gebhart/patrepeval huggingface dataset:
WaveNano: a signal‐level nanopore base‐caller via simultaneous prediction of nucleotide labels and move labels through bi‐directional WaveNets (2018)

Background The Oxford MinION nanopore sequencer is the recently appealing third‐generation genome sequencing device that is portable and no larger than a cellphone. Despite the benefits of MinION to sequence ultra‐long reads in real‐time, the high error rate of the existing base‐calling methods, especially indels (insertions and deletions), prevents its use in a variety of applications. Methods In this paper, we show that such indel errors are largely due to the segmentation process on the input electrical current signal from MinION. All existing methods conduct segmentation and nucleotide label prediction in a sequential manner, in which the errors accumulated in the first step will irreversibly influence the final base‐calling. We further show that the indel issue can be significantly reduced via accurate labeling of nucleotide and move labels directly from the raw signal, which can then be efficiently learned by a bi‐directional WaveNet model simultaneously through feature sharing. Our bi‐directional WaveNet model with residual blocks and skip connections is able to capture the extremely long dependency in the raw signal. Taking the predicted move as the segmentation guidance, we employ the Viterbi decoding to obtain the final base‐calling results from the smoothed nucleotide probability matrix. Results Our proposed base‐caller, WaveNano, achieves good performance on real MinION sequencing data from Lambda phage. Conclusions The signal‐level nanopore base‐caller WaveNano can obtain higher base‐calling accuracy, and generate fewer insertions/deletions in the base‐called sequences.
Synthesis and Surface Properties of Amphiphilic Star-Shaped and Dendrimer-like Copolymers Based on Polystyrene Core and Poly(ethylene oxide) Corona (2003)

Polystyrene (PS)/poly(ethylene oxide) (PEO) amphiphilic star-block copolymers and dendrimer-like architectures were prepared using a core-first method. PS stars were first obtained by atom transfer radical polymerization using three and four functional benzyl halides. The chain ends of these star polymers were subsequently modified to generate either the same or twice the number of hydroxyl groups that served to grow the PEO blocks by anionic polymerization of ethylene oxide. Well-defined PSn-b-PEOn (n = 3 or 4) stars and PS3-b-PEO6 dendrimer-like copolymers exhibiting a monomodal and narrow molar mass distribution were obtained in this way. When spread at the air/water interface, these stars proved to be surface active, forming stable reproducible films. Isotherms yielded A0 (theoretical surface area occupied by a film at zero pressure) values, allowing for quantitative comparisons between the stars and linear diblock analogues. Both structures demonstrated similar behavior, passing from liquid expanded regions to highly compressed structures at comparable molecular areas.
Activation of human B cells by phosphorothioate oligodeoxynucleotides. (1996)

To investigate the potential of DNA to elicit immune responses in man, we examined the capacity of a variety of oligodeoxynucleotides (ODNs) to stimulate highly purified T cell-depleted human peripheral blood B cells. Among 47 ODNs of various sequences tested, 12 phosphorothioate oligodeoxynucleotides (sODNs) induced marked B cell proliferation and Ig production. IL-2 augmented both proliferation and production of IgM, IgG, and IgA, as well as IgM anti-DNA antibodies, but was not necessary for B cell stimulation. Similarly, T cells enhanced stimulation, but were not necessary for B cell activation. After stimulation with the active sODNs, more than 95% of B cells expressed CD25 and CD86. In addition, B cells stimulated with sODNs expressed all six of the major immunoglobulin VH gene families. These results indicate that the human B cell response to sODN is polyclonal. Active sODN coupled to Sepharose beads stimulated B cells as effectively as the free sODN, suggesting that stimulation resulted from engagement of surface receptors. These data indicate that sODNs can directly induce polyclonal activation of human B cells in a T cell-independent manner by engaging as yet unknown B cell surface receptors.
On the mechanism of the .gamma.-aminobutyric acid receptor in the mammalian (mouse) cerebral cortex. Chemical kinetic investigations with a 10-ms time resolution adapted to measurements of neuronal receptor function in single cells (1992)

The gamma-aminobutyric acidA (GABA) receptor belongs to a superfamily of proteins involved in chemical reactions that regulate signal transmission between cells of the nervous system and is the target of some of the agents most frequently used in medicine to control disorders of the central nervous system. In contrast to the nicotinic acetylcholine receptor, which initiates signal transmission and is the best characterized member of the superfamily, the GABA receptor forms anion-specific transmembrane channels and inhibits signal transmission. The chemical kinetic experiments described here, in which fast chemical reaction techniques were used, indicate that both receptor proteins may operate by the same mechanism. Also described is the use of a chemical kinetic technique with a 10-ms time resolution that we have developed for making measurements with single cells isolated from specific areas of the nervous system, in this case the cerebral cortex of embryonic mice. A flow device was used to equilibrate receptors on the cell surface with GABA, and the concentration of open transmembrane channels in the cells was then measured by recording the whole-cell currents at pH 7.2, 21-23 degrees C, and a transmembrane voltage of -70 mV. Two different receptor forms, A alpha and A beta, were detected in cerebral cortical cells. Although the ratio of A alpha to A beta varied from cell to cell, on average 35% and 65% of the receptor-controlled current was associated with receptor forms A alpha and A beta, respectively. At saturating concentrations of GABA, the rate coefficients of desensitization, alpha and beta, associated with these two forms have maximal values of 4.4 and 0.7 s-1, respectively. The constants of a mechanism that accounts for the open transmembrane channels of both receptor forms were evaluated over a 50-fold range of GABA concentration. The dissociation constant of the site controlling channel opening was 40 microM for A alpha and 320 microM for A beta. The channel-opening equilibrium constant, phi-1, was 3.5 for A alpha and 20 for A beta. The evaluated constants allow one to calculate Po, the conditional probability that at a given concentration of GABA the receptor-channel is open. Po could also be determined in the presence of 100 microM GABA by an independent method in which different assumptions are made in the interpretation of the experimental results, the single-channel current-recording technique. The value of Po obtained (0.56) was in good agreement with the Po value (0.61) calculated for receptor form A alpha from chemical kinetic measurements at 100 microM GABA.(ABSTRACT TRUNCATED AT 400 WORDS)
Inhibition of StearoylCoA Desaturase Activity Blocks Cell Cycle Progression and Induces Programmed Cell Death in Lung Cancer Cells (2010)

Lung cancer is the most frequent form of cancer. The survival rate for patients with metastatic lung cancer is approximately 5%, hence alternative therapeutic strategies to treat this disease are critically needed. Recent studies suggest that lipid biosynthetic pathways, particularly fatty acid synthesis and desaturation, are promising molecular targets for cancer therapy. We have previously reported that inhibition of stearoylCoA desaturase-1 (SCD1), the enzyme that produces monounsaturated fatty acids (MUFA), impairs lung cancer cell proliferation, survival and invasiveness, and dramatically reduces tumor formation in mice. In this report, we show that inhibition of SCD activity in human lung cancer cells with the small molecule SCD inhibitor CVT-11127 reduced lipid synthesis and impaired proliferation by blocking the progression of cell cycle through the G(1)/S boundary and by triggering programmed cell death. These alterations resulting from SCD blockade were fully reversed by either oleic (18:1n-9), palmitoleic acid (16:1n-7) or cis-vaccenic acid (18:1n-7) demonstrating that cis-MUFA are key molecules for cancer cell proliferation. Additionally, co-treatment of cells with CVT-11127 and CP-640186, a specific acetylCoA carboxylase (ACC) inhibitor, did not potentiate the growth inhibitory effect of these compounds, suggesting that inhibition of ACC or SCD1 affects a similar target critical for cell proliferation, likely MUFA, the common fatty acid product in the pathway. This hypothesis was further reinforced by the observation that exogenous oleic acid reverses the anti-growth effect of SCD and ACC inhibitors. Finally, exogenous oleic acid restored the globally decreased levels of cell lipids in cells undergoing a blockade of SCD activity, indicating that active lipid synthesis is required for the fatty acid-mediated restoration of proliferation in SCD1-inhibited cells. Altogether, these observations suggest that SCD1 controls cell cycle progression and apoptosis and, consequently, the overall rate of proliferation in cancer cells through MUFA-mediated activation of lipid synthesis.
Detection of Trace Palladium in Flasks and Metal Reagents Using a Fluorogenic Tsuji–Trost Reaction (2012)

Metal detector: A previously developed method using a fluorescent chemodosimeter that could readily detect palladium at a 0.1 ppb level is now demonstrated to be capable of detecting residual palladium in metal reagents and used reaction flasks. This method can be readily employed on site.
The Cellular Distribution of Fluorescently Labeled Arrestins Provides a Robust, Sensitive, and Universal Assay for Screening G Protein-Coupled Receptors (2002)

G protein-coupled receptors (GPCRs) have proven to be a rich source of therapeutic targets; therefore, finding compounds that regulate these receptors is a critical goal in drug discovery. The Transfluor technology utilizes the redistribution of fluorescently labeled arrestins from the cytoplasm to agonist-occupied receptors at the plasma membrane to monitor quantitatively the activation or inactivation of GPCRs. Here, we show that the Transfluor technology can be quantitated on the INCell Analyzer system (INCAS) using the vasopressin V(2) receptor (V(2)R), which binds arrestin with high affinity, and the beta(2)-adrenergic receptor (beta(2)AR), which binds arrestin with low affinity. U2OS cells stably expressing an arrestin-green fluorescent protein conjugate and either the V(2)R or the beta(2)AR were plated in 96-well plastic plates and analyzed by the INCAS at a screening rate of 5 min per plate. Agonist dose-response and antagonist dose-inhibition curves revealed signal-to-background ratios of approximately 25:1 and 8:1 for the V(2)R and beta(2)AR, respectively. EC(50) values agreed closely with K(d) values reported in the literature for the different receptor agonists. In addition, small amounts of arrestin translocation induced by sub-EC(50) doses of agonist were distinguished from the background noise of untreated cells. Furthermore, differences in the magnitude of arrestin translocation distinguished partial agonists from full agonists, and Z' values for these ligands were >0.5. These data show that the Transfluor technology, combined with an automated image analysis system, provides a direct, robust, and universal assay for high throughput screening of known and orphan GPCRs.
Magrolimab in combination with azacitidine for untreated higher-risk myelodysplastic syndromes (HR-MDS): 5F9005 phase 1b study results. (2022)

7017 Background: Magrolimab is a monoclonal antibody that blocks CD47, a “don’t eat me” signal overexpressed on cancer cells. CD47 blockade by magrolimab induces macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine (AZA) via upregulation of “eat me” signals. Here we report final Phase 1b data in patients (pts) with untreated HR-MDS (NCT03248479). Methods: Pts with previously untreated intermediate-/high-/very high-risk MDS per IPSS-R received magrolimab IV as a priming dose (1 mg/kg) followed by ramp-up to a 30 mg/kg weekly or Q2W maintenance dose. AZA 75 mg/m 2 was administered IV or SC on Days 1–7 of each 28-day cycle. Primary endpoints were safety/tolerability and complete remission (CR) rate. Results: 95 pts (median age 69 years [range 28, 91]) were treated. IPSS-R risk was intermediate, high, or very high in 27%, 52%, and 21%, respectively. MDS was therapy-related in 22%; 26% (n=25) had a TP53 mutation and 62% had poor-risk cytogenetics (27% complex). Median (range) number of cycles was 6 (1, 27). The most common TEAEs included constipation (68%), thrombocytopenia (55%), anemia (52%), neutropenia (47%), nausea (46%), and diarrhea (44%). The most common Grade 3/4 TEAEs included anemia (47%), neutropenia (46%), thrombocytopenia (46%), and WBC count decreased (30%). 6 pts discontinued treatment due to AEs. 60-day mortality was 2%. Median Hb change from baseline (BL) at first post-dose sample was –0.7 g/dL (range –3.1, +2.4). CR and objective response (OR) rates were 33% and 75% with 31% of evaluable OR pts with abnormal cytogenetics at BL having cytogenetic CR. Median time to first OR, duration of CR (DCR), duration of OR, and PFS were 1.9, 11.1, 9.8, and 11.6 mos. OS rates at 12 and 24 mos were 75% and 52%, respectively (median NR with 17.1 mos follow-up for OS). For patients evaluated with sequential WES with a VAF cutoff of 5%, 3 of 3 pts with TP53 mutation who achieved CR had TP53 VAF &lt;5% by C5D1. Favorable outcomes were observed in both TP53 mutant (40% CR, median OS 16.3 months) and wildtype pts (31% CR, median OS NR; Table). Conclusions: Magrolimab+AZA was well tolerated with promising efficacy in pts with untreated HR-MDS including those with TP53-mut and TP53-wt disease. A Phase 3 trial of magrolimab/placebo+AZA (ENHANCE: NCT04313881) is ongoing. Clinical trial information: NCT03248479. [Table: see text]
Comparison of three approaches to doxorubicin therapy: free doxorubicin, liposomal doxorubicin, and beta-glucuronidase-activated prodrug (HMR 1826). (2000)

The efficacy of HMR 1826 is equal to or better than that of doxorubicin and Doxil at a safe dose and schedule, indicating that the beta-glucuronidase activated prodrug approach is safe and effective.
Exploring the Structural Basis of Substrate Preferences in Baeyer-Villiger Monooxygenases (2012)

Steroid monooxygenase (STMO) from Rhodococcus rhodochrous catalyzes the Baeyer-Villiger conversion of progesterone into progesterone acetate using FAD as prosthetic group and NADPH as reducing cofactor. The enzyme shares high sequence similarity with well characterized Baeyer-Villiger monooxygenases, including phenylacetone monooxygenase and cyclohexanone monooxygenase. The comparative biochemical and structural analysis of STMO can be particularly insightful with regard to the understanding of the substrate-specificity properties of Baeyer-Villiger monooxygenases that are emerging as promising tools in biocatalytic applications and as targets for prodrug activation. The crystal structures of STMO in the native, NADP(+)-bound, and two mutant forms reveal structural details on this microbial steroid-degrading enzyme. The binding of the nicotinamide ring of NADP(+) is shifted with respect to the flavin compared with that observed in other monooxygenases of the same class. This finding fully supports the idea that NADP(H) adopts various positions during the catalytic cycle to perform its multiple functions in catalysis. The active site closely resembles that of phenylacetone monooxygenase. This observation led us to discover that STMO is capable of acting also on phenylacetone, which implies an impressive level of substrate promiscuity. The investigation of six mutants that target residues on the surface of the substrate-binding site reveals that enzymatic conversions of both progesterone and phenylacetone are largely insensitive to relatively drastic amino acid changes, with some mutants even displaying enhanced activity on progesterone. These features possibly reflect the fact that these enzymes are continuously evolving to acquire new activities, depending on the emerging availabilities of new compounds in the living environment.
Innovation of Switched-Capacitor Voltage Multiplier: Part 1: A Brief History (2016)

The switched-capacitor (SC) voltage multiplier is becoming one of the most critical IC blocks for energy harvesting in wireless sensor nodes to generate a voltage high enough for microwatt sensing and computing ICs in a nanometer complementary metal?oxide?semiconductor (CMOS) from environmental energy sources such as mechanical vibration, electromagnetic wave, and temperature gradient. However, its origin was a 10 m-scale particle accelerator generating 1 MV back to 1920s. There have been several innovative design techniques to realize integrated SC voltage multipliers since the original one. This article overviews such innovations for the last century and describes how 10 m-scale SC voltage multipliers have been integrated in microwatt ICs and what technical considerations are critical for area- and power-efficient design. It also summarizes how device parameters determine circuit performance such as output voltage current and power efficiency. There have been also several design innovations in switching circuits to enable to work at extremely low voltages. This article shows state of the art for switching circuits for both dc-dc and ac-dc voltage multipliers and their applications as well.
A programmable video codec system for low-bit-rate communication (1997)

We have developed a programmable video codec system using a video codec DSP called VDSP1 X for low-bit-rate communication which performs realtime encoding and decoding using discrete cosine transform (DCT)-based algorithms, such as ITU-T H.261, H.263, and wavelet-based subband encoding algorithms. This system realizes real time encoding and decoding for QCIF frame sizes for both DCT-based algorithms and wavelet-based subband encoding algorithms in the same environment.
Creation of SiOF films with SiF4/O2 plasmas: From gas-surface interactions to film formation (2004)

Fluorinated SiO2 (SiOF) films have been studied because of their relatively low dielectric constant and their potential as a replacement for SiO2 in the microelectronics industry. Despite the intense scrutiny, many of the details of the mechanisms for SiOF film deposition remain unclear. Here, we examined the macroscopic and molecular level chemistry of SiOF film deposition using SiF4/O2 plasmas. In the film formation studies, the plasma parameters of SiF4 fraction in the feed gases, F, defined as SiF4/(SiF4+O2), and applied rf power (P) were examined as well as the effects of ion bombardment and substrate temperature on film deposition. Fluorine incorporation in the film increases with both F and P. Film-deposition rate also increases with P, whereas its dependence on F is more complex. Ion bombardment decreases the film deposition rate and affects film composition significantly. On the molecular level, we examined the surface reactivity of SiF and SiF2 during SiOF film deposition using the imaging of radicals interacting with surfaces technique. SiF2 shows significant surface production during film deposition. The scattering coefficient S varies from 1.63±0.07 to 2.01±0.07. In contrast, SiF shows high surface reactivity R (defined as 1−S for S⩽1), which varies from 0.96±0.13 to 0.73±0.09, depending on plasma parameters. The surface interactions of SiF and SiF2, along with plasma gas-phase composition, were correlated with film characteristics to reveal possible film-deposition mechanisms.
Numerical Inversion of Laplace Transforms Using a Fourier Series Approximation (1976)

A method is presented for numerically inverting a Laplace transform that requires, in addition to the transform function itself, only sine, cosine, and exponential functions. The method is conceptually much like the method of Dubner and Abate, which approximates the inverse function by means of a Fourier cosine series. The method presented here, however, differs from theirs in two important respects. First of all, the Fourier series contains additional terms involving the sine function selected such that the error in the approximation is less than that of Dubner and Abate and such that the Fourier series approximates the inverse function on an interval of twice the length of the corresponding interval in Dubner and Abate's method. Second, there is incorporated into the method in this paper a transformation of the approximating series into one that converges very rapidly. In test problems using the method it has routinely been possible to evaluate inverse transforms with considerable accuracy over a wide range of values of the independent variable using a relatively few determinations of the Laplace transform itself.
Generalized RBF feature maps for Efficient Detection (2010)

Kernel methods yield state-of-the-art performance in certain applications such as image classification and object detection. However, large scale problems require machine learning techniques of at most linear complexity and these are usually limited to linear kernels. This unfortunately rules out gold-standard kernels such as the generalized RBF kernels (e.g. exponential-c 2 ). Recently, Maji and Berg [13] and Vedaldi and Zisserman [20] proposed explicit feature maps to approximate the additive kernels (intersection, c 2 , etc.) by linear ones, thus enabling the use of fast machine learning technique in a non-linear context. An analogous technique was proposed by Rahimi and Recht [14] for the translation invariant RBF kernels. In this paper, we complete the construction and combine the two techniques to obtain explicit feature maps for the generalized RBF kernels. Furthermore, we investigate a learning method using l 1 regularization to encourage sparsity in the final vector representation, and thus reduce its dimension. We evaluate this technique on the VOC 2007 detection challenge, showing when it can improve on fast additive kernels, and the trade-offs in complexity and accuracy.
A Compound Sensor for Simultaneous Measurement of Packing Density and Moisture Content of Silage (2017)

Packing density and moisture content are important factors in investigating the ensiling quality. Low packing density is a major cause of loss of sugar content. The moisture content also plays a determinant role in biomass degradation. To comprehensively evaluate the ensiling quality, this study focused on developing a compound sensor. In it, moisture electrodes and strain gauges were embedded into an ASABE Standard small cone for the simultaneous measurements of the penetration resistance (PR) and moisture content (MC) of silage. In order to evaluate the performance of the designed sensor and the theoretical analysis being used, relevant calibration and validation tests were conducted. The determination coefficients are 0.996 and 0.992 for PR calibration and 0.934 for MC calibration. The validation indicated that this measurement technique could determine the packing density and moisture content of the silage simultaneously and eliminate the influence of the friction between the penetration shaft and silage. In this study, we not only design a compound sensor but also provide an alternative way to investigate the ensiling quality which would be useful for further silage research.