gebhart/patrepeval huggingface dataset:
Functional characterization of calcium-sensing receptor mutations expressed in human embryonic kidney cells. (1996)

The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that plays a key role in extracellular calcium ion homeostasis. We have engineered 11 CaR mutants that have been described in the disorders familial benign hypercalcemia (FBH), neonatal severe hyperparathyroidism (NSHPT), and autosomal dominant hypocalcaemia (ADH), and studied their function by characterizing intracellular calcium [Ca2+]i transients in response to varying concentrations of extracellular calcium [Ca2+]o or gadolinium [Gd3+]o. The wild type receptor had an EC50 for calcium (EC50[Ca2+]o) (the value of [Ca2+]o producing half of the maximal increase in [Ca2+]i) of 4.0 mM (+/- 0.1 SEM). However, five missense mutations associated with FBH or NSHPT, (P55L, N178D, P221S, R227L, and V817I) had significantly higher EC50[Ca2+]os of between 5.5 and 9.3 mM (all P < 0.01). Another FBH mutation, Y218S, had an EC50[Ca2+]o of > 50 mM but had only a mildly attenuated response to gadolinium, while the FBH mutations, R680C and P747fs, were unresponsive to either calcium or gadolinium. In contrast, three mutations associated with ADH, (F128L, T151M, and E191K), showed significantly reduced EC50[Ca2+]os of between 2.2 and 2.8 mM (all P < 0.01). These findings provide insights into the functional domains of the CaR and demonstrate that mutations which enhance or reduce the responsiveness of the CaR to [Ca2+]o cause the disorders ADH, FBH, and NSHPT, respectively.
Passage to Nonselective Media Transiently Alters Growth of Mycophenolic Acid-Resistant Mammalian Cells Expressing theEscherichia coliXanthine–Guanine Phosphoribosyltransferase Gene: Implications for Sequential Selection Strategies (1996)

The Escherichia coli xanthine-guanine phosphoribosyltransferase gene (Ecogpt) rescues mammalian cells from inhibition of purine nucleotide biosynthesis by mycophenolic acid (MPA). We used Ecogpt and other selectable markers to obtain subclones of NIH 3T3 derivatives (EN/NIH) stably expressing transfected genes of interest. In their respective selective mediums, growth of MPA-resistant (MPA(R)) isolates was indistinguishable from that of aminoglycoside-resistant counterparts expressing selectable marker genes conferring resistance to protein synthesis inhibitors hygromycin B, puromycin, and G418. Growth of aminoglycoside-resistant isolates remained unaltered on passage to nonselective media. In contrast, MPA(R) cells transferred from MPA complete media to nonselective media displayed morphologic changes with static growth. These findings resolved completely by third passage in nonselective media and were independent of the gene of interest cis-linked to the selectable marker. Sequential selection strategies involving cell culture conditions resulting in these altered growth characteristics significantly impaired detection (by selection in G418) of genomic events associated with reactivation of enhancerless, transcriptionally silent neointegrants present in MPA(R) EN/NIH isolates. We explored the cause of these cell culture findings and defined transfection and sequential selection strategies for MPA(R) derivatives that successfully circumvented these effects.
Intelligent Unmanned Ground Vehicles: Autonomous Navigation Research at Carnegie Mellon (1997)

From the Publisher:
Intelligent Unmanned Ground Vehicles describes the technology developed and the results obtained by the Carnegie Mellon Robotics Institute in the course of the DARPA Unmanned Ground Vehicle (UGV) project. The goal of this work was to equip off-road vehicles with computer-controlled, unmanned driving capabilities. The book describes contributions in the area of mobility for UGVs including: tools for assembling complex autonomous mobility systems; on-road and off-road navigation; sensing techniques; and route planning algorithms. In addition to basic mobility technology, the book covers a number of integrated systems demonstrated on the field in realistic scenarios. The approaches presented in this book can be applied to a wide range of mobile robotics applications, from automated passenger cars to planetary exploration, construction and agricultural machines.
System for inspection of large high-resolution radiography datasets (2011)

High-resolution image collections pose unique challenges to analysts tasked with managing the associated data assets and deriving new information from them. While significant progress has been made towards rapid automated filtering, alignment, segmentation, characterization, and feature identification from image collections, the extraction of new insights still strongly depends on human intervention. In real-time capture and immediate-mode analysis environments where image data has to be continuously and interactively processed, a broad set of challenges in the image-driven verification and analysis cycle have to be addressed. A framework for interactive and intuitive inspection of large, high-resolution image data sets is presented, leveraging the strength of the human visual system for large-scale image processing. A case study is provided for an X-ray radiography system, covering the scanner-to-screen data management and representation pipeline, resulting in a visual analytics environment enabling analytical reasoning by means of interactive and intuitive visualization.
Evolution and predictive factors of thyroid disorder due to interferon alpha in the treatment of hepatitis C (2009)

In this monocentric population of CHC, dysthyroidism, especially hyperthyroidism, developed in 10% of patients. Low fibrosis was found to be a predictive factor of dysthyroidism. Thyroid disorder recovered in 16/30 patients (53%) and recovery was better in the non-autoimmune form.
Efficient networks for quantum factoring (1996)

We consider how to optimize memory use and computation time in operating a quantum computer. In particular, we estimate the number of memory quantum bits (qubits) and the number of operations required to perform factorization, using the algorithm suggested by Shor [in Proceedings of the 35th Annual Symposium on Foundations of Computer Science, edited by S. Goldwasser (IEEE Computer Society, Los Alamitos, CA, 1994), p. 124]. A K-bit number can be factored in time of order ${\mathit{K}}^{3}$ using a machine capable of storing 5K+1 qubits. Evaluation of the modular exponential function (the bottleneck of Shor's algorithm) could be achieved with about 72${\mathit{K}}^{3}$ elementary quantum gates; implementation using a linear ion trap would require about 396${\mathit{K}}^{3}$ laser pulses. A proof-of-principle demonstration of quantum factoring (factorization of 15) could be performed with only 6 trapped ions and 38 laser pulses. Though the ion trap may never be a useful computer, it will be a powerful device for exploring experimentally the properties of entangled quantum states. \textcopyright{} 1996 The American Physical Society.
The Aryl Hydrocarbon Receptor (2012)

The aryl hydrocarbon receptor (AHR), which has been central to studies in toxicology for years as the receptor for the toxicant dioxin, is rapidly gaining interest in immunology based on its ability to influence T-cell differentiation. Multiple studies have documented that binding of this receptor with certain ligands favors T-cell differentiation toward regulatory T cells, and paradoxically, binding of this same receptor with different ligands enhances Th17 effector cell differentiation. This finding has been confirmed in both in vitro and in vivo models, where different ligands are able to either ameliorate or conversely aggravate autoimmunity in experimental autoimmune encephalomyelitis. The AHR has both an endogenous role that is important in development and normal physiology and an exogenous role as a receptor for manmade toxicants, with their binding leading to transcription of cytochrome P450 enzymes that metabolize these same ligands. Based on recent reports that will be summarized in this overview, we will consider the role that the AHR might play as a sensor to the outside environment, leading to alteration of the acquired immune system that might have relevance in transplantation or other medical conditions. In addition to describing the data in normal physiology and T-cell differentiation, we will present examples of the importance of this receptor in preclinical models of disease and highlight specific ligands that target the AHR and will have efficacy in treating transplant rejection and in tolerance protocols.
Product Accumulate Codes: A Class of Codes With Near-Capacity Performance and Low Decoding Complexity (2004)

We propose a novel class of provably good codes which are a serial concatenation of a single-parity-check (SPC)-based product code, an interleaver, and a rate-1 recursive convolutional code. The proposed codes, termed product accumulate (PA) codes, are linear time encodable and linear time decodable. We show that the product code by itself does not have a positive threshold, but a PA code can provide arbitrarily low bit-error rate (BER) under both maximum-likelihood (ML) decoding and iterative decoding. Two message-passing decoding algorithms are proposed and it is shown that a particular update schedule for these message-passing algorithms is equivalent to conventional turbo decoding of the serial concatenated code, but with significantly lower complexity. Tight upper bounds on the ML performance using Divsalar's (1999) simple bound and thresholds under density evolution (DE) show that these codes are capable of performance within a few tenths of a decibel away from the Shannon limit. Simulation results confirm these claims and show that these codes provide performance similar to turbo codes but with significantly less decoding complexity and with a lower error floor. Hence, we propose PA codes as a class of prospective codes with good performance, low decoding complexity, regular structure, and flexible rate adaptivity for all rates above 1/2.
Identification and Characterization of a Novel Human Sphingosine-1-phosphate Phosphohydrolase, hSPP2 (2003)

Sphingosine 1-phosphate (S1P) is a bioactive lipid molecule that acts as both an extracellular signaling mediator and an intracellular second messenger. S1P is synthesized from sphingosine by sphingosine kinase and is degraded either by S1P lyase or by S1P phosphohydrolase. Recently, mammalian S1P phosphohydrolase (SPP1) was identified and shown to constitute a novel lipid phosphohydrolase family, the SPP family. In this study we have identified a second human S1P phosphohydrolase, SPP2, based on sequence homology to human SPP1. SPP2 exhibited high phosphohydrolase activity against S1P and dihydrosphingosine 1-phosphate. The dihydrosphingosine-1-phosphate phosphohydrolase activity was efficiently inhibited by excess S1P but not by lysophosphatidic acid, phosphatidic acid, or glycerol 3-phosphate, indicating that SPP2 is highly specific to sphingoid base 1-phosphates. Immunofluorescence microscopic analysis demonstrated that SPP2 is localized to the endoplasmic reticulum. Although the enzymatic properties and localization of SPP2 were similar to those of SPP1, the tissue-specific expression pattern of SPP2 was different from that of SPP1. Thus, SPP2 is another member of the SPP family that may play a role in attenuating intracellular S1P signaling.
Evidence that prolyl endopeptidase participates in the processing of brain angiotensin (1991)

In order to understand angiotensin metabolism in the canine brain, we determined the molecular forms of angiotensin peptides present in the hypothalamus of the dog and carried out measurements of the metabolism of 125I-angiotensin I in homogenates of that tissue. Angiotensin peptides were extracted from canine hypothalamic tissue and quantified by specific radioimmunoassays combined with high-performance liquid chromatography. The major angiotensin peptides detected were angiotensin-(2-7) (391.2 +/- 16.8 pg/g tissue) and angiotensin-(3-7) (864.8 +/- 128.1 pg/g). Angiotensin II immunoreactivity was mainly composed of angiotensin-(3-8) (117.5 +/- 64 pg/g) and trace amounts of angiotensin II and angiotensin III. Angiotensin I immunoreactivity was composed of angiotensin I (52.3 +/- 5.8 pg/g). In separate experiments, addition of 125I-angiotensin I into supernatants (18,000 g for 2 min) of canine hypothalamic homogenates resulted in the accumulation of 125I-angiotensin-(1-7) as the major peptide product (14% of the total 125I-radioactivity) at 2 min. Incubation of the homogenate supernatants with enalaprilat (1 mumol/l), phosphoramidon (10 mumol/l), or ethylenediamine tetraacetic acid (1 mmol/l) did not inhibit the production of 125I-angiotensin-(1-7). In contrast, addition of Z-Pro-Prolinal (1 mumol/l), a specific inhibitor of prolyl endopeptidase, prevented the generation of 125I-angiotensin-(1-7) from 125I-angiotensin I by 47.0 +/- 8.0% (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
Tight clustering and hemizygosity of apomixis-linked molecular markers in Pennisetum squamulatum implies genetic control of apospory by a divergent locus that may have no allelic form in sexual genotypes (1998)

Apomixis is a naturally occurring mode of reproduction that results in embryo formation without the involvement of meiosis or fertilization of the egg. Seed-derived progeny of an apomictic plant are genetically identical to the maternal parent. We are studying a form of apomixis called apospory that occurs in the genus Pennisetum, a taxon in the grass family. A cultivated member of this genus, pearl millet (Pennisetum glaucum), reproduces sexually. A wild relative of pearl millet, Pennisetum squamulatum, that is an obligate aposporous species, is cross-compatible with pearl millet when used as a pollen donor in the interspecific cross. We present herein the genetic mapping of 13 molecular markers in an interspecific hybrid population of 397 individuals that segregates for apomixis and sexuality. Surprisingly, 12 of the 13 markers strictly cosegregated with aposporous embryo sac development, clearly defining a contiguous apospory-specific genomic region in which no genetic recombination was detected. Lack of or suppression of recombination may be coincidentally associated with the chromosomal context of the apomixis locus or it may be a consequence of its evolution that is essential for preservation of gene function as has been previously shown in studies of complex loci in both plant and animal species.
Pro-atrial natriuretic peptide1-126 is processed in the human circulation to a mature GC-A activating peptide with therapeutic potential in heart failure (2013)

Purpose: Atrial natriuretic peptide (ANP), a stimulator of cGMP through its receptor, GC-A, circulates in various molecular forms in humans. Importantly, mature ANP1-28 and Urodilatin, which is ANP1-28 plus 4 additional N-terminus added amino acids, are used as drugs for acute decompensated heart failure (HF). GC-A activation in the heart is characterized by anti-hypertrophic and anti-fibrotic responses in vivo and in vitro. To date it remains unclear if the precursor; proANP1-126 is processed by convertase corin into active forms in the circulation of normal and HF with the possibility that if converted could serve as a long-acting ANP like peptide for HF. Studies report that corin is reduced in the circulation in HF and thus proANP processing might be impaired. Methods: Fresh serum was obtained from normals (n=13) and patients with NYHA III to IV HF (n=14). Samples were incubated with or without Histidine-tagged exogenous proANP1-126 in the C-terminus to facilitate isolation of processed forms which were isolated by immunoprecipitation and detected by Western Blot (WB), and then sequenced. GC-A or GC-B expressing HEK293 cells were treated with/without mature ANP1-28, proANP1-126, the isolated peptides from proANP1-126 in serum, and the cGMP activity determined by specific assay was measured so as to test biological activity of processed ANP. In addition, cGMP activity and TGF beta-1 stimulated Collagen type I (Col I) mRNA expression measured by qPCR in human cardiac fibroblasts (CFs) in which corin protein exist were examined with or without treatment with ANP1-28 or proANP1-126. Results: ProANP1-126 was processed into ANP1-28 in normal serum; processed ANP1-28 appeared at 5 min and then decreased but remained present at 180 min. In HF serum proANP1-126 was processed at the same rate as in normals The processed peptide from proANP1-126 as well as unprocessed proANP1-126 stimulated cGMP production in GC-A cells, but processed peptide had significantly higher cGMP stimulation than unprocessed proANP1-126. In addition, proANP1-126 had equivalent cGMP activating and Col I mRNA inhibiting actions compared to ANP in CFs. Conclusions: Exogenous proANP1-126 is processed into biologically active GC-A peptides in both normal and HF human serum. ProANP1-126 and its processed form possess significant cGMP activating and anti-fibrotic actions in vitro in human CFs. Importantly, proANP1-126 appears to have a longer half-life than mature ANP1-28 ex vivo, suggesting the emerging concept that proANP1-126 may have a therapeutic opportunity as a long acting GC-A agonist for HF.
Overexpression and sequence of the Escherichia coli cheY gene and biochemical activities of the CheY protein (1984)

We overexpressed the CheY protein by fusing the cheY gene to the tryptophan promoter from Serratia marcescens. Expression of the trp promoter-cheY fusion and subsequent purification of the protein resulted in the isolation of up to 20 mg of homogeneously pure CheY protein from 100 mg of the cytoplasmic supernatant fraction. Purification of the CheY protein was accomplished by exploiting the affinity of CheY protein to cibacron blue dye and molecular sieve chromatography. Preliminary biochemical characterization of the pure CheY protein revealed specific interactions with S-adenosylmethionine and cibacron blue dye. Additional kinetic analysis showed that CheY protein inhibits EcoRI methyltransferase. The amino acid composition of the CheY protein predicted by the DNA sequence of the cheY gene and the amino acid analysis of the CheY protein were in agreement, confirming the authenticity of the purified CheY protein.
Analysis of Stresses Along the Underfill/chip Interface (2002)

The stresses of the underfill/chip interface due to thermal loading was studied using the finite element method. At first, the effective properties of underfill for several volume fractions of silica particles were calculated by Mori-Tanaka method for three different material sets, and the parameters of singularity for the bimaterial edge and the bimaterial wedge were calculated. Consequently, the stresses at the underfill/chip interface with volume fraction of silica particles were investigated. Five different geometric models of flip-chip assembly involving two kinds of bimaterial strips and three kinds of three-layer models were considered under the assumption that the underfill is homogeneous. It was assumed that all components of the flip-chip assembly were linear elastic and isotropic, and their properties were temperature independent. The analysis was conducted in the context of the uncoupled plane thermo-elasticity under a plane strain assumption.
Radiolabeled Somatostatin Analog [177Lu-DOTA0,Tyr3]Octreotate in Patients With Endocrine Gastroenteropancreatic Tumors (2005)

Treatment with 177Lu-octreotate results in tumor remission in a high percentage of patients with GEP tumors. Serious side effects are rare. The median time to progression compares favorably with chemotherapy. Results are better in patients with a limited tumor load. Therefore, early treatment, even in patients who have no PD, may be better.
TNF-Related Apoptosis-Inducing Ligand (TRAIL) Induces Apoptosis in Fas Ligand-Resistant Melanoma Cells and Mediates CD4 T Cell Killing of Target Cells (1998)

We have previously shown that melanoma cells were resistant to apoptosis induced by TNF family members Fas ligand (FasL), TNF-alpha, and CD40L. FasL also was not involved in CD4 T cell-mediated killing of melanoma cells. In the present study, we have tested melanoma cells for their susceptibility to apoptosis induced by human TNF-related apoptosis-inducing ligand (TRAIL) and the ability of a mAb against TRAIL to inhibit apoptosis and CD4 CTL-mediated killing of melanoma and Jurkat target cells. The results show that TRAIL-induced apoptosis in cells from 7 of 10 melanoma cell lines tested as well as in Jurkat T cells. Susceptibility to apoptosis was increased in some of the cell lines by treatment with cyclohexamide or actinomycin D. The melanoma cells were resistant to apoptosis induced by FasL, TNF-alpha, and CD40L. mAb M180 against TRAIL inhibited apoptosis induced by TRAIL. It was also found to inhibit CD4 CTL-mediated killing of Jurkat T cells as well as autologous and allogeneic melanoma cells. The degree of inhibition produced by the mAb varied between different clones of CTL and according to the susceptibility of the target cells to TRAIL-induced apoptosis. These results suggest that TRAIL is an important mediator of cell death induced by CTL and may have an important therapeutic role against human melanoma.
pH-Mediated field-amplified sample stacking of pharmaceutical cations in high-ionic strength samples (2001)

Capillary electrophoretic separation of samples of physiological origin typically have both poor resolution and efficiency due to destacking. We have previously reported a stacking method for concentration of catecholamines in artificial dialysate, or Ringer's solution. However, pH-mediated sample stacking of other cations has not been investigated. In this report, pH-mediated stacking has been extended to eletripan, dofetilide, doxazosin, sildenafil, UK-103,320, UK-202,581, and CP-122,288. These compounds were chosen without prior structural screening except that they were cationic at the pH of our background electrolyte (BGE). Capillary electrophoretic behavior of samples in BGE is compared with those of samples in Ringer's solution with and without pH-mediated acid stacking. Results indicate that the peak heights and efficiencies for acid-stacked samples are increased compared to the unstacked samples in Ringer's solution or BGE. For example, the peak efficiencies for 5 s injections of eletriptan in BGE and Ringer's solution are 138,000 and 72,000 plates, respectively. In contrast, a 10 s injection of eletriptan followed by acid injection for 16 s produces a peak with 246,000 plates. Evaluation of the stacking effect was performed by comparison of the peak height at similar peak efficiencies for samples in Ringer's solution with and without stacking. Using this method, pH-mediated acid stacking provides a 10- to 27-fold sensitivity enhancement for the seven cations.