gebhart/patrepeval huggingface dataset:
Gene Structure Prediction and Alternative Splicing Analysis Using Genomically Aligned ESTs (2001)

With the availability of a nearly complete sequence of the human genome, aligning expressed sequence tags (EST) to the genomic sequence has become a practical and powerful strategy for gene prediction. Elucidating gene structure is a complex problem requiring the identification of splice junctions, gene boundaries, and alternative splicing variants. We have developed a software tool, Transcript Assembly Program (TAP), to delineate gene structures using genomically aligned EST sequences. TAP assembles the joint gene structure of the entire genomic region from individual splice junction pairs, using a novel algorithm that uses the EST-encoded connectivity and redundancy information to sort out the complex alternative splicing patterns. A method called polyadenylation site scan (PASS) has been developed to detect poly-A sites in the genome. TAP uses these predictions to identify gene boundaries by segmenting the joint gene structure at polyadenylated terminal exons. Reconstructing 1007 known transcripts, TAP scored a sensitivity (Sn) of 60% and a specificity (Sp) of 92% at the exon level. The gene boundary identification process was found to be accurate 78% of the time. also reports alternative splicing patterns in EST alignments. An analysis of alternative splicing in 1124 genic regions suggested that more than half of human genes undergo alternative splicing. Surprisingly, we saw an absolute majority of the detected alternative splicing events affect the coding region. Furthermore, the evolutionary conservation of alternative splicing between human and mouse was analyzed using an EST-based approach. (See http://stl.wustl.edu/~zkan/TAP/)
Demonstration of an erbium-doped microdisk laser on a silicon chip (2006)

An erbium-doped microlaser is demonstrated utilizing $\mathrm{Si}{\mathrm{O}}_{2}$ microdisk resonators on a silicon chip. Passive microdisk resonators exhibit whispering-gallery-type modes (WGM's) with intrinsic optical quality factors of up to $6\ifmmode\times\else\texttimes\fi{}{10}^{7}$ and were doped with trivalent erbium ions (peak concentration $\ensuremath{\sim}3.8\ifmmode\times\else\texttimes\fi{}{10}^{20}\phantom{\rule{0.3em}{0ex}}{\mathrm{cm}}^{\ensuremath{-}3}$) using MeV ion implantation. Coupling to the fundamental WGM of the microdisk resonator was achieved by using a tapered optical fiber. Upon pumping of the $^{4}I_{15∕2}\ensuremath{\rightarrow}^{4}I_{13∕2}$ erbium transition at $1450\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$, a gradual transition from spontaneous to stimulated emission was observed in the $1550\text{\ensuremath{-}}\mathrm{nm}$ band. Analysis of the pump-output power relation yielded a pump threshold of $43\phantom{\rule{0.3em}{0ex}}\ensuremath{\mu}\mathrm{W}$ and allowed measuring the spontaneous emission coupling factor: $\ensuremath{\beta}\ensuremath{\approx}1\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}$.
Controlling the Dissociation of Ligands from the Adenosine A 2A Receptor through Modulation of Salt Bridge Strength (2016)

The association and dissociation kinetics of ligands binding to proteins vary considerably, but the mechanisms behind this variability are poorly understood, limiting their utilization for drug discovery. This is particularly so for G protein-coupled receptors (GPCRs) where high resolution structural information is only beginning to emerge. Engineering the human A2A adenosine receptor has allowed structures to be solved in complex with the reference compound ZM241385 and four related ligands at high resolution. Differences between the structures are limited, with the most pronounced being the interaction of each ligand with a salt bridge on the extracellular side of the receptor. Mutagenesis experiments confirm the role of this salt bridge in controlling the dissociation kinetics of the ligands from the receptor, while molecular dynamics simulations demonstrate the ability of ligands to modulate salt bridge stability. These results shed light on a structural determinant of ligand dissociation kinetics and identify a means by which this property may be optimized.
Cerebrospinal Fluid Biomarkers of Alzheimer's Disease (2010)

Alzheimer's disease will reach epidemic proportions within the next 20-30 years if left unchecked. Currently, there are no treatments that prevent or slow Alzheimer's disease but many are being developed. Parallel efforts to develop biomarkers to aid in disease diagnosis and prognosis, and assess disease risk are currently underway. Clinicopathological and biomarker studies have demonstrated that Alzheimer's disease pathology can be detected preclinically. Using biomarkers to identify affected individuals prior to the onset of clinical symptoms and associated synaptic/neuronal loss should enable novel clinical trial design and early mechanism-based therapeutic intervention. This article summarizes the most promising cerebrospinal fluid biomarkers, highlights novel applications and current challenges, and provides a prediction on how the field may evolve in 5-10 years.
Discovery of a Potent, Selective, and Orally Available Class I Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Kinase Inhibitor (GDC-0980) for the Treatment of Cancer (2011)

The discovery of 2 (GDC-0980), a class I PI3K and mTOR kinase inhibitor for oncology indications, is described. mTOR inhibition was added to the class I PI3K inhibitor 1 (GDC-0941) scaffold primarily through the substitution of the indazole in 1 for a 2-aminopyrimidine. This substitution also increased the microsomal stability and the free fraction of compounds as evidenced through a pairwise comparison of molecules that were otherwise identical. Highlighted in detail are analogues of an advanced compound 4 that were designed to improve solubility, resulting in 2. This compound, is potent across PI3K class I isoforms with IC(50)s of 5, 27, 7, and 14 nM for PI3Kα, β, δ, and γ, respectively, inhibits mTOR with a K(i) of 17 nM yet is highly selective versus a large panel of kinases including others in the PIKK family. On the basis of the cell potency, low clearance in mouse, and high free fraction, 2 demonstrated significant efficacy in mouse xenografts when dosed as low as 1 mg/kg orally and is currently in phase I clinical trials for cancer.
Identification of novel HXT genes in Saccharomyces cerevisiae reveals the impact of individual hexose transporters on qlycolytic flux (1995)

In Saccharomyces cerevisiae, hexose uptake is mediated by HXT proteins which belong to a superfamily of monosaccharide facilitators. We have identified three more genes that encode hexose transporters (HXT5, 6, 7). Genes HXT6 and HXT7 are almost identical and located in tandem 3' adjacent to HXT3 on chromosome IV. We have constructed a set of congenic strains expressing none or any one of the seven known HXT genes and followed growth and flux rates for glucose utilization. The hxt null strain does not grow on glucose, fructose or mannose, and both glucose uptake and flux rate were below the detection level. Expression of either HXT1, 2, 3, 4, 6 or 7 is basically sufficient for aerobic growth on these sugars. In most of the constructs, glucose was the preferred substrate compared to fructose or mannose. There is a considerable variation in flux and growth rates with 1% glucose, dependent on the expression of the individual HXT genes. Expression of either HXT2, 6 or 7 in the null background is sufficient for growth on 0.1% glucose, while growth of strains with only HXT1, 3 or 4 requires higher (> or = 1%) glucose concentrations. These results demonstrate that individual HXT proteins can function independently as hexose transporters, and that most of the metabolically relevant HXT transporters from S. cerevisiae have been identified.
On the Flexible 5G Dense Deployment Air Interface for Mobile Broadband (2014)

In this paper we contemplate 5G frame structure for dense deployment. We discuss harmonized OFDM concept, in which the cyclic prefix length and subcarrier spacing are functions of carrier frequency while FFT size and base clock remain constant. The subframe structure consists of time separated contr
A structural view of the Cedar programming environment (1986)

This paper presents an overview of the Cedar programming environment, focusing on its overall structure—that is, the major components of Cedar and the way they are organized. Cedar supports the development of programs written in a single programming language, also called Cedar. Its primary purpose is to increase the productivity of programmers whose activities include experimental programming and the development of prototype software systems for a high-performance personal computer. The paper emphasizes the extent to which the Cedar language, with run-time support, has influenced the organization, flexibility, usefulness, and stability of the Cedar environment. It highlights the novel system features of Cedar, including automatic storage management of dynamically allocated typed values, a run-time type system that provides run-time access to Cedar data type definitions and allows interpretive manipulation of typed values, and a powerful device-independent imaging model that supports the user interface facilities. Using these discussions to set the context, the paper addresses the language and system features and the methodologies used to facilitate the integration of Cedar applications. A comparison of Cedar with other programming environments further identifies areas where Cedar excels and areas where work remains to be done.
Surface functionalization of thin-film diamond for highly stable and selective biological interfaces (2010)

Carbon is an extremely versatile family of materials with a wide range of mechanical, optical, and mechanical properties, but many similarities in surface chemistry. As one of the most chemically stable materials known, carbon provides an outstanding platform for the development of highly tunable molecular and biomolecular interfaces. Photochemical grafting of alkenes has emerged as an attractive method for functionalizing surfaces of diamond, but many aspects of the surface chemistry and impact on biological recognition processes remain unexplored. Here we report investigations of the interaction of functionalized diamond surfaces with proteins and biological cells using X-ray photoelectron spectroscopy (XPS), atomic force microscopy, and fluorescence methods. XPS data show that functionalization of diamond with short ethylene glycol oligomers reduces the nonspecific binding of fibrinogen below the detection limit of XPS, estimated as &gt; 97% reduction over H-terminated diamond. Measurements of different forms of diamond with different roughness are used to explore the influence of roughness on nonspecific binding onto H-terminated and ethylene glycol (EG)-terminated surfaces. Finally, we use XPS to characterize the chemical stability of Escherichia coli K12 antibodies on the surfaces of diamond and amine-functionalized glass. Our results show that antibody-modified diamond surfaces exhibit increased stability in XPS and that this is accompanied by retention of biological activity in cell-capture measurements. Our results demonstrate that surface chemistry on diamond and other carbon-based materials provides an excellent platform for biomolecular interfaces with high stability and high selectivity.
Dissecting Cooperative and Additive Binding Energetics in the Affinity Maturation Pathway of a Protein-Protein Interface (2003)

When two proteins associate they form a molecular interface that is a structural and energetic mosaic. Within such interfaces, individual amino acid residues contribute distinct binding energies to the complex. In combination, these energies are not necessarily additive, and significant positive or negative cooperative effects often exist. The basis of reliable algorithms to predict the specificities and energies of protein-protein interactions depends critically on a quantitative understanding of this cooperativity. We have used a model protein-protein system defined by an affinity maturation pathway, comprising variants of a T cell receptor Vbeta domain that exhibit an overall affinity range of approximately 1500-fold for binding to the superantigen staphylococcal enterotoxin C3, in order to dissect the cooperative and additive energetic contributions of residues within an interface. This molecular interaction has been well characterized previously both structurally, by x-ray crystallographic analysis, and energetically, by scanning alanine mutagenesis. Through analysis of group and individual maturation and reversion mutations using surface plasmon resonance spectroscopy, we have identified energetically important interfacial residues, determined their cooperative and additive energetic properties, and elucidated the kinetic and thermodynamic bases for molecular evolution in this system. The summation of the binding free energy changes associated with the individual mutations that define this affinity maturation pathway is greater than that of the fully matured variant, even though the affinity gap between the end point variants is relatively large. Two mutations in particular, both located in the complementarity determining region 2 loop of the Vbeta domain, exhibit negative cooperativity.
Preparation of monodisperse nanoparticles containing poly(propylene imine)(NH2)32‐polystyrene (2009)

Abstract Polypropylenimine dendrimer (DAB‐Am‐32, generation 4.0) was converted into a macroinitiator DAB‐Am‐32‐Cl via reaction with 2‐chloropropionyl chloride. Monodisperse nanoparticles containing poly(propylene imine)(NH 2 ) 32 ‐polystyrene were prepared by emulsion atom transfer radical polymerization (ATRP) of styrene (St), using the DAB‐Am‐32‐Cl/CuCl/bpy as initiating system. The structure of macroinitiator was characterized by FTIR spectrum, 1 H NMR, and 13 C NMR. The structure of poly(propylene imine)(NH 2 ) 32 ‐polystyrene was characterized by FT‐IR spectrum and 1 H NMR; the molecular weight and molecular weight distribution of poly(propylene imine)(NH 2 ) 32 ‐polystyrene were characterized by gel permeation chromatograph (GPC). The morphology, size and size distribution of the nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The effects of monomer/macroinitiator ratio and surfactant concentration on the size and size distribution of the nanoparticles were investigated. It was found that the diameters of the nanoparticles were smaller than 100 nm (30–80 nm) and monodisperse; moreover, the particle size could be controlled by monomer/macroinitiator ratios and surfactant concentration. With the increasing of the ratio of St/DAB‐Am‐32‐Cl, the number‐average diameter ( D n ), weight‐average diameter ( D w ) were both increased gradually. With enhancing the surfactant concentration, the measured D h of the nanoparticles decreased, while the polydispersity increased. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2892–2904, 2009
Spectroscopic ellipsometry and reflectometry: a user's guide (1999)

While single wave ellipsometry has been around for years, spectroscopic ellipsometry is fast becoming the method of choice for measuring the thickness and optical properties of thin films. This book provides the first practical introduction to spectroscopic ellipsometry and the related techniques of reflectometry. A guide for practitioners and researchers in a variety of disciplines, it addresses a broad range of applications in physics, chemistry, electrical engineering, and materials science.
Theory of Metal Surfaces: Work Function (1971)

In a recent paper we presented a contribution to the theory of metal surfaces with emphasis on the shape of the electron-density distribution and the surface energy. The present paper extends this analysis to a consideration of the work function. Some general theoretical relationships are established. Effects of the ions are included using a simple pseudopotential theory, permitting the calculation of the variation of the work function from one crystal face to another. For simple metals (Li, Na, K, Rb, Cs, Al, Pb, Zn, and Mg), agreement with available experimental data is good (5-10%); for the noble metals, the computed work functions are 15-30% too low.
Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer. (2001)

Determined values for serum BSP in ng/ml were 285 +/- 19 for prostate, 373 +/- 19 for colon, 318 +/- 18 for breast, 155 +/- 11 for lung cancer sera, and 154 +/- 13 for normal sera. Values of OPN in ng/ml were 653 +/- 39 for prostate, 449 +/- 22 for colon, 814 +/- 53 for breast, 724 +/- 33 for lung, and 439 +/- 30 for normal sera. The assays provide a high degree of sensitivity and specificity that enables the detection of colon, breast, prostate, and lung cancer.
Utility of serum tartrate‐resistant acid phosphatase (TRACP5b) as a bone resorption marker in patients with chronic kidney disease: independence from renal dysfunction (2008)

Serum TRACP5b may be a good marker for serum bone resorption in predialysis CKD patients, as it is not affected by renal dysfunction.
Wound Induced Tanscriptional Regulation of Benzylisoquinoline Pathway and Characterization of Wound Inducible PsWRKY Transcription Factor from Papaver somniferum (2013)

Wounding is required to be made in the walls of the green seed pod of Opium poppy prior exudation of latex. To withstand this kind of trauma plants regulate expression of some metabolites through an induced transcript level. 167 unique wound-inducible ESTs were identified by a repetitive round of cDNA subtraction after 5 hours of wounding in Papaver somniferum seedlings. Further repetitive reverse northern analysis of these ESTs revealed 80 transcripts showing more than two fold induction, validated through semi-quantitative RT-PCR & real time expression analysis. One of the major classified categories among identified ESTs belonged to benzylisoquinoline transcripts. Tissue specific metabolite analysis of benzylisoquinoline alkaloids (BIAs) in response to wounding revealed increased accumulation of narcotine and papaverine. Promoter analysis of seven transcripts of BIAs pathway showed the presence of W-box cis-element with the consensus sequence of TGAC, which is the proposed binding site for WRKY type transcription factors. One of the Wound inducible 'WRKY' EST isolated from our subtracted library was made full-length and named as 'PsWRKY'. Bacterially expressed PsWRKY interacted with the W-box element having consensus sequence TTGACT/C present in the promoter region of BIAs biosynthetic pathway genes. PsWRKY further activated the TYDC promoter in yeast and transiently in tobacco BY2 cells. Preferential expression of PsWRKY in straw and capsule and its interaction with consensus W-box element present in BIAs pathway gene transcripts suggest its possible involvement in the wound induced regulation of BIAs pathway.
Wear of Gamma-Crosslinked Polyethylene Acetabular Cups Against Roughened Femoral Balls (1999)

Crosslinking of ultrahigh molecular weight polyethylene has been shown to markedly improve its wear resistance in clinical studies and laboratory tests using hip joint simulators. However, because most of the laboratory studies have been done under clean conditions using prosthesis-quality, highly polished counterfaces, there is concern regarding how well an intentionally crosslinked polyethylene acetabular cup will resist abrasion by a femoral ball that has been damaged by third-body abrasion in vivo. To investigate this, conventional and radiation crosslinked-remelted acetabular cups of ultra-high molecular weight polyethylene were tested in a hip joint simulator bearing against smooth femoral balls and against balls with moderate and severe roughening. Cups were tested with and without aging to accelerate any oxidative degradation. The crosslinked cups were produced by exposing extruded GUR 4150 bar stock of ultrahigh molecular weight polyethylene to 5 Mrad gamma radiation under a partial vacuum and then the bars were remelted to extinguish residual free radicals. Artificial aging at 70 degrees C under 5 atm oxygen for 14 days induced negligible oxidation in the crosslinked and remelted material. Against smooth balls, the wear of the crosslinked cups, with or without aging, averaged approximately 15% of that of the conventional cups. Against the moderately rough balls, the wear rate of the conventional cups was unchanged, whereas the wear rate increased slightly for the nonaged and aged crosslinked cups, but was still only 26% and 20% of that of the conventional cups, respectively. Against extremely rough balls, the mean wear rates increased markedly for each material such that during the final 1 million cycle interval, the average wear rates of the nonaged and the aged crosslinked cups were 72% and 47% of that of the conventional cups, respectively. That is, the crosslinked polyethylene showed substantially better wear resistance than conventional polyethylene across the range of ball roughnesses, with or without accelerated aging.
Calorie restriction mimetics: an emerging research field (2006)

When considering all possible aging interventions evaluated to date, it is clear that calorie restriction (CR) remains the most robust. Studies in numerous species have demonstrated that reduction of calories 30-50% below ad libitum levels of a nutritious diet can increase lifespan, reduce the incidence and delay the onset of age-related diseases, improve stress resistance, and decelerate functional decline. A current major focus of this research area is whether this nutritional intervention is relevant to human aging. Evidence emerging from studies in rhesus monkeys suggests that their response to CR parallels that observed in rodents. To assess CR effects in humans, clinical trials have been initiated. However, even if results from these studies could eventually substantiate CR as an effective pro-longevity strategy for humans, the utility of this intervention would be hampered because of the degree and length of restriction required. As an alternative strategy, new research has focused on the development of 'CR mimetics'. The objective of this strategy is to identify compounds that mimic CR effects by targeting metabolic and stress response pathways affected by CR, but without actually restricting caloric intake. For example, drugs that inhibit glycolysis (2-deoxyglucose), enhance insulin action (metformin), or affect stress signaling pathways (resveratrol), are being assessed as CR mimetics (CRM). Promising results have emerged from initial studies regarding physiological responses which resemble those observed in CR (e.g. reduced body temperature and plasma insulin) as well as protection against neurotoxicity (e.g. enhanced dopamine action and up-regulated neurotrophic factors). Ultimately, lifespan analyses in addition to expanded toxicity studies must be accomplished to fully assess the potential of any CRM. Nonetheless, this strategy clearly offers a very promising and expanding research endeavor.