gebhart/patrepeval huggingface dataset:
Discrimination between biothreat agents and ‘near neighbor’ species using a resequencing array (2008)

Timely identification of biothreat organisms from large numbers of clinical or environmental samples in potential outbreak or attack scenario is critical for effective diagnosis and treatment. This study aims to evaluate the potential of resequencing arrays for this purpose. Albeit suboptimal, this report demonstrated that respiratory pathogen microarray version 1 can identify Bacillus anthracis, Francisella tularensis, Yersinia pestis and distinguish them from benign 'near neighbor' species in a single assay. Additionally, the sequence information can discriminate strains and possibly the sources of the strains. With further development, it is possible to use resequencing microarrays for biothreat surveillance.
Improving Treatment Efficacy of In Situ Forming Implants via Concurrent Delivery of Chemotherapeutic and Chemosensitizer (2020)

P-glycoprotein (Pgp), a member of the ATP-binding cassette family, is one of the major causes of multidrug resistance in tumors. Current clinical treatments to overcome MDR involve the co-delivery of a Pgp inhibitor and a chemotherapeutic. A concern for this treatment that has led to varied clinical trial success is the associated systemic toxicities involving endogenous Pgp. Local drug delivery systems, such as in situ forming implants (ISFIs), alleviate this problem by delivering a high concentration of the drug directly to the target site without the associated systemic toxicities. ISFIs are polymeric drug solutions that undergo a phase transition upon injection into an aqueous environment to form a solid drug eluting depot allowing for a high initial intratumoral drug concentration. In this study, we have developed an ISFI capable of overcoming the Pgp resistance by co-delivering a chemotherapeutic, Doxorubicin (Dox), with a Pgp inhibitor, either Pluronic P85 or Valspodar (Val). Studies investigated in vitro cytotoxicity of Dox when combined with either Pgp inhibitor, effect of the inhibitors on release of Dox from implants in PBS, in vivo Dox distribution and retention in a subcutaneous flank colorectal murine tumor, and therapeutic response characterized by tumor growth curves and histopathology. Dox + Val showed a 4-fold reduction in the 50% lethal dose (LD<sub>50</sub>) after 48 hours. Concurrent delivery of Dox and Val showed the greatest difference at 16 days post injection for both Dox penetration and retention. This treatment group had a 5-fold maximum Dox penetration compared to Dox alone ISFIs (0.53 ± 0.22 cm vs 0.11 ± 0.11 cm, respectively, from the center of the ISFI). Additionally, there was a 3-fold increase in normalized total intratumoral Dox intensity with the Dox + Val ISFIs compared to Dox alone ISFIs (0.54 ± 0.11 vs 0.18 ± 0.09, respectively). Dox + Val ISFIs showed a 2-fold reduction in tumor growth and a 27.69% increase in necrosis 20 days post-injection compared to Dox alone ISFIs. These findings demonstrate that co-delivery of Dox and Val via ISFI can avoid systemic toxicity issues seen with clinical Pgp inhibitors.
The phospholipides of Ehrlich ascites carcinoma cells: composition and intracellular distribution. (1960)

Summary The phospholipide content and the intracellular distribution of lipide phosphorus of Ehrlich ascites carcinoma cells have been studied. The lipides, 58 per cent of which are phospholipides, comprise 16 per cent of the dry weight. The nuclei contain 13.7 per cent of the lipide phosphorus; mitochondria, 29 per cent; microsomes, 52.5 per cent; and supernatant, 5.4 per cent. The phospholipides include 12.5 per cent acetal phosphatides and 81.93 per cent nitrogen-containing phospholipides; 3 per cent of the lipide phosphorus is contributed by phosphatidic acid and 4–16 per cent by inositol phosphatides. The molar ratio of nitrogen to phosphorus in Ehrlich ascites carcinoma phospholipides is 1.08. Choline contributes 53 per cent of the total nitrogen; ethanolamine, 30 per cent; sphingosine, 14 per cent; serine, 7 per cent; and amino acids other than serine, 3 per cent. About 6 per cent of the ethanolamine phosphatide appears to be in peptide linkage with serine and other amino acids. The significance of these findings is discussed in the light of the micromorphologic characteristics of ascites carcinoma cells.
Robustness of the Unscented Kalman Filter for State and Parameter Estimation in an Elastic Transmission (2010)

The Unscented Kalman Filter (UKF) was applied to state and parameter estimation of a one degree of freedom robot link with an elastic, cable-driven transmission. Only motor encoder and command torque data was used as input to the ﬁlter. The UKF was used ofﬂine for joint state and model-parameter estimation, and online for state estimation. This paper presents an analysis of the robustness of the UKF to unknown/unmodeled variation in inertia, cable tension and contact forces, using experimental data collected with the robot. Using model parameters found ofﬂine the UKF successfully estimated motor and link angles and velocities online. Although the transmission was very stiff, and hence the motor and link states almost equal, information about the individual states was obtained. Irrespective of variation from nominal conditions the UKF link angle estimate was better than using motor position as an approximation (i.e. inelastic transmission assumption). The angle estimates were particularly robust to variation in operating conditions, velocity estimates less so. A near-linear relationship between contact forces and estimation errors suggested that contact forces might be estimated using this error information. (Best Paper Award Candidate)
Improved Bit-Flipping Algorithm for Successive Cancellation Decoding of Polar Codes (2018)

The interest in polar codes has been increasing significantly since their adoption for use in the 5$^{\rm th}$ generation wireless systems standard. Successive cancellation (SC) decoding algorithm has low implementation complexity, but yields mediocre error-correction performance at the code lengths of interest. SC-Flip algorithm improves the error-correction performance of SC by identifying possibly erroneous decisions made by SC and re-iterates after flipping one bit. It was recently shown that only a portion of bit-channels are most likely to be in error. In this work, we investigate the average log-likelihood ratio (LLR) values and their distribution related to the erroneous bit-channels, and develop the Thresholded SC-Flip (TSCF) decoding algorithm. We also replace the LLR selection and sorting of SC-Flip with a comparator to reduce the implementation complexity. Simulation results demonstrate that for practical code lengths and a wide range of rates, TSCF shows negligible loss compared to the error-correction performance obtained when all single-errors are corrected. At matching maximum iterations, TSCF has an error-correction performance gain of up to $0.45$ dB compared with SC-Flip decoding. At matching error-correction performance, the computational complexity of TSCF is reduced by up to $40\%$ on average, and requires up to $5\times$ lower maximum number of iterations.
ChemInform Abstract: Synthesis of (2S,3S)‐β‐Methyltryptophan. (2001)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Single molecule recordings of lysozyme activity (2013)

Single molecule bioelectronic circuits provide an opportunity to study chemical kinetics and kinetic variability with bond-by-bond resolution. To demonstrate this approach, we examined the catalytic activity of T4 lysozyme processing peptidoglycan substrates. Monitoring a single lysozyme molecule through changes in a circuit's conductance helped elucidate unexplored and previously invisible aspects of lysozyme's catalytic mechanism and demonstrated lysozyme to be a processive enzyme governed by 9 independent time constants. The variation of each time constant with pH or substrate crosslinking provided different insights into catalytic activity and dynamic disorder. Overall, ten lysozyme variants were synthesized and tested in single molecule circuits to dissect the transduction of chemical activity into electronic signals. Measurements show that a single amino acid with the appropriate properties is sufficient for good signal generation, proving that the single molecule circuit technique can be easily extended to other proteins.
Molecular mechanisms of growth factor action in diabetic retinopathy (1999)

During the preceding three decades, major advances have been made in our understanding of the natural history of diabetic retinopathy and the development and validation of therapeutic modalities. These accomplishments permit remarkable reductions in the visual loss commonly associated with this disease if timely and appropriate ocular care is provided to all patients with diabetes. However, until recently, our understanding of the molecular mechanisms underlying the development and progression of diabetic retinopathy and its associated complications has been less comprehensive. Scientific investigations during the past few years have dramatically expanded our appreciation of these basic molecular mechanisms. Although advances in the molecular understanding of diabetic ocular complications have been made on many scientific fronts, some of the newest and most detailed involve the molecular mechanisms underlying growth factor action in diabetic retinopathy. Recent developments in this rapidly evolving field have suggested novel interventional approaches, some of which are currently being evaluated in clinical trials. These new therapeutic approaches offer the hope of equivalent or improved efficacy without the side effects inherent in current treatment modalities.
Pharmacological hallmarks of allostery at the M4 muscarinic receptor elucidated through structure and dynamics (2023)

Allosteric modulation of G protein-coupled receptors (GPCRs) is a major paradigm in drug discovery. Despite decades of research, a molecular-level understanding of the general principles that govern the myriad pharmacological effects exerted by GPCR allosteric modulators remains limited. The M<sub>4</sub> muscarinic acetylcholine receptor (M<sub>4</sub> mAChR) is a validated and clinically relevant allosteric drug target for several major psychiatric and cognitive disorders. In this study, we rigorously quantified the affinity, efficacy, and magnitude of modulation of two different positive allosteric modulators, LY2033298 (LY298) and VU0467154 (VU154), combined with the endogenous agonist acetylcholine (ACh) or the high-affinity agonist iperoxo (Ipx), at the human M<sub>4</sub> mAChR. By determining the cryo-electron microscopy structures of the M<sub>4</sub> mAChR, bound to a cognate G<sub>i1</sub> protein and in complex with ACh, Ipx, LY298-Ipx, and VU154-Ipx, and applying molecular dynamics simulations, we determine key molecular mechanisms underlying allosteric pharmacology. In addition to delineating the contribution of spatially distinct binding sites on observed pharmacology, our findings also revealed a vital role for orthosteric and allosteric ligand-receptor-transducer complex stability, mediated by conformational dynamics between these sites, in the ultimate determination of affinity, efficacy, cooperativity, probe dependence, and species variability. There results provide a holistic framework for further GPCR mechanistic studies and can aid in the discovery and design of future allosteric drugs.
Graphical Analysis of Value of Information in Decision Models (2001)

We review and extend the qualitative relationships about the informational relevance of variables in graphical decision models based on conditional independencies revealed through graphical separations of nodes from nodes representing utility on outcomes. W exploit these qualitative relationships to generate non-numerical graphical procedures for identifying partial orderings over chance variables in a decision model in terms of their informational relevance. We describe an efficient algorithm based on a consideration of local properties of a property we refer to as u-separation. Finally, we present results of computational efficiencies gained via the application of the new policies, based on analyses of sample networks with different degrees of connectivity. 1
Supplementary Figure S4 from Rapid Expansion of Highly Functional Antigen-Specific T Cells from Patients with Melanoma by Nanoscale Artificial Antigen-Presenting Cells (2023)

&lt;p&gt;Functional analysis of MART-1 Tet+ CD8+ T-cells against melanoma cell lines.&lt;/p&gt;
Differential Regulation of IGF-Binding Protein Gene Expression by cAMP in Rat C6 Glioma Cells (2001)

We previously reported that cAMP inhibits autocrine IGF-I gene expression in rat C6 glioma cells. In this study we examined the influence of cAMP on IGF-binding protein gene expression in C6 cells. cAMP potently inhibited IGF-binding protein-3 mRNA and, to a lesser extent, IGF-binding protein-4 mRNA and transiently stimulated IGF-binding protein-5 mRNA. The changes in secreted IGF-binding proteins whose molecular weights were consistent with IGF-binding protein-3 and -5 correlated with those of mRNA levels. cAMP decreased the IGF-binding protein-3 mRNA half-life, but did not alter IGF-binding protein-4 and -5 mRNA half-lives. An IGF-binding protein-5 promoter/luciferase fusion construct containing 888 bp of 5'-flanking sequence and the first 114 bp of exon 1 sequence was stimulated by cAMP after 24 h by approximately 2-fold in transient transfection assays. 5'- or 3'-deletion to -33 or +10 (the transcription start site was designated as +1), respectively, did not alter the increase caused by cAMP. Site-directed mutagenesis of the region from -14 to -5 led to a loss of the ability of the IGF-binding protein-5 promoter to respond to cAMP. H89, a cell-permeable protein kinase A inhibitor, did not alter the regulation of IGF-binding protein mRNAs in response to cAMP.
Bound states in the continuum in plasmonic metasurfaces (2022)

Being inspired by the structure of butterfly wings, we design and demonstrate experimentally novel types of plasmonic metasurfaces supporting high-Q collective lattice resonances (Q~89) in the mid-IR region revealed by focused light beams with large apertures.
A MEMS tunable asymmetric Fabry-Perot quantum well modulator (2003)

Asymmetric Fabry-Perot quantum well modulators have proven difficult to optimize due to the sensitive dependence of the cavity mode and exciton wavelength on layer thicknesses, alloy composition, temperature, and angle. We demonstrate that a tunable optical cavity using a MEMS mirror removes this sensitivity.
Video 3 from <i>In Vivo</i> Fluorescence Imaging of the Activity of CEA TCB, a Novel T-Cell Bispecific Antibody, Reveals Highly Specific Tumor Targeting and Fast Induction of T-Cell–Mediated Tumor Killing (2023)

&lt;p&gt;&lt;i&gt;Ex vivo&lt;/i&gt; analysis of the CEA TCB (magenta) mediated cross-linking of CFSE labeled T-cells (green) to tumor cells. 3D reconstructions of confocal z-stacks acquired on tumor sections obtained from huPBMC (CFSE labeled T-cells)/LS174T RFP co-grafts, 24 h after intravenous A647 labeled CEA TCB injections are shown. Bar, 10 ÃŽÂ¼m. Cell nuclei (DAPI) are shown in blue.&lt;/p&gt;
Structure and dynamics of ?-MSH using DRISM integral equation theory and stochastic dynamics (1999)

The structural and dynamical features of the hormone alpha-MSH in solution have been examined over a 100 ns time scale by using free energy molecular mechanics models at room temperature. The free energy surface has been modeled using methods from integral equation theory and the dynamics by the Langevin equation. A modification of the accessible surface area friction drag model was used to calculate the atomic friction coefficients. The molecule shows a stable beta-turn conformation in the message region and a close interaction between the side chains of His6, Phe7, and Trp9. A salt bridge between Glu5 and Arg8 was found not to be a preferred interaction, whereas a Glu5 and Lys11 salt bridge was not sampled, presumably due to relatively high free energy barriers. The message region was more conformationally rigid than the N-terminal region. Several structural features observed here agree well with experimental results. The conformational features suggest a receptor-hormone interaction model where the hydrophobic side chains of Phe7 and Trp9 interact with the transmembrane portion of the MC1 receptor. Also, the positively charged side chain of Arg8 and the imidazole side chain of His6 may interact with the negatively charged portions of the receptor which may even be on the receptor's extracellular loops.
Lipocortin 2 (annexin 2) is a major substrate for constitutive tyrosine kinase activity in chondrocytes (1994)

Treatment of cultured bovine articular chondrocytes with 100 microM orthovanadate, in the absence of serum, results in the production of a single major tyrosine phosphorylated protein with an apparent molecular mass of 36 kDa (p36). Chondrocytes were found to contain proteins reactive with anti-lipocortin 1, 2, and 5 antibodies. p36 comigrated on SDS-polyacrylamide gels with lipocortin 2, but not with other members of the lipocortin family. The distribution of p36 between the particulate and soluble cell fractions was also similar to that of lipocortin 2. p36 that was purified on an anti-phosphotyrosine immunoaffinity column cross-reacted with anti-lipocortin 2 antibodies. Similarly, lipocortin 2 purified on an anti-lipocortin 2 immunoaffinity column reacted with anti-phosphotyrosine antibodies. Furthermore, cyanogen bromide cleavage fragments of purified lipocortin 2 and p36 were similar. These data demonstrate that the major constitutively tyrosine phosphorylated protein, in chondrocytes, is lipocortin 2. Tyrosine phosphorylated p36 required SDS buffers for extraction due to a loss of the tyrosine phosphate group under other solubilization conditions using Triton X-100 or sodium cholate. This study provides a system for the study of the effects of tyrosine phosphorylation on lipocortin 2 function. What role lipocortin 2 plays in chondrocyte biology remains to be determined.
Optimal Training Sequences for Joint Channel and Frequency-Dependent IQ Imbalance Estimation in OFDM-based Receivers (2006)

Nowadays OFDM is combined with advanced multiple access and multiple antenna techniques in order to improve the link capacity. In this context, a lot of effort is spent on developing inexpensive wireless OFDM-based receivers. Direct-conversion radio frequency receivers are appealing because they avoid costly IF filters. This kind of receivers implies analog RF I/Q separation introducing an unwanted in-band image interfearence encedue to the mismatch between the in-phase and quadrature branches. Unfortunately, systems combining OFDM with multiple antennas and multiple access techniques are very sensitive to I/Q mismatch, mostly when high order modulation schemes are applied. A digital compensation of this un-wanted effect is required. In this paper, we propose a method for estimating jointly the frequency dependent I/Q imbalance and the propagation channel in the frequency domain. First the channel is estimated based on a pilot optimized to suppress the interference caused by I/Q imbalance. Second I/ C imbalance is estimated and compensated relying on the estimated channel. Both steps are low cost in terms of implementation complexity. Finally, it is shown that the performance of the channel estimate is not degraded by I/Q imbalance. The proposed algorithm enables the system to work at high SNRs.
XAFS and Crystallographic Studies of Ni(II) Porphyrins in Single Crystals and Solution (1997)

Nickel porphyrins serve as models for the active sites of several biological processes. Crystallographic and EXAFS results for a Ni meso-tetrapropyl porphyrin (NiTPrP) yield different Ni-N distances in solution and in the solid State. The Ni-N distances determined by single crystal polarized XAS and X-ray diffraction agree well. Polarized XANES experiments further establish that the pre-edge feature observed in square planar Ni(II) complexes is a 1s-4pz transition. The single crystal and solution EXAFS results demonstrate that conformational variations of the porphyrin macrocycle can readily be imposed by environmental and/or packing forces and can thereby modulate the chemical and physical properties of porphyrinic chromophores and prosthetic groups.
Supplementary Figure 5 from Cancer Immunotherapy Based on Killing of <i>Salmonella</i>-Infected Tumor Cells (2023)

Supplementary Figure 5 from Cancer Immunotherapy Based on Killing of &lt;i&gt;Salmonella&lt;/i&gt;-Infected Tumor Cells
Congo red and thioflavin‐T analogs detect Aβ oligomers (2007)

Several small molecule ligands for amyloid-beta (Abeta) fibrils deposited in brain have been developed to facilitate radiological diagnosis of Alzheimer's disease (AD). Recently, the build-up of Abeta oligomers (AbetaO) in brain has been recognized as an additional hallmark of AD and may play a more significant role in early stages. Evidence suggests that quantitative assessment of AbetaO would provide a more accurate index of therapeutic effect of drug trials. Therefore, there is an urgent need to develop methods for efficient identification as well as structural analysis of AbetaO. We found that some well established amyloid ligands, analogs of Congo red and thioflavin-T (ThT), bind AbetaO with high affinity and detect AbetaO in vitro and in vivo. Binding studies revealed the presence of binding sites for Congo red- and thioflavin-T-analogs on AbetaO. Furthermore, these ligands can be used for imaging intracellular AbetaO in living cells and animals and as positive contrast agent for ultrastructural imaging of AbetaO, two applications useful for structural analysis of AbetaO in cells. We propose that by improving the binding affinity of current ligands, in vivo imaging of AbetaO is feasible by a 'signal subtraction' procedure. This approach may facilitate the identification of individuals with early AD.
Imagined versus Remembered Stories: Quantifying Differences in Narrative Flow (2022)

Lifelong experiences and learned knowledge lead to shared expectations about how common situations tend to unfold. Such knowledge of narrative event flow enables people to weave together a story. However, comparable computational tools to evaluate the flow of events in narratives are limited. We quantify the differences between autobiographical and imagined stories by introducing sequentiality, a measure of narrative flow of events, drawing probabilistic inferences from a cutting-edge large language model (GPT-3). Sequentiality captures the flow of a narrative by comparing the probability of a sentence with and without its preceding story context. We applied our measure to study thousands of diary-like stories, collected from crowdworkers about either a recent remembered experience or an imagined story on the same topic. The results show that imagined stories have higher sequentiality than autobiographical stories and that the sequentiality of autobiographical stories increases when the memories are retold several months later. In pursuit of deeper understandings of how sequentiality measures the flow of narratives, we explore proportions of major and minor events in story sentences, as annotated by crowdworkers. We find that lower sequentiality is associated with higher proportions of major events. The methods and results highlight opportunities to use cutting-edge computational analyses, such as sequentiality, on large corpora of matched imagined and autobiographical stories to investigate the influences of memory and reasoning on language generation processes.
Microwave Catalysis for Chemical Reactions (2022)

A keynote presentation delivered at 26th Canadian Catalysis Symposium virtually on microwave work at NETL.