gebhart/patrepeval huggingface dataset:
ShrinkCRISPR : A flexible method for differential fitness analysis of CRISPR-Cas9 screen data (2022)

Abstract CRISPR screens provide large-scale assessment of cellular gene functions. Pooled libraries typically consist of several single guide RNAs (sgRNAs) per gene, for a large number of genes, which are transduced in such a way that every cell receives at most one sgRNA, resulting in the disruption of a single gene in that cell. This approach is often used to investigate effects on cellular fitness, by measuring sgRNA abundance at different time points. Comparing gene knockout effects between different cell populations is challenging due to variable cell-type specific parameters and between replicates variation. Failure to take those into account can lead to inflated or false discoveries. We propose a new, flexible approach called ShrinkCRISPR that can take into account multiple sources of variation. Impact on cellular fitness between conditions is inferred by using a mixed-effects model, which allows to test for gene-knockout effects while taking into account sgRNA-specific variation. Estimates are obtained using an empirical Bayesian approach. ShrinkCRISPR can be applied to a variety of experimental designs, including multiple factors. In simulation studies, we compared ShrinkCRISPR results with those of drugZ and MAGeCK, common methods used to detect differential effect on cell fitness. ShrinkCRISPR yielded as many true discoveries as drugZ using a paired screen design, and outperformed both drugZ and MAGeCK for an independent screen design. Although conservative, ShrinkCRISPR was the only approach that kept false discoveries under control at the desired level, for both designs. Using data from several publicly available screens, we showed that ShrinkCRISPR can take data for several time points into account simultaneously, helping to detect early and late differential effects. ShrinkCRISPR is a robust and flexible approach, able to incorporate different sources of variations and to test for differential effect on cell fitness at the gene level. These improve power to find effects on cell fitness, while keeping multiple testing under the correct control level and helping to improve reproducibility. ShrinkCrispr can be applied to different study designs and incorporate multiple time points, making it a complete and reliable tool to analyze CRISPR screen data.
A Selective Novel Peroxisome Proliferator-Activated Receptor (PPAR)-α Antagonist Induces Apoptosis and Inhibits Proliferation of CLL Cells In Vitro and In Vivo (2015)

Tumor-specific metabolic changes can reveal new therapeutic targets. Our findings implicate a supporting role for fatty acid metabolism in chronic lymphocytic leukemia (CLL) cell survival. Peroxisome proliferator-activated receptor (PPAR)-α, a major transcriptional regulator of fatty acid oxidation, was recently shown to be upregulated in CLL. To evaluate PPARα as a potential therapeutic target, we developed a highly selective, potent small molecule antagonist of PPARα, NXT629. NXT629 inhibited agonist-induced transcription of PPARα-regulated genes, demonstrating target engagement in CLL cells. Furthermore, NXT629 induced apoptosis of CLL cells even in the presence of a protective microenvironment. To mimic the proliferative lymphoid compartment of CLL, we examined the activity of NXT629 on CLL cells that were stimulated to proliferate in vitro. NXT629 reduced the number of leukemia cells undergoing cell division. In addition, in two xenograft mouse models of CLL (one a model for nondividing and one for dividing CLL), NXT629 reduced the number of viable CLL cells in vivo. Overall, these results suggest that fatty acid metabolism promotes survival and proliferation of primary CLL cells and that inhibiting PPARα gene regulation could be a new therapeutic approach to treating CLL.
The time-course of component processes of selective attention (2019)

Attentional selection shapes human perception, enhancing relevant information, according to behavioral goals. While many studies have investigated individual neural signatures of attention, here we used multivariate decoding of electrophysiological brain responses (MEG/EEG) to track and compare multiple component processes of selective attention. Auditory cues instructed participants to select a particular visual target, embedded within a subsequent stream of displays. Combining single and multi-item displays with different types of distractors allowed multiple aspects of information content to be decoded, distinguishing distinct components of attention, as the selection process evolved. Although the task required comparison of items to an attentional "template" held in memory, signals consistent with such a template were largely undetectable throughout the preparatory period but re-emerged after presentation of a non-target choice display. Choice displays evoked strong neural representation of multiple target features, evolving over different timescales. We quantified five distinct processing operations with different time-courses. First, visual properties of the stimulus were strongly represented. Second, the candidate target was rapidly identified and localized in multi-item displays, providing the earliest evidence of modulation by behavioral relevance. Third, the identity of the target continued to be enhanced, relative to distractors. Fourth, only later was the behavioral significance of the target explicitly represented in single-item displays. Finally, if the target was not identified and search was to be resumed, then an attentional template was weakly reactivated. The observation that an item's behavioral relevance directs attention in multi-item displays prior to explicit representation of target/non-target status in single-item displays is consistent with two-stage models of attention.
DB-GAN: Boosting Object Recognition Under Strong Lighting Conditions (2021)

Driven by deep learning, object recognition has recently made a tremendous leap forward. Nonetheless, its accuracy often still suffers from several sources of variation that can be found in real-world images. Some of the most challenging variations are induced by changing lighting conditions. This paper presents a novel approach for tackling brightness variation in the domain of 2D object detection and 6D object pose estimation. Existing works aiming at improving robustness towards different lighting conditions are often grounded on classical computer vision contrast normalisation techniques or the acquisition of large amounts of annotated data in order to achieve invariance during training. While the former cannot generalise well to a wide range of illumination conditions, the latter is neither practical nor scalable. Hence, We propose the usage of Generative Adversarial Networks in order to learn how to normalise the illumination of an input image. Thereby, the generator is explicitly designed to normalise illumination in images so to enhance the object recognition performance. Extensive evaluations demonstrate that leveraging the generated data can significantly enhance the detection performance, outperforming all other state-of-the-art methods. We further constitute a natural extension focusing on white balance variations and introduce a new dataset for evaluation.
Passive mode locking in erbium-doped fibre laser by carbon nanotubes (2011)

Passively mode locked fibre lasers have a variety of applications ranging from telecommunication to medical photonics. Carbon nanotubes (CNTs) have attracted recently a great deal of attention as a promising solution for saturable absorber elements required for laser mode locking (see e.g. [1–3] and references therein). CNTs can be used as a saturable absorber in passively mode locked fibre laser directly [1,2] or as a CNTs polymer composites [3]. An attractive feature of CNT-based solutions in fibre lasers is a possibility to maintain the compactness, robustness of all-fibre format and low cost through using all standard telecom compatible components. The two important technical challenges in such type of lasers are: (i) to achieve stable polarization properties of the generated radiation without using complex control elements, and, (ii) to avoid low frequency instabilities of the mode-locked pulse train. In this paper we report results of the experiments on mode-locked soliton fibre laser using the following standard components: ∼1m of highly doped erbium fibre (Liekki Er80-8/125) serves as the gain medium with nominal absorption of 80 dB/m at 1530 nm; a 976 nm laser diode providing up to ∼310mW power is used to pump the laser via a 980/1550 wavelength division multiplexing; an isolator is employed to ensure single direction oscillation; SMF-28 is used to create necessary amount of anomalous dispersion to form soliton pulse making the total cavity length around 7.83 m; the CNT-polyvinyl alcohol polymer saturable absorber sandwiched in the FC/PC connector is used as a mode-locker device (see [3] for details).
SYNTHESIS AND CHARACTERIZATION OF FRUCTOSYLTRANSFERASE FROM Aspergillus oryzae IPT-301 FOR HIGH FRUCTOOLIGOSACCHARIDES PRODUCTION (2019)

are mainly produced by microbial fructosyltransferases (FTase, E.C.2.4.1.9), and Aspergillus oryzae IPT-301 has shown high fructosyl transferring and low hydrolytic activities, which leads to high FOS production yields, but the main operating parameters for its best performance have been scarcely studied. Thus, this work aimed to evaluate the cellular growth, production and characterization of mycelial and extracellular FTases by Aspergillus oryzae IPT-301. Experimental design showed that the extracellular FTase performance was optimized (high transfructosylation activity and low hydrolytic activity) for reaction pH 5.5 -6.75 and temperature of 45-50 C and was fitted by the Michaelis-Menten model, while the mycelial FTase showed better performance at pH below 6.5 and temperature above 46 C and was better fitted by the Hill model. The results obtained showed that the fungus represents a promising source for FOS production on a laboratorial scale.
Cloning, Characterization and Site-Directed Mutagenesis of Canine Renin (2007)

Inhibition of renin has been shown to be successful in managing hypertension and maintaining cardiac health. Canine models have played a key role in preclinical assessment of renin inhibitors. Here we report the cloning of canine prorenin gene. The amino acid sequence of mature canine renin was approximately 70% identical to that of human renin. The full-length prorenin was expressed in HEK 293 cells, purified and converted to its active form by trypsin-mediated cleavage of the 43 residue propeptide. The mature enzyme was characterized by steady-state kinetics using a peptide corresponding to the canine angiotensinogen sequence, Ac-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser-OH (cleavage between Leu(10)-Leu(11)). The reaction followed Michaelis-Menten kinetics with a K(M) of 120 microM and a second-order rate constant (k(cat)/K(M)) of 1.7 x 10(5) M(-)(1)s(-)(1). The enzyme was inhibited by various human renin inhibitors, but at reduced potency compared to the human renin. The basis of the species specificity was investigated by mutagenesis. Based on primary sequence and structural alignments, three mutants were prepared (G149S-S150T, V286L, G149S-S150T-V286L). Each mutant yielded catalytically active enzymes with lower specific activities than native canine renin. V286L had the greatest effect on substrate specificity, while G149S, S150T mutations produced enzymes with inhibitor profiles similar to human renin.
Monolithic Systems Using Standard Three-Leg Inverter Supplying Independently Two Motors (2008)

This paper presents two series-connected motor drive system topologies. These configurations have been designed for applications in which it is necessary to control two motors independently by using a standard three-leg inverter. The systems will be called in this work as a monolithic systems, since both machines and the three legs inverter have been considered as the same product. The monolithic systems are seen as a potentially viable industrial solution for applications requiring one high- power (three-phase machine) and one low-power machine (single- phase machine). Furthermore, the paper presents: i) relevant characteristics of the systems, ii) pulse-width modulation techniques; iii) control strategies; iv) voltage and current analysis; v) unconventional induction machine design to improve the performance of the monolithic system; and vi) simulated and experimental results.
Reward-Weighted Regression with Sample Reuse for Direct Policy Search in Reinforcement Learning (2011)

Direct policy search is a promising reinforcement learning framework, in particular for controlling continuous, high-dimensional systems. Policy search often requires a large number of samples for obtaining a stable policy update estimator, and this is prohibitive when the sampling cost is expensive. In this letter, we extend an expectation-maximization-based policy search method so that previously collected samples can be efficiently reused. The usefulness of the proposed method, reward-weighted regression with sample reuse (R3), is demonstrated through robot learning experiments. (This letter is an extended version of our earlier conference paper: Hachiya, Peters, & Sugiyama, 2009 .).
Genetically encoded sensors enable real-time observation of metabolite production (2016)

Engineering cells to produce valuable metabolic products is hindered by the slow and laborious methods available for evaluating product concentration. Consequently, many designs go unevaluated, and the dynamics of product formation over time go unobserved. In this work, we develop a framework for observing product formation in real time without the need for sample preparation or laborious analytical methods. We use genetically encoded biosensors derived from small-molecule responsive transcription factors to provide a fluorescent readout that is proportional to the intracellular concentration of a target metabolite. Combining an appropriate biosensor with cells designed to produce a metabolic product allows us to track product formation by observing fluorescence. With individual cells exhibiting fluorescent intensities proportional to the amount of metabolite they produce, high-throughput methods can be used to rank the quality of genetic variants or production conditions. We observe production of several renewable plastic precursors with fluorescent readouts and demonstrate that higher fluorescence is indeed an indicator of higher product titer. Using fluorescence as a guide, we identify process parameters that produce 3-hydroxypropionate at 4.2 g/L, 23-fold higher than previously reported. We also report, to our knowledge, the first engineered route from glucose to acrylate, a plastic precursor with global sales of $14 billion. Finally, we monitor the production of glucarate, a replacement for environmentally damaging detergents, and muconate, a renewable precursor to polyethylene terephthalate and nylon with combined markets of $51 billion, in real time, demonstrating that our method is applicable to a wide range of molecules.
Dimethylamino- and trimethylammonium-tipped oxyethylene–oxybutylene diblock copolymers and their use as structure-directing agents in the preparation of mesoporous silica (2002)

Oxyethylene–oxybutylene diblock copolymers with a dimethylamino tip to the hydrophilic block were prepared by anionic polymerization, using aminoalcohol initiators in a dry aprotic medium. Conversion of a high percentage of the alcohol to alkoxide minimized the formation of unwanted by-products, but slightly broadened the molar mass distribution of the copolymers. Trimethylammonium-tipped copolymers were prepared by quaternization with methyl iodide. The copolymers were utilised as structure-directing agents in the preparation of silica under acidic conditions, where all the copolymers carry a positive charge, and subsequent removal of the copolymers by calcination gave mesoporous materials. The silica mesostructure depended on the relative sizes of the polymer blocks, changing from body-centred cubic to three-dimensional hexagonal to two-dimensional hexagonal on decreasing the proportion of hydrophilic units. The overall silica mesostructure dimensions, as determined from X-ray analysis, increased with an increase in micelle size, and the mesopore dimensions, as determined from nitrogen adsorption analysis, increased with an increase in the size of the core hydrophobic block. A simple model is suggested in which the hydrophilic chains are embedded in the silica walls in the uncalcined silica, generating micropores on calcination, whilst the hydrophobic chains form a separate microphase, giving rise to mesopores on calcination. The effect of charged tips, as compared with equivalent nonionic diblock copolymers, is to expand the dimensions of the mesostructures obtained and to generate higher surface areas in the calcined silica products.
Plasminogen Activator Inhibitor Activity in Bacterial Infection (1988)

It has been experimentally shown that endotoxin induces a marked increase in the levels of a fast-acting inhibitor of plasminogen activator (PAI). The plasma PAI activity and tissue-type plasminogen activator (t-PA) concentrations were measured in 61 patients with human septicaemia and results were compared with those observed in healthy controls. There was a markedly significant increase of PAI in plasma and platelet extracts of patients with septicaemia as compared to controls (p less than 0.0001). No correlation between PAI and endotoxin concentration was observed. Fibrin autography of plasma samples confirmed that activator inhibition was associated with the formation of an enzyme-inhibitor complex. t-PA activity was similar in patients and controls, whereas t-PA Ag showed a significant increase in patients (p less than 0.0001). A significant inverse correlation between t-PA activity and PAI was observed (p less than 0.05). PAI activity was higher in patients with positive blood cultures (p less than 0.0001) and gram-negative septicaemia (p less than 0.0001). There was also a significant increase of PAI levels in patients with disseminated intravascular coagulation (DIC) as compared with patients without DIC (p less than 0.001). We conclude that there is a marked increase of PAI in patients with sepsis. Increased PAI activity may contribute to the pathogenesis of DIC associated with septicaemia.
Data-Driven Chance-Constrained Regulation Capacity Offering for Distributed Energy Resources (2018)

This paper studies the behavior of a strategic aggregator offering regulation capacity on behalf of a group of distributed energy resources (DERs, e.g., plug-in electric vehicles) in a power market. Our objective is to maximize the aggregator's revenue while controlling the risk of penalties due to poor service delivery. To achieve this goal, we propose data-driven risk-averse strategies to effectively handle uncertainties in: 1) the DER parameters (e.g., load demands and flexibilities) and 2) subhourly regulation signals (to the accuracy of every few seconds). We design both the day-ahead and the hour-ahead strategies. In the day-ahead model, we develop a two-stage stochastic program to roughly model the above uncertainties, which achieves computational efficiency by leveraging novel aggregate models of both DER parameters and sub-hourly regulation signals. In the hour-ahead model, we formulate a data-driven distributionally robust chance-constrained program to explicitly model the aforementioned uncertainties. This program can effectively control the quality of regulation service based on the aggregator's risk aversion. Furthermore, it learns the distributions of the uncertain parameters from empirical data so that it outperforms existing techniques (e.g., robust optimization or traditional chance-constrained programming) in both modeling accuracy and cost of robustness. Finally, we derive a conic safe approximation for it which can be efficiently solved by commercial solvers. Numerical experiments are conducted to validate the proposed method.
PROTEIN ADSORPTION ON MESOPOROUS APATITE AGGREGATES (2005)

Adsorption properties of proteins on c-axis oriented mesoporous HAp aggregates were investigated by liquid chromatography using the mesoporous HAp aggregates as an adsorbent. Elution molarity ratios of acidic proteins on the mesoporous HAp aggregates between before and after heat-treatment at 600°C increased with increasing the molecular weight in the order of ferritin > fibrinogen > catalase > BSA, whereas the elution molarity ratios of basic proteins were considerably lower than those of acidic proteins. These results suggested that the acidic proteins could be penetrated into the pore of the mesoporous HAp aggregates after heat treatment and were selectively adsorbed on the mesoporous wall consisting of the a-surface of the HAp aggregate. On the other hand, the basic proteins could be adsorbed on the wide outer surface of the plate-like HAp aggregates. Therefore, the elution molarity ratios of basic proteins decreased with decreasing the specific surface area by the heat treatment, independent of the mesoporous structure.
Studying the interaction of polyoma virus middle T antigen with cellular proteins (1994)

The oncogenic mouse polyoma virus encodes six proteins, two of which (the large and middle T antigens), when expressed together in primary rodent cells, generate an alteration of growth patterns commonly known as cellular transformation. The transformed cells grow with an unlimited life span and when introduced into immunocompromised mice rapidly form tumours. The large T gene product confers an indefinite growth potential on primary cells; however, the middle T gene product has been identified as bringing about the changes which ultimately allow the cell to form tumours. The 55 kDa middle T antigen has been shown to associate with a number of cellular enzymes involved in regulation of growth factor signalling pathways, all of which were identified as being components of the immunocomplexes that can be isolated from transformed cells using middle T antigen specific antibodies. Two-dimensional gels have assisted the search for less prominent species present in these complexes. These methods represents one approach to investigating associating proteins, and as such, select for those interactions that are stable under the conditions used. In order to explore the possibility that middle T antigen could form complexes with other cellular proteins given different conditions, recombinant middle T antigen was used in a series of "filter overlay" experiments.
A 2.5 V 50 MHz ΔΣ-modulator for digital cellular telephones (2005)

This paper discusses the design of a 50 MHz switched-capacitor /spl Delta//spl Sigma/-modulator with a 2.5 V supply voltage implemented in a 0.5 /spl mu/m BiCMOS process. The problems caused by the low analog supply voltage are addressed with special biasing and common-mode arrangements. Simulation results verifying a peak SNDR of 83 dB are presented.
Multi-block mesh extrusion driven by a globally elliptic system (2000)

This paper investigates the possibility of using a boundary integral equation to facilitate the generation of multi-block grid systems about semi-complex geometries. The integral equation utilized is that for a source density distribution over the surface of the body about which the conforming grid system is sought. Advantages of and restrictions to the current method are discussed in relation with other gridding techniques. Sample grid systems are provided for several dissimilar geometric shapes which illustrate the quality and robustness of the present scheme. Copyright © 2000 John Wiley & Sons, Ltd.