gebhart/patrepeval huggingface dataset:
Ultrasensitive detection of disease biomarkers using an immuno-wall device with enzymatic amplification (2019)

We present an ultrasensitive immunoassay system for disease biomarkers utilizing the immuno-wall device and an enzymatic amplification reaction. The immuno-wall device consisted of 40 microchannels, each of which contained an antibody-modified wall-like structure along the longitudinal axis of the microchannel. The wall was fabricated with a water-soluble photopolymer containing streptavidin by photolithography, and biotinylated capture antibodies were immobilized on the sides through streptavidin-biotin interaction. For an assay, introducing the target biomarker and secondary and labeled antibodies produced a sandwich complex anchored on the sides of the wall. A conventional immuno-wall device uses a fluorescence-labeled antibody as a labeling antibody. To achieve an ultrasensitive detection of a trace biomarker, we used an enzyme label and amplified the signal with the enzymatic reaction with a fluorogenic substrate in the microchannel. The highest signal/background ratio was obtained by using alkaline phosphatase-labeled antibody and 9H-(1,3-dichloro-9,9-dimethylacridin-2-one-7-yl) phosphate. To evaluate the device performance, we detected human C-reactive protein (CRP) as a model biomarker. The detection limit (LOD) of CRP in phosphate-buffered saline was 2.5 pg mL<sup>-1</sup> with a sample volume of 0.25 μL. This LOD was approximately 3 orders of magnitude lower than that obtained with fluorescent-dye (DyLight 650)-labeled antibody. In addition, the present device provided a wide detection range of 0.0025-10 ng mL<sup>-1</sup> for CRP. We successfully developed an ultrasensitive immunoassay system with simple operation and only a small sample volume.
Isolation, Structure, and Antibacterial Activity of Philipimycin, A Thiazolyl Peptide Discovered from Actinoplanes philippinensis MA7347 (2008)

Bacterial resistance to antibiotics, particularly to multiple drug resistant antibiotics, is becoming cause for significant concern. The only really viable course of action is to discover new antibiotics with novel mode of actions. Thiazolyl peptides are a class of natural products that are architecturally complex potent antibiotics but generally suffer from poor solubility and pharmaceutical properties. To discover new thiazolyl peptides potentially with better desired properties, we designed a highly specific assay with a pair of thiazomycin sensitive and resistant strains of Staphylococcus aureus, which led to the discovery of philipimycin, a new thiazolyl peptide glycoside. It was isolated along with an acid-catalyzed degradation product by bioassay-guided fractionation. Structure of both compounds was elucidated by extensive application of 2D NMR, 1D TOCSY, and HRESIFT-MS/MS. Both compounds showed strong antibacterial activities against Gram-positive bacteria including MRSA and exhibited MIC values ranging from 0.015 to 1 μg/mL. Philipimycin was significantly more potent than the degradation product. Both compounds showed selective inhibition of protein synthesis, indicating that they targeted the ribosome. Philipimycin was effective in vivo in a mouse model of S. aureus infection exhibiting an ED50 value of 8.4 mg/kg. The docking studies of philipimycin suggested that a part of the molecule interacts with the ribosome and another part with Pro23, Pro22, and Pro26 of L11 protein, which helped in explaining the differential of activities between the sensitive and resistant strains. The design and execution of the bioassay, the isolation, structure, in vitro and in vivo antibacterial activity, and docking studies of philipimycin and its degradation product are described.
Bayesian Incentive-Compatible Bandit Exploration (2015)

Individual decision-makers consume information revealed by the previous decision makers, and produce information that may help in future decision makers. This phenomenon is common in a wide range of scenarios in the Internet economy, as well as elsewhere, such as medical decisions. Each decision maker when required to select an action, would individually prefer to exploit, select the highest expected reward action conditional on her information. At the same time, each decision maker would prefer previous decision makers to explore, producing information about the rewards of various actions. A social planner, by means of carefully designed information disclosure, can incentivize the agents to balance the exploration and exploitation, and maximize social welfare. We formulate this problem as a multi-arm bandit problem (and various generalizations thereof) under incentive-compatibility constraints induced by agents' Bayesian priors. We design an incentive-compatible bandit algorithm for the social planner with asymptotically optimal regret. Further, we provide a black-box reduction from an arbitrary multi-arm bandit algorithm to an incentive-compatible one, with only a constant multiplicative increase in regret. This reduction works for very general bandit settings, even ones that incorporate contexts and arbitrary partial feedback.
O1–01–05: Human iPSC‐derived neurons reveal novel effects of the APP London mutation and show cell fate‐specific Alzheimer's disease relevant phenotypes (2013)

Alzheimer's disease (AD) is characterized by extracellular plaques containing amyloid β-protein (Aβ) and intracellular tangles containing hyperphosphorylated Tau protein. Distinct brain regions are differentially susceptible to neurodegeneration in AD, with the cortex and hippocampus being primarily affected and the cerebellum and spinal cord being relatively spared. While familial AD (fAD) comprises <1% of cases, analyses of these patients have advanced understanding of molecular mechanisms and therapeutic approaches for all AD cases. We describe the generation of inducible pluripotent stem cells (iPSCs) from humans harboring the London fAD APP mutation (V717I), and examine AD-relevant phenotypes following directed differentiation of these cells to rostral forebrain neuronal fates vulnerable in AD, as well as more caudal fates, which are relatively spared in AD. Immunostaining, qPCR, Nanostring analyses and Western blotting were used to examine expression of factors central to APP cleavage. In addition, ELISAs were utilized to measure the generation and secretion of APP cleavage products. In all fates examined, the APP V717I mutation led to elevated production of Aβ42 and Aβ38. Unexpectedly, this mutation, which lies near the γ -secretase cleavage site in the transmembrane domain of APP, also led to increased β-secretase cleavage of APP. This increase was abolished by inhibiting γ -secretase, suggesting that the two protease activities are functionally linked. Interestingly, directing cells to different neuronal fates resulted in altered cleavage patterns of APP. From both control and fAD lines, Aβ generated from neurons directed to forebrain cortical fates showed a higher Aβ42 to Aβ40 ratio relative to neurons directed to more caudal fates of the hindbrain and spinal cord. Moreover, consistent with fate-specific biochemical effects on Aβ, the APP V717I mutation led to increased Tau expression in forebrain cultures but not in more caudally directed neurons. These studies identify previously unappreciated effects of an fAD APP mutation in human neurons and demonstrate that human iPSC technology provides a powerful system for analyzing the effects of both genetic alterations and cell types on processes directly relevant to human brain diseases.
ChemInform Abstract: Pyrrolobenzothiazepinones and Pyrrolobenzoxazepinones: Novel and Specific Non‐Nucleoside HIV‐1 Reverse Transcriptase Inhibitors with Antiviral Activity. (1996)

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.
Directing Data Center Traffic (2013)

A data center design based on an integrated chip-scale approach will be required to deal with the increasing volumes of Internet traffic.
Monitoring Nylon-6,6 Thermochemistry by Solid-State NMR (1998)

Solid-state 13C and 15N NMR spectroscopy was used to study the structure and thermochemistry of nylon-6,6. Experiments were performed on samples of nylon-6,6 heated in the presence of labeled adipic acid and hexamethylenediamine (HMD) monomers as well as labeled bis(hexamethylenetriamine) (BHMT), a molecule previously implicated as a potential nylon cross-linker. The uptake and subsequent reaction of labeled materials were characterized by a variety of solid-state NMR techniques. Reaction of the central (α) nitrogen of BHMT to form an amide occurs very rapidly. With time, transamidation causes this position to become indistinguishable from the bulk amide nitrogen in nylon. Rotational-echo double resonance (REDOR), a solid-state NMR experiment that permits the quantitative measurement of 13C−15N labeled chemical bonds, was used to detect the formation and breaking of carbon−nitrogen bonds due to polymerization and transamidation. The reaction of adipic acid and hexamethylenediamine (HMD) and the transamidation reaction between the resulting oligomers and bulk nylon were studied by heating nylon-6,6 in the presence of [13C]adipic acid and [15N]HMD and characterizing the resulting polymers with REDOR. The combination of stable isotope labeling and NMR spectroscopy illustrated in this work should be applicable to the study of a wide variety of polymers.
ERTS computer compatible tape data processing and analysis. Appendix 1: The utility of imaging radars for the study of lake ice (1972)

There are no author-identified significant results in this report. Remotely sensed multispectral scanner and return beam vidicon imagery from ERTS-1 is being used for: (1) water depth measurements in the Virgin Islands and Upper Lake Michigan areas; (2) mapping of the Yellowstone National Park; (3) assessment of atmospheric effects in Colorado; (4) lake ice surveillance in Canada and Great Lakes areas; (5) recreational land use in Southeast Michigan; (6) International Field Year on the Great Lakes investigations of Lake Ontario; (7) image enhancement of multispectral scanner data using existing techniques; (8) water quality monitoring of the New York Bight, Tampa Bay, Lake Michigan, Santa Barbara Channel, and Lake Erie; (9) oil pollution detection in the Chesapeake Bay, Gulf of Mexico southwest of New Orleans, and Santa Barbara Channel; and (10) mapping iron compounds in the Wind River Mountains.
A 50&#x03BC;W biasing feedback loop with 6ms settling time for a MEMS microphone with digital output (2012)

A MEMS microphone is a variable capacitor where the distance d between the compliant membrane and the rigid backplate is proportional to the air (acoustic) pressure. If the charge Q at the plates remains constant, there is a linear relationship between the voltage across the plates and the distance given by: ΔV=Q×Δd/εA. A practical charge source implementation (Fig. 11.3.1) is a DC-DC converter (V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">d</inf> ) with a very high series resistance in the form of bipolar diodes (D <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1, 2</inf> ) [1]. A capacitor (C <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">g</inf> ) provides the signal ground for the microphone (C <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">mems</inf> ). An ADC performs continuous-time voltage readout of the microphone signal pin. Preferably its DC bias is equal to the ADC common-mode voltage. This paper deals with a biasing feedback loop (BFL) that realizes this function.
Structural evolution of an enzyme specificity. The structure of rat carboxypeptidase A2 at 1.9-A resolution. (1991)

The structure of rat carboxypeptidase A2 (CPA2), which has a unique specificity for tryptophan-containing COOH-terminal peptides, has been determined in an unliganded state at 1.9-A resolution and refined to a crystallographic R-factor of 18.3%. Comparison of the structure of CPA2 with that of bovine carboxypeptidase A (referred to here as CPA1) reveals that the specificity of the former for larger amino acids probably arises from two amino acid replacements within the binding cavity (Thr268----Ala and Leu203----Met), coupled with differences in the positions of conserved residues in a surface loop on one face of the specificity pocket. The position of the reactive-site surface loop may be affected also by a disulfide bridge between Cys210 and Cys244. In this unliganded form of the enzyme, Tyr248 takes up a position interior to the specificity pocket and is distinct from that observed in bovine CPA1. The structural differences between CPA1 and CPA2 correlate strongly with crystallographically determined temperature factors and thus appear to be largest where the enzyme is flexible.
Electron-Rich Dipyrrolonaphthyridinediones: Synthesis and Optical Properties (2018)

This article describes the design rationale for highly electron-rich dipyrrolonaphthyridinedione (DPND) derivatives bearing substituted amino groups at the 3 and 9 positions, which exhibit absorption in the red and emission in the red/NIR region of the spectrum. These novel dyes are easily synthesized through a two-step protocol consisting of bromination of the DPND molecule followed by Buchwald-Hartwig amination. We demonstrated that the diamino-dipyrrolonaphthyridinediones have high ionization energies (∼4.7 eV) and that the spectroelectrochemical properties can be rationally tuned by altering the nature of the peripheral substituted amino groups. All amino-DPNDs exhibit solvatofluorochromism, which has not been previously reported for dyes possessing this core. Theoretical calculations reveal that in all cases, the strongest absorption is exhibited by the S<sub>1</sub> states which clearly correlate with the HOMO-LUMO orbital transition. As all higher states have lower oscillator strengths, it is clear that fluorescence is completely dominated by the excitation/deexcitation sequence S<sub>0</sub> → S<sub>1</sub>, S<sub>1</sub> → S<sub>0</sub> and that there are no contributions to the fluorescence from excitations to higher states.
Performance of the CFHT Adaptive Optics Bonnette (1997)

Extensive results from the commissioning phase of PUEO, the adaptive optics instrument adaptor for the Canada-France-Hawaii telescope, are presented and discussed. Analyses of more than 750 images recorded with a CCD and a near-IR camera on 16 nights in wavelengths from B to H are used to derive the properties of the compensated wavefront and images in a variety of conditions. The performance characteristics of the system are analyzed and presented in several ways, in terms of delivered Strehl ratios, full-width-half-maxima, and quantities describing the improvements of both. A qualitative description is given of how the properties of the corrected images result from the structure function of the compensated phase. Under median seeing conditions, PUEO delivers essentially diffraction-limited images at H and K, images with FWHM ~0.1" at J and I, and provides significant gains down to B, with guide stars as faint as R = 14. During good conditions, substantial gains were realized with guide stars as faint as R = 17. A simple user-interface and software which automatically and continuously optimizes the mode gains during observations makes the operational efficiency extremely high. A few astronomical examples are briefly discussed.
Genetic Markers Linked to the Dwarfing Trait of Apple Rootstock ‘Malling 9’ (2008)

Little is known of the precise physiological or genetic basis of the phenomenon of rootstock-induced dwarfing in apple ( Malus × domestica Borkh.). Phenotypic assessment and genetic marker analysis of a segregating population of apple rootstocks derived from a cross between the dwarfing rootstock ‘Malling 9’ (‘M.9’) and the vigorous rootstock ‘Robusta 5’ (‘R5’) was undertaken over a 5-year growth period. Clear segregation of the appearance of the ‘Braeburn’ scions permitted expert visual classification of each tree into four growth habit classes: dwarfed, semidwarfed, intermediate, or vigorous. Measurements of the cross-sectional area of the trunk of each tree correlated clearly with the expert-assigned phenotypic class. This clear segregation facilitated bulked segregant analysis (BSA) of the ‘M.9’ × ‘R5’ population, and the Dwarfing 1 ( Dw1 ) gene was located in a 2.5-cM region at the top of the linkage group 5 of ‘M.9’. The gene Dw1 was mapped between the random amplified polymorphic DNA marker NZraAM18_700 and the microsatellite marker CH03a09, identified by BSA and the genome scanning approach, respectively. Dw1 is the first reported mapped locus controlling the dwarfing ability of the apple rootstock and maps to a chromosome region not previously known to contain quantitative trait loci or major genes that contribute to tree architecture and development. The identification of a group of trees in the ‘M.9’ × ‘R5’ population exhibiting a vigorous phenotype although their rootstocks possess alleles from the Dw1 region of ‘M.9’ suggests that more loci may be involved in conditioning the dwarfing phenotype. Dw1 is a major component of dwarfing, as most of the dwarfing and semidwarfing rootstocks carried the dwarfing allele of this locus. Genetically mapping Dw1 is a major step in unraveling the mechanism behind the dwarfing ability of apple rootstocks.
Essential thrombocythemia terminating in pure erythroleukemia (2004)

Transformation into acute leukemia is a rare event in essential thrombocythemia (ET). The blasts are usually of myeloid, rarely of megakaryoblastic differentiation. We present the case of a patient with pure erythroleukemia after a nearly 10-year course of ET, which was treated with hydroxyurea. The patient, a 58-year-old male, presented with an elevated thrombocyte count (926,000/microL) and normal values of hemoglobin and leukocytes. After 10 years of therapy with hydroxyurea, the patient developed acute leukemia of solely erythroid differentiation. Chemotherapy with cytarabine and daunorubicin resulted in incomplete remission. The patient died 2 months after diagnosis of acute erythroleukemia. Transformation of ET into erythroleukemia may demonstrate the pluripotent potential of the neoplastic hemopoietic stem cell, with the ability to cause acute leukemia not only of myeloid or megakaryoblastic but also of erythroid lineage.
Reality Check (2010)

Contributors 1. Introduction: The Challenge of Evaluating Voluntary Programs 2. The U.S. 33/50 Voluntary Program: Its Design and Effectiveness 3. Japan s Keidanren Voluntary Action Plan on the Environment 4. Climate Change Agreements in the United Kingdom: A Successful Policy Experience? 5. Evaluation of the Danish Agreements on Industrial Energy Efficiency 6. Assessing Voluntary Commitments in the German Cement Industry: The Importance of Baselines 7. Evaluating Voluntary U.S. Climate Programs: The Case of Climate Wise 8. The Evaluation of Residential Utility Demand-Side Management Programs in California 9. Concluding Observations: What Can We Learn from the Case Studies? Index
Optical properties of elliptical reflectors (2004)

Elliptical reflectors are widely used in illumination engineering as a means to concentrate the light of a source in the secondary focal plane. To collect as much light from the source as possible, the reflector must cover a wide angular range of the emitted radiation, hence forward and backward reflections on the reflector must be discussed and conditions for paraxial optics do not apply. We develop a framework of relations that describe the image of an extended source in the secondary focal plane of the ellipsoid. After deriving basic relations between object and image spaces, the propagation of rays depending of their origin and on their direction is investigated. As a result, the function and the aberrations of the reflector can be expressed in terms of an angular dependent magnification for longitudinal and lateral coordinates. With that, one cannot not only calculate luminance and illuminance distributions in the secondary focal plane in a straightforward manner, but can easily understand their properties and their dependence on ellipse parameters. On the basis of the developed relations, implications for the design of "elliptical" short arc high-intensity-discharge (HID) lamps for video projection are discussed.
Dose selection for the investigational anticancer agent alisertib (MLN8237): Pharmacokinetics, pharmacodynamics, and exposure–safety relationships (2014)

We report population pharmacokinetic, pharmacodynamic, and pharmacokinetic-safety analyses to support phase II/III dose/regimen selection of alisertib, a selective Aurora A kinase (AAK) inhibitor. Phase I studies in adult cancer patients evaluated dosing on Days 1-7 in 21-day cycles or Days 1-21 in 35-day cycles, with corresponding maximum tolerated doses of 50 mg twice daily (BID) and 50 mg QD, respectively. Population pharmacokinetic analyses supported dose- and time-linear pharmacokinetics without identification of clinically meaningful covariates. Exposure-related increases in skin mitotic index and decreases in chromosomal alignment/spindle bipolarity in tumor mitotic cells confirmed AAK inhibition. Exposures in the 7-day schedule at or near 50 mg BID are expected to result in tumor AAK inhibition based on pharmacodynamic assessment in patient tumors. Exposure-safety analyses of data from patients receiving doses of 5-200 mg/day in the 7-day schedule support a low (∼7%) predicted incidence of dose-limiting toxicity at 50 mg BID. Taken together, these analyses support a pharmacologically active and acceptably tolerated dose range of alisertib for future clinical development.
Benefits of Short Interimplant Delays in Children Receiving Bilateral Cochlear Implants (2009)

Benefits of bilateral implantation in the short term are clearest in children with limited delays between implantation.
Analytic quantification of the bleaching effect of a 4-hydroxyanisole-tretinoin combination on actinic lentigines. (2008)

Both the visual ratings and the objective bioinstrumental methods indicate the rapid lightening effect of the 4HA/tretinoin formulation. After stopping treatment, the rate of repigmentation appeared to have slowed compared to the depigmentation phase.