gebhart/patrepeval huggingface dataset:
Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells. (1988)

Cultured cells subjected to oxygen deprivation have been shown to undergo anomalous DNA synthesis, which can result in DNA overreplication and the generation of cellular variants [Rice, G. C., Hoy, C. & Schimke, R. T. (1986) Proc. Natl. Acad. Sci. USA 83, 5978-5982]. In the present study, murine tumor cells were exposed to severe hypoxia and then tested for their ability to form experimental metastases. Upon reoxygenation, cells transiently, yet dramatically, increased their metastatic potential. Flow cytometric analysis confirmed that hypoxia and reoxygenation induced cell cycle perturbations and DNA overreplication in these tumor cell lines. Fibrosarcoma cells with overreplicated DNA isolated by fluorescence-activated cell sorting proved to be highly metastatic, although cells with 2-4 times the haploid DNA content in populations treated with hypoxia were also markedly more metastatic than oxic populations. These results support the hypothesis that hypoxic conditions existing in regions of solid tumors promote cellular heterogeneity and tumor progression.
Preparation of N‐Fmoc‐Protected β2‐ and β3‐Amino Acids and their use as building blocks for the solid‐phase synthesis of β‐peptides (1998)

Abstract N ‐Fmoc‐Protected (Fmoc = (9 H ‐fluoren‐9‐ylmethoxy)carbonyl) β‐amino acids are required for an efficient synthesis of β‐oligopeptides on solid support. Enantiomerically pure Fmoc‐β 3 ‐amino acids β 3 : side chain and NH 2 at C(3)(= C(β)) were prepared from Fmoc‐protected ( S )‐ and ( R )‐α‐amino acids with aliphatic, aromatic, and functionalized side chains, using the standard or an optimized Arndt‐Eistert reaction sequence. Fmoc‐β 2 ‐ Amino acids (β 2 side chain at C(2), NH 2 at C(3)(= C(β))) configuration bearing the side chain of Ala, Val, Leu, and Phe were synthesized via the Evans ' chiral auxiliary methodology. The target β 3 ‐heptapeptides 5–8 , a β 3 ‐ pentadecapeptide 9 and a β 2 ‐heptapeptide 10 were synthesized on a manual solid‐phase synthesis apparatus using conventional solid‐phase peptide synthesis procedures ( Scheme 3 ). In the case of β 3 ‐peptides, two methods were used to anchor the first β‐amino acid: esterification of the ortho ‐chlorotrityl chloride resin with the first Fmoc‐β‐amino acid 2 ( Method I, Scheme 2 ) or acylation of the 4‐(benzyloxy)benzyl alcohol resin ( Wang resin) with the ketene intermediates from the Wolff rearrangement of amino‐acid‐derived diazo ketone 1 ( Method II, Scheme 2 ). The former technique provided better results, as exemplified by the synthesis of the heptapeptides 5 and 6 ( Table 2 ). The intermediate from the Wolff rearrangement of diazo ketones 1 was also used for sequential peptide‐bond formation on solid support (synthesis of the tetrapeptides 11 and 12 ). The CD spectra of the β 2 ‐ and β 3 ‐peptides 5 , 9 , and 10 show the typical pattern previously assigned to an ( M ) 3 1 helical secondary structure ( Fig. ). The most intense CD absorption was observed with the pentadecapeptide 9 (strong broad negative Cotton effect at ca. 213 nm); compared to the analogous heptapeptide 5 , this corresponds to a 2.5 fold increase in the molar ellipticity per residue!
Tea Tree Oil: A Systematic Review of Randomized Clinical Trials (2000)

It is concluded that, so far, there is no compelling evidence to show that TTO is efficacious in any dermatological condition. However, in view of promising findings, TTO deserves to be investigated more closely.
Early afterdepolarizations: mechanism of induction and block. A role for L-type Ca2+ current. (1989)

Early afterdepolarizations (EADs) are a type of triggered activity found in heart muscle. We used voltage-clamped sheep cardiac Purkinje fibers to examine the mechanism underlying EADs induced near action potential plateau voltages with the Ca2+ current agonist Bay K 8644 and the effect of several interventions known to suppress or enhance these EADs. Bay K 8644 produced an inward shift of the steady-state current-voltage relation near plateau voltages. Tetrodotoxin, lidocaine, verapamil, nitrendipine, and raising [K]o abolish EADs and shift the steady-state current-voltage relations outwardly. Using a two-pulse voltage-clamp protocol, an inward current transient was present at voltages where EADs were induced. The voltage-dependence of availability of the inward current transient and of EAD induction were similar. The time-dependence of recovery from inactivation of the inward current transient and of EAD amplitude were nearly identical. Without recovery of the inward current transient, EADs could not be elicited. The inward current transient was enhanced with Bay K 8644 and blocked by nitrendipine, but was not abolished by tetrodotoxin or replacement of [Na]o with an impermeant cation. These results support a hypothesis that the induction of EADs near action potential plateau voltages requires 1) a conditioning phase controlled by the sum of membrane currents present near the action potential plateau and characterized by lengthening and flattening of the plateau within a voltage range where, 2) recovery from inactivation and reactivation of L-type Ca2+ channels to carry the depolarizing charge can occur. Our results suggest an essential role for the L-type Ca2+ "window" current and provide a framework for understanding the role of several membrane currents in the induction and block of EADs.
A Simple Technique to Passively Gravity-Balance Articulated Mechanisms (1995)

A simple method to counter the effects of gravity in articulated mechanisms is proposed. The scheme uses kinematics and linear springs to produce a nonlinear restoring force to oppose the gravitational moment. The method equilibrates a rotational mechanism for all postures. A solution for one link is obtained then general equations for n links are derived. The method is simpler than previous schemes and has applications in robotics, orthotics and a host of everyday mechanisms.
Promoter specific sensitivity to inhibition of histone deacetylases: implications for hormonal gene control, cellular differentiation and cancer. (2000)

Alterations in histone acetylation status appear to play a central role in the regulation of neoplasia, tumor suppression, cell cycle control, hormone responsiveness and senescence. These alterations of chromatin control gene transcription. The histone acetylation status is regulated by the equilibrium of histone acetyl-transferase activity (HAT) and the histone deacetylase activity (HDAC). Commonly, DNA-transfection assays are used to measure the effect of histone acetylation and deacetylation on gene transcription. Here we have analyzed the response of various viral long terminal repeats and vertebrate promoters to the specific histone deacetylase inhibitor trichostatin A (TSA). We show that the activity of many, but not all, promoters is increased upon TSA treatment. Interestingly, the lysozyme promoter exhibited TSA resistance, while the activity of metallothionine, the human growth hormone, and the thymidine kinase promoters was increased. Furthermore, we found that all tested viral promoters are induced by TSA. Analysis of the transcriptional behaviour of the thyroid hormone receptor (TR), the cellular homologue of the v-erbA oncogene, revealed that TSA reduced the gene silencing function but had no influence on the hormone-induced gene activation function of the receptor. These results on gene specific effects, together with the HDAC structural data (1), may be a basis for the development of HDAC inhibitors as antitumor agents.
A Single Preoperative Oral Dose of Valdecoxib, a New Cyclooxygenase-2 Specific Inhibitor, Relieves Post-Oral Surgery or Bunionectomy Pain (2002)

Preoperative orally administered valdecoxib provides well-tolerated and effective analgesia for mild to moderate postoperative pain.
Icatibant in hereditary angioedema: news and challenges (2011)

Hereditary angioedema (HAE) is a rare condition. Its prognosis depends on whether there is laryngeal involvement with a risk of asphyxia, which is present in 25% of such cases. Improved understanding of the pathophysiology of this disease has resulted in the development of targeted therapies including icatibant, which acts as an antagonist at bradykinin B2 receptors. This agent has been shown to be effective in the treatment of attacks of HAE in three Phase III randomized double-blind published studies. Efficacy data have been collected in all types of attack: cutaneous, abdominal and laryngeal. Safety data are also encouraging. Icatibant is administered subcutaneously, with the potential for patients to self-administer. In the future, this therapy may offer increased independence for HAE patients.
Diversity of Historically Important Sweet Corn Inbreds as Estimated by RFLPs, Morphology, Isozymes, and Pedigree (1994)

Historical records indicate that sweet corn ( Zea Mays L.) germplasm is largely derived from the Northern Flint race of corn. In addition, most of the publicly available inbreds were derived from three cultivars: ‘Stowell's Evergreen’, ‘Country Gentleman’, and ‘Golden Bantam’. In order to better understand sweet corn germplasm, 43 historically important sweet corn inbreds and three dent corn inbreds were examined by pedigree information, restriction fragment length polymorphisms (RFLPs), isozyme markers, and morphological traits. Data sets were developed from 71 RFLP probes, 27 isozyme loci, 24 morphological traits, and pedigree coefficients of relationship, and these data sets were subjected to cluster analysis. Isozymes and especially morphology did not accurately group these inbreds according to known pedigree relationships. The RFLP distance showed good agreement with pedigree distance ( r = 0.54**). Based on cluster analysis of these two data sets this sweet corn germplasm can be divided into two major groups, inbreds that contain Golden Bantam germplasm, and inbreds with Stowell's Evergreen, Country Gentleman germplasm, or both. Several inbreds were not closely aligned with either group, and these unique inbreds have been widely used by sweet corn breeders. The amount of genetic diversity present in this material, with an average of 2.22 alleles per isozyme locus and RFLPs averaging 4.14 variants per probe, is within the range of diversity reported for Corn Belt Dent inbreds.
Cytokines and adhesion molecules in patients with polymyalgia rheumatica (1998)

Serum levels of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1ra), tumour necrosis factor alpha (TNF-alpha), IL-6, soluble IL-6 receptor (sIL-6R), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin were measured in 15 patients with newly diagnosed polymyalgia rheumatica (PMR) before and after 3 months of corticosteroid therapy. Both IL-6 and IL-1ra were significantly increased in untreated PMR and remained elevated compared with controls during therapy, although significantly only for sIL-1ra. sICAM-1 was raised in 12/15 (87%) patients at diagnosis and remained high in 10/14 (71%) patients; soluble E-selectin levels were initially raised in 6/15 (40%) patients and decreased with therapy in those with the highest levels. IL-6, IL-1ra and sICAM-1 are sensitive indicators of continuing immunological activation in PMR; the advantages of these markers in assessing the response to therapy should be investigated in a longitudinal study.
Endogenously inhibited protein kinase C in transgenicDrosophila embryonic neuroblasts down regulates the outgrowth of type I and II processes of cultured mature neurons (1996)

Embryonic neurons were cultured from transgenic Drosophila melanogaster expressing a highly specific pseudosubstrate inhibitor of protein kinase C (PKC). Flies homozygous for this transgene, which is under the control of the yeast UAS promoter, were crossed to flies homozygous for the yeast heat shock inducible transcription factor GAL 4. Following heat shock, the progeny express the pseudosubstrate inhibitor at high levels. This strategy, which has the advantage of avoiding the non-specific effects of drugs, was used to study the role of PKC in process growth of cultured, differentiating neuroblasts. An external gold particle labeling procedure using a cell surface antigen expressed by mature neurons and processes was used to visualize neuronal processes directly in the scanning electron microscope. We observed that cell cultures expressing a low concentration of the pseudosubstrate inhibitor showed a significant decrease in the number of type I and II processes as compared to control cultures, while the proportions of neuroblasts, ganglion mother cells (GMCs), and mature neurons in the clusters were little affected.
Myocardial Extracellular Matrix (2014)

The cardiac extracellular matrix (ECM) is a complex architectural network consisting of structural and nonstructural proteins, creating strength and plasticity. The nonstructural compartment of the ECM houses a variety of proteins, which are vital for ECM plasticity, and can be divided into 3 major groups: glycoproteins, proteoglycans, and glycosaminoglycans. The common denominator for these groups is glycosylation, which refers to the decoration of proteins or lipids with sugars. This review will discuss the fundamental role of the matrix in cardiac development, homeostasis, and remodeling, from a glycobiology point of view. Glycoproteins (eg, thrombospondins, secreted protein acidic and rich in cysteine, tenascins), proteoglycans (eg, versican, syndecans, biglycan), and glycosaminoglycans (eg, hyaluronan, heparan sulfate) are upregulated on cardiac injury and regulate key processes in the remodeling myocardium such as inflammation, fibrosis, and angiogenesis. Albeit some parallels can be made regarding the processes these proteins are involved in, their specific functions are extremely diverse. In fact, under varying conditions, individual proteins can even have opposing functions, making spatiotemporal contribution of these proteins in the rearrangement of multifaceted ECM very hard to grasp. Alterations of protein characteristics by the addition of sugars may explain the immense, yet tightly regulated, variability of the remodeling cardiac matrix. Understanding the role of glycosylation in altering the ultimate function of glycoproteins, proteoglycans, and glycosaminoglycans in the myocardium may lead to the development of new biochemical structures or compounds with great therapeutic potential for patients with heart disease.
The LIM domain-containing homeo box gene Xlim-1 is expressed specifically in the organizer region of Xenopus gastrula embryos. (1992)

A novel cysteine-rich motif, named LIM, has been identified in the homeo box genes lin-11, Isl-1, and mec-3; the mec-3 and lin-11 genes determine cell lineages in Caenorhabditis elegans. We isolated LIM class homeo box genes from Xenopus laevis that are closely related to lin-11 and mec-3 in the LIM and homeo domains. This paper deals with one of these genes, Xlim-1. Xlim-1 mRNA is found at low abundance in the unfertilized egg, has a major expression phase at the gastrula stage, decreases, and rises again during the tadpole stage. In adult tissues the brain shows the highest abundance, by far, of Xlim-1 mRNA. The maternal and late expression phases of the Xlim-1 gene suggest that it has multiple functions at different stages of the Xenopus life cycle. In the gastrula embryo, Xlim-1 mRNA is localized in the dorsal lip and the dorsal mesoderm, that is, in the region of Spemann's organizer. Explant experiments showed that Xlim-1 mRNA is induced by the mesoderm-inducer activin A and by retinoic acid, which is not a mesoderm inducer but affects patterning during Xenopus embryogenesis; application of activin A and retinoic acid together results in synergistic induction. The structure, inducibility, and localized expression in the organizer of the Xlim-1 gene suggest that it has a role in establishing body pattern during gastrulation.
A role for p21ras/MAP kinase in TCR-mediated activation of LFA-1. (1998)

LFA-1 is a beta2 integrin that plays well-characterized roles in adhesion of T lymphocytes to APC, T cell-mediated cytolysis, and leukocyte-endothelial cell interactions. Although it is clear that LFA-1 must undergo affinity or avidity changes to bind its cellular ligand ICAM-1, the intracellular signaling pathways involved are not well characterized. Here, we show that the Ras-mitogen-activated protein kinase (MAPK) signaling pathway is also involved in TCR-activated LFA-1 adhesion. Expression of a dominant negative form of p21ras in a thymocyte cell line inhibits, while constitutively active p21ras both enhances and sustains, subsequent TCR-triggered adhesion to isolated ICAM-1. However, the Ras/MAPK pathway alone is not sufficient for activating T cell LFA-1, as inhibition of both downstream MAPK/extracellular regulated kinase kinase (MEK) activity and phosphatidylinositol 3-kinase activity is required for complete inhibition of adhesion.
High-Resolution Microcoil 1 H-NMR for Mass-Limited, Nanoliter-Volume Samples (1995)

High-resolution, proton nuclear magnetic resonance (NMR) spectra of 5-nanoliter samples have been obtained with much higher mass sensitivity [signal-to-noise ratio (S/N) per micromole] than with traditional methods. Arginine and sucrose show a mean sensitivity enhancement of 130 compared to 278-microliter samples run in a 5-millimeter tube in a conventional, commercial probe. This can reduce data acquisition time by a factor of &gt;16,000 or reduce the needed sample mass by a factor of about 130. A linewidth of 0.6 hertz was achieved on a 300-megahertz spectrometer by matching the magnetic susceptibility of the medium that surrounds the detection cell to that of the copper coil. For sucrose, the limit of detection (defined at S/N = 3) was 19 nanograms (56 picomoles) for a 1-minute data acquisition. This technique should prove useful with mass-limited samples and for use as a detector in capillary separations.
A Single-Dose, Crossover, Placebo- and Moxifloxacin-Controlled Study to Assess the Effects of Neratinib (HKI-272) on Cardiac Repolarization in Healthy Adult Subjects (2010)

Abstract Purpose: Neratinib is an orally administered, small-molecule, irreversible pan-ErbB inhibitor in development for the treatment of ErbB2-positive breast cancer. This study assessed the effects of therapeutic and supratherapeutic neratinib concentrations on cardiac repolarization, in accordance with current regulatory guidance. Experimental Design: This was a two-part study in healthy subjects. In part 1, subjects were randomized to receive placebo, 400 mg moxifloxacin, or 240 mg neratinib (therapeutic dose) following a high-fat meal. In part 2, after a washout period, subjects received placebo plus 400 mg ketoconazole or 240 mg neratinib plus ketoconazole (supratherapeutic dose). ANOVA was used to compare the baseline-adjusted QTc interval for neratinib with that of placebo (reference), and for neratinib plus ketoconazole with that of placebo plus ketoconazole (reference). Pharmacokinetic/pharmacodynamic analyses and categorical summaries of interval data were done. Assay sensitivity was evaluated by the effect of moxifloxacin on QTc compared with placebo. Results: Sixty healthy subjects were enrolled in this study. The upper bounds of the 90% confidence interval for baseline-adjusted QTcN (population-specific corrected QT) were ≤10 milliseconds greater than the corresponding reference at all postdose time points under conditions of both therapeutic and supratherapeutic plasma concentrations of neratinib. Pharmacokinetic/pharmacodynamic analysis revealed no relationship between neratinib concentrations and QTc interval. No subjects had QTcI, QTcF, or QTcN intervals &amp;gt;450 milliseconds or change from baseline &amp;gt;30 milliseconds. Moxifloxacin produced a significant increase in QTcN compared with placebo (P &amp;lt; 0.05). Conclusions: Therapeutic and supratherapeutic plasma concentrations of neratinib do not prolong the QTc interval in healthy subjects. Clin Cancer Res; 16(15); 4016–23. ©2010 AACR.
Targeted gene mutations in Drosophila. (1989)

A cloned gene can be of interest because of its expression in a particular tissue or at a certain developmental stage, or because of homology to an interesting gene from another organism. In Drosophila its location in the genome is readily determined by in situ hybridization to the banded larval salivary gland polytene chromosomes, but it is more difficult to isolate mutations that may reveal its function. This paper describes a general method for detecting transposable element insertions into the gene in question. This "reverse genetics" then offers the possibility of observing a consequent mutant phenotype, providing a key to the normal function of the gene. The sensitivity of the polymerase chain reaction makes it possible to detect the occurrence of a single appropriate P-element transposon insertion among a population of mutagenized flies. This is accomplished by the use of oligonucleotide primers--one a sequence from within the cloned gene and the other homologous to the terminal sequence of the P-element DNA--to prime synthesis into the DNA flanking an insertion site. A segment of DNA, bounded by the two primers, will be a target for amplification only in a fly in which a P-element has inserted within about 2 kilobases of the gene primer. This technique has been used to detect P-element insertions near a gene expressed in the Drosophila compound eye. Potential problems with the technique and possible refinements in the screen are discussed. In principle, it could be utilized to detect insertion of a foreign element into any gene for which at least a partial sequence is known and could be extended to other organisms.
Polarization effects on scatterer sizing accuracy analyzed with frequency-domain angle-resolved low-coherence interferometry (2007)

Angle-resolved low-coherence interferometry (a/LCI) enables us to make depth-resolved measurements of scattered light that can be used to recover subsurface structural information such as the size of cell nuclei. Endoscopic frequency-domain a/LCI (fa/LCI) acquires data by using a novel fiber probe in a fraction of a second, making it a clinically practical system. However, birefringent effects in fiber-based systems can alter the polarization state of the incident light and potentially skew the collected data. We analyze the effect the polarization state of the incident light has on scattering data collected from polystyrene microsphere tissue phantoms and in vitro cell samples and examine the subsequent accuracy of the determined sizes. It is shown that the endoscopic fa/LCI system accurately determines the size of polystyrene microspheres without the need to control the polarization of the incident beam, but that epithelial cell nuclear sizes are accurately determined only when the polarization state of the incident light is well characterized.
Poly(propylene imine) Dendrimers: Large‐Scale Synthesis by Hetereogeneously Catalyzed Hydrogenations (1993)

In kilogram quantities ; pure poly(propylene imine) dendrimers can be prepared in an extremely simple reaction sequence comprising Michael addition (primary amines to acrylonitrile) and heterogeneous hydrogenation with a Raney cobalt catalyst. Both steps proceed quantitatively and selectively and can be employed with many core and end groups.