gebhart/patrepeval huggingface dataset:
Duplex high‐throughput flow cytometry screen identifies two novel formylpeptide receptor family probes (2008)

Of recent, clinical interest have been two related human G-protein coupled receptors: formylpeptide receptor (FPR), linked to antibacterial inflammation and malignant glioma cell metastasis; and FPR like-1 (FPRL1), linked to chronic inflammation in systemic amyloidosis, Alzheimer's disease, and prion diseases. In association with the National Institutes of Health (NIH) Molecular Library Screening Network, we implemented a flow-cytometry-based high-throughput screening (HTS) approach for identifying selective small molecule FPR and FPRL1 ligands. The screening assay measured the ability of test compounds to competitively displace a high-affinity, fluorescein- labeled peptide ligand from FPR, FPRL1, or both. U937 cells expressing FPR and rat basophil leukemia (RBL) cells expressing FPRL1 were tested together in a "duplex" format. The U937 cells were color coded with red-fluorescent dye allowing their distinction during analysis. Compounds, cells, and fluorescent ligand were sequentially combined (no wash) in 15 microl assay volumes in 384-well plates. Throughput averaged approximately 11 min per plate to analyze approximately 4,000 cells ( approximately 2,000/receptor) in a 2 microl aspirate from each well. In primary single concentration HTS of 24,304 NIH Small Molecule Repository compounds, 253 resulted in inhibition >30% (181 for FPR, 72 for FPRL1) of which 40 had selective binding inhibition constants (K(i)) < or = 4 microM (34 for FPR and 6 for FPRL1). An additional 1,446 candidate compounds were selected by structure-activity-relationship analysis of the hits and screened to identify novel ligands for FPR (3570-0208, K(i) = 95 +/- 10 nM) and FPRL1 (BB-V-115, K(i) = 270 +/- 51 nM). Each was a selective antagonist in calcium response assays and the most potent small molecule antagonist reported for its respective receptor to date. The duplex assay format reduced assay time, minimized reagent requirements, and provided selectivity information at every screening stage, thus proving to be an efficient means to screen for selective receptor ligand probes.
Corticotropin-Releasing Hormone Receptor Antagonists:  Framework Design and Synthesis Guided by Ligand Conformational Studies (1999)

As described in the preceding paper (Arvanitis et al. J. Med. Chem. 1999, 42), anilinopyrimidines I were identified as potent antagonists of corticotropin-releasing hormone-1 receptor (CRH1-R, also referred to as corticotropin-releasing factor, CRF1-R). Our next goal was to understand the receptor-bound conformation of the antagonists and to use this information to help guide preclinical optimization of the series and to develop new leads. Since receptor structural information was not available, we assumed that these small, high-affinity antagonists would tend to bind in conformations at or energetically close to their global minima and that rigid analogues that maintained the important stereoelectronic features of the bound anilinopyrimidine would also bind tightly. Conformational preferences and barriers to rotation of the anilinopyrimidines were determined by semiempirical methods, and X-ray and variable-temperature NMR spectroscopy provided experimental results that correlated well with calculated structures. Using these data, a key dihedral angle was constrained to design fused-ring analogues, substituted N-arylpyrrolopyridines II, synthesis of which provided CRH1 receptor antagonists with potency equal to that of the initial congeneric leads (Ki = 1 nM) and which closely matched the conformation held by the original compound, as determined by crystallography. In addition to providing a useful template for further analogue synthesis, the study unequivocally determined the active conformation of the anilinopyrimidines. Theoretical and spectroscopic studies, synthesis, and receptor binding data are presented.
Zebra: Static and Dynamic Genome Cover Thresholds with Overlapping References (2022)

Assigning taxonomy remains a challenging topic in microbiome studies, due largely to ambiguity of reads which overlap multiple reference genomes. With the Web of Life (WoL) reference database hosting 10,575 reference genomes and growing, the percentage of ambiguous reads will only increase. The resulting artifacts create both the illusion of co-occurrence and a long tail end of extraneous reference hits that confound interpretation. We introduce genome cover, the fraction of reference genome overlapped by reads, to distinguish these artifacts. We show how to dynamically predict genome cover by read count and examine our model in Staphylococcus aureus monoculture. Our modeling cleanly separates both S. aureus and true contaminants from the false artifacts of reference overlap. We next introduce saturated genome cover, the true fraction of a reference genome overlapped by sample contents. Genome cover may not saturate for low abundance or low prevalence bacteria. We assuage this worry with examination of a large human fecal data set. By compositing the metric across like samples, genome cover saturates even for rare species. We note that it is a threshold on saturated genome cover, not genome cover itself, which indicates a spurious reference hit or distant relative. We present Zebra, a method to compute and threshold the genome cover metric across like samples, a recurrence to estimate genome cover and confirm saturation, and provide guidance for choosing cover thresholds in real world scenarios. Standalone genome cover and integration into Woltka are available: https://github.com/biocore/zebra_filter, https://github.com/qiyunzhu/woltka. <b>IMPORTANCE</b> Taxonomic assignment, assigning sequences to specific taxonomic units, is a crucial processing step in microbiome analyses. Issues in taxonomic assignment affect interpretation of what microbes are present in each sample and may be associated with specific environmental or clinical conditions. Assigning importance to a particular taxon relies strongly on independence of assigned counts. The false inclusion of thousands of correlated taxa makes interpretation ambiguous, leading to underconstrained results which cannot be reproduced. The importance sometimes attached to implausible artifacts such as anthrax or bubonic plague is especially problematic. We show that the Zebra filter retrieves only the nearest relatives of sample contents enabling more reproducible and biologically plausible interpretation of metagenomic data.
Comparison of Outcomes 1 Year After Rotator Cuff Repair With and Without Concomitant Biceps Surgery (2017)

Level III, retrospective comparative study.
Distributed multi-hop scheduling and medium access with delay and throughput constraints (2001)

Providing quality of service in random access multi-hop wireless networks requires support from both medium access and packet scheduling algorithms. However, due to the distributed nature of ad hoc networks, nodes may not be able to determine the next packet that would be transmitted in a (hypothetical) centralized and ideal dynamic priority scheduler. In this paper, we develop two mechanisms for QoS communication in multi-hop wireless networks. First, we devise distributed priority scheduling a technique that piggybacks the priority tag of a node's head-of-line packet onto handshake and data packets; e.g., RTS/DATA packets in IEEE 802.11. By monitoring transmitted packets, each node maintains a scheduling table which is used to assess the node's priority level relative to other nodes. We then incorporate this scheduling table into existing IEEE 802.11 priority back-off schemes to approximate the idealized schedule. Second, we observe that congestion, link errors, and the random nature of medium access prohibit an exact realization of the ideal schedule. Consequently, we devise a scheduling scheme termedmulti-hop coordinationso that downstream nodes can increase a packet's relative priority to make up for excessive delays incurred upstream. We next develop a simple analytical model to quantitatively explore these two mechanisms. In the former case, we study the impact of the probability of overhearing another packet's priority index on the scheme's ability to achieve the ideal schedule. In the latter case, we explore the role of multi-hop coordination in increasing the probability that a packet satisfies its end-to-end QoS target. Finally, we perform a set of ns-2 simulations to study the scheme's performance under more realistic conditions.
Supplementary Figure S3 from Functional Kinomics Identifies Candidate Therapeutic Targets in Head and Neck Cancer (2023)

&lt;p&gt;Figure S3. Correlation plots of autologous HNSCC cell line pairs utilizing kinomic profile&lt;/p&gt;
Palladium(II) and Platinum(II) Polyamine Complexes: X-Ray Crystal Structures of (SP-4-2)-Chloro{N-[(3-amino-κN)propyl]propane-1,3-diamine-κN,κN′}palladium(1+) Tetrachloropalladate (2-) (2 : 1) and (R,S)-Tetrachloro[μ-(spermine)]dipalladium(II) (={μ-{N,N′-Bis[(3-amino-κN)propyl]butane-1,4-diamine-κN:κN′}}tetrachlorodipalladium) (1999)

The reactivity of the polyamines L, i.e., N-(3-aminopropyl)propane-1,3-diamine (1), spermidine (=N-(3-aminopropyl)butane-1,4-diamine; 2), and spermine (=N,N′-bis(3-aminopropyl)butane-1,4-diamine; 3) vs. palladium(II) and platinum(II) salts is studied. These reactions allowed us to prepare and characterize a wide variety of PdII and PtII complexes containing the polyamines. Compounds of the general formula [MCl(L)]2[MCl4] (L=1; 1a: M=Pd; 1b: M=Pt) or [MCl(L)]Cl (L=1; 1′a: M=Pd; 1′b: M=Pt) were isolated after treatment of K2[MCl4] or cis-[MCl2(dmso)2] respectively, with 1. The reaction of K2[MCl4] with 2 led to [MCl(L)]2[MCl4] (L=2; 2a: M=Pd; 2b: M=Pt), while that with 3 gave the neutral dinuclear compounds [M2Cl4(L)] (L=3; 3a: M=Pd; 3b: M=Pt). A comparative study of the results obtained in these reactions allowed us to evaluate the influence of i) the number of N-atoms in the polyamine, ii) their basicity, and iii) the palladium or platinum salt, upon the nature of the final product. Compounds 1a and (R,S)-3a were characterized by their X-ray crystal-structure analysis. Both exhibited the monoclinic crystal system, 1a the space group P21/c, and 3a the space group P21/n.
Whole blood RNA-seq demonstrates an increased host immune response in individuals with cystic fibrosis who develop nontuberculous mycobacterial pulmonary disease (2022)

In contrast to the non-cystic fibrosis population, the gene expression signature of patients with cystic fibrosis who develop NTM-PD is characterized by increased innate immune responses.
Design of a 100 W, 500000 rpm permanent-magnet generator for mesoscale gas turbines (2005)

Mesoscale gas turbine generator systems are a promising solution for high energy and power density portable devices. This paper focuses on the design of a 100 W, 500000 rpm generator suitable for use with a gas turbine. The design procedure selects the suitable machine type and bearing technology, and determines the electromagnetic characteristics. The losses caused by the high frequency operation are minimized by optimizing the winding and the stator core material. The final design is a permanent-magnet machine with a volume of 3.5 cm/sup 3/ and experimental measurements from a test bench are presented.
The N Terminus of Bradykinin When Bound to the Human Bradykinin B2 Receptor Is Adjacent to Extracellular Cys20 and Cys277 in the Receptor (1996)

Chemical cross-linking combined with site-directed mutagenesis was used to evaluate the role of extracellular cysteines and their positions relative to the binding site for the agonist bradykinin (BK) in the human BK B2 receptor. All extracellular cysteines, Cys20, Cys103, Cys184, and Cys277, in the receptor were mutated to serines, and single and double mutants were transfected into COS-7 cells. The Ser20 and Ser277 single mutants and the Ser20/Ser277 double mutant bound [3H]BK and the antagonist [3H]NPC17731 with pharmacological profiles identical to the wild-type B2 receptor. In contrast, the Ser103 and Ser184 single mutants were unable to bind either of the two radioligands. However, these mutants were still expressed as determined by immunoblotting with anti-B2 receptor antibodies. Previous studies on the bovine B2 receptor showed that bifunctional reagents, which are reactive to amines at one end and to free sulfhydryls in the opposite end, cross-link the N terminus of receptor-bound BK to a sulfhydryl in the receptor (Herzig, M. C. S., and Leeb-Lundberg, L. M. F. (1995) J. Biol. Chem. 270, 20591-20598). Here, we show that m-maleimidobenzoyl-N-hydroxysuccinimide ester and 1,5-difluoro-2, 4-dinitrobenzene cross-linked BK to the wild-type human B2 receptor and the Ser20 and Ser277 single mutant receptors, whereas these reagents were unable to cross-link BK to the Ser20/Ser277 double mutant. These results show that Cys103 and Cys184 are both required for expression of high affinity agonist and antagonist binding sites in the human B2 receptor, while Cys20 and Cys277 are not required. Furthermore, the results provide direct biochemical evidence that the N terminus of BK, when bound to the B2 receptor, is adjacent to Cys277 in extracellular domain 4 and Cys20 in extracellular domain 1 of the receptor.
Temperature estimation using ultrasonic spatial compound imaging (2004)

The feasibility of temperature estimation during high-intensity focused ultrasound therapy using pulse-echo diagnostic ultrasound data has been demonstrated. This method is based upon the measurement of thermally-induced modifications in backscattered RF echoes due to thermal expansion and local changes in the speed of sound. It has been shown that strong ripple artifacts due to the thermo-acoustic lens effect severely corrupt the temperature estimates behind the heated region. We propose here a new imaging technique that improves the temperature estimation behind the heated region and reduces the variance of the temperature estimates in the entire image. We replaced the conventional beamforming on transmit with multiple steered plane wave insonifications using several subapertures. A two-dimensional temperature map is estimated from axial displacement maps between consecutive RF images of identically steered plane wave insonifications. Temperature estimation is then improved by averaging the two-dimensional maps from the multiple steered plane wave insonifications. Experiments were conducted in a tissue-mimicking gelatin-based phantom and in fresh bovine liver.
Building and Sustaining Diverse Functioning Networks Using Social Media and Digital Platforms to Improve Diversity and Inclusivity (2018)

There has long been a focus on building inclusion and diversity in the sciences through a range of efforts intended to increase representation and access. Despite expansive efforts supported by higher education institutions, funding agencies and others, a need persists to support broad participation and success. Digital platforms, including blogs and social media such as Twitter™, offer emergent paths for scientists to proactively build supportive communities, even where structural diversity or numerical representation of diverse groups remains low. Use of these platforms can range from community building, to proactive mentoring and advocacy, as well as more customary uses for supporting scholarly success of diverse individuals, including dissemination and accessible discussions of research. I discuss specific uses of social-media digital platforms for building and cultivating communities of underrepresented scholars and facilitating engagement around issues of broad concern to groups underrepresented in science and higher education. These uses include mentoring a nd support to promote equity, inclusion and diversity, promoting self-definition and personal agency, community building, and advocacy. I draw on published literature about using social media and digital platforms in higher education to build and cultivate “social networks” for connecting widely distributed individuals from underrepresented backgrounds to cultivate communities of interest, support and practice, including a focus on mentoring, sponsorship and advocacy. I highlight the power of Twitter™ and social media platforms to build and cultivate connections of individuals underrepresented in science and the academy and to offer meaningful means for mitigating local deficits related to low structural diversity and inequity.
A Non-Isothermal Process Model for Consolidation and Void Reduction during In-Situ Tow Placement of Thermoplastic Composites (1995)

In in-situ composites processing, heat and pressure are applied locally to composite tows to achieve consolidation. During the consolidation of thermoplastic composite tows or plies, a modest amount of flow takes place. Due to the high viscosity of thermoplastics, the fibers and the matrix move together. We propose a novel approach to model this process-approximate the medium as a compressible viscous continuum rather than use Darcy's law which has been successful in modeling thermoset composites processing. The void content of the composite changes during the consolidation process due to various mechanisms. A consolidation model for thermoplastic composite that incorporates—the relevant void growth and transport phenomena has been developed. The model is capable of predicting the final void fraction and the final thickness of a composite part as a function of the processing speed and the consolidation pressure under non-isothermal conditions.
Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer (2021)

Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing this kinase, through either RNA interference or CRISPR, sensitized tumor cells to chemotherapy and hindered metastasis in vitro and in vivo in a tail vein injection model. Drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduced all effects of RSK4 silencing in vitro and in/ex vivo using lung cancer xenograft and genetically engineered mouse models and bladder tumor explants. Through x-ray structure determination and Markov transient and Deuterium exchange analyses, we identified the allosteric binding site and revealed how this compound blocks RSK4 kinase activation through binding to an allosteric site and mimicking a kinase autoinhibitory mechanism involving the RSK4's hydrophobic motif. Last, we show that patients undergoing chemotherapy and adhering to prophylactic levofloxacin in the large placebo-controlled randomized phase 3 SIGNIFICANT trial had significantly increased (<i>P</i> = 0.048) long-term overall survival times. Hence, we suggest that RSK4 inhibition may represent an effective therapeutic strategy for treating lung and bladder cancer.
Porous, Fluorescent, Covalent Triazine‐Based Frameworks Via Room‐Temperature and Microwave‐Assisted Synthesis (2012)

Porous, fluorescent, covalent triazine-based frameworks (CTFs) are obtained in an unprecedentedly mild reaction, opening up a scalable pathway for molecular building blocks previously thought incompatible with this chemistry. Choice of monomers and synthetic conditions determines the optical properties and nano-scale ordering of these highly microporous materials with BET surface areas exceeding 1100 m(2) g(-1) and exceptional CO(2) capacities (up to 4.17 mmol g(-1)).
Compositional Modeling of Oil-Based Mud-Filtrate Cleanup During Wireline Formation Tester Sampling (2006)

Abstract Miscible oil-based mud (OBM) filtrate contamination poses a major challenge to the acquisition of representative fluid samples using wireline formation testers (WFTs). A sound understanding of the physics of OBM filtrate clean-up and identification of first-order impact parameters is of paramount importance for the design of new generation WFT probes that can operate in OBM filtrate environments with enhanced efficiency. Analytical as well as numerical models reported in the formation testing literature rely predominantly on simplifying assumptions in terms of the compositions of flowing fluid phases. These models characteristically assume single-component phases in the case of two-phase immiscible formulation, or a two-/three-component hydrocarbon phase in cases of black-oil/extended black-oil formulations. In turn, compositional interactions are entirely neglected or represented through simplistic empirical correlations. Such conventional models are deemed sufficient for pre-job planning and interpretation of measurements acquired in formations subject to water-base mud (WBM) filtrate contamination. Dynamics of flow in OBM filtrate contaminated formations is significantly more complex. A time-dependent coupling between fluid dynamics and phase behavior constitutes the governing physics of OBM filtrate clean-up process. Therefore, for OBM filtrate environments, accuracy of conventional formulations in representing the actual physics of flow is limited. We have constructed a numerical model for the OBM filtrate clean-up within the framework of an equation-of-state (EOS) compositional fluid-flow simulator. Our numerical framework simultaneously honors the physics of multi-component fluid flow and the thermodynamics of phase behavior. The numerical model was verified against analytical solutions for zeroth-order models for which analytical solutions exist. Simulation results exhibited close agreement with the analytical predictions and with field data for the time dependence of contamination during sampling. A rapid approximate response surface based model, which can serve as a pre-job planning or real-time analysis tool, was derived from extensive simulations conducted with the compositional numerical model. Our simulation and rapid modeling results compare well with empirical observations made in the field. In particular, the rate of change of miscible contamination with time has been found empirically to vary as t5/12. For the first time, modeling has been shown to give essentially the same results as empirical observations. The agreement between our model and common field observation motivates use of our model to analyze the more complex WFT probes, which have recently become available.
Imaging the Lateral Migration of Subsurface Moisture using Electromagnetic Induction (2002)

Identifying the subsurface paths by which water moves within the vadose zone isdifficult. Limited scientific data are available that detail agrochemical migration for theinnumerable combinations of soil and hydrological factors, and for the wide array of agriculturalproduction practices. We are using electromagnetic induction (EMI) sensing in a unique timeelapsedimaging format to target high-, moderate-, and low-risk moisture movement patterns.Our research on loess-over-alluvium soils demonstrates that subsurface water movement ishighly variable and site-specific. Often a small soil volume conducts a large water flow volume.Site-specific soil structural features usually cause this concentrated flow. Water moves rapidlyoffsite from certain areas of fields, while little or no lateral subsurface flow occurs in other areas.We are targeting those field areas that have high potential for offsite movement ofagrochemicals using Geographic Information Systems (GIS) and Differential Global PositioningSystems (DGPS) technologies. This paper gives an overview of our dynamic imaging processfor temporal and spatial mapping of soil conductivity for visualizing near-surface watermovement.