gebhart/patrepeval huggingface dataset:
Crystallographic and biochemical investigation of the lead(II)-catalyzed hydrolysis of yeast phenylalanine tRNA (1985)

X-ray diffraction data from monoclinic crystals of yeast tRNAPhe soaked in dilute lead(II) acetate solutions at pH 5.0 and at pH 7.4 have been collected to a resolution of 3 A, and the Pb(II) binding sites have been obtained by difference Fourier analyses. The same three Pb(II) binding sites are observed at both of these pH values. At pH 7.4 an extra peak of negative electron density appears on the difference map close to one of the Pb(II) binding sites and at the position of phosphate-18, indicating cleavage of the sugar-phosphate-chain between residues D-17 and G-18 of the tRNAPhe molecule in this derivative. Chain scission does not occur to any observable extent in the structure at pH 5.0, and we have, therefore, a picture of the reactants (at pH 5.0) and products (at pH 7.4) of this cleavage reaction. Polyacrylamide gel electrophoresis as well as sequencing experiments confirms the cleavage of the tRNAPhe molecule into one-fourth and three-fourth fragments, with the shorter fragment consisting essentially of residues G-1 through D-17 while the larger fragment contains residues G-18 through A-76. End-group analyses suggest a ribose cyclic 2',3'-phosphate at D-17 of the one-fourth fragment with a 5'-OH at G-18 of the three-fourth fragment. Cleavage of the tRNAPhe molecule does not occur in the absence of Pb(II), and the proximity of one of these metal ions to the cleavage site strongly implicates this metal ion in the cleavage reaction. Consideration of several possible mechanisms for the reaction, taking into account the biochemical and crystallographic facts presented above, suggests that the cleavage involves removal of the proton from the 2'-OH of ribose-17 by a Pb(II)-bound hydroxyl group. Subsequent nucleophilic attack of the resulting 2'-O- on the phosphorus atom of phosphate-18, presumably through a pentacoordinate phosphorus cyclic intermediate (as in the action of pancreatic ribonuclease A), results in chain scission. It cannot be decided whether the displacement, within the pentacoordinate intermediate, proceeds via an in-line or adjacent pathway, but an exploration of the likelihood of either pathway is presented. Strand cleavage at the particular site occurs fortuitously because the aquo Pb(II) ion binds at the correct distance and presumably in such a manner as to present a hydroxyl group in the correct orientation to effect the proton abstraction.(ABSTRACT TRUNCATED AT 400 WORDS)
Unraveling the primate fovea during development (2011)

Shortly after joining the brand new University of Washington Department of Ophthalmology in 1966, I discovered the classic book on human retinal development by Ida Mann. When a friend in the UW Primate Center asked me if I wanted the eyes from 16 timed fetal and infant M. nemestrina, I had my first opportunity to discover for myself the very strange development of the fovea. This talk will review the evidence that I and my collaborators have amassed on foveal development, and will present an integrated model of primate foveal development based on these data. Classic paper: Yuodelis, C., & Hendrickson, A. E. (1986). A qualitative and quantitative analysis of the human fovea during development. Vision Research, 26, 847–855.
High-Dose Aprotinin in Cardiac Surgery: Is High-Dose High Enough? (2006)

In this retrospective analysis we tested the hypothesis that aprotinin doses of more than 6 x 10(6) kallikrein inhibiting units (KIU) per patient may be more effective in reducing bleeding compared with the high-dose regimen of 5-6 x 10(6) KIU aprotinin. The aprotinin doses administered for 8281 adult cardiac surgical patients were correlated to body weight and time of operation and calculated in KIU per kg body weight and minute of operation. Linear and logistic regression models were designed to detect potential associations between dose and postoperative bleeding, transfusion, and other covariates. The 6-h chest tube drainage in the lowest quartile dosing group was 447 +/- 319 mL (mean +/- sd) compared with 360 +/- 290 mL in the highest quartile dosing group (P < 0.001). The proportion of patients requiring allogeneic blood transfusion was reduced from 55% to 47% comparing the lowest with the highest dosing group (P < 0.01). Aprotinin dose was also an independent predictor for rethoracotomy for surgical hemostasis (1.9% in the highest quartile to 2.4% in the lowest dosing quartile; P < 0.01). The risk of renal failure requiring dialysis (2.3% in the highest dosing group vs 3.3% in the lowest dosing group; P < 0.01) or impairment of renal function (creatinine increase of >or=2 mg/dL postoperatively, 6.4% in the highest dosing group vs 10.0% in the lowest dosing group; P < 0.01) was lower with higher doses of aprotinin. Thus, there was no association between aprotinin dose and renal function. Our results support the hypothesis that a more individualized aprotinin regimen with potentially higher doses may optimize the effectiveness of aprotinin therapy in cardiac surgery.
Experimental Study Of The Cross‐Polarization Characteristics Of Rectangular Microstrip Antennas (1989)

Abstract The cross polarization characteristics of rectangular patch antennas are studied experimentally. Data are presented showing the dependence of the copolarization to cross‐polarization ratio on the aspect ratio in both the E and H planes. Three substrate thicknesses are included und the variation with resonant frequency is examined.
Identification of sbcD mutations as cosuppressors of recBC that allow propagation of DNA palindromes in Escherichia coli K-12 (1992)

The function of an open reading frame (orf-45) located upstream of the sbcC gene of Escherichia coli was investigated. Mutations that inactivate sbcC improve the ability to propagate lambda red gam phage that carry a palindromic sequence in their DNA. They also act with sbcB mutations as cosuppressors of the defects in recombination, DNA repair, and cell viability associated with recBC mutations. A 1,282-bp cassette encoding resistance to kanamycin was used to disrupt orf-45. The mutation, which has a polar effect on the expression of sbcC, allowed stable propagation of palindromic lambda phage even when the sbcC gene product was provided in trans. Additional nonpolar mutations in orf-45 were isolated on the basis of their ability to improve the growth of recBC sbcB strains. These mutations also confer resistance to mitomycin C, allow efficient recombination in Hfr crosses, and facilitate stable propagation of palindromic phage. It is concluded that the products of orf-45 and sbcC are functionally related. The orf-45 gene is therefore renamed sbcD.
Insulin-Like Growth Factor-II Receptors (1990)

In the past few years there has been an explosive increase in interest in peptides of the insulin-like growth factor (IGF) family. This follows a period of over two decades, dating back to the discovery of "somatomedins," as the IGFs were originally known, in the late 1950s. Independent research groups isolated and characterized peptides with three apparently unrelated groups of biological activities: "sulfation factor," peptides that stimulate proteoglycan synthesis in cartilage; "nonsuppressible insulin-like activity," peptides with the ability to mimic the various actions of insulin, such as the stimulation of glucose oxidation by fat cells; and "multiplication-stimulating activity" or MSA, peptides that promote cell replication (Baxter, 1986). In time it was realized that all of these properties were in fact possessed by all of the peptides in the three groups; these, in turn, were eventually categorized, on the basis of their primary sequences, into two peptide groups, IGF-I and IGF-II. For example, MSA is now regarded as rat IGF-II (Marquardt et al., 1981). Although there have been suggestions that different IGF classes (such as "fetal somatomedins") might exist, it can be concluded from recent protein and cDNA sequencing studies that, notwithstanding the many proven or predicted structural variants of each peptide type, all known IGFs may be classified as either IGF-I or IGF-II.KeywordsAffinity ColumnMicrosomal MembraneSodium HEPESNonimmune Rabbit SerumStimulate Proteoglycan SynthesisThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Reduced Ubiquitin-Dependent Degradation of c-Jun After Phosphorylation by MAP Kinases (1997)

The proto-oncogene-encoded transcription factor c-Jun activates genes in response to a number of inducers that act through mitogen-activated protein kinase (MAPK) signal transduction pathways. The activation of c-Jun after phosphorylation by MAPK is accompanied by a reduction in c-Jun ubiquitination and consequent stabilization of the protein. These results illustrate the relevance of regulated protein degradation in the signal-dependent control of gene expression.
Increased Hepatobiliary Clearance of Unconjugated Thyroxine Determines DMP 904-Induced Alterations in Thyroid Hormone Homeostasis in Rats (2005)

4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine (DMP 904) is a potent and selective antagonist of corticotropin releasing factor receptor-1 (CRF1 receptor) with an efficacious anxiolytic profile in preclinical animal models. In subchronic toxicity studies in Sprague-Dawley rats, DMP 904 produced thyroid follicular cell hypertrophy and hyperplasia, and a low incidence of follicular cell adenoma. The current investigations were designed to determine the mode of action by which DMP 904 disrupts thyroid homeostasis in male rats. Five-day treatment with DMP 904 (300 mg/kg/day) dramatically lowered serum thyroxine (T4) to levels below detectable limits (< 1 microg/dl) by 72 h, with concurrent decreases in triiodothyronine (T3, about a 70% decrease) and increases in thyroid stimulating hormone (TSH; about a three-fold increase). DMP 904 increased [125I]T4 total body clearance (Cl tb) (38.21 +/- 10.45 ml/h) compared to control (5.61 +/- 0.59 ml/h) and phenobarbital-treated rats (7.92 +/- 1.62 ml/h). This increase in Cl(tb) was associated with a significant increase in biliary clearance (Cl bile) of unconjugated [125I]T4 (nearly 80-times control rates) and increased liver:blood ratios of T4, suggestive of enhanced hepatic uptake of T4. A single dose of DMP 904 (200 mg/kg) increased mRNA levels of hepatic cytochrome P450s (CYP 3A1 and CYP 2B1) and UDP-glucuronosyltransferases (UGT 1A1 and UGT 1A2). DMP 904 also induced mRNAs of the canalicular transporter, multi-drug resistance protein-2 (Mrp2) and sinusoidal transporters, organic anion transporting proteins (Oatp1 and Oatp2) within 24 h. Western blot analysis confirmed DMP 904 related increases in Oatp2 protein expression. Collectively, these data suggest that DMP 904 is an agonist of the constitutive androstane receptor (CAR) and pregnane X receptor (PXR) and that the decreased serum levels of T4 and T3 resulted from increased hepatobiliary clearance. However, DMP 904 is distinguished from other compounds associated with similar effects on thyroid hormone homeostasis because its effects were primarily related to increased biliary excretion of unconjugated T4.
Comparison of the Steady-State Pharmacokinetics, Metabolism, and Variability of a Transdermal Testosterone Patch Versus a Transdermal Testosterone Gel in Hypogonadal Men (2005)

These findings reflect the different mechanisms of transdermal absorption from the patch and gel and provide new considerations for selecting testosterone replacement therapies in hypogonadal men.
Building Better Chimeric Antigen Receptors for Adoptive T Cell Therapy (2010)

The last few years have seen the transfer of two decades of research into Chimeric Antigen Receptors (CARs) into clinical trials. Despite this extensive research, there is still a great deal of debate into the optimal design strategy for these, primarily, anti-cancer entities. The archetypal CAR consists of a single-chain antibody fragment, specific to a tumour-associated antigen, fused to a component of the T-cell receptor complex (typically CD3zeta) which on antigen binding primes the engrafted T-cell for anti-tumour activity. The modular nature of these artificial receptors has enabled researchers to modify aspects of their structure, including the extracellular spacer, transmembrane and cytoplasmic domain, to achieve laboratory defined optimal activity. Despite this there is no consensus on the optimal structure, a problem exacerbated by conflicting results using identical receptors. In this review, we provide a structural overview of CAR development and highlight areas that require further refinement. We also attempt to identify possible reasons for conflicting results in the hope that this information will inspire future rational design strategies for optimal tumour targeting using CARs.
Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus (1993)

A monoclonal antibody (MCI20.6) which inhibited measles virus (MV) binding to host cells was previously used to characterize a 57- to 67-kDa cell surface glycoprotein as a potential MV receptor. In the present work, this glycoprotein (gp57/67) was immunopurified, and N-terminal amino acid sequencing identified it as human membrane cofactor protein (CD46), a member of the regulators of complement activation gene cluster. Transfection of nonpermissive murine cells with a recombinant expression vector containing CD46 cDNA conferred three major properties expected of cells permissive to MV infection. First, expression of CD46 enabled MV to bind to murine cells. Second, the CD46-expressing murine cells were able to undergo cell-cell fusion when both MV hemagglutinin and MV fusion glycoproteins were expressed after infection with a vaccinia virus recombinant encoding both MV glycoproteins. Third, M12.CD46 murine B cells were able to support MV replication, as shown by production of infectious virus and by cell biosynthesis of viral hemagglutinin after metabolic labeling of infected cells with [35S]methionine. These results show that the human CD46 molecule serves as an MV receptor allowing virus-cell binding, fusion, and viral replication and open new perspectives in the study of MV pathogenesis.
Demonstration of free radical generation in "stunned" myocardium of intact dogs with the use of the spin trap alpha-phenyl N-tert-butyl nitrone. (1988)

Recent studies suggest that oxygen free radicals may mediate postischemic myocardial dysfunction ("stunning"), but all the evidence for this hypothesis is indirect. Thus, we used electron paramagnetic resonance (EPR) spectroscopy and the spin trap, alpha-phenyl N-tert-butyl nitrone (PBN), to directly investigate whether free radicals are produced after a 15-min coronary artery occlusion and subsequent reperfusion in 30 open-chest dogs. After intracoronary infusion of PBN, EPR signals characteristic of oxygen- and carbon-centered radical adducts were detected in the venous blood draining from the ischemic/reperfused vascular bed. The myocardial release of PBN adducts began during coronary occlusion but increased dramatically in the first few minutes after reperfusion. After this initial burst, the production of radicals abated but did not cease, persisting up to 3 h after reflow. The EPR spectra (aH beta = 2.67-2.79 G, aN = 14.75-15.00 G) were consistent with the trapping by PBN of secondary oxygen- and carbon-centered radicals, such as alkoxy and alkyl radicals, which could be formed by reactions of primary oxygen radicals with membrane lipids. There was a linear, direct relationship between the magnitude of PBN adduct production and the degree of ischemic flow reduction. Recovery of contractile function (measured as systolic wall thickening) after reperfusion was greater (P less than 0.05) in dogs given PBN than in controls. This study demonstrates that reversible regional myocardial ischemia in the intact animal is associated with prolonged free radical generation, and that the intensity of such generation is related to the severity of ischemia. The results provide direct evidence to support the hypothesis that reactive oxygen metabolites contribute to the persistent contractile dysfunction (myocardial stunning) observed after brief ischemia in vivo.
Functional analysis of cardiac MR images using SPHARM modeling (2005)

Visualization and quantification of cardiac function can provide direct and reliable indicators of cardiac health. The heart's operation occurs in three dimensions, and is dependent on three dimensional forces and ventricular geometry, making the observation of its shape important. Many approaches have been presented to extract cardiac shape and do functional analysis from a variety of imaging modalities. We apply a spherical harmonics (SPHARM) model to cardiac function analysis using magnetic resonance (MR) images. Our three dimensional SPHARM approach increases measurement accuracy over two dimensional approaches and also simplifies the management and indexing of clinical data by providing access to many important functional measures directly from the SPHARM representation.
Probing Single Molecules and Single Nanoparticles by Surface-Enhanced Raman Scattering (1997)

Optical detection and spectroscopy of single molecules and single nanoparticles have been achieved at room temperature with the use of surface-enhanced Raman scattering. Individual silver colloidal nanoparticles were screened from a large heterogeneous population for special size-dependent properties and were then used to amplify the spectroscopic signatures of adsorbed molecules. For single rhodamine 6G molecules adsorbed on the selected nanoparticles, the intrinsic Raman enhancement factors were on the order of 10(14) to 10(15), much larger than the ensemble-averaged values derived from conventional measurements. This enormous enhancement leads to vibrational Raman signals that are more intense and more stable than single-molecule fluorescence.
Role of neutrophils in generalized reperfusion injury associated with resuscitation from shock. (1989)

Recent studies suggest that neutrophils are an important factor in the organ injury associated with ischemia and shock. Increased neutrophil-endothelial adhesiveness is essential for neutrophil-mediated vascular injury. To examine the role of neutrophils and neutrophil adhesiveness in the development of injury after hypovolemic shock, and to determine whether this injury is a consequence of reperfusion, we used the monoclonal antibody (MAb) 60.3 (directed to the primary human neutrophil adherence glycoprotein, CD18) to block neutrophil adherence functions at the time of resuscitation in a rabbit model of hemorrhagic shock. None of the unanesthetized control animals subjected to 2 hours of shock (cardiac output, 30% of baseline) followed by resuscitation survived 5 days. All had gross and histologic evidence of injury to lungs, liver, and gastrointestinal mucosa. In contrast, 71% of the animals that received MAb 60.3 immediately before resuscitation survived 5 days (p less than 0.005), and visceral organ injury was absent or markedly attenuated. We conclude that a significant proportion of injury resulting from shock and resuscitation occurs after the ischemic insult and that increased neutrophil adhesiveness plays an important role in the development of multiple organ injury and death following shock and resuscitation (in this model). This injury may be significantly reduced by blocking neutrophil adherence functions with the MAb 60.3--even if administration is delayed until resuscitation.
The vitronectin-binding function of PAI-1 exacerbates lung fibrosis in mice (2011)

Plasminogen activator inhibitor-1 (PAI-1) is increased in the lungs of patients with pulmonary fibrosis, and animal studies have shown that experimental manipulations of PAI-1 levels directly influence the extent of scarring that follows lung injury. PAI-1 has 2 known properties that could potentiate fibrosis, namely an antiprotease activity that inhibits the generation of plasmin, and a vitronectin-binding function that interferes with cell adhesion to this extracellular matrix protein. To determine the relative importance of each PAI-1 function in lung fibrogenesis, we administered mutant PAI-1 proteins that possessed either intact antiprotease or vitronectin-binding activity to bleomycin-injured mice genetically deficient in PAI-1. We found that the vitronectin-binding capacity of PAI-1 was the primary determinant required for its ability to exacerbate lung scarring induced by intratracheal bleomycin administration. The critical role of the vitronectin-binding function of PAI-1 in fibrosis was confirmed in the bleomycin model using mice genetically modified to express the mutant PAI-1 proteins. We conclude that the vitronectin-binding function of PAI-1 is necessary and sufficient in its ability to exacerbate fibrotic processes in the lung.
91. The dehydration and racemisation of N-acyl-L-aspartic acids by acetic anhydride (1953)

C. C. Barker, J. Chem. Soc., 1953, 453 DOI: 10.1039/JR9530000453
Publishing perils include single-blind review (2007)

The Letters section of the January 2007 issue of Physics Today (page 10) contained a discussion about the exacting and often confusing electronic paper submission process as an obstacle to getting published. I think a much more important and corrosive impediment to publication is single-blind peer review.Peer review is the cornerstone of scientific research and advancement. It recognizes the importance of the objective reality and is a manifestation of the scientific method. It also keeps crackpots and just plain bad science out of the journals.However, the single-blind peer review system has a fundamental flaw. It allows reviewers to assess the author(s) of a paper along with the scientific content and thereby permits nonscientific considerations to creep in. As is often true in other aspects of professional life, in peer review who you know can be as important as what you know.Single-blind peer review discourages scientists from publishing in new fields, suppresses research from unknown or unaffiliated scientists, and adds irrelevant considerations to the review of scientific content. It may, in fact, be robbing science of its greatest breakthroughs right now. More than 100 years after Einstein's miracle year, what are the chances that an unknown 24-year-old patent clerk could revolutionize physical law in a peer-reviewed journal today? It seems extremely unlikely.The arXiv.org server suffers the same problem in that an author must have a personal reference in order to publish; in fact, there the personal relationship is paramount and is presumed to subsume scientific merit.If journals are really about scientific truth and integrity, and if we believe in the objective reality, peer review must be double blind. The single-blind system is intellectual laziness at best, cronyism at worst.© 2007 American Institute of Physics.