gebhart/patrepeval huggingface dataset:
Melatonin receptor pharmacology: toward subtype specificity (1997)

The recent cloning of three distinct melatonin receptor subtypes (Mel1a, Mel1b and Mel1c) which are part of a new family of G-protein coupled receptors, and probably mediate the physiological actions of the hormone, has spurred interest in the design of analogues with subtype selectivity. The 5-methoxyl and N-acetyl groups of melatonin are important for binding to and activation of the receptor. The indole nucleus serves to hold these two groups at the correct distance from one another and allows them to adopt the required orientation for interaction with the receptor binding pocket. We have investigated the subtype selectivity of a number of analogues of melatonin in which the structure has systematically been modified in order to probe the similarities and differences in the interaction of ligand and receptor subtype. At all three subtypes 5-methoxyl and N-acetyl groups of melatonin are important for high affinity binding. However, replacing the 5-methoxyl group (eg with 5-H, 5-OH, 5-Me or 5-BzO) reduces affinity much less at the Mel1b receptor subtype than at either Mel1a or Mel1c cloned subtypes. This suggests differences between the Mel1b and Mel1a/1c subtypes in the size and shape of the binding pocket or in the manner in which melatonin interacts with the receptor at this position. Further studies have revealed that analogues with longer N-acyl carbon chains behave similarly at each subtype. These observations suggest that the 'pocket' into which the N-acetyl group fits is very similar for each subtype. Substitutions at the 2-position on the indole ring improved affinity at each receptor subtype but did not give selective analogues. The systematic 'mapping' of the requirements for binding at each receptor subtype should allow the design of more selective agonists and antagonists, which will be valuable tools for the characterization and classification of functional melatonin receptors.
Analysis of zinc binding sites in protein crystal structures (1998)

The geometrical properties of zinc binding sites in a dataset of high quality protein crystal structures deposited in the Protein Data Bank have been examined to identify important differences between zinc sites that are directly involved in catalysis and those that play a structural role. Coordination angles in the zinc primary coordination sphere are compared with ideal values for each coordination geometry, and zinc coordination distances are compared with those in small zinc complexes from the Cambridge Structural Database as a guide of expected trends. We find that distances and angles in the primary coordination sphere are in general close to the expected (or ideal) values. Deviations occur primarily for oxygen coordinating atoms and are found to be mainly due to H-bonding of the oxygen coordinating ligand to protein residues, bidentate binding arrangements, and multi-zinc sites. We find that H-bonding of oxygen containing residues (or water) to zinc bound histidines is almost universal in our dataset and defines the elec-His-Zn motif. Analysis of the stereochemistry shows that carboxyl elec-His-Zn motifs are geometrically rigid, while water elec-His-Zn motifs show the most geometrical variation. As catalytic motifs have a higher proportion of carboxyl elec atoms than structural motifs, they provide a more rigid framework for zinc binding. This is understood biologically, as a small distortion in the zinc position in an enzyme can have serious consequences on the enzymatic reaction. We also analyze the sequence pattern of the zinc ligands and residues that provide elecs, and identify conserved hydrophobic residues in the endopeptidases that also appear to contribute to stabilizing the catalytic zinc site. A zinc binding template in protein crystal structures is derived from these observations.
Maximizing the Business Value of Networked Embedded Systems through Process-Level Integration into Enterprise Software (2007)

Building applications on resource-constrained networked embedded systems (the front-end) such as automation devices, (wireless) sensor networks etc, and integrating them into business processes of an enterprise (the back-end) is a complex, challenging task that has to be repeated for each combination of back-end and front-end application. We argue that using modelling on top of service-oriented architecture in networked embedded systems simplifies application development and enables easy enterprise-wide integration by using executable descriptions of cross-system business processes. We derive requirements for networked embedded systems, the communication points with enterprise software to support this model-driven software design, and directions for their implementation.
<scp>FMS</scp> Kinase Inhibitors: Current Status and Future Prospects (2012)

FMS, first discovered as the oncogene responsible for Feline McDonough Sarcoma, is a type III receptor tyrosine kinase that binds to the macrophage or monocyte colony-stimulating factor (M-CSF or CSF-1). Signal transduction through that binding results in survival, proliferation, and differentiation of monocyte/macrophage lineage. Overexpression of CSF-1 and/or FMS has been implicated in a number of disease states such as the growth of metastasis of certain types of cancer, in promoting osteoclast proliferation in bone osteolysis, and many inflammatory disorders. Inhibition of CSF-1 and/or FMS may help treat these pathological conditions. This article reviews FMS gene, FMS kinase, CSF-1, IL-34, and their roles in bone osteolysis, cancer biology, and inflammation. Monoclonal antibodies, FMS crystal structure, and small molecule FMS kinase inhibitors of different chemical scaffolds are also reviewed.
A novel application of cyclic voltammetry for direct investigation of metabolic intermediates in microsomal azo reduction (1991)

We have established that reduction of azo dyes structurally related to 4-(dimethylamino)-azobenzene (DAB) by rat liver microsomal cytochrome P-450 requires a polar electron-donating substituent on one ring. Reduction of azo dyes containing only electron-donating substituents is insensitive to both oxygen and CO (I substrates). However, reduction of azo dyes containing electron-withdrawing substituents as well is sensitive to both oxygen and CO (S substrates). Positive, irreversible potentials were observed by cyclic voltammetry (CV) in anhydrous solutions for both I and S substrates but not for the nonreducible azo dyes. This positive potential permits electron transfer to dyes from NADPH-cytochrome P-450 reductase and from cytochrome P-450, both of which have negative potentials. Reduction products retaining electron-donating groups (amino, phenolic) also exhibited positive potentials, implying that these groups contribute the positive potential in the dye molecule. All substrates also exhibited two negative potentials with a clear distinction between I and S substrates. The latter exhibited, on average, potentials that were less negative than the former by about 0.6 V. This is consistent with the more rapid reduction of S substrates by liver microsomes [Zbaida and Levine (1990) Biochem. Pharmacol. 40, 2415-2423]. Admitting air to the system quenched the first potential for S but not for I substrates, which is consistent with the oxygen sensitivities of their reduction. Addition of water significantly shifted the second negative potential to a more positive value, ultimately leading to single negative potential. The water permits rapid protonation of the two-electron-reduced intermediate, facilitating further reduction.(ABSTRACT TRUNCATED AT 250 WORDS)
An algorithm for centroid-based tracking of moving objects (1999)

This article addresses the problem of tracking moving objects using deformable models. A Kalman-based algorithm is presented, inspired by a new class of constrained clustering methods, proposed by Abrantes and Marques (1996) in the context of static shape estimation. A set of data centroids is tracked using intra-frame and inter-frame recursions. Centroids are computed as weighted sums of the edge points belonging to the object boundary. The use of centroids introduces competitive learning mechanisms in the tracking algorithm leading to improved robustness with respect to occlusion and contour sliding. Experimental results with traffic sequences are provided.
Disease modeling for Ebola and Marburg viruses (2009)

The filoviruses Ebola and Marburg are zoonotic agents that are classified as both biosafety level 4 and category A list pathogens. These viruses are pathogenic in humans and cause isolated infections or epidemics of viral hemorrhagic fever, mainly in Central Africa. Their natural reservoir has not been definitely identified, but certain species of African bat have been associated with Ebola and Marburg infections. Currently, there are no licensed options available for either treatment or prophylaxis. Different animal models have been developed for filoviruses including mouse, guinea pig and nonhuman primates. The 'gold standard' animal models for pathogenesis, treatment and vaccine studies are rhesus and cynomolgus macaques. This article provides a brief overview of the clinical picture and the pathology/pathogenesis of human filovirus infections. The current animal model options are discussed and compared with regard to their value in different applications. In general, the small animal models, in particular the mouse, are the most feasible for high biocontainment facilities and they offer the most options for research owing to the greater availability of immunologic and genetic tools. However, their mimicry of the human diseases as well as their predictive value for therapeutic efficacy in primates is limited, thereby making them, at best, valuable initial screening tools for pathophysiology, treatment and vaccine studies.
Infection in Massive Bone Allografts (2005)

We studied a series of 945 patients who received cadaveric allografts implanted for nonpelvic bone or soft tissue tumor lesions since 1971. We specifically were interested in the role of infection in the graft process, and, more specifically its history, frequency, and affect on outcome. Primary infections (not related to reoperations for nonunions or fractures of the graft) occurred in 75 patients (7.9%), and an additional 46 patients had infections related to reoperations, increasing the total number of patients with infections to 121 (12.8%). The highest frequency of infection occurred in patients with soft tissue tumors, radiated sites, Musculoskeletal Tumor Society Stage IIB tumors, or surgeries consisting of an allograft arthrodesis. Most of the infected grafts failed; however, none of the patients died. One patient had hepatitis C develop, and one patient became HIV positive after receiving the virus from a blood transfusion. A comparison with other series of surgically treated patients, including those receiving metallic devices, suggests that the infection rate may be related to the surgery or the graft's immunologic resistance, rather than the graft. The problem of infection is a major issue for tumor surgeons. Suggestions regarding how to decrease the frequency of this complication are presented.
LiPS: A Cost-Efficient Data and Task Co-Scheduler for MapReduce (2013)

We introduce LiPS, a new cost-efficient data and task co-scheduler for MapReduce in a cloud environment. LiPS allows flexible control of job make spans, multi-resource management, and fairness. By using linear programming to simultaneously co-schedule data and tasks, LiPS helps to achieve minimized dollar cost globally. We evaluated LiPS both analytically and on Amazon EC2 in order to measure actual dollar charges. The results were significant; LiPS saved 58-79% of the dollar costs when compared with the Hadoop default scheduler, while also allowing users to fine-tune the cost-performance tradeoff.
Optimized Bit Extraction Using Distortion Modeling in the Scalable Extension of H.264/AVC (2009)

The newly adopted scalable extension of H.264/AVC video coding standard (SVC) demonstrates significant improvements in coding efficiency in addition to an increased degree of supported scalability relative to the scalable profiles of prior video coding standards. Due to the complicated hierarchical prediction structure of the SVC and the concept of key pictures, content-aware rate adaptation of SVC bit streams to intermediate bit rates is a nontrivial task. The concept of quality layers has been introduced in the design of the SVC to allow for fast content-aware prioritized rate adaptation. However, existing quality layer assignment methods are suboptimal and do not consider all network abstraction layer (NAL) units from different layers for the optimization. In this paper, we first propose a technique to accurately and efficiently estimate the quality degradation resulting from discarding an arbitrary number of NAL units from multiple layers of a bitstream by properly taking drift into account. Then, we utilize this distortion estimation technique to assign quality layers to NAL units for a more efficient extraction. Experimental results show that a significant gain can be achieved by the proposed scheme.
Fast quantitative MRI using controlled saturation magnetization transfer (2018)

This work demonstrates that conventional single pool relaxometry, which is highly efficient for human studies, results in unreliable parameter estimates in biological tissues because of MT effects. The proposed CSMT framework is shown to allow single-pool assumptions to be valid, enabling reliable and efficient quantitative imaging to be performed.
Identification of the inertial parameters of a humanoid robot using unactuated dynamics of the base link (2008)

The inertial parameters are important to generate motion patterns for humanoid robots. Conventional identification methods can be used to estimate these parameters; however they required the joint torque estimates that can be obtained by modeling of the transmission or by direct measurements. To overcome that issue we have recently developed a new method to estimate the inertial parameters of legged systems. By using the base-link equations only, we obtain a reduced identification model that is free of joint torque estimates. In this paper we propose to apply the method to a human-size humanoid robot. The preliminary experimental results are given and discussed.
Social media ownership (2011)

Social media, by its very nature, introduces questions about ownership. Ownership comes into play most crucially when we investigate how social media is saved or archived; how it is reused; and whether it can be removed or deleted. We investigate these social media ownership issues using a Mechanical Turk survey of Twitter users; the survey uses open-ended questions and statements of belief about realistic Twitter-based scenarios to give us a window onto current attitudes and beliefs. Our findings reveal that respondents take a liberal attitude toward saving and storing the tweets that they encounter. More caution is exercised with republishing the material, and still more with sharing the material among friends and associates. Respondents approach removal of this type of lightweight social media most cautiously. The material's provenance and the respondents' relationship to the material (whether they are the author or subject) has considerable bearing on what they feel they can do with it.
DIAGNOSTIC VALUE OF SERUM TUMOR MARKERS FOR LUNG CANCER (2003)

Objective To appraise the value of tumor markers TPA, NSE, CA15 3 and CEA in the diagnosis of lung Methods The levels of TPA, NSE, CA15 3 and CEA were measured by ELISA in serum of 36 patients with lung cancer and 28 with benign lung diseases. Results The levels of TPA, NSE, CA15 3 and CEA in cancer patients were significantly higher than that of benign ones ( t=1.992-3.271, P 0.05, 0.01). The rise of TPA was most obviously in squamous cell carcinoma, while adenocarcinoma as well as small cell lung cancer(SCLC) the next. NSE increased in more obvious in SCLC. The increase of CA15 3 was higher in adenocarcinoma , then spuamous cell one and SCLC . The specificity of TPA, NSE, CA15 3 and CEA was 89%, 96%, 93% and 100%; the sensitivity was 71.3%, 27.3%, 58.8% and 53.7%, respectively. Conclusion TPA, CA15 3 and CEA have important diagnostic value for NSCLC, but NSE, CA15 3, CEA for SCLC.A combination of multiple tumor markers may increase the diagnostic specificity and sensitivity of lung cancer.
A Comparison of Three Different Scales for Rating Contact Lens Handling (2002)

Although all three scales can be used to provide measures of lens handling, VAS may provide a simple and repeatable tool for measuring subjective responses.
Algorithm for Conformance Monitoring in Air Traffic Control (2010)

Conformance monitoring in air traffic control is an approach that is used to detect any deviations of the aircraft from its cleared (or planned) flight path that might compromise safety and efficiency. This task is made difficult by the fact that some deviations are normally expected of a conforming aircraft due to uncertainties. In this paper, a conformance monitoring algorithm that uses a stochastic linear hybrid system model is proposed. The stochastic linear hybrid system model divides the aircraft dynamics into a number of flight modes and is able to describe the random deviations in (conforming) aircraft trajectories. The detection of any nonconforming trajectories is determined by a fault detection technique. First, a hybrid estimation algorithm is used to estimate the hybrid state of the stochastic linear hybrid system and generate a residual vector based on the measurements. The statistical characteristics of the residual expected of a conforming aircraft are derived. Then, a statistical decision test is used to detect any deviation of the observed residual from the expected residual. Two illustrative examples are presented to demonstrate the performance of the proposed algorithm.
Entrepreneurial firms and cluster competitiveness: institutions and public policy determinants (2013)

Globalisation brings many competitive challenges to emerging economies, particularly to small and medium-size firms (SMEs). Focusing on the information technology cluster in Brazil, Latin America’s largest economy, and a high-tech municipality (Campinas) the researchers examined the role of governmental institutions and their interaction with business and academe to foster competitiveness. Despite a high quality infrastructure and an excellent workforce, most public sector initiatives are not specific to SMEs nor to the needs of companies located in Campinas. Factors like: 1) the lack of a governance structure to coordinate policies in support of SMEs; 2) the absence of sufficient public resources to support innovation and bring new products to market; 3) the inaccessibility of research centres for small firms hinders the growth and development of Campinas as a dynamic IT cluster. The researchers propose 15 specific actions to improve the competitiveness of SME technology firms in Campinas and in the cluster.
Surface Complexation Modeling for Waterflooding of Sandstones (2012)

Summary A theoretical surface coordination model of oil attraction to sandstone-reservoir surfaces confirms the two primary oil/mineral coordination reactions to be electrostatic linking of anionic kaolinite-edge sites to protonated nitrogen bases at pH &lt; 6 and calcium carboxylate groups at pH &gt; 6. Kaolinite basal planes are calculated to link to oil through oil –NH+ groups at pH &lt; 6–7 and through oil –COOCa+ groups at pH &gt; 6–7, and may be important to oil attraction where basal planes are more exposed than edges (the ranges shift, depending on the oil, acid, and base numbers). Model predictions are most sensitive to the dissociation constant of oil surface carboxylate groups but are relatively insensitive to other surface equilibria and temperature. The model shows that, although low-salinity, low-Ca waterfloods can enhance oil recovery by decreasing the number of Ca2+ bridges and anionic kaolinite-edge sites, dissolution of sandstone carbonate minerals dampens the low-salinity effect by buffering decreases in waterflood Ca2+ levels. Better model predictions require more-accurate predictions of Ca2+ levels during waterflooding, high-temperature sulfate-adsorption analyses, and more-precise measurements of oil acidity and basicity.
Hebrew or Japanese (2012)

1. INTRODUCTION It is quite common that, for any two languages, there will be words that look or sound alike, but with different meanings. French words that look like English words but with different meanings in the two languages are called faux amis ("false friends"). In some cases they are from unrelated roots (e.g. French pain means "bread" and rue means "street". In other cases, words that began the same evolved different meanings. From its Latin roots, concurrence basically means "running along side of", which in English came to mean "agreement", but in French it means "competition."
Gordon-Haus jitter suppression using an intra-span phase modulator and post transmission dispersion compensator (1996)

We analyze the reduction of Gordon-Haus jitter using a mid-span phase modulator and post transmission dispersion compensator. The timing jitter variance at the the receiver may in principle be reduced by a factor of 20, however pulse broadening considerations may reduce this. We also examine how the phase modulator may cause nonGaussian statistics at the receiver.
Implementation and Performance Evaluation of Network Coding for Cooperative Mobile Devices (2008)

In this work a performance evaluation of network coding for cooperative wireless networks is carried out. Implementing network coding on commercially available mobile devices, the performance is presented in terms of throughput, delay and energy consumption. In contrast to purely cellular systems, where the mobile devices are only connected to the base station, in cooperative wireless networks, the mobile device, in addition to the cellular communication, establishes short range links to neighboring mobile devices within its proximity. In prior work it has been shown that the newly formed cooperative cluster, also referred as wireless grid, can offer each participating mobile device a better performance in terms of data rate, delay, robustness, security, and energy consumption in contrast to any stand alone device. To improve the performance within the cooperative cluster even more, network coding seems to be a promising technology as it decreases the number of packets to be interchanged among cooperative mobile devices leading to a decreased packet delay. The energy saved by fewer packet transmissions is confronted with the energy needed to carry out the network coding and related overhead. The findings of this paper show that network coding is always beneficial in terms of throughput and delay for the cooperative cluster.
Detection and manipulation of live antigen-expressing cells using conditionally stable nanobodies (2016)

The ability to detect and/or manipulate specific cell populations based upon the presence of intracellular protein epitopes would enable many types of studies and applications. Protein binders such as nanobodies (Nbs) can target untagged proteins (antigens) in the intracellular environment. However, genetically expressed protein binders are stable regardless of antigen expression, complicating their use for applications that require cell-specificity. Here, we created a conditional system in which the stability of an Nb depends upon an antigen of interest. We identified Nb framework mutations that can be used to rapidly create destabilized Nbs. Fusion of destabilized Nbs to various proteins enabled applications in living cells, such as optogenetic control of neural activity in specific cell types in the mouse brain, and detection of HIV-infected human cells by flow cytometry. These approaches are generalizable to other protein binders, and enable the rapid generation of single-polypeptide sensors and effectors active in cells expressing specific intracellular epitopes.