discuss the mechanisms of GC resistance, and to summarize the relevant literature. Possible levels of resistance relate to the diffusion of GC through the cell membrane, binding to the GC receptor (GCR), activation of the GC-GCR complex, translocation of the complex into the nucleus, binding to DNA, endonuclease-mediated DNA fragmentation, and DNA repair. A low number of GCR has been shown to be the cause of resistance in some children with ALL. However, GC resistance is likely to be caused at the post-receptor level in most leukemias. Unfortunately, there is still a lack of knowledge relating to the clinical relevance of mechanisms of GC resistance at the post-receptor level. Studies on the mechanisms of GC resistance other than those directly related to the GCR should be initiated, especially if patient material is used, as the results might indicate ways to circumvent or modulate GC resistance. A further increase in our knowledge regarding the relation between GC resistance and patient and cell biological features, the clinical relevance of GC resistance, and the mechanisms of GC resistance in leukemia patients, may contribute to further improvement in the results of GC therapy in leukemia.
Selective-area and lateral epitaxial overgrowth of III–N materials by metal organic chemical vapor deposition (1998)

We describe the characteristics of single-crystal GaN regions obtained by selective-area and subsequent lateral epitaxial overgrowth using metal organic chemical vapor deposition. Under certain deposition conditions, the surface kinetics of the metal organic chemical vapor deposition process results in lateral growth of single-crystal GaN over the masked region. The lateral-to-vertical relative growth rate depends upon the orientation of stripe openings, the ratio of the “open” stripe width to the “masked” stripe width, and the growth conditions (e.g., temperature and V/III ratio). The specific orientations of the growth facets on the sidewalls of the laterally growing stripes are also dependent upon the growth conditions. The cathodoluminescence intensity of the GaN films indicate that improved materials are grown over the oxide mask.