gebhart/patrepeval huggingface dataset:
Sulfoximine and sulfodiimine transition state analog inhibitors for carboxypeptidase A (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSulfoximine and sulfodiimine transition state analog inhibitors for carboxypeptidase AWilliam L. Mock and Jiu Tsair TsayCite this: J. Am. Chem. Soc. 1989, 111, 12, 4467–4472Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://pubs.acs.org/doi/10.1021/ja00194a049https://doi.org/10.1021/ja00194a049research-articleACS PublicationsRequest reuse permissionsArticle Views382Altmetric-Citations50LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Cell-specific physical and functional coupling of human 5-HT1A receptors to inhibitory G protein .alpha.-subunits and lack of coupling to Gs.alpha. (1993)

We have studied the physical and functional linkages of heterologously expressed human 5-HT1A receptors to G protein alpha-subunits in HeLa and CHO-K1 cells. HeLa cells expressed immunoreactivity to G(i) proteins with an apparent rank order of G(i) alpha 3 (approximately 1 pmol/mg of protein) >> G(i) alpha 1 (approximately 0.1 pmol/mg) >> G(i) alpha 2 (< 0.02 pmol/mg), whereas CHO-K1 cells expressed immunoreactivity to G(i) alpha 2 (approximately 5 pmol/mg) >> G(i) alpha 3 (approximately 0.7 pmol/mg), but not to G(i) alpha 1. Both cell lines expressed large and small forms of Gs alpha, but neither expressed detectable G(o) alpha. Agonist-promotable physical coupling of the 5-HT1A receptor to G proteins was examined with high-affinity agonist binding and with co-immunoprecipitation using rabbit anti-receptor IgG fractions. Agonist treatment induced coupling of the 5-HT1A receptors to G proteins with an apparent rank order of G(i) alpha 3 > G(i) alpha 1, G(i) alpha 2 in HeLa cells and G(i) alpha 3 > G(i) alpha 2 in CHO-K1 cells. Agonist-promotable functional coupling of the 5-HT1A receptors to inhibition of adenylylcyclase was measured in membranes derived from HeLa and CHO-K1 cells expressing approximately 2.5-3 pmol of receptors/mg of protein by preincubation with antisera raised against the carboxyl termini of the G(i) protein alpha-subunits. A noteworthy difference between the two cell types was that antisera against the predominant G protein (G(i) alpha 2) were substantially more efficacious than G(i) alpha 3 antisera at blocking functional coupling to adenylylcyclase inhibition in CHO-K1 cells, whereas in HeLa cells, antisera against nonpredominant G proteins (G(i) alpha 1/G(i) alpha 2) were equally as effective as those against the predominant G protein (G(i) alpha 3). No physical or functional coupling of the 5-HT1A receptor to Gs alpha isoforms was detected in either cell line. These findings suggest that the 5-HT1A receptor can physically couple to multiple distinct G(i) proteins in mammalian cell membranes and that functional coupling to adenylylcyclase inhibition may be mediated by G(i) alpha 1, G(i) alpha 2, and G(i) alpha 3. One factor influencing the relative importance of those G proteins for 5-HT1A receptor-inhibited adenylylcyclase activity appears to be their-relative levels of expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Fbxw7 suppresses cancer metastasis by inhibiting niche formation (2015)

Fbxw7 has been identified as an oncosuppressor protein in many types of cancer. We have recently shown that loss of Fbxw7 in bone marrow-derived stromal cells (BMSCs) promotes cancer metastasis by increasing production of the chemokine CCL2, which attracts monocytic myeloid-derived suppressor cells (Mo-MDSCs) and macrophages to the metastatic niche.
Building Continuous Arterial Blood Pressure Prediction Models Using Recurrent Networks (2016)

This paper presents a methodology for developing highly-accurate, continuous Arterial Blood Pressure (ABP) models using only Photoplethysmography (PPG). In contrast to prior approaches, we develop a system that exhibits dynamic temporal behavior which leads to increased accuracy in modeling ABP. We validate our approach using data from patients in the intensive care unit (ICU). We show that it is possible to build highly accurate, continuous blood pressure models using only finger pulse oximeters. Our methodology achieves accurate systolic blood pressure estimation with a root mean square error 2.58 ± 1.23 across the patient sample used. Furthermore, the continuous ABP signal is estimated with a root mean square error of 6.042 ± 3.26 and correlation coefficient of 0.95 ± 0.045. Our method enables designing robust Remote Health Monitoring Systems (RMS) for Heart Failure patients without requiring traditional blood pressure monitors.
Waveguide Channels And Gratings In Polydiacetylene Films Using Photo-Induced Bleaching (1990)

Poly[5,7-dodecadiyn-1,12-diol-bis(n-butoxycarbonyl-methyl-urethane)], or poly-4BCMU, thin films permanently bleach when irradiated with light in the absorption band. The resulting decrease in refractive index has been measured and is sufficient to allow formation of waveguide channels and gratings. The optical properties of the bleached material are discussed. A waveguide grating coupler is fabricated by periodic bleaching and demonstrated.
Towards Reference Passing in Web Service and Workflow-Based Applications (2009)

In a Service-Oriented Architecture (SOA) based on Web Service technology the services typically communicate with each other by passing data values directly from one service to another. In the case the services are orchestrated by workflows the services receive their input values from the workflow engine and return their calculated results back to the engine by value. In this paper we show several use cases where such value passing behavior has drawbacks. To address this challenge we introduce the concept of pointers in SOA. Pointers allow services to pass their data by reference which is a fundamental advantage for Web Service communication. Furthermore we show an extension of BPEL that introduces reference variables as new type of data containers in workflows. In addition, for the management of pointers we present the Reference Resolution System which can be used in very flexible setups either as central or distributed system.
Peptoids: Emerging Therapeutics for Neurodegeneration (2017)

In recent decades, the increasing prevalence of age-associated neurodegenerative diseases has underscored the need for targeted therapeutic strategies and novel diagnostics. Peptide-based neurotherapeutics offer high specificity and tolerability but are limited by proteolytic degradation in vivo. Peptoids, or N-substituted glycines, are versatile peptidomimetics that evade proteolytic degradation yet maintain many qualities that render peptides attractive neurotherapeutic candidates. These molecules may be engineered to their application through modifications that enhance structural stability and reactivity and can withstand various physiological stressors to retain their intended function within anomalous microenvironments.
High-accuracy position-sensing with fiber-coupled white-light interferometers (1984)

Multimode fibers connect two Michelson interferometers, source,and detector. The mirror position of the transmitting interferometer is reconstructed in the receiving interferometer by periodically scanning through three 'white-liciiit' fringes (laser reference, 6 mm range, 0.1 μpm resolution).
Error tolerance of the boson-sampling model for linear optics quantum computing (2012)

Linear optics quantum computing is a promising approach to implementing scalable quantum computation. However, this approach has very demanding physical resource requirements. Recently, Aaronson and Arkhipov (e-print arXiv:1011.3245) showed that a simplified model, which avoids the requirement for fast feed-forward and postselection, while likely not capable of solving BQP-complete problems efficiently, can solve an interesting sampling problem believed to be classically hard. Loss and mode mismatch are the dominant sources of error in such systems. We provide evidence that even lossy systems or systems with mode mismatch are likely to be classically hard to solve. This is of practical interest to experimentalists wishing to demonstrate such systems since it suggests that, even with errors in their implementation, they are likely implementing an algorithm that is classically hard to solve. Our results also equivalently apply to the multiwalker quantum walk model.
Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease (2001)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages dopaminergic neurons in the substantia nigra pars compacta (SNpc) as seen in Parkinson's disease. Here, we show that the pro-apoptotic protein Bax is highly expressed in the SNpc and that its ablation attenuates SNpc developmental neuronal apoptosis. In adult mice, there is an up-regulation of Bax in the SNpc after MPTP administration and a decrease in Bcl-2. These changes parallel MPTP-induced dopaminergic neurodegeneration. We also show that mutant mice lacking Bax are significantly more resistant to MPTP than their wild-type littermates. This study demonstrates that Bax plays a critical role in the MPTP neurotoxic process and suggests that targeting Bax may provide protective benefit in the treatment of Parkinson's disease.
Involvement of Plateletâ€“Tumor Cell Interaction in Immune Evasion. Potential Role of Podocalyxin-Like Protein 1 (2014)

Besides their essential role in hemostasis and thrombosis, platelets are involved in the onset of cancer metastasis by interacting with tumor cells. Platelets release secretory factors that promote tumor growth, angiogenesis, and metastasis. Furthermore, the formation of platelet-tumor cell aggregates in the bloodstream provides cancer cells with an immune escape mechanism by protecting circulating malignant cells from immune-mediated lysis by natural killer (NK) cells. Platelet-tumor cell interaction is accomplished by specific adhesion molecules, including integrins, selectins, and their ligands. Podocalyxin-like protein 1 (PCLP1) is a selectin-ligand protein in which overexpression has been associated with several aggressive cancers. PCLP1 expression enhances cell adherence to platelets in an integrin-dependent process and through the interaction with P-selectin expressed on activated platelets. However, the involvement of PCLP1-induced tumor-platelet interaction in tumor immune evasion still remains unexplored. The identification of selectin ligands involved in the interaction of platelets with tumor cells may provide help for the development of effective therapies to restrain cancer cell dissemination. This article summarizes the current knowledge on molecules that participate in platelet-tumor cell interaction as well as discusses the potential role of PCLP1 as a molecule implicated in tumor immune evasion.
Workforce Diversity and HR Challenges (2011)

In the 21st century, the expected trans-formation of economic environment, cutting across borders, advances in technology, the ensuing intense competitive global and domestic markets have created enormous pressure on organization to manage their workforce. In particular, the rapid expansion of firms in new markets outside their resident economy has made employment of workforce from these new markets imperative. The cross cultural, cross border mingling has resulted in the creation of a new class of people- global citizen with global attitudes, tastes and networks. This has been posing challenges to the corporate world, culminating in Olympian competition. Thus, globalization requires that organizations increase their ability to learn and collaborate to manage diversity.
Micro/Nanobinary Structure of Silver Films on Copper Alloys with Stable Water-Repellent Property under Dynamic Conditions (2009)

Facile galvanic replacement was adopted to grow cauliflower-like and dendrite coral-like silver films on commercial copper alloy substrates. Both types of silver films possess micro/nanobinary structures, the formation and evolution of which are achieved through the oriented attachment growth mechanism. After modification by a monolayer of n-dodecanethiol, the cauliflower-like silver film becomes hydrophobic with a contact angle (CA) of 115 +/- 1 degrees and a CA hysteresis of 74 +/- 1 degrees and the dendrite coral-like silver film exhibits the extreme hydrophobicity characterized by a CA of 158 +/- 1 degrees and a CA hysteresis of less than 2 +/- 1 degrees . Furthermore, the bouncing property of millimeter-sized water droplets on the modified dendrite coral-like silver surface is much better than that on the modified cauliflower-like silver surface. The different wetting property between the two silver films is attributed to the surface roughness. Larger surface roughness provided by the dendrite coral-like silver film means more air pockets, among the micro/nanobinary structures, that bounce water droplets back more strongly. The dynamic bouncing behavior of water droplets, such as restitution coefficient and contact time, on the superhydrophobic modified cauliflower-like silver surface was also investigated at different impact velocities.
Thermal expansion coefficient of titanium casting (2001)

A reliable measurement of the thermal expansion coefficient (alpha) value is required to achieve a positive thermal mismatch between metal and porcelain for porcelain-fused to metal crowns. Heating rate and specimen conditions may significantly influence the alpha value and the effects of these factors were studied. Commercially pure cast titanium rods, 'as cast' and sandblasted, were heated at various conditions. According to this study, the discrepancy of alpha values between heating and cooling conditions was insignificant when the heating (cooling) rate was reduced to 1 degrees C min(-1). It was revealed that alpha values obtained from 1 degrees C min(-1) cooling rates should be utilized. Dental porcelain with an alpha value lower than 8.5 x 10(-6) degrees C will be suitable for titanium-ceramic applications.
Bone and mineral metabolism in aged male rats: short and long term effects of androgen deficiency (1992)

Both short and long term effects of androgen deficiency and steroid replacement therapy on skeletal homeostasis were investigated in aged (13-month-old) male rats. The animals were either sham operated (n = 28) or orchidectomized (orch; n = 89). The orch animals were divided into 5 groups; 26 rats received an empty sc Silastic implant (orch), all others received an implant containing testosterone (T), 5 alpha-dihydrotestosterone (DHT), 17 beta-estradiol (E2), or nandrolone (Nandro; 15-16 rats in each group). Half of the rats were killed 1 month (short term experiment) after implantation; the others were killed 4 months after implantation (long term experiment). Short term androgen deficiency caused a significant increase in both serum osteocalcin and histomorphometric parameters of bone turnover measured at the proximal tibial metaphysis, but not in a significant decrease in bone mass at this site. This increase in bone turnover was prevented not only by T and DHT, but also by E2 and Nandro. Long term androgen deficiency resulted in a decrease in the calcium content of both tibia and lumbar vertebrae. Cancellous bone volume in the proximal tibial metaphysis was +/- 50% lower in the orch group (P less than 0.001) 4 months after orchidectomy. At the same time, cortical bone was lost in orch rats; femoral cortical thickness was reduced by 12% (P less than 0.01), and cortical density tended to be lower. T, DHT, E2, or Nandro treatment completely prevented this decrease in cortical thickness and density. T and Nandro were also able to prevent the cancellous bone loss. DHT could only partly prevent cancellous bone loss. E2 treatment resulted not only in a sustained decrease in both serum osteocalcin concentrations and histomorphometric indices of bone turnover, but also in a net gain of cancellous bone volume (P less than 0.05 vs. sham). No significant differences in serum concentrations of vitamin D metabolites or nephrogenous cAMP were observed between groups in both short and long term experiments. We conclude that bone mass in aged male rats was significantly decreased 4 months after orchidectomy, preceded by an early increase in bone turnover. Both the early increase in bone turnover and the later decrease in bone mass were prevented by aromatizable and nonaromatizable androgens by estrogen and by nandralone.
Lessons learned from a SIRT2-selective inhibitor (2016)

Developing targeted cancer therapies typically starts with the identification of oncoproteins that are mutated or over-activated in tumors, followed by the development of small molecules that target the oncoproteins. A paradigm example is the development of Gleevec targeting the BCR-ABL oncoprotein in chronic myeloid leukemia. Many other targeted therapies follow this logic, such as compounds that target RAS mutants or overexpressed Myc (reviewed in [1]). We recently developed a potent and selective SIRT2 inhibitor, TM, which exhibits broad anticancer activity partly by decreasing the protein level of Myc (Figure ​(Figure1)1) [2]. Here we summarize several lessons we learned from this study with the intention that they may help other researchers developing targeted cancer therapies.
The Movement Toward Mysticism in Gustavo Gutiérrez’s Thought: Is This an Open Door to Pentecostal Dialogue? (2011)

Abstract Over the last few years a distinct shift has occurred within the thought of liberation theology’s most famous proponent, Gustavo Gutiérrez. Specifically, Gutiérrez has ventured into mysticism. With this movement a fascinating question can be posed: Does the incorporation of mysticism open up a door for dialogue with Latin America’s other popular theology, Pentecostalism? Conversely, should Pentecostalism reflexively understand itself historically and theologically as a liberating movement of the poor? Placed together, an emphasis on praxis seems to reveal, at minimum, a common starting point. The methodology of the paper incorporates a detailed historical analysis of Gutiérrez’s position on mysticism and moves to the conclusion that the shift in emphasis opens the door, albeit a small crack, to one of the most exciting opportunities to occur within the history of Christianity: the marriage of Pentecostal spirituality with liberating social action.
Model compression via distillation and quantization (2018)

Deep neural networks (DNNs) continue to make significant advances, solving tasks from image classification to translation or reinforcement learning. One aspect of the field receiving considerable attention is efficiently executing deep models in resource-constrained environments, such as mobile or embedded devices. This paper focuses on this problem, and proposes two new compression methods, which jointly leverage weight quantization and distillation of larger teacher networks into smaller student networks. The first method we propose is called quantized distillation and leverages distillation during the training process, by incorporating distillation loss, expressed with respect to the teacher, into the training of a student network whose weights are quantized to a limited set of levels. The second method, differentiable quantization, optimizes the location of quantization points through stochastic gradient descent, to better fit the behavior of the teacher model. We validate both methods through experiments on convolutional and recurrent architectures. We show that quantized shallow students can reach similar accuracy levels to full-precision teacher models, while providing order of magnitude compression, and inference speedup that is linear in the depth reduction. In sum, our results enable DNNs for resource-constrained environments to leverage architecture and accuracy advances developed on more powerful devices.
Second-harmonic phase determination by real-time in situ interferometry (2017)

Second Harmonic Generation (SHG) has emerged as a highly sensitive probe of protein conformation. SHG can also be used to determine the tilt angle of an SHG-active moiety bound to a surface-adsorbed protein through polarization-dependent measurements. However, due to the coherent nature of SHG, interference occurs between the SHG produced by the SHG-active moieties and background sources at a solid-liquid interface, obscuring the signal of interest. In order to separate the protein-specific signal from the background signal, the phase difference between these two different sources of SHG must be determined. Although the phase difference can be obtained through a conventional interferometric approach involving a phase-modulated SHG source external to the sample, it can be sensitive to drift and other instabilities. We present here a simple, convenient, and crucially, model-independent method to determine the phase difference for any system in which the intensity of SHG-active moieties can be varied. We demonstrate the approach with time-resolved measurements of an SHG-active labeled protein binding to a supported lipid bilayer surface using a total internal reflection (TIR) geometry. This approach requires no additional optics beyond what is required to measure SHG and is highly stable since the interferometry occurs in situ, within the sample over a nanometer length scale, rather than external to it. To validate our measurements and the general approach, we constructed a dual-beam, external SHG interferometer in a TIR geometry. We also validated our approach by applying the in situ method to previously published measurements of the phase difference, obtaining the same values without recourse to a specific adsorption model.