gebhart/patrepeval huggingface dataset:
A Rapid Method for the Estimation of Bile Salts in Complex Tanning Brines by RPHPLC (2003)

Abstract To preserve bovine hides until they are processed into leather, they are often cured in large raceways of saturated brine. This process prevents the growth of most microorganisms, but under some conditions these hides are still susceptible to decomposition by halophilic archaebacteria. Low amounts of porcine bile added to the brine used for curing, have exhibited control of growth of these primitive microorganisms. Reversed‐phase high pressure liquid chromatography (RPHPLC) has been applied to monitor bile concentration in saturated brine mixtures containing contaminants associated with animal hides (bacteria, blood, dirt, fats, hair, manure, urine, etc.). With minimal sample preparation, this method can be used by either the hide curing, packing, or tanning industry to assess the need to charge brine solutions with additional porcine bile during the continuous process of hide addition and removal. Calibration curves of porcine bile added to highly contaminated raceway brine have demonstrated linearity of detection between 25–340 ppm bile. The method of standard addition was used to identify and quantify a porcine bile component, glycochenodeoxycholic acid. Reversed‐phase high pressure liquid chromatography was also used to determine the relative solubility of porcine vs. bovine bile in solutions of varying salt concentration. Keywords: ArchaebacteriaBileBrineHalophilesReversed phase HPLC Acknowledgments Mention of brand or firm names does not constitute an endorsement by the U.S. Department of Agriculture over others of a similar nature not mentioned. We thank Jeffrey Brewster, Michael Kurantz, and Alan Lightfield, from the Eastern Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, for their technical support and assistance in this project. In addition, we acknowledge the advice and participation of our research partners, Southeast Applied Research (Diamondhead, MS), under Cooperative Research and Development Agreement # 58‐3K95‐M‐625. Abbreviations GCDC= glycochenodeoxycholic acid RPHPLC= reversed‐phase high pressure liquid chromatography
Mesomorphism and Luminescence Properties of Platinum(II) Complexes with Tris(alkoxy)phenyl‐Functionalized Pyridyl Pyrazolate Chelates (2010)

A series of new mesomorphic platinum(II) complexes 1-4 bearing pyridyl pyrazolate chelates are reported herein. In this approach, pyridyl azolate ligands have been strategically functionalized with tris(alkoxy)phenyl groups with various alkyl chain lengths. As a result, they are ascribed to a class of luminescent metallomesogens that possess distinctive morphological properties, such as their intermolecular packing arrangement and their associated photophysical behavior. In CH(2) Cl(2), independent of the applied concentration in the range 10(-6)-10(-3) M, all Pt(II) complexes exhibit bright phosphorescence centered at around 520 nm, which is characteristic for monomeric Pt(II) complexes. In stark contrast, the single-crystal X-ray structure determination of [Pt(C4pz)(2)] (1) shows the formation of a dimeric aggregate with a notable Pt⋅⋅⋅Pt contact of 3.258 Å. Upon heating, all Pt(II) complexes 1-4 melted to form columnar suprastructures, for which similar intracolumnar Pt⋅⋅⋅Pt distances of approx. 3.4-3.5 Å are observed within an exceptionally wide temperature range (>250 °C), according to the powder XRD data. Upon casting into a neat thin film at RT, the luminescence of 1-4 is dominated by a red emission that spans 630-660 nm, which originates from the one-dimensional, chainlike structure with Pt-Pt interaction in the ground state. Taking complex 4 as a representative, the emission intensity and wavelength were significantly decreased and blueshifted, respectively, on heating from RT to 250 °C. Further heating to liquefy the sample alters the red emission back to the green phosphorescence of the monomer. The results highlight the pivotal role of tris(alkoxy)phenyl groups in the structural versus luminescence behavior of these Pt(II) complexes.
Structural basis for the unique ganglioside and cell membrane recognition mechanism of botulinum neurotoxin DC (2017)

Botulinum neurotoxins (BoNTs), the most potent toxins known, are potential bioterrorism agents. It is well established that all seven serotypes of BoNTs (BoNT/A-G) require complex gangliosides as co-receptors. Here, we report that BoNT/DC, a presumed mosaic toxin between BoNT/D and BoNT/C1, binds and enters efficiently into neurons lacking complex gangliosides and shows no reduction in toxicity in mice deficient in complex gangliosides. The co-crystal structure of BoNT/DC with sialyl-Thomsen-Friedenreich antigen (Sialyl-T) suggests that BoNT/DC recognizes only the sialic acid, but not other moieties in gangliosides. Using liposome flotation assays, we demonstrate that an extended loop in BoNT/DC directly interacts with lipid membranes, and the co-occurring sialic acid binding and loop-membrane interactions mediate the recognition of gangliosides in membranes by BoNT/DC. These findings reveal a unique mechanism for cell membrane recognition and demonstrate that BoNT/DC can use a broad range of sialic acid-containing moieties as co-receptors.
Enhanced drug transport through alginate biofilms using magnetic nanoparticles (2009)

The development of microbiological biofilms greatly reduces the efficacy of antibiotic therapies and is a serious problem in chronic infection and for implantable medical devices. We investigated the potential of superparamagnetic nanoparticles to increase transport through <i>in vitro</i> models of alginate biofilms. An <i>in vitro</i> alginate biofilm model was developed to mimic the composition of in vivo samples of <i>P. aeruginosa</i> infections. Transport through this model biofilm was performed using both bulk diffusion methods and single particle tracking techniques in the presence and absence of an external magnetic field. Bulk diffusion of nanoparticles through the biofilm was significantly enhanced in the presence of a magnetic field, both visually and quantitatively. Nanoparticle trajectories also showed transport increases were significantly higher when magnetic fields were applied. We also showed that surface chemistry (cationic, anioni, or neutral) of the nanoparticles significantly influenced transport rates. Finally, nanoparticle size also influenced the transport rates and variability of transport rates through the biofilm. In these first studies using magnetic nanoparticles in bacterial biofilms, we demonstrate that transport enhancement can be achieved and further studies are warranted.
Relieving the elicitation burden of Bayesian belief networks (2008)

In this paper we present a new method(EBBN) that aims at reducing the need toelicit formidable amounts of probabilities forBayesian belief networks, by reducing thenumber of probabilities that need to be specified in the quantification phase. This methodenables the derivation of a variableâs conditional probability table (CPT) in the general case that the states of the variable areordered and the states of each of its parent nodes can be ordered with respect to the influence they exercise. EBBN requires only a limited amount of probability assessments from experts to determine a variableâs full CPT and uses piecewise linear interpolation. The number of probabilities to be assessed in this method is linear in the number of conditioning variables. EBBNâs performance wascompared with the results achieved by applying both the normal copula vine approach from Hanea & Kurowicka (2007), and by using a simple uniform distribution.
Characterization of the MUC1-C Cytoplasmic Domain as a Cancer Target (2015)

Mucin 1 (MUC1) is a heterodimeric protein that is aberrantly expressed in diverse human carcinomas and certain hematologic malignancies. The oncogenic MUC1 transmembrane C-terminal subunit (MUC1-C) functions in part by transducing growth and survival signals from cell surface receptors. However, little is known about the structure of the MUC1-C cytoplasmic domain as a potential drug target. Using methods for structural predictions, our results indicate that a highly conserved CQCRRK sequence, which is adjacent to the cell membrane, forms a small pocket that exposes the two cysteine residues for forming disulfide bonds. By contrast, the remainder of the MUC1-C cytoplasmic domain has no apparent structure, consistent with an intrinsically disordered protein. Our studies thus focused on targeting the MUC1 CQCRRK region. The results show that L- and D-amino acid CQCRRK-containing peptides bind directly to the CQC motif. We further show that the D-amino acid peptide, designated GO-203, blocks homodimerization of the MUC1-C cytoplasmic domain in vitro and in transfected cells. Moreover, GO-203 binds directly to endogenous MUC1-C in breast and lung cancer cells. Colocalization studies further demonstrate that GO-203 predominantly binds to MUC1-C at the cell membrane. These findings support the further development of agents that target the MUC1-C cytoplasmic domain CQC motif and thereby MUC1-C function in cancer cells.
A Mucin 16 bispecific T cell–engaging antibody for the treatment of ovarian cancer (2019)

Advanced ovarian cancer is frequently treated with combination chemotherapy, but high recurrence rates show the need for therapies that can produce durable responses and extend overall survival. Bispecific antibodies that interact with tumor antigens on cancer cells and activating receptors on immune cells offer an innovative immunotherapy approach. Here, we describe a human bispecific antibody (REGN4018) that binds both Mucin 16 (MUC16), a glycoprotein that is highly expressed on ovarian cancer cells, and CD3, thus bridging MUC16-expressing cells with CD3<sup>+</sup> T cells. REGN4018 induced T cell activation and killing of MUC16-expressing tumor cells in vitro. Binding and cytotoxicity of REGN4018 in vitro were minimally affected by high concentrations of CA-125, the shed form of MUC16, which is present in patients. In preclinical studies with human ovarian cancer cells and human T cells in immunodeficient mice, REGN4018 potently inhibited growth of intraperitoneal ovarian tumors. Moreover, in a genetically engineered immunocompetent mouse expressing human CD3 and human MUC16 [humanized target (HuT) mice], REGN4018 inhibited growth of murine tumors expressing human MUC16, and combination with an anti-PD-1 antibody enhanced this efficacy. Immuno-PET imaging demonstrated localization of REGN4018 in MUC16-expressing tumors and in T cell-rich organs such as the spleen and lymph nodes. Toxicology studies in cynomolgus monkeys showed minimal and transient increases in serum cytokines and C-reactive protein after REGN4018 administration, with no overt toxicity. Collectively, these data demonstrate potent antitumor activity and good tolerability of REGN4018, supporting clinical evaluation of REGN4018 in patients with MUC16-expressing advanced ovarian cancer.
Spray Formed Al MMCs via In-situ Reactions (2002)

Reactive spray atomization and deposition processing is currently being studied as an approach for the in-situ synthesis of Al metal matrix composites (MMCs). In the present paper, the latest developments in this field are reviewed, with an emphasis on in-situ reaction kinetics, grain size refinement and mechanisms, and superplastic forming behavior; and future work is also discussed.
All-optical regeneration of differential phase-shift keying signals based on phase-sensitive amplification (2004)

All-optical regeneration of differential phase-shift keying signals based on phase-sensitive amplification is described. Nearly ideal phase regeneration can be achieved in the undepleted-pump regime, and simultaneous amplitude and phase regeneration can be realized in the depleted-pump regime.
Trigger-Action-Circuits (2017)

The dramatic decrease in price and increase in availability of hobbyist electronics has led to a wide array of embedded and interactive devices. While electronics have become more widespread, developing and prototyping the required circuitry for these devices is still difficult, requiring knowledge of electronics, components, and programming. In this paper, we present Trigger-Action-Circuits (TAC), an interactive system that leverages generative design to produce circuitry, firmware, and assembly instructions, based on high-level, behavioural descriptions. TAC is able to generate multiple candidate circuits from a behavioural description, giving the user a number of alternative circuits that may be best suited to their use case (e.g., based on cost, component availability or ease of assembly). The generated circuitry uses off-the-shelf, commodity electronics, not specialized hardware components, enabling scalability and extensibility. TAC supports a range of common components and behaviors that are frequently required for prototyping electronic circuits. A user study demonstrated that TAC helps users avoid problems encountered during circuit design and assembly, with users completing their circuits significantly faster than with traditional methods.
Development of Bifunctional Anion-Exchange Resins with Improved Selectivity and Sorptive Kinetics for Pertechnetate:  Batch-Equilibrium Experiments (2000)

A novel class of strong-base anion-exchange resins, bearing two different types of exchange sites, is described. These bifunctional resins have anion-exchange sites composed of two separate and differently sized trialkylammonium groups. In pertechnetate (TcO4-) uptake experiments from a solution matrix containing anions commonly encountered in groundwater, bifunctional resins containing exchange sites derived from tri-n-hexylamine in combination with either triethylamine, tri-n-propylamine, or tri-n-butylamine were shown to possess superior 24-h distribution ratios (Kd) for pertechnetate over all monofunctional anion-exchange resins (derived from a single trialkylamine) examined. For example, although monofunctional resins containing a tri-n-hexylammonium exchange site possessed excellent selectivity for pertechnetate over other anions, the exchange kinetics were poor. The superior performance of these resins can be attributed to the combination of a large trialkylammonium site for enhanced selectivity for large anions and a smaller trialkylammonium site for the retention of good exchange kinetics.
Primary structure of nitrile hydratase deduced from the nucleotide sequence of a <i>Rhodococcus</i> species and its expression in <i>Escherichia coli</i> (1989)

The nitrile hydratase (NHase) of Rhodococcus species N-774, which is composed of two subunits, alpha and beta, catalyzes the hydration of various nitrile compounds to the corresponding amides. The amino acid sequences of the NH2 termini and the fragments obtained by digesting each of the two subunits with lysyl endopeptidase were determined for preparation of synthetic oligonucleotides as hybridization probes. A 4.4-kb SphI fragment which contained DNA sequences hybridizing to several of the probes was cloned in pBR322 in Escherichia coli. The nucleotide sequences together with the determined amino acid sequences indicated that the alpha and beta subunits of NHase consisted of 207 amino acids (Mr, 22918) and 212 amino acids (Mr, 23428), respectively. The open reading frame for the alpha subunit includes that for the beta subunit with a short interval of only 26 base pairs; the two genes are probably translated in a polycistronic manner. Although large amounts of the alpha- and beta-subunit proteins were produced as insoluble forms in E. coli when the cloned genes were placed under the control of the lac promoter, no enzymatic activity was detected. The activity of the enzyme was restored, to some extent, by solubilization of the proteins with 8 M urea and subsequent dialysis for refolding at pH 10 in the presence of Fe2+ and pyrroloquinoline quinone.
Abstract A235: Structure-guided evolution of potent and selective oral inhibitors of CHK1 through scaffold morphing. (2011)

Abstract The DNA damage response network ensures the fidelity of DNA replication and controls the repair of damage arising during cellular replication or from exogenous agents such as genotoxic drugs. Checkpoint Kinase 1 (CHK1) is a serine/threonine kinase occupying a central position in this complex network of cell regulatory and DNA repair mechanisms. G1/S, S or G2/M cell cycle checkpoints are activated in response to genotoxic antitumor drugs to provide an opportunity for repair of damaged DNA or to activate apoptotic pathways. Unlike normal cells, human cancer cells frequently have functional defects in the tumor suppressor p53 with consequent loss of G1/S checkpoint control and greater reliance on S and G2/M checkpoints. Thus CHK1 inhibitors which abrogate the S and G2/M checkpoints will selectively sensitize p53 deficient cancer cells to DNA damaging agents. CHK1 inhibition by siRNA and several small molecule inhibitors have confirmed this in preclinical studies. The challenges of improving the CHK1 potency and selectivity of our initial, fragment derived pyrazolopyridine inhibitors, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps. Initial hit compounds were optimised into potent inhibitors of CHK1 using iterative cycles of design, synthesis, assay and crystallography, progressing through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and isoquinolines. The potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, and potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts when dosed i.p. in nude mice. Further lead optimisation led to orally bioavailable analogues with good in vitro ADME and in vivo pharmacokinetic properties, exemplified by CCT244747. CCT244747 has demonstrated both in vivo pharmacodynamic modulation of signaling through CHK1 and potentiation of cytotoxic drugs in human tumor xenografts. In summary, we show how a fragment derived compound with weak, micromolar activity against CHK1 evolved through a scaffold hopping strategy to give the selective CHK1 isoquinoline inhibitor SAR-020106, from which optimisation of pharmacokinetic properties led to potent, selective and orally bioavailable CHK1 inhibitors such as CCT244747. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A235.
Virtual Memory Window for a Portable Reconfigurable Cryptography Coprocessor (2004)

Reconfigurable system-on-chip (SoC) platforms that incorporate hard-core processors surrounded by large amounts of FPGA are today's commodities: the reconfigurable logic is often used to speed up execution of applications by implementing critical parts of the code as application-specific coprocessors. Cryptography applications are a good example of coprocessor applications: they are known to benefit significantly from spatial execution in hardware and have an increasing importance for mobile and ubiquitous computing. One of the main limits of FPGA-based coprocessors for these systems is the fact that both the coprocessor hardware description and the software program invoking are inevitably ridden with system details of the specific interface FPGA/processor: this limits significantly design reuse, impacts time-to-market, and makes development more complex. In this paper, we present a portable reconfigurable cryptography coprocessor designed for a virtual memory window (VMW) system. A VMW is a generic virtualisation layer composed of a hardware and an operating system component; it lowers the complexity of interfacing, increases portability, and makes it possible for the coprocessor to access the user-space virtual memory. The approach is illustrated here with the IDEA cryptography application running under Linux on a reconfigurable SoC, having its critical function mapped on the FPGA. A significant fraction of the speed-up inherent to hardware execution in the FPGA is preserved, while the hardware and software designs of the cryptography application become perfectly portable.
Anomalous Diffusion in Molecular Communication (2015)

We consider anomalous diffusion to model a molecular communication channel. To account for general and practical molecular propagation, we use the fractional diffusion equation and derive the distribution of first passage time in terms of Fox's H-function. We then analyze the bit error rate for timing and amplitude binary modulation schemes in anomalous diffusion.
Design of an adaptive randomized clinical trial of intravenous citrulline for sickle cell pain crisis in the emergency department (2023)

This ED based sickle cell adaptive trial will determine the optimal dose for IV citrulline and whether the intervention improves outcome as a potential novel therapy for VOC in SCD.
MEK Inhibitors, Novel Anti-Adhesive Molecules, Reduce Sickle Red Blood Cell Adhesion In Vitro and In Vivo, and Vasoocclusion In Vivo (2014)

In sickle cell disease, sickle erythrocyte (SSRBC) interacts with endothelial cells, leukocytes, and platelets, and activates coagulation and inflammation, promoting vessel obstruction, which leads to serious life-threatening complications, including acute painful crises and irreversible damage to multiple organs. The mitogen-activated protein kinase, ERK1/2, is abnormally activated in SSRBCs. However, the therapeutic potential of SSRBC ERK1/2 inactivation has never been investigated. I tested four different inhibitors of MEK1/2 (MEK), the kinase that activates ERK1/2, in a model of human SSRBC adhesion to TNFα-activated endothelial cells (ECs). SSRBC MEK inhibition abrogated adhesion to non-activated and TNFα-activated ECs to levels below baseline SSRBC adhesion to non-activated ECs in vitro. SSRBC MEK inhibition also prevented SSRBCs from activating naïve neutrophils to adhere to endothelium. To determine the effect of MEK inhibitors on SSRBC adherence in vivo, sham-treated or MEK inhibitor-treated SSRBCs were infused to nude mice previously treated with TNFα. Sham-treated SSRBCs displayed marked adhesion and occlusion of enflamed vessels, both small and large. However, SSRBC treatment with MEK inhibitors ex vivo showed poor SSRBC adhesion to enflamed vessels with no visible vasoocclusion in vivo. In addition, MEK inhibitor treatment of SSRBCs reduced SSRBC organ trapping and increased the number of SSRBCs circulating in bloodstream. Thus, these data suggest that SSRBC ERK1/2 plays potentially a critical role in sickle pathogenesis, and that MEK inhibitors may represent a valuable intervention for acute sickle cell crises.
The Genus-Specific Antigen of <i>Chlamydia</i> : Resemblance to the Lipopolysaccharide of Enteric Bacteria (1983)

A strong immunological cross-reaction between a major glycolipid antigen of Chlamydia and the innermost (Re) core of the lipopolysaccharide of enteric bacteria was demonstrated with the aid of mutants in which the Re structure is exposed. The chlamydial glycolipid resembled the Re lipopolysaccharide in molecular size, solubility, and endotoxic properties and may thus be functionally equivalent to lipopolysaccharide, an essential and characteristic component of the outer membrane of Gram-negative bacteria.