gebhart/patrepeval huggingface dataset:
Identification of Acidic Residues in the Extracellular Loops of the Seven-transmembrane Domain of the Human Ca2+ Receptor Critical for Response to Ca2+ and a Positive Allosteric Modulator (2002)

We investigated the role of the eight acidic residues in the extracellular loops (exo-loops) of the seven-transmembrane domain of the human Ca(2+) receptor (hCaR) in receptor activation by Ca(2+) and in response to a positive allosteric modulator, NPS R-568. Both in the context of the full-length receptor and of a truncated receptor lacking the extracellular domain (Rho-C-hCaR), we mutated each acidic residue to alanine, singly and in combination, and tested the effect on expression of the receptor, on activation by Ca(2+), and on NPS R-568 augmentation of sensitivity to Ca(2+). Of the eight acidic residues, mutation of any of three in exo-loop 2, Asp(758), Glu(759), and Glu(767), increased the sensitivity of both the full-length hCaR and of Rho-C-hCaR to activation by Ca(2+). Mutation of all five acidic residues in exo-loop 2, whether in the full-length receptor or in Rho-C-hCaR, impaired cell surface expression of the mutant receptor and thereby largely abolished response to Ca(2+). Mutation of Glu(837) in exo-loop 3 to alanine did not alter Ca(2+) sensitivity of the full-length receptor, but in both the latter context and in Rho-C-hCaR, alanine substitution of Glu(837) drastically reduced sensitivity to NPS R-568. Our data point to a key role of three specific acidic residues in exo-loop 2 in hCaR activation and to Glu(837) at the junction between exo-loop 3 and transmembrane helix seven in response to NPS R-568. We speculate on the basis of these results that the three acidic residues we identified in exo-loop 2 help maintain an inactive conformation of the seven-transmembrane domain of the hCaR.
Novel Multiplex PCR Assay for Characterization and Concomitant Subtyping of Staphylococcal Cassette ChromosomemecTypes I to V in Methicillin-ResistantStaphylococcus aureus (2005)

Staphylococcal cassette chromosome mec (SCCmec) typing is essential for understanding the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA). SCCmec elements are currently classified into types I to V based on the nature of the mec and ccr gene complexes, and are further classified into subtypes according to their junkyard region DNA segments. Previously described traditional SCCmec PCR typing schemes require multiple primer sets and PCR experiments, while a previously published multiplex PCR assay is limited in its ability to detect recently discovered types and subtypes such as SCCmec type V and subtypes IVa, b, c, and d. We designed new sets of SCCmec type- and subtype-unique and specific primers and developed a novel multiplex PCR assay allowing for concomitant detection of the methicillin resistance (mecA gene) (also serving as an internal control) to facilitate detection and classification of all currently described SCCmec types and subtypes I, II, III, IVa, b, c, d, and V. Our assay demonstrated 100% sensitivity and specificity in accurately characterizing 54 MRSA strains belonging to the various known SCCmec types and subtypes, when compared with previously described typing methods. Further application of our assay in 453 randomly selected local clinical isolates confirmed its feasibility and practicality. This novel assay offers a rapid, simple, and feasible method for SCCmec typing of MRSA, and may serve as a useful tool for clinicians and epidemiologists in their efforts to prevent and control infections caused by this organism.
Performance and stimulation of horizontal wells (1989)

The authors discusses the contrast between the performance of unfractured horizontal wells with fractured and unfractured vertical wells. This article describes the technology for obtaining these fractures in a horizontal completion. Some of the complexity associated with propagation prediction is because of the moving boundary. Fracture geometry continuously changes to expend the available energy while minimizing the energy required for propagation. For fractures growing from deviated wellbores, the situation is particularly complex because of the three-dimensionality associated with the rotation of fractures (nonplanar propagation).
Sum and Difference Histograms for Texture Classification (1986)

The sum and difference of two random variables with same variances are decorrelated and define the principal axes of their associated joint probability function. Therefore, sum and difference histograms are introduced as an alternative to the usual co-occurrence matrices used for texture analysis. Two maximum likelihood texture classifiers are presented depending on the type of object used for texture characterization (sum and difference histograms or some associated global measures). Experimental results indicate that sum and difference histograms used conjointly are nearly as powerful as cooccurrence matrices for texture discrimination. The advantage of the proposed texture analysis method over the conventional spatial gray level dependence method is the decrease in computation time and memory storage.
Making computers easier for older adults to use (1997)

Article Free Access Share on Making computers easier for older adults to use: area cursors and sticky icons Authors: Aileen Worden Psychology, Georgia Institute of Technology, Atlanta, Georgia Psychology, Georgia Institute of Technology, Atlanta, GeorgiaView Profile , Nef Walker Psychology, Georgia Institute of Technology, Atlanta, Georgia Psychology, Georgia Institute of Technology, Atlanta, GeorgiaView Profile , Krishna Bharat GVR, Georgia Institute of Technology, Atlanta, Georgia GVR, Georgia Institute of Technology, Atlanta, GeorgiaView Profile , Scott Hudson GVR, Georgia Institute of Technology, Atlanta, Georgia GVR, Georgia Institute of Technology, Atlanta, GeorgiaView Profile Authors Info & Claims CHI '97: Proceedings of the ACM SIGCHI Conference on Human factors in computing systemsMarch 1997 Pages 266–271https://doi.org/10.1145/258549.258724Published:27 March 1997Publication History 193citation3,057DownloadsMetricsTotal Citations193Total Downloads3,057Last 12 Months119Last 6 weeks16 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Identification of Cross-Linked Peptides after Click-Based Enrichment Using Sequential Collision-Induced Dissociation and Electron Transfer Dissociation Tandem Mass Spectrometry (2009)

Chemical cross-linking combined with mass spectrometry can be a powerful approach for the identification of protein-protein interactions and for providing constraints on protein structures. However, enrichment of cross-linked peptides is crucial to reduce sample complexity before mass spectrometric analysis. In addition compact cross-linkers are often preferred to provide short spacer lengths, surface accessibility to the protein complexes, and must have reasonable solubility under conditions where the native complex structure is stable. In this study, we present a novel compact cross-linker that contains two distinct features: (1) an alkyne tag and (2) a small molecule detection tag (NO(2)) to maintain reasonable solubility in water. The alkyne tag enables enrichment of the cross-linked peptides after proteolytic cleavage and coupling of an affinity tag using alkyne-azido click chemistry. Neutral loss of the small NO(2) moiety provides a secondary means of detecting cross-linked peptides in MS/MS analyses, providing additional confidence in peptide identifications. We show the labeling efficiency of this cross-linker, which we termed CLIP (click-enabled linker for interacting proteins) using ubiquitin. The enrichment capability of CLIP is demonstrated for cross-linked ubiquitin in highly complex E. coli cell lysates. Sequential collision-induced dissociation tandem mass spectrometry (CID-MS/MS) and electron transfer dissociation (ETD)-MS/MS of intercross-linked peptides (two peptides connected with a cross-linker) are also demonstrated for improved automated identification of cross-linked peptides.
Ligation of CD47 mediates phosphatidylserine expression on erythrocytes and a concomitant loss of viability in vitro (2005)

CD47 ligation has been shown to induce phosphatidylserine (PS) expression as part of a death pathway in nucleated blood cells. Using Annexin V binding assays we showed that ligation of CD47 with the specific CD47-binding peptide 41NK, anti-CD47 monoclonal antibody, and its natural ligand thrombospondin-1 also induced PS expression on enucleated erythrocytes. PS expression was associated with a concomitant loss of erythrocyte viability in vitro. Further characterisation of the CD47-PS signalling pathway on erythrocytes may help develop clinical strategies to further preserve the life of blood donations and improve our understanding of certain types of haemolytic anaemias.
Quantifying the benefits of extending electric vehicle charging deadlines with solar generation (2014)

Significant cost reduction in recent years has made solar power an economically competitive power source in many regions today. In view of this, and the widespread introduction of electric vehicles (EVs) to the mass market, we study public EV charging stations with on-site solar generation that are backed up by conventional power from the grid. Since the carbon footprint of conventional power is higher than solar power, charging deadlines can critically affect the total solar energy available to charging stations and therefore the overall carbon footprint of the charging service. In this paper, we propose a method to quantify how much carbon footprint can be reduced as a function of the charging deadline by describing a performance-guaranteed fair power allocation algorithm in a public charging station. This enables us to study the three-way tradeoff between the charging deadline, the utility of EV owners, and the carbon footprint of EV charging. We find that our algorithm makes nearly optimal use of available green energy, while still guaranteeing that solar charging performs no worse than grid charging.
Correlation between Ferumoxytol Uptake in Tumor Lesions by MRI and Response to Nanoliposomal Irinotecan in Patients with Advanced Solid Tumors: A Pilot Study (2017)

<b>Purpose:</b> To determine whether deposition characteristics of ferumoxytol (FMX) iron nanoparticles in tumors, identified by quantitative MRI, may predict tumor lesion response to nanoliposomal irinotecan (nal-IRI).<b>Experimental Design:</b> Eligible patients with previously treated solid tumors had FMX-MRI scans before and following (1, 24, and 72 hours) FMX injection. After MRI acquisition, R2* signal was used to calculate FMX levels in plasma, reference tissue, and tumor lesions by comparison with a phantom-based standard curve. Patients then received nal-IRI (70 mg/m<sup>2</sup> free base strength) biweekly until progression. Two percutaneous core biopsies were collected from selected tumor lesions 72 hours after FMX or nal-IRI.<b>Results:</b> Iron particle levels were quantified by FMX-MRI in plasma, reference tissues, and tumor lesions in 13 of 15 eligible patients. On the basis of a mechanistic pharmacokinetic model, tissue permeability to FMX correlated with early FMX-MRI signals at 1 and 24 hours, while FMX tissue binding contributed at 72 hours. Higher FMX levels (ranked relative to median value of multiple evaluable lesions from 9 patients) were significantly associated with reduction in lesion size by RECIST v1.1 at early time points (<i>P</i> < 0.001 at 1 hour and <i>P</i> < 0.003 at 24 hours FMX-MRI, one-way ANOVA). No association was observed with post-FMX levels at 72 hours. Irinotecan drug levels in lesions correlated with patient's time on treatment (Spearman <i>ρ</i> = 0.7824; <i>P</i> = 0.0016).<b>Conclusions:</b> Correlation between FMX levels in tumor lesions and nal-IRI activity suggests that lesion permeability to FMX and subsequent tumor uptake may be a useful noninvasive and predictive biomarker for nal-IRI response in patients with solid tumors. <i>Clin Cancer Res; 23(14); 3638-48. ©2017 AACR</i>.
Light scattering from human hair fibers (2003)

Light scattering from hair is normally simulated in computer graphics using Kajiya and Kay's classic phenomenological model. We have made new measurements of scattering from individual hair fibers that exhibit visually significant effects not predicted by Kajiya and Kay's model. Our measurements go beyond previous hair measurements by examining out-of-plane scattering, and together with this previous work they show a multiple specular highlight and variation in scattering with rotation about the fiber axis. We explain the sources of these effects using a model of a hair fiber as a transparent elliptical cylinder with an absorbing interior and a surface covered with tilted scales. Based on an analytical scattering function for a circular cylinder, we propose a practical shading model for hair that qualitatively matches the scattering behavior shown in the measurements. In a comparison between a photograph and rendered images, we demonstrate the new model's ability to match the appearance of real hair.
Scholarship, Policy, Debate and Conflict: Why We Study the Middle East and Why It Matters (2004)

This has been a difficult year for people who study the Middle East – as it has been for people who live there. Memorable mostly for its dilemmas and disappointments, it has not been the kind of year on which one would ordinarily dwell. Yet there are important lessons in this year, lessons about the relationship between scholarship and policy, about the responsibilities imposed by an academic life in a time of deeply divisive debate and conflict, and about why what we do is profoundly important, not just to the small community of our professional peers but for the health of our society and of our world. It is to those questions – and the lessons I believe we must draw from the experience of this year – that I want to devote our attention this evening.
Fire Suppression Tests Using a Handheld Water Mist Extinguisher Designed for the International Space Station (2012)

ADA Technologies, Inc. has been developing a portable fire extinguisher for use in a microgravity environment for several years and has now started to transfer the technology to the specific platform of the International Space Station (ISS). ADA’s patent-pending device employs the principle of fine water mist, with advantages in compatibility, fire suppression efficiency, and minimal mass and volume for spacecraft use. The first ISS prototype is a scaled-up version of ADA’s earlier designs and is built around the same atomization technology. This larger extinguisher was first validated through droplet size measurements before being tested in a variety of fire test scenarios designed to represent worst-case situations aboard the ISS. ADA performed fire tests corresponding to an open cabin fire involving burning sheets of poly(methyl-methacrylate) (PMMA) and secondly, a heavily obstructed instrument rack fire where flames were ignited in remote zones of the enclosure. All open cabin fires were easily extinguished by a firefighter using the prototype. More than 90% of the rack fires were extinguished as well, but in two instances a flame survived the test, showing that further improvements to the design are recommended. Development of the hardware continues, with the goal of producing flight-qualified hardware in the next 18 months.
A New Rational Hypothesis for the Pharmacophore of the Active Metabolite of Leflunomide, a Potent Immunosuppressive Drug (1997)

Leflunomide is one of the most promising disease-modifying antirheumatic drug now in clinical trials for the treatment of rheumatoid arthritis. Metabolic studies have indicated that leflunomide is rapidly processed in vivo to an active metabolite, A771726 (2). To identify the chemical characteristics necessary for the immunosuppressive activity of 2, configurational and conformational studies were carried out on the latter and its inactive analogues (ethyl 3-hydroxy-2-((4-(trifluoromethyl)phenyl)carbamoyl)but-2-enoate, 3a, and 3-hydroxy-2-nitro-N-(4-(trifluoromethyl)phenyl)but-2-enamide, 3b). These studies suggested that the pharmacophore responsible for the immunosuppressive activity of 2 is a beta-keto amide with the enolic hydroxy group cis to the amidic moiety. To verify this hypothesis, a new class of immunosuppressive agents was designed and synthesized. Their testing in vitro and in vivo identified compounds which were more potent than both leflunomide and 2 and above all confirmed our hypothesis as to the key structural and chemical determinants for the immunosuppressive properties of 2 and our compounds.
Binding of macrophage colony-stimulating factor to serum proteins. (1996)

Although three molecular forms of macrophage colony-stimulating factor (M-CSF) have been reported, Western blot analysis of immunoaffinity-purified M-CSF from human blood has shown that the major species of M-CSF in the serum has a molecular weight (MW) of 85 kD. Superose-12 gel filtration chromatography of immunoaffinity-purified serum M-CSF showed the presence of M-CSF-positive fraction in a higher MW area compared with the elution profile of recombinant human (rh) 85-kD M-CSF. Western blot analysis of the higher MW fraction showed that the M-CSF was the same as rh 85-kD M-CSF (not proteoglycan form of M-CSF), indicating that, in the serum, M-CSF exists bound to some serum proteins. To detect the serum proteins, we performed M-CSF-bound column chromatography. The eluate contained at least three serum proteins including albumin and IgG. This result was supported by chromatography using biotinylated M-CSF and avidin-agarose. The binding between rhM-CSF and albumin or IgG was also demonstrated by high-performance liquid chromatography (HPLC) fractionation of the mixture and enzyme-linked immunosorbent assay (ELISA) of the fractions. In the serum, a fraction of M-CSF seems to be complexed with serum proteins such as albumin and IgG.
Identification of counterfeit drugs using near-infrared spectroscopy (2001)

This work was aimed at the investigation of the use of near-infrared spectroscopy (NIRS) for the identification of counterfeit drugs. The identification is based on the comparison of the NIR spectrum of a sample with typical spectra of the authentic drug using multivariate modelling and classification algorithms (PCA/SIMCA). Initially, NIRS was evaluated for spectrum acquisition of various drugs, selected in order to observe the diversity of physico-chemical characteristics found among commercial products. The parameters which could affect the spectra of a given drug (especially if presented in solid form) were investigated and the results showed that the first derivative can minimise spectral changes associated with tablet geometry, physical differences in their faces and position in relation to the probe beam. The power of NIRS in distinguishing among similar pharmaceuticals was demonstrated and a protocol is proposed to construct a multivariate model and to include it in a library allowing testing for drug authenticity. The methodology was evaluated with real samples of counterfeit drugs and was able to recognise all those presenting changes in composition as false. The results show unequivocally the potential of NIRS for rapid, on-site and non-destructive identification of counterfeit pharmaceuticals.
Novel Peptide Inhibitors of Angiotensin-converting Enzyme 2 (2003)

Angiotensin-converting enzyme 2 (ACE2), a recently identified human homolog of ACE, is a novel metallocarboxypeptidase with specificity, tissue distribution, and function distinct from those of ACE. ACE2 may play a unique role in the renin-angiotensin system and mediate cardiovascular and renal function. Here we report the discovery of ACE2 peptide inhibitors through selection of constrained peptide libraries displayed on phage. Six constrained peptide libraries were constructed and selected against FLAG-tagged ACE2 target. ACE2 peptide binders were identified and classified into five groups, based on their effects on ACE2 activity. Peptides from the first three classes exhibited none, weak, or moderate inhibition on ACE2. Peptides from the fourth class exhibited strong inhibition, with equilibrium inhibition constants (K(i) values) from 0.38 to 1.7 microm. Peptides from the fifth class exhibited very strong inhibition, with K(i) values < 0.14 microm. The most potent inhibitor, DX600, had a K(i) of 2.8 nm. Steady-state enzyme kinetic analysis showed that these potent ACE2 inhibitors exhibited a mixed competitive and non-competitive type of inhibition. They were not hydrolyzed by ACE2. Furthermore, they did not inhibit ACE activity, and thus were specific to ACE2. Finally, they also inhibited ACE2 activity toward its natural substrate angiotensin I, suggesting that they would be functional in vivo. As novel ACE2-specific peptide inhibitors, they should be useful in elucidation of ACE2 in vivo function, thus contributing to our better understanding of the biology of cardiovascular regulation. Our results also demonstrate that library selection by phage display technology can be a rapid and efficient way to discover potent and specific protease inhibitors.
A core protein epitope of the polymorphic epithelial mucin detected by the monoclonal antibody SM‐3 is selectively exposed in a range of primary carcinomas (1989)

The monoclonal antibody (MAb) SM-3, which was raised to chemically deglycosylated milk mucin, reacts with an epitope present on the core protein of this mucin which we have referred to as PEM (polymorphic epithelial mucin). Although this mucin is abundantly expressed by both the lactating breast and breast carcinomas, the antibody SM-3 shows very little or no reactivity on the former but does react with 92% of breast carcinomas. Furthermore, SM-3 stains primary carcinomas of the lung, colon and ovary, but on the corresponding normal tissue the epitope is expressed at a much reduced level or not at all. These results indicate that an epitope masked in the normal mucin is exposed in the mucin produced by tumour cells, perhaps due to aberrant glycosylation. An extensive immunohistochemical study of other normal tissues reveals that the majority show only weak focal staining with SM-3 or none at all, the distal tubules and collecting ducts of the kidney, and sebaceous glands being the only normal tissues studied to show homogeneously positive staining.
Correction: Type I Interferon: Potential Therapeutic Target for Psoriasis? (2009)

Background: Psoriasis is an immune-mediated disease characterized by aberrant epidermal differentiation, surface scale formation, and marked cutaneous inflammation. To better understand the pathogenesis of this disease and identify potential mediators, we used whole genome array analysis to profile paired lesional and nonlesional psoriatic skin and skin from healthy donors.