gebhart/patrepeval huggingface dataset:
Three Parallel Quorum-Sensing Systems Regulate Gene Expression in <i>Vibrio harveyi</i> (2004)

In a process called quorum sensing, bacteria communicate using extracellular signal molecules termed autoinducers. Two parallel quorum-sensing systems have been identified in the marine bacterium Vibrio harveyi. System 1 consists of the LuxM-dependent autoinducer HAI-1 and the HAI-1 sensor, LuxN. System 2 consists of the LuxS-dependent autoinducer AI-2 and the AI-2 detector, LuxPQ. The related bacterium, Vibrio cholerae, a human pathogen, possesses System 2 (LuxS, AI-2, and LuxPQ) but does not have obvious homologues of V. harveyi System 1. Rather, System 1 of V. cholerae is made up of the CqsA-dependent autoinducer CAI-1 and a sensor called CqsS. Using a V. cholerae CAI-1 reporter strain we show that many other marine bacteria, including V. harveyi, produce CAI-1 activity. Genetic analysis of V. harveyi reveals cqsA and cqsS, and phenotypic analysis of V. harveyi cqsA and cqsS mutants shows that these functions comprise a third V. harveyi quorum-sensing system that acts in parallel to Systems 1 and 2. Together these communication systems act as a three-way coincidence detector in the regulation of a variety of genes, including those responsible for bioluminescence, type III secretion, and metalloprotease production.
Potent human uric acid transporter 1 inhibitors: in vitro and in vivo metabolism and pharmacokinetic studies (2012)

Human uric acid transporter 1 (hURAT1; SLC22A12) is a very important urate anion exchanger. Elevated urate levels are known to play a pivotal role in cardiovascular diseases, chronic renal disease, diabetes, and hypertension. Therefore, the development of potent uric acid transport inhibitors may lead to novel therapeutic agents to combat these human diseases. The current study investigates small molecular weight compounds and their ability to inhibit 14C-urate uptake in oocytes expressing hURAT1. Using the most promising drug candidates generated from our structure-activity relationship findings, we subsequently conducted in vitro hepatic metabolism and pharmacokinetic (PK) studies in male Sprague-Dawley rats. Compounds were incubated with rat liver microsomes containing cofactors nicotinamide adenine dinucleotide phosphate and uridine 5'-diphosphoglucuronic acid. In vitro metabolism and PK samples were analyzed using liquid chromatography/mass spectrometry-mass spectrometry methods. Independently, six different inhibitors were orally (capsule dosing) or intravenously (orbital sinus) administered to fasting male Sprague-Dawley rats. Blood samples were collected and analyzed; these data were used to compare in vitro and in vivo metabolism and to compute noncompartmental model PK values. Mono-oxidation (Phase I) and glucuronidation (Phase II) pathways were observed in vitro and in vivo. The in vitro data were used to compute hepatic intrinsic clearance, and the in vivo data were used to compute peak blood concentration, time after administration to achieve peak blood concentration, area under the curve, and orally absorbed fraction. The experimental data provide additional insight into the hURAT1 inhibitor structure-activity relationship and in vitro-in vivo correlation. Furthermore, the results illustrate that one may successfully prepare potent inhibitors that exhibit moderate to good oral bioavailability.
npd gene functions of Rhodococcus (opacus) erythropolis HL PM-1 in the initial steps of 2,4,6-trinitrophenol degradation b bThe GenBank accession number for the sequence reported in this paper is AF435009. (2002)

Rhodococcus (opacus) erythropolis HL PM-1 grows on 2,4,6-trinitrophenol (picric acid) or 2,4-dinitrophenol (2,4-DNP) as sole nitrogen source. A gene cluster involved in picric acid degradation was recently identified. The functional assignment of three of its genes, npdC, npdG and npdI, and the tentative functional assignment of a fourth one, npdH, is reported. The genes were expressed in Escherichia coli as His-tag fusion proteins that were purified by Ni-affinity chromatography. The enzyme activity of each protein was determined by spectrophotometry and HPLC analyses. NpdI, a hydride transferase, catalyses a hydride transfer from reduced F420 to the aromatic ring of picric acid, generating the hydride sigma-complex (hydride Meisenheimer complex) of picric acid (H(-)-PA). Similarly, NpdI also transformed 2,4-DNP to the hydride sigma-complex of 2,4-DNP. A second hydride transferase, NpdC catalysed a subsequent hydride transfer to H(-)-PA, to produce a dihydride sigma-complex of picric acid (2H(-)-PA). All three reactions required the activity of NpdG, an NADPH-dependent F420 reductase, for shuttling the hydride ions from NADPH to F420. NpdH converted 2H(-)-PA to a hitherto unknown product, X. The results show that npdC, npdG and npdI play a key role in the initial steps of picric acid degradation, and that npdH may prove to be important in the later stages.
Coupling Characteristics of Three-Guide Tapered Coupler for Optical Isolator with Si Guiding Layer (2006)

An optical isolator employing a nonreciprocal phase shift is composed of a three-guide tapered coupler. The coupling characteristics of the three-guide tapered coupler for an integrated optical isolator with a Si guiding layer are demonstrated.
Bayesian Reconstruction of 3D Human Motion from Single-Camera Video (1999)

The three-dimensional motion of humans is underdetermined when the observation is limited to a single camera, due to the inherent 3D ambiguity of 2D video. We present a system that reconstructs the 3D motion of human subjects from single-camera video, relying on prior knowledge about human motion, learned from training data, to resolve those ambiguities. After initialization in 2D, the tracking and 3D reconstruction is automatic; we show results for several video sequences. The results show the power of treating 3D body tracking as an inference problem. 1
Coenzyme A contained in mothers' milk is associated with the potential to induce atopic dermatitis (2011)

T(h)2 adjuvant activity can be qualitatively and quantitatively evaluated using a mixed lymphocyte reaction and by changes in the intracellular cyclic adenosine 3',5'-monophosphate concentration, using human dendritic cells in vitro. The current study shows that mothers, whose children (n = 55) developed atopic dermatitis (AD) within 6 months after birth, often demonstrate a higher T(h)2 adjuvant activity in their milk, in comparison to those whose children did not develop such symptoms. Such an activity was recovered in a liquid phase of mothers' milk and was eluted as a single fraction by reversed-phase HPLC. Further analysis of this fraction by mass spectrometry showed that signals originating from a factor with a molecular weight of 767.53 are observed, exclusively in milk with a high T(h)2 adjuvant activity. The mass is exactly that of Coenzyme A (CoA), and indeed, a low concentration of CoA exhibited T(h)2 adjuvant activity both in vitro and in vivo. Moreover, mesenteric lymph node non-T cells obtained from mice that were orally treated with CoA led allogeneic naive CD4(+) T cells to differentiate into T(h)2. Furthermore, the oral administration of CoA induced rough skin, hyperplasia of the epidermis, hypergranulosis in the spinous layer and the thickening of the stratum in mice. These data collectively indicate that some of the patients with AD were exposed to mothers' milk carrying high T(h)2 adjuvant activity right after birth, which may be attributable to presence of CoA contained in the milk.
Abstract A46: Pharmacodynamic biomarkers for OSI-906, an insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitor, in cancer patients with advanced solid tumors (2009)

Abstract Background: OSI-906 is a potent small molecule inhibitor of the insulin-like growth factor 1 receptor (IGF-1R), a receptor tyrosine kinase that is overexpressed in several human cancer types and implicated in resistance to chemotherapy. Disruption of the growth hormone-IGF1 signaling axis can affect levels of biomarkers such as IGF1, growth hormone (GH) and insulin and can affect glucose homeostasis, making these potentially useful markers for demonstrating the activity of IGF-1R inhibitors in solid tissues. Methods: Two phase I dose escalation trials were initiated in cancer patients with advanced solid tumors who received OSI-906 on either continuous or intermittent dosing schedules. Pharmacodynamic (PD) and pharmacokinetic (PK) assessments were included as secondary objectives of these studies. Circulating biomarkers, including total IGF1, IGFBP3 and non-fasting GH and insulin levels, were measured at various times during the dosing cycle (21 days for continuous dosing; 14 days for intermittent dosing) and changes were correlated with plasma concentrations of OSI-906. Results: To date, patients have been treated with up to 450 mg QD and 200 mg BID on the continuous dosing schedule and up to 750 mg QD on the intermittent dosing schedule. Maximum tolerated dose (MTD) was determined to be 400 mg QD and 150 mg BID for continuous dosing and 600 mg QD for intermittent dosing. Preliminary analysis of the PK data suggests that the exposure of OSI-906 increased with dose. Median plasma concentrations of OSI-906 at MTD exceeded the predicted concentration required for efficacy based on the preclinical models (1 µM). Total IGF1 concentrations in plasma were increased relative to predose levels at doses ≥ 450 mg QD on the intermittent dosing schedule and ≥ 150 mg QD or 40 mg BID on the continuous dosing schedule. Elevations in non-fasting plasma insulin levels were also observed in patients with plasma concentrations of OSI-906 exceeding 5000 ng/mL. PK/PD relationships were observed for IGF1 and insulin. OSI-906 did not affect plasma IGFBP3 levels in most patients. Analysis of additional biomarkers, including GH, is ongoing. Conclusions: At or below MTD, plasma concentrations of OSI-906 could be achieved that exceed concentrations required for anti-tumor efficacy based on the preclinical models. The pharmacodynamic data indicate that pharmacologically-relevant concentrations of OSI-906 were achieved in tissues involved in regulating the GH-IGF1 signaling axis. Together, these PK and PD data indicate that the current recommended dosing regimens may provide sufficient exposure for activity against solid tumors. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A46.
IM-OFDMA: A Novel Spectral Efficient Uplink Multiple Access Based on Index Modulation (2019)

This paper proposes a novel uplink multiple access scheme to enhance the overall spectral efficiency of wireless systems. The core idea is to exploit index modulation (IM) concept in orthogonal frequency division multiple access (OFDMA) systems. In the proposed scheme, entitled IM-OFDMA, part of the transmitted bits of each user is conventionally modulated, while the rest of the bits determine the index of the active subcarrier that will be used to communicate the modulated symbol. Unlike OFDMA, IM-OFDMA does not require any scheduling algorithm, which results in data collision between the user's received messages. Yet, it is revealed that IM-OFDMA outperforms OFDMA and state of the art uplink non-orthogonal multiple access (NOMA) over a wide range of system and channel parameters. Besides, it is reported that IM-OFDMA can serve up to 3 times the number of served users in OFDMA system while maintaining similar error performance per user. The average bit error rate of IM-OFDMA scheme is derived in a closed form expression that is substantiated through Monte Carlo simulation results.
Association of CR/VGPR with progression-free survival in rituximab-naïve WM patients undergoing rituximab-based therapy, as predicted by polymorphisms in FcγRIIIA-158. (2010)

8108 Background: The incorporation of rituximab into various regimens has improved depth of response in Waldenstrom's macroglobulinemia (WM), though the impact of achieving better responses remains to be determined, as also are determinants including Fcγ receptor polymorphisms. Methods: We examined the impact of categorical responses on progression free survival (PFS) in 159 rituximab-naïve WM patients who received rituximab-based therapy. Baseline characteristics: median age 62 years; serum IgM 3,670 mg/dL; hematocrit 31.7%; serum B2M ≥3.0 g/L (52%); previously untreated 67.3%. All patients received a rituximab containing regimen with either cyclophosphamide, fludarabine, bortezomib, or an immunomodulatory agent. The median follow-up was 33.5 months, and categorical responses were as follows: CR (8.8%); VGPR (13.2%); PR (50%); MR (18.9%); Non-Responders (8.8%). Sequencing for polymorphic variants at FcγRIIA, FcγRIIB, and FcγRIIIA was performed for 75 patients for whom genomic DNA was available, and impact on categorical responses determined. Results: Achievement of better categorical responses was incrementally associated with improved PFS (p<0.0001). No separation was observed between VGPR and CR, and minor responses showed improved PFS over non-responders. Median TTP for CR/VGPR patients was 71.8 versus 38.6 months for MR/PR patients (p=0.03). Neither age, baseline serum IgM level, hematocrit, platelet count, serum B2M level, WM ISS score, and treatment group predicted for CR/VGPR. In contrast, polymorphisms at FcγRIIIA-158, FcγRIIIA-48, and FcγRIIA-131 were associated with improved categorical responses, particularly attainment of CR/VGPR (p≤0.03). A clear linkage between these polymorphisms was also detected, with the presence of at least one valine at FcγRIIIA-158 serving as the primary determinant of CR/VGPR responses. Conclusions: The attainment of CR/VGPR is associated with significantly longer PFS in rituximab-naïve WM patients undergoing rituximab-based therapy, and is predicted by the presence of at least one valine (V/V or V/F) at FcγRIIIA-158. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogen Idec, Celgene, Genentech, Millennium Biogen Idec, Celgene, Millennium Celgene, Millennium
An immune cell-selective interleukin 4 agonist (1998)

Interleukin 4 (IL-4) is a pleiotropic cytokine. Of the cell types responsive to IL-4, T cells express one IL-4 receptor (IL-4R) type, IL-4Ralpha/IL-2Rgamma (class I IL-4R), whereas endothelial cells express another type, IL-4Ralpha/IL-13Ralpha (class II IL-4R). It was hypothesized that IL-4 variants could be generated that would be selective for cell types expressing the different IL-4Rs. A series of IL-4 muteins were generated that were substituted in the region of IL-4 implicated in interactions with IL-2Rgamma. These muteins were evaluated in T cell and endothelial cell assays. One of these muteins, containing the mutation Arg-121 to Glu (IL-4/R121E), exhibited complete biological selectivity for T cells, B cells, and monocytes, but showed no activity on endothelial cells. Receptor binding studies indicated that IL-4/R121E retained physical interaction with IL-2Rgamma but not IL-13Ralpha; consistent with this observation, IL-4/R121E was an antagonist of IL-4-induced activity on endothelial cells. IL-4/R121E exhibits a spectrum of activities in vitro that suggest utility in the treatment of certain autoimmune diseases.
Probabilistic mud slowness estimation from sonic array data (2008)

There are various ways to get an estimate of the mud slowness. The most common one consists in performing acoustic measurement at the surface using mud sample or using empirical laws linking mud slowness as a function of mud density and type. In this case, the estimation of mud slowness is said to be indirect as the estimated mud value is not the one measured in the well at the time the tool recorded the data. The second approach consists in analyzing dispersive modes contained in recorded data and from this study deriving an estimate of the mud slowness. The drawback of this non automatic method is that it relies heavily on the skill of the person that will analyze the dispersion plots. Therefore, there is a need for a general framework capable to provide reliable and accurate mud slowness estimation with minimum supervision. In order to overcome this need a probabilistic approach combining the high frequency monopole data and the output from the monopole radial profiling to get an estimate of the mud slowness has been developed. Robustness and efficiency of this algorithm will be illustrated on real field data.
Aptamer Selection Express: A Rapid Single-Step Selection of Double Stranded DNA Capture Elements (Briefing Charts) (2009)

Abstract : Advantages of aptamers. ALISA, Where we came from. Dot Blot Format, Other possibilities. One step Quantum Dot De-quenching Assay Why we need a double-stranded DNA aptamer. Comparing SELEX to Aptamer Selection Express (ASExpP). Reagentless electronic sensors (RFIDs). Emerging disease agents and finding an unknown Why we need a rapid technique for aptamer selection.
Adding Physical Objects to an Interactive Game Improves Learning and Enjoyment (2016)

Can experimenting with three-dimensional (3D) physical objects in mixed-reality environments produce better learning and enjoyment than flat-screen two-dimensional (2D) interaction? We explored this question with EarthShake: a mixed-reality game bridging physical and virtual worlds via depth-camera sensing, designed to help children learn basic physics principles. In this paper, we report on a controlled experiment with 67 children, 4--8 years old, that examines the effect of observing physical phenomena and collaboration (pairs vs. solo). A follow-up experiment with 92 children tests whether adding simple physical control, such as shaking a tablet, improves learning and enjoyment. Our results indicate that observing physical phenomena in the context of a mixed-reality game leads to significantly more learning and enjoyment compared to screen-only versions. However, there were no significant effects of adding simple physical control or having students play in pairs vs. alone. These results and our gesture analysis provide evidence that children's science learning can be enhanced through experiencing physical phenomena in a mixed-reality environment.
Nonlinear Crosstalk Mitigation in Superchannels Using Unequal Subcarrier Spacing (2015)

We propose a novel technique to mitigate nonlinear crosstalk in superchannels by allocating wider spacing between center subcarriers compared to the edge. We demonstrate that it can equalize subcarriers performance and extend reach by 15%.
Pretreatment of Corn Fiber to Enrich Corn Fiber Oil and its Phytosterol Compounds (2002)

The unique phytosterol-containing oil in the corn fiber (corn fiber oil) has potential useas a natural LDL-cholesterol-lowering nutraceutical but its low concentration in fiber (1-3%)makes it is difficult and expensive to extract. Pre-treatment of corn fiber with dilute acid and/orglucosidases removed non-lipid components of fiber, producing oil-enriched fractions thatshould be more amenable to efficient and inexpensive oil extraction. Analytical results showedthat acid as well as enzymes significantly increased the content of corn fiber oil and itsphytosterol compounds by hydrolyzing (and removing) the starch and non-starch (cell wall)polysaccharides from the wet milled corn fiber. Dual treatment of the fiber with acid andenzyme gave a greater increase in the final concentration of corn fiber oil and its phytosterolcomponents when compared to acid or enzyme treatments alone. Depending upon thetreatment, the oil concentration in the residual solids increased from 88-807% and the total phytosterol concentration increased by 64 to 710%, compared to the untreated fiber sample(control sample).
Enhancing the Resolution of a Sensor Via Negative Correlation: A Biologically Inspired Approach (2012)

We demonstrate that a neuronal system, underpinned by "fire-then-reset" dynamics, can display an enhanced resolution R~T(ob)(-1) where T(ob) is the observation time of the measurement; this occurs when the interspike intervals are negatively correlated and T(ob)<Δ/ε, where ε is a parameter characterizing the level of correlation between interspike intervals and Δ is the average interspike interval. We also show that by introducing negative correlations into the time domain response of a nonlinear dynamical sensor it is possible to replicate this enhanced scaling of the resolution. Thus, we demonstrate the potential for designing a novel class of biomimetic sensors that afford improved signal resolution by functionally utilizing negative correlations.
Peptidomimetic Inhibitors of Herpes Simplex Virus Ribonucleotide Reductase with Improved <i>in Vivo</i> Antiviral Activity (1996)

We have been investigating the potential of a new class of antiviral compounds. These peptidomimetic derivatives prevent association of the two subunits of herpes simplex virus (HSV) ribonucleotide reductase (RR), an enzyme necessary for efficient replication of viral DNA. The compounds disclosed in this paper build on our previously published work. Structure-activity studies reveal beneficial modifications that result in improved antiviral potency in cell culture in a murine ocular model of HSV-induced keratitis. These modifications include a stereochemically defined (2,6-dimethylcyclohexyl)amino N-terminus, two ketomethylene amide bond isosteres, and a (1-ethylneopentyl)amino C-terminus. These three modifications led to the preparation of BILD 1351, our most potent antiherpetic agent containing a ureido N-terminus. Incorporation of the C-terminal modification into our inhibitor series based on a (phenylpropionyl)valine N-terminus provided BILD 1357, a significantly more potent antiviral compound than our previously published best compound, BILD 1263.
Biphasic Activation of WNT Signaling Facilitates the Derivation of Midbrain Dopamine Neurons from hESCs for Translational Use v1 (2021)

Human pluripotent stem cells show considerable promise for applications in regenerative medicine, including the development of cell replacement paradigms for the treatment of Parkinson’s disease. Protocols have been developed to generate authentic midbrain dopamine (mDA) neurons capable of reversing dopamine-related deficits in animal models of Parkinson’s disease. However, the generation of mDA neurons at clinical scale suitable for human application remains an important challenge. Here, we present an mDA neuron derivation protocol based on a two-step WNT signaling activation strategy that improves expression of midbrain markers, such as Engrailed-1 (EN1), while minimizing expression of contaminating posterior (hindbrain) and anterior (diencephalic) lineage markers. The resulting neurons exhibit molecular, biochemical, and electrophysiological properties of mDA neurons. Cryopreserved mDA neuron precursors can be successfully transplanted into 6-hydroxydopamine (6OHDA) lesioned rats to induce recovery of amphetamine-induced rotation behavior. The protocol presented here is the basis for clinical-grade mDA neuron production and preclinical safety and efficacy studies.
In Vitro Selection of glmS Ribozymes (2009)

Riboswitches modulate gene expression in eubacteria and eukaryotes in response to changing concentrations of small molecule metabolites. In most examples studied to date, riboswitches achieve both metabolite sensing and gene control functions without the obligate involvement of protein factors. These findings validate the hypothesis that RNA molecules could be engineered to function as designer gene control elements that sense and respond to different ligands. We believe that reverse engineering natural riboswitches could provide an intellectual foundation for those who wish to build synthetic riboswitches. Also, natural riboswitches might serve as starting points for efforts to change ligand specificity or gene control function through mutation and selection in vitro. In this chapter, we describe how in vitro selection can be used to create variant glmS ribozymes. Additionally, we discuss how these techniques can be extended to other riboswitch classes.