gebhart/patrepeval huggingface dataset:
5′-Leader of a Photosystem I Gene in Nicotiana sylvestris, psaDb, Contains a Translational Enhancer (1995)

Messenger RNA primary structures responsible for translational efficiency of a photosystem I gene, psaDb, of Nicotiana sylvestris were studied using a transgenic tobacco system. The entire 5'-leader (23 base pairs) with the first four amino acid codons of the protein coding region was fused in frame with the beta-glucuronidase (GUS) gene under the control of the 35 S promoter of cauliflower mosaic virus (CaMV). This construct (CaMV::psaDb-GUS') was introduced into tobacco. GUS activity and GUS mRNA levels were determined for individual transformants, revealing that the insertion of the psaDb sequence greatly enhanced the GUS activity relative to GUS mRNA abundance. The GUS activity/GUS mRNA was 14 times higher in the CaMV::psaDb-GUS' transformants than in the control CaMV::GUS' transformants. The high GUS activity/GUS mRNA of the CaMV::psaDb-GUS' transformants was reduced 20-fold when 13 bases within the psaDb leader were altered. These 13 bases are common to the leaders of an Arabidopsis ferredoxin gene and the psaDb gene of N. sylvestris. Since GUS proteins encoded by these chimeric GUS genes have identical amino acid sequences, these results indicate that the 5'-leader of the psaDb mRNA contains a translational enhancer element.
A Self-Instuctional Program (1977)

1Coordinator, Staff Development The University of Nebraska Medical Center, Omaha 2Director of Training and Development Saint Joseph Hospital, Omaha
Identification and characterization of glycine-extended post-translational processing intermediates of progastrin in porcine stomach. (1985)

We developed a radioimmunoassay specific for glycine-extended progastrin processing intermediates (G-Gly) using antisera generated against the synthetic peptide Tyr-Gly-Trp-Met-Asp-Phe-Gly. Distribution of immunoreactivity in the porcine gastrointestinal tract obtained with this antibody paralleled that of gastrin with the mucosa containing the highest quantity, 116 +/- 22 pmol/g, wet weight (mean +/- S.E., n = 5), or roughly 4% of gastrin concentration. This immunoreactivity was localized specifically to antral mucosal G-cells by immunohistochemistry. On Sephadex G-50 column chromatography of porcine antral mucosal extracts glycine-extended progastrin processing intermediates were separated into three principal molecular forms, each corresponding to known molecular forms of gastrin, component I, tetratriacontagastrin (G34) and heptadecagastrin (G17). Following purification by antibody-coupled affinity chromatography, one molecular form corresponding to G17 in size was shown to have an amino terminus identical to that of G17. Another molecular form corresponding to G34 in size could be converted to the molecular form corresponding to G17 by tryptic digestion. Our findings indicate that glycine-extended progastrin processing intermediates may serve as immediate precursors for each molecular form of gastrin, thus suggesting an alternative pathway for gastrin biosynthesis more complex than that previously conceived.
Pharmacokinetics of thalidomide in an elderly prostate cancer population (1999)

Thalidomide, a glutamic acid derivative, has recently been shown to inhibit in vitro angiogenesis, the process of formation of new blood vessels. This Phase II study examined the pharmacokinetics of thalidomide in patients with clinically progressive hormone-refractory prostate cancer. Patients (aged 55 to 80 years) were randomized to two different arms, low dose versus high dose. Patients in the low-dose group were given 200 mg of thalidomide and patients in the high-dose group received 200 mg of thalidomide, with subsequent dose escalations to 1200 mg. Serial serum or blood samples were obtained for pharmacokinetic assessment after administration of a single oral dose or multiple daily dosing of thalidomide and were assayed by reversed-phase HPLC. Pharmacokinetic parameters for both the single and multiple dosing were calculated with ADAPT II. A one-compartment model best fit the data. After single dosing, the oral clearance and apparent volume of distribution for the low-dose regimen (n = 13) were 7.41 +/- 2.05 L/h and 66.93 +/- 34.27 L, respectively, whereas for the high-dose regimen (n = 11), these values were 7.21 +/- 2.89 L/h and 165.81 +/- 84.18 L, respectively. The elimination half-lives for the low and high dose were 6.52 +/- 3.81 and 18.25 +/- 14.08 h, respectively. After the multiple dosing of thalidomide, the oral clearance and apparent volume of distribution for the low-dose group (n = 10) were 6.35 +/- 1.64 L/h and 64.63 +/- 23.20 L, respectively, whereas for the high-dose group (n = 11), these values were 7.73 +/- 2.27 L/h and 167.85 +/- 82.08 L, respectively. The elimination half-lives for the low and high dose were 7.08 +/- 1.87 and 16.19 +/- 9.57 h, respectively. For both the single and multiple dosing of thalidomide, the apparent volume of distribution and half-life were significantly higher for the high-dose group than those for the low-dose group. The higher apparent volume of distribution may be attributable to several factors, such as change in absorption, protein binding, etc. A dose-proportional increase in thalidomide steady-state concentrations was seen after multiple daily dosing of thalidomide.
Diffusion-limited component of reactions catalyzed by Bacillus cereus .beta.-lactamase I (1984)

The Bacillus cereus beta-lactamase I catalyzes the hydrolysis of a wide variety of penicillins and cephalosporins with values of k(cat)/K(m) varying over several orders of magnitude. The values of this parameter for the most reactive of these compounds, benzylpenicillin, I, and furylacryloyl-penicillin, II (k(cat)/K(m) = 2.43 x 10(7) M(-1) s(-1) and 2.35 x 10(7) M(-1) s(-1), respectively, at pH 7.0 in potassium phosphate buffer containing 0.17 M KCl, I(c) = 0.63, 25 degrees C) are decreased markedly by increasing viscosity in sucrose- or glycerol-containing buffers. The relative sensitivities to viscosity of k(cat)/K(m) values for I and for cephaloridine, III, were found to be virtually unchanged at pH 3.8 from those observed at pH 7.0. The differential effects of viscosity on the reactive vs. the sluggish [e.g., cephalothin (IV), k(cat)/K(m) = 1 x 10(4) M(-1) s(-1)] substrates support the contention that the rates of reaction of the former with the enzyme are in part diffusion controlled. Quantitative analysis gives values for the association rate constants, k(1), of 7.6 x 10(7) M(-1) s(-1), 4 x 10(7) M(-1) s(-1), and 1.1 x 10(7) M(-1) s(-1) for I, II, and III, respectively. As both reactive and sluggish substrates associate with the active site of the enzyme with relatively similar rate constants, the variation in k(cat)/K(m) values is primarily due to the variation in the partition ratios k(-1)/k(2), for the ES complex, which are 2.3, 0.77, and 30 for I, II, and III, respectively. The preceding analysis is based on direct application of the Stokes-Einstein diffusion law to enzyme kinetics. The range of applicability of this law to the diffusion of substrate size molecules and the mechanics of diffusion of ionic species through viscous solutions of sucrose vs. polymers are explored.
Heparanase expression in invasive trophoblasts and acute vascular damage (2000)

Heparan sulfate proteoglycans play a pivotal role in tissue function, development, inflammation, and immunity. We have identified a novel cDNA encoding human heparanase, an enzyme thought to cleave heparan sulfate in physiology and disease, and have located the HEP gene on human chromosome 4q21. Monoclonal antibodies against human heparanase located the enzyme along invasive extravillous trophoblasts of human placenta and along endothelial cells in organ xenografts targeted by hyperacute rejection, both sites of heparan sulfate digestion. Heparanase deposition was evident in arterial walls in normal tissues; however, vascular heparan sulfate cleavage was coincident with heparanase enzyme during inflammatory episodes. These findings suggest that heparanase elaboration and control of catalytic activity may contribute to the development and pathogenesis of vascular disease and suggest that heparanase intervention might be a useful therapeutic target.
Large area confocal microscopy (2007)

Imaging large tissue areas with microscopic resolution in vivo may offer an alternative to random excisional biopsy. We present an approach for performing confocal imaging of large tissue surface areas using spectrally encoded confocal microscopy (SECM). We demonstrate a single-optical-fiber SECM apparatus, designed for imaging luminal organs, that is capable of imaging with a transverse resolution of 2.1 microm over a subsurface area of 16 cm2 in less than 1 min. Due to the unique probe configuration and scanning geometry, the speed and resolution of this new imaging technology are sufficient for comprehensively imaging large tissues areas at a microscopic scale in times that are appropriate for clinical use.
Randomized Phase III Trial Comparing Irinotecan/Cisplatin With Etoposide/Cisplatin in Patients With Previously Untreated Extensive-Stage Disease Small-Cell Lung Cancer (2006)

Treatment with this dose and schedule of IP did not result in improved survival when compared with EP. Fewer patients receiving IP had grade 3/4 anemia, thrombocytopenia, neutropenia, and febrile neutropenia compared with patients receiving EP, but more had grade 3/4 diarrhea and vomiting.
Measurement of geometric distortion in a turbulent atmosphere (1986)

A technique for determining the vector displacement that maximizes the spatially local cross-correlation between an image and a reference image as a continuous function of the image space is presented. This is applied to solar observations of granulation made during a condition of rapidly changing atmospheric distortion, a particular turbulence condition wherein features are remapped without loss of spatial resolution.
Improved Peak Detection and Deconvolution of Native Electrospray Mass Spectra from Large Protein Complexes (2015)

Native electrospray-ionization mass spectrometry (native MS) measures biomolecules under conditions that preserve most aspects of protein tertiary and quaternary structure, enabling direct characterization of large intact protein assemblies. However, native spectra derived from these assemblies are often partially obscured by low signal-to-noise as well as broad peak shapes because of residual solvation and adduction after the electrospray process. The wide peak widths together with the fact that sequential charge state series from highly charged ions are closely spaced means that native spectra containing multiple species often suffer from high degrees of peak overlap or else contain highly interleaved charge envelopes. This situation presents a challenge for peak detection, correct charge state and charge envelope assignment, and ultimately extraction of the relevant underlying mass values of the noncovalent assemblages being investigated. In this report, we describe a comprehensive algorithm developed for addressing peak detection, peak overlap, and charge state assignment in native mass spectra, called PeakSeeker. Overlapped peaks are detected by examination of the second derivative of the raw mass spectrum. Charge state distributions of the molecular species are determined by fitting linear combinations of charge envelopes to the overall experimental mass spectrum. This software is capable of deconvoluting heterogeneous, complex, and noisy native mass spectra of large protein assemblies as demonstrated by analysis of (1) synthetic mononucleosomes containing severely overlapping peaks, (2) an RNA polymerase II/α-amanitin complex with many closely interleaved ion signals, and (3) human TriC complex containing high levels of background noise. Graphical Abstract ᅟ.
Optical rotation in excess of 100 rad generated by Rb vapor in a multipass cell (2011)

Paramagnetic Faraday rotation is a powerful technique for atom sensing widely used in quantum nondemolition measurements, fundamental symmetry tests, and other precision measurements. We demonstrate the use of a multipass optical cell for Faraday rotation spectroscopy and observe polarization rotation in excess of 100 rad from spin-polarized Rb vapor. Unlike optical cavities, multipass cells have a deterministic number of light passes and can be used to measure large optical rotations. We also observe a tenfold suppression of transverse spin relaxation when Rb atoms are placed in a coherent superposition state immune to spin-exchange collisions.
Presentation of antigenic peptides by products of the major histocompatibility complex (1998)

Molecules encoded by the major histocompatibility complex (MHC) are polymorphic integral membrane proteins adapted to the presentation of peptide fragments of foreign antigens to antigen-specific T-cells. The diversity of infectious agents to which an immune response must be mounted poses a unique problem for receptor–ligand interactions; how can proteins whose polymorphism is necessarily limited bind an array of peptides almost infinite in its complexity? Both MHC class I and class II determinants have achieved this goal by harnessing a limited number of peptide side chains to anchor the epitope in place while exploiting conserved features of peptide structure, independent of their primary sequence. While class I molecules interact predominantly with the N- and C-termini of peptides, class II determinants form an extensive hydrogen bonding network along the length of the peptide backbone. Such a strategy ensures high-affinity binding, while selectively exposing the unique features of each ligand for recognition by the T-cell receptor. © 1998 European Peptide Society and John Wiley & Sons, Ltd.
Phosphorodiamidates as a Promising New Phosphate Prodrug Motif for Antiviral Drug Discovery: Application to Anti-HCV Agents (2011)

We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterified amino acids, both d and l, and also from various simple amines. All of the compounds were evaluated versus hepatitis C virus in replicon assay, and nanomolar activity levels were observed. Many compounds were noncytotoxic at 100 μM, leading to high antiviral selectivities. The agents are stable in acidic, neutral, and moderately basic media and in selected biological media but show efficient processing by carboxypeptidases and efficiently yield the free nucleoside monophosphate in cells. On the basis of in vitro data, eight leads were selected for additional in vivo evaluation, with the intent of selecting one candidate for progression toward clinical studies. This phosphorodiamidate prodrug method may have broad application outside of HCV and antivirals as it offers many of the advantages of phosphoramidate ProTides but without the chirality issues present in most cases.
Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C (1993)

The protein kinase C (PKC) family of isoenzymes is believed to mediate a wide range of signal-transduction pathways in many different cell types. A series of bisindolylmaleimides have been evaluated as inhibitors of members of the conventional PKC family (PKCs-alpha, -beta, -gamma) and of a representative of the new, Ca(2+)-independent, PKC family, PKC-epsilon. In contrast with the indolocarbazole staurosporine, all the bisindolylmaleimides investigated showed slight selectivity for PKC-alpha over the other isoenzymes examined. In addition, bisindolylmaleimides bearing a conformationally restricted side-chain were less active as inhibitors of PKC-epsilon. Most noticeable of these was Ro 32-0432, which showed a 10-fold selectivity for PKC-alpha and a 4-fold selectivity for PKC-beta I over PKC-epsilon.
Actinic keratoses arising only on sun-exposed vitiligo skin (1999)

A 71-year-old woman with vitiligo developed multiple actinic keratoses only on the vitiligo skin of sun-exposed areas. She had worked outdoors as a farmer for a long period. Although actinic skin cancers arising on vitiligo skin have rarely been reported, the present case demonstrates that vitiligo skin is more susceptible to actinic damage than normal skin. Patients with vitiligo should be well informed about the importance of sun protection.
PREDICTION OF BOUNDARIES BETWEEN INTRINSICALLY ORDERED AND DISORDERED PROTEIN REGIONS (2002)

Using proteins with both disordered and ordered regions collected through literature searches and database scanning, we assembled a set of 24-residue long segments centered on their order/disorder boundaries as well as a larger set of non-boundary segments consisting of either order or disorder. We analyzed position-specific amino acid compositions around the order/disorder boundaries and found more than thirty significant (p < 0.05) compositional differences between boundary and non-boundary data. From this analysis, we constructed several logistic regression predictors of order/disorder boundaries using slightly different data modeling approaches. Exact boundary prediction accuracies were estimated to be in the range from 74% to 80% for the different predictors.
Some aspects of the chemistry of pyrimido[1,2‐B]pyridazinones (1988)

Abstract On reacting the 3‐aminopyridazines 1a,d,e with dimethyl acetylenedicarboxylate (DMAD), the pyrimido[1,2‐ b ]pyridazin‐2‐(2 H )‐ones 2e‐g , whereas starting from 1f , the 4(4 H )‐ones 5a and 3b,d were prepared. In the 2(2 H )‐one series, the reactions of 2b with various amino compounds resulted in various types of products. The reaction of N ‐methylaminopyridazines 1g,h with DMAD led to the endo‐N ‐substituted derivatives 8a,b , whereas 1h with diethyl ethoxymethylenemalonate (DEM) gave the exo‐N ‐substituted compound 1k. The constitution of the compounds was proved by spectroscopic and chemical evidences.
Antibodies against ganglioside GT3 in the sera of patients with type I diabetes mellitus. (1989)

Clinical and experimental data support the concept that type I diabetes mellitus results from autoimmune destruction of pancreatic beta cells. Although both proteins and glycolipids are targets of anti-islet cell antibodies, the Ag have not been purified or characterized. Previously, we observed that rat insulinoma (RIN) cell lines varied in their reactivity with both human antibodies and murine mAb A2B5, which binds to polysialo gangliosides. To determine the chemical basis of the varied immunoreactivity, we analyzed the glycosphingolipids of 5 RIN lines. Glycolipids bound by two mAb and by antibodies in the sera of type I diabetics were identified. The more immunoreactive RIN lines contained a much higher content of gangliosides and a higher proportion of complex gangliosides. The major gangliosides were GM3, GD3, and GT3. By high performance TLC immunostaining, we demonstrated that A2B5 and R2D6, an anti-beta cell murine mAb, bound most strongly to ganglioside GT3. The binding of human sera to gangliosides was analyzed by an ELISA assay. Although both normal and diabetic sera contained antibodies to various glycolipids, binding to GT3 was significantly elevated in 31 new-onset type I diabetics (p less than 0.001). The presence of the GT3 trisialosyl epitope on human islet cells was shown by immunofluorescent staining by both R2D6 and A2B5. These findings support previous suggestions that gangliosides play an important role in the immunopathology of type I diabetes, and identify for the first time a specific ganglioside Ag that is the target for autoantibodies in a subset of diabetic patients.
A dynamic range resource reservation protocol for QoS support in wireless networks (2005)

Summary form only given. In order to provide support for multimedia applications in mobile ad hoc networks (MANETs), quality of service (QoS) support becomes an important component in their design. In this paper, we present a dynamic range bandwidth reservation protocol for TDMA-based MANETs. In this protocol, a source node S, that needs to send data, sends a request message (QREQ) to reserve a QoS path to the desired destination node D. In the reservation message, the source node specifies a dynamic range [b/sub min/, b/sub max/] of the number of slots needed to transmit the data. The intermediate nodes along the path try to reserve a number of slots, b/sub cur/, that is equal to the maximum number of slots that are "available" within this range (b/sub min/ /spl ges/ b/sub cur/ /spl ges/ b/sub max/). The protocol also permits intermediate nodes to dynamically "downgrade" existing paths that are functioning above their minimum requirements in order to allow the successful reservation for the maximum number of requested paths. When the network traffic load is later decreased, the existing paths are able to be "upgraded" to function with higher bandwidth requirements. This allows the network to admit new QoS paths instead of denying such requests by allowing for "graceful degradation" of other paths. The paper also presents several optimization techniques which are designed to increase the efficiency and throughput of the network. This protocol allows a higher level of flexibility in providing and maintaining QoS support in MANETs.
Antibody engineering--IBC's Tenth International Conference. 6-9 December 1999, La Jolla, CA, USA. (2000)

This meeting covered emergent antibody technologies through preclinical and clinical development of antibodies to the latest clinical data with antibody drugs. On the technology front, human antibody phage libraries have increased in size and quality, and have been combined with high-throughput screening methods. Such phage libraries have become powerful tools for the generation of antibody therapeutics and may also prove useful in the identification of new therapeutic targets. Indeed, four high affinity human antibodies from phage libraries are currently in clinical trials. Transgenic mice containing human immunoglobulin genes have also emerged as a route to high affinity human antibodies, including two that have progressed into the clinic. Molecular evolution of scFv fragments to increase their stability has led to improved localization to tumors in animal models and to their enhanced performance as intrabodies. In clinical trials, significant efficacy with minimal or acceptable toxicities were reported for the chimeric Fab fragment, ReoPro (abciximab; Centocor Inc), in coronary artery disease; the humanized anti-HER2 antibody, Herceptin (trastuzumab; Genentech Inc), in metastatic breast cancer; and, the humanized anti-IgE antibody, E25 (Genentech Inc), in asthma and allergic rhinitis.