gebhart/patrepeval huggingface dataset:
Transient enhanced diffusion of ion-implanted boron in Si during rapid thermal annealing (1988)

Transient enhanced diffusion of ion-implanted boron at a dose of 1014 cm−2 during rapid thermal annealing has been studied. The boron diffusion coefficient of the enhanced diffusion arising from implantation damage decreases with time t in the form of D0 exp(−t/τ), where D0 is the diffusion coefficient at t=0 and τ is the lifetime of the point defect causing the enhanced diffusion. The temperature dependence of D0 and τ is revealed, and the point defect causing the transient enhanced diffusion is shown to be a vacancy. It is shown that final profile broadening due to the enhanced diffusion is smaller for higher temperatures. Furthermore, it is found that both D0 and τ increase with an increase in implantation energy.
Increased Carotenoid Production by the Food Yeast Candida utilis through Metabolic Engineering of the Isoprenoid Pathway (1998)

The yeast Candida utilis does not possess an endogenous biochemical pathway for the synthesis of carotenoids. The central isoprenoid pathway concerned with the synthesis of prenyl lipids is present in C. utilis and active in the biosynthesis of ergosterol. In our previous study, we showed that the introduction of exogenous carotenoid genes, crtE, crtB, and crtI, responsible for the formation of lycopene from the precursor farnesyl pyrophosphate, results in the C. utilis strain that yields lycopene at 1.1 mg per g (dry weight) of cells (Y. Miura, K. Kondo, T. Saito, H. Shimada, P. D. Fraser, and N. Misawa, Appl. Environ. Microbiol. 64:1226-1229, 1998). Through metabolic engineering of the isoprenoid pathway, a sevenfold increase in the yield of lycopene has been achieved. The influential steps in the pathway that were manipulated were 3-hydroxy methylglutaryl coenzyme A (HMG-CoA) reductase, encoded by the HMG gene, and squalene synthase, encoded by the ERG9 gene. Strains overexpressing the C. utilis HMG-CoA reductase yielded lycopene at 2.1 mg/g (dry weight) of cells. Expression of the HMG-CoA catalytic domain alone gave 4.3 mg/g (dry weight) of cells; disruption of the ERG9 gene had no significant effect, but a combination of ERG9 gene disruption and the overexpression of the HMG catalytic domain yielded lycopene at 7.8 mg/g (dry weight) of cells. The findings of this study illustrate how modifications in related biochemical pathways can be utilized to enhance the production of commercially desirable compounds such as carotenoids.
Effects of Ingredients on Cigarette Smoke Composition and Biological Activity: A Literature Overview (2002)

Abstract This paper presents a literature review of published scientific studies of the effects of tobacco product ingredients and various experimental additives on cigarette smoke composition and its biological activity. The format of this work is that of an uncommented reference paper rather than a critical scientific review. Therefore, the mention of an ingredient in this survey does not imply that it is used by the tobacco industry or that it is covered by any existing national regulations. A broad range of scientific papers and patents on tobacco ingredients is included as well as studies on experimental ingredients. This review may provide public health officials as well as scientists in government agencies and in the tobacco industry with a helpful overview of published information on tobacco product ingredients, their transfer into mainstream cigarette smoke, pyrolysis products, and influence on the biological activity of mainstream cigarette smoke.
Striatal β-Amyloid Deposition in Parkinson Disease With Dementia (2008)

Dementia is common in Parkinson disease (PD), although its anatomic and pathologic substrates remain undefined. Recently, striatal abnormalities in Lewy body diseases have been described, but their clinical relevance is not clear. Thirty PD cases from the United Kingdom Parkinson's Disease Society Tissue Bank were grouped as demented (PDD; n = 16) and nondemented (PD; n = 14) based on a review of clinical records. The extent of alpha-synuclein, tau, and amyloid beta peptide (Abeta) deposition in the caudate nucleus, putamen, and nucleus accumbens was assessed. All cases showed severe dopaminergic striatal terminal denervation based on tyrosine hydroxylase immunohistochemistry. Alpha-synuclein and tau deposition in the striatum were rare in both groups, but the Abeta burden was significantly greater in the striatum of PD cases with dementia than present in the nondemented PD group. Striatal Abeta deposition was type-independent of Alzheimer disease changes in the cortex and was minimal in nondemented PD cases. We conclude that Abeta deposition in the striatum strongly correlates with dementia in PD.
Interventions for stimulus deprivation amblyopia (2006)

It is not possible to conclude how effective treatment for SDA is or which treatment regime produces the best results. There is a need for further study in this area.
Effects of Exogenous Insulin‐Like Growth Factor I on Insulin‐Like Growth Factor Binding Proteins in a Case of Growth Hormone Insensitivity (Laron‐Type) (1991)

The electrophoretic profiles of serum insulin-like growth factor binding proteins (IGFBPs) from an 18-year-old patient with growth hormone (GH) insensitivity were analysed by Western ligand blotting before and after administration of recombinant human insulin-like growth factor I (IGF-I). Under basal conditions, the profile was the same as that observed in all cases of GH deficiency or insensitivity, that is, low IGFBP-3 (seen as two bands of 41.5 and 38.5 kDa) and enhanced IGFBP-2 and, to a lesser extent, IGFBP-1. Subcutaneous injection of IGF-I, 40 micrograms/kg, provoked an increase in serum IGF-I levels to close to the lower limits of the normal range and a small increase in IGFBP-3, suggesting that IGF-I has a direct effect on the synthesis of this GH/IGF-I-dependent IGFBP. Moderate increases were also observed in IGFBP-2 and IGFBP-4. Repeated doses of IGF-I over 7 days had no further effect on these changes, which persisted for a few days after the last injection.
Closing the ring: Links between SMC proteins and chromosome partitioning, condensation, and supercoiling (2000)

A gratifying story is emerging on how  the complementary strands of the DNA double helix are unlinked and partitioned after replication with astonishing accuracy as finished chromosomes to daughter cells. There are three key conclusions: 

The paper by Sawitzke and Austin (1) ties together all three conclusions. Their work concerns the Muk (from the Japanese mukaku , meaning anucleate) protein complex of Escherichia coli , which was discovered and characterized by Hiraga and coworkers (2). Mutations in any of the three muk genes, mukB , mukE , and mukF , disrupt chromosome segregation such that many progeny have missing or incomplete chromosomes that have been guillotined by septation. What links this fate of muk − bacteria to our story is that their chromosomes are decondensed (3) and that MukB is the structural and functional analogue of the ubiquitous SMC family of proteins (4). These huge molecules form coiled-coil dimers that, along with associated proteins, are thought to bind DNA segments separated by as much as 1,000 A and then to contract the intervening DNA at the expense of ATP (5). Sawitzke and Austin show that the severity of the Muk phenotype can be controlled by changing the level of supercoiling in the cell. The harsh consequences of being Mukless are suppressed by just a modest increase in chromosomal supercoiling, and muk − cells are hypersensitive to gyrase inhibitors. The authors conclude that Muk and supercoiling cooperate in condensing DNA, which drives partitioning. These findings fit beautifully with those from biophysics to cell biology in a …
Epicardial velocity estimation using wavelets (2002)

A wavelet-based method is introduced to estimate the spatially and temporally local velocity of both activation and recovery wavefronts in epicardial potential distributions recorded by a sensor array. The method takes advantage of the space/time link inherent in wavefront propagation. It is tested on simulated idealized wavefronts and on recorded canine data.
Smart-antenna systems for mobile communication networks. Part 1. Overview and antenna design (2002)

This paper focuses on the interaction and integration of several critical components of a mobile communication network using smart-antenna systems. This wireless network is composed of communicating nodes that are mobile, and its topology is continuously changing. One of the central motivations for this work comes from the observed dependence of the overall network throughput on the design of the adaptive antenna system and its underlying signal processing algorithms. Part 1 of this two-part paper gives a brief overview of smart-antenna systems, including the different types of smart-antenna systems, and the reason for their having gained popularity. Moreover, details of typical antenna array designs suitable for the wireless communication devices are included in this part.
Individualized model of human thermoregulation for the simulation of heat stress response (2001)

A population-based dynamic model of human thermoregulation was expanded with control equations incorporating the individual person's characteristics (body surface area, mass, fat%, maximal O(2) uptake, acclimation). These affect both the passive (heat capacity, insulation) and active systems (sweating and skin blood flow function). Model parameters were estimated from literature data. Other data, collected for the study of individual differences (working at relative or absolute workloads in hot-dry [45 degrees C, 20% relative humidity (rh)], warm-humid [35 degrees C, 80% rh], and cool [21 degrees C, 50% rh] environments), were used for validation. The individualized model provides an improved prediction [mean core temperature error, -0.21 --> -0.07 degrees C (P < 0.001); mean squared error, 0.40 --> 0.16 degrees C, (P < 0.001)]. The magnitude of improvement varies substantially with the climate and work type. Relative to an empirical multiple-regression model derived from these specific data sets, the analytical simulation model has between 54 and 89% of its predictive power, except for the cool climate, in which this ratio is zero. In conclusion, individualization of the model allows improved prediction of heat strain, although a substantial error remains.
Identification of Bioactive Molecules by Adipogenesis Profiling of Organic Compounds (2003)

An important step in the postgenomic drug discovery is the construction of high quality chemical libraries that generate bioactive molecules at high rates. Here we report a cell-based approach to composing a focused library of biologically active compounds. A collection of bioactive non-cytotoxic chemicals was identified from a divergent library through the effects on the insulin-induced adipogenesis of 3T3-L1 cells, one of the most drastic and sensitive morphological alterations in cultured mammalian cells. The resulting focused library amply contained unique compounds with a broad range of pharmacological effects, including glucose-uptake enhancement, cytokine inhibition, osteogenesis stimulation, and selective suppression of cancer cells. Adipogenesis profiling of organic compounds generates a focused chemical library for multiple biological effects that are seemingly unrelated to adipogenesis, just as genetic screens with the morphology of fly eyes identify oncogenes and neurodegenerative genes.
Nature of the Antibody Combining Site (1987)

Despite the enormous progress of molecular biology in bringing understanding of the generation of antibody complementarity and diversity to the gene level, we do not yet have a comprehensive picture of which individual amino acid side chains are functionally important, e.g., involved in determining antibody complementarity either by contacting the antigenic determinant directly, or by playing a conformational role, or are neutral non-contacting residues, or are involved in idiotypic specificity, or may reduce ability of the determinant to enter the site.
A novel maxizyme vector targeting a bcr-abl fusion gene induced specific cell death in Philadelphia chromosome-positive acute lymphoblastic leukemia (2004)

Patients with Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) generally have a poor prognosis and would benefit from the development of new therapeutic approaches. We previously demonstrated that an allosterically controllable ribozyme, maxizyme (Mz), can induce apoptosis in chronic myelogenous leukemia (CML) cells. Ph(+) ALL cells harbor a bcrabl fusion gene (e1a2) encoding a 190-kDa fusion protein (p190) involved in disease pathogenesis. In this study, we have designed a Mz that specifically cleaves e1a2 mRNA and transduced this e1a2Mz into Ph(+) ALL cells using a third-generation lentiviral vector system. In 3 of 5 Ph(+) ALL cell lines, e1a2Mz transduction resulted in a significant decrease in viability and increased cell apoptosis. We observed a decrease in e1a2 mRNA in all Ph(+) ALL cells transduced with e1a2Mz, and the e1a2 mRNA level was higher in e1a2Mz-resistant cells than in e1a2Mz-sensitive cells. All samples of primary Ph(+) ALL cells tested showed e1a2Mz-induced growth inhibition and apoptosis. Importantly, e1a2Mz did not influence the colony formation of normal CD34(+) cord blood cells. These results indicate that e1a2Mz kills Ph(+) ALL cells specifically, suggesting that it may be used as a novel gene therapy strategy for Ph(+) ALL.
Role of cysteine residues in ribonuclease H from Escherichia coli. Site-directed mutagenesis and chemical modification (1990)

The role of the three cysteine residues at positions 13, 63 and 133 in Escherichia coli RNAase H, an enzyme that is sensitive to N-ethylmaleimide [Berkower, Leis & Hurwitz (1973) J. Biol. Chem. 248, 5914-5921], was examined by using both site-directed mutagenesis and chemical modification. Novel aspects that were found are as follows. First, none of the cysteine residues is required for activity. Secondly, chemical modification of either Cys-13 or Cys-133 with thiol-blocking reagents inactivates the enzyme, but that of Cys-63 does not. Thus the sensitivity of E. coli RNAase H to N-ethylmaleimide arises not from blocking of the thiol group but from steric hindrance by the modifying group incorporated at either Cys-13 or Cys-133.
Possible Mechanism of Irreversible Nerve Injury Caused by Local Anesthetics (2004)

These results show that all four local anesthetics form molecular aggregations in the same manner as dodecyltrimethylammonium chloride, a common surfactant. At osmotic pressures insufficient to affect the membrane, local anesthetics caused membrane disruption at the same concentrations at which molecular aggregation occurred. This shows that disruption of the model membrane results from the detergent nature of local anesthetics. Nerve membrane solubilization by highly concentrated local anesthetics may cause irreversible neural injury.
Biochemical and Microbial Changes during the Storage of Minimally Processed Cantaloupe (2000)

The effect of storage time on pH, titratable acidity, degrees Brix, organic acids, sugars, amino acids, and color of minimally processed cantaloupe melon (Cucumis melo L. var. reticulatus Naud. cv. Mission) was determined at 4 degrees C and 20 degrees C. Changes in most of the biochemical parameters with storage time were relatively slow at the lower temperature. At 20 degrees C, a 17% loss in soluble solids and a 2-fold increase in acidity occurred after 2 days. Organic acid content also increased considerably with time at this temperature as a result of the production of lactic acid. Oxalic, citric, malic, and succinic acids were the organic acids, and glucose, fructose, and sucrose were the sugars present in the freshly cut cantaloupe. Malic acid concentration decreased concurrently with lactic acid production indicating the possible involvement of anaerobic malo-lactic fermentation along with sugar utilization by lactic acid bacteria. The effect of storage on microbial growth was determined at 4, 10, and 20 degrees C. Gram-negative stained rods grew at a slower rate at 4 degrees C and 10 degrees C than the Gram-positive mesophilic bacteria that dominated microorganism growth at 20 degrees C. Eighteen amino acids were identified in fresh cantaloupe: aspartic acid, glutamic acid, asparagine, serine, glutamine, glycine, histidine, arginine, threonine, alanine, proline, tyrosine, valine, methionine, isoleucine, leucine, phenyl alanine, and lysine. The dominant amino acids were aspartic acid, glutamic acid, arginine, and alanine. Total amino acid content decreased rapidly at 20 degrees C, but only a slight decrease occurred at 4 degrees C after prolonged storage. Changes in lightness (L), chroma, and hue at both temperatures indicate the absence of browning reactions. The results indicate the potential use of lactic acid and lactic acid bacteria as quality control markers in minimally processed fruits.
Differential gene expression during capillary morphogenesis in 3D collagen matrices (2001)

We have performed a screening analysis of differential gene expression using a defined in vitro model of human capillary tube formation. Gene array, differential display and cDNA library screening were used to identify both known and novel differentially expressed genes. Major findings include: the upregulation and functional importance of genes associated with basement membrane matrix assembly; the upregulation of growth factors, transcription factors, anti-apoptotic factors, markers of endothelial cell differentiation, JAK-STAT signalling molecules, adhesion receptors, proteinase inhibitors and actin regulatory proteins; and expression changes consistent with inhibition of cell cycle progression, increased cholesterol biosynthesis, decreased ubiquitin-proteasome mediated degradation, and activation of G-protein signaling pathways. Using DNA microarray analysis, the most induced genes at 8, 24 and 48 hours compared with those at 0 hours were jagged-1, stanniocalcin and angiopoietin-2, whereas the most repressed genes were connective tissue growth factor, fibulin-3 and RGS-5. In addition, the full length coding sequence of two novel regulated capillary morphogenesis genes (CMGs) are presented. CMG-1 encodes a predicted intracellular 65 kDa protein with coiled-coil domains. A CMG-1-green fluorescent protein (GFP) chimera was observed to target to an intracellular vesicular compartment. A second novel gene, CMG-2, was found to encode a predicted intracellular protein of 45 kDa containing a transmembrane segment and a CMG-2-GFP chimera was observed to target to the endoplasmic reticulum. A recombinant portion of CMG-2 was found to bind collagen type IV and laminin, suggesting a potential role in basement membrane matrix synthesis and assembly. These data further elucidate the genetic events regulating capillary tube formation in a 3D matrix environment.
The Use of HLA A2.1/p53 Peptide Tetramers to Visualize the Impact of Self Tolerance on the TCR Repertoire (2000)

p53 is an attractive target for cancer immunotherapy since it is overexpressed in half of all tumors. However, it is also expressed in normal lymphoid tissue, and self tolerance leaves a p53-specific repertoire purged of high avidity CTL. To better understand the mechanism of tolerance and the basis for such low avidity interaction, p53-specific CTL from p53 deficient (p53-) and sufficient (p53+) A2.1/Kb transgenic mice were compared with respect to their ability to bind HLA-A2.1 tetramers containing cognate murine p53 peptide Ag, p53 261-269. Since the murine CD8 molecule cannot interact with human HLA-A2.1, this tests the ability of the TCR to bind the A2.1/peptide complex tetramer. CTL from p53- mice demonstrated strong binding of such A2.1/p53 261-269 tetramers; however, the CTL from tolerant p53+ mice were devoid of tetramer-binding CD8+ T cells. Examination of TCR expression at the clonal level revealed that CTL from p53+ and p53- mice each expressed comparable levels of the p53-specific TCR. These results indicate that normal expression of p53 promotes elimination of T cells expressing TCRs with sufficient affinity to achieve stable binding of the A2.1/p53 261-269 tetramers.
A Notch1 Ectodomain Construct Inhibits Endothelial Notch Signaling, Tumor Growth, and Angiogenesis (2008)

Notch signaling is required for vascular development and tumor angiogenesis. Although inhibition of the Notch ligand Delta-like 4 can restrict tumor growth and disrupt neovasculature, the effect of inhibiting Notch receptor function on angiogenesis has yet to be defined. In this study, we generated a soluble form of the Notch1 receptor (Notch1 decoy) and assessed its effect on angiogenesis in vitro and in vivo. Notch1 decoy expression reduced signaling stimulated by the binding of three distinct Notch ligands to Notch1 and inhibited morphogenesis of endothelial cells overexpressing Notch4. Thus, Notch1 decoy functioned as an antagonist of ligand-dependent Notch signaling. In mice, Notch1 decoy also inhibited vascular endothelial growth factor-induced angiogenesis in skin, establishing a role for Notch receptor function in this process. We tested the effects of Notch1 decoy on tumor angiogenesis using two models: mouse mammary Mm5MT cells overexpressing fibroblast growth factor 4 (Mm5MT-FGF4) and NGP human neuroblastoma cells. Exogenously expressed FGF4 induced Notch ligand expression in Mm5MT cells and xenografts. Notch1 decoy expression did not affect tumorigenicity of Mm5MT-FGF4 cells in vitro but restricted Mm5MT-FGF4 xenograft growth in mice while markedly impairing neoangiogenesis. Similarly, Notch1 decoy expression did not affect NGP cells in vitro but disrupted vessels and decreased tumor viability in vivo. These results strongly suggest that Notch receptor signaling is required for tumor neoangiogenesis and provides a new target for tumor therapy.
Synthesis and Preliminary Biological Evaluations of CC-1065 Analogues:  Effects of Different Linkers and Terminal Amides on Biological Activity (2000)

CC-1065 analogues possessing a biologically active CBI functional group and amide-substituted indole and benzofuran were synthesized. The IC(50) values of compounds 26, bearing two indoles, and 25, bearing only one indole, are 0.4 and 3 nM, respectively, against U937 leukemia cells in vitro. The IC(50) values of compounds 28, bearing a butyramino group, and 27, bearing an acetamino group, are 0.008 and 0.4 nM, respectively, against U937 leukemia cells in vitro. Compound 29, bearing a double-bond linker, is about 4-fold more potent than 25, bearing no double-bond linker. Compound 26 is highly potent against all cell lines tested in the NCI in vitro screening with IC(50) values in the 0.1-5 nM range for most cell lines. Compounds 26 and 30 are highly active against L1210 leukemia in mice. Compound 26 is also active against B16BL6 melanoma in mice. Most importantly, 26 and 30 are not myelosuppressive at therapeutically effective doses. The mechanism of tumor cell death is through induction of apoptosis, and is accompanied by DNA fragmentation.