gebhart/patrepeval huggingface dataset:
Supplemental Movie 4 from AXL Inhibition Sensitizes Mesenchymal Cancer Cells to Antimitotic Drugs (2023)

&lt;p&gt;Timelapse movie of HeLa cells treated with docetaxel (3nM) in combination with R428 (1ÃŽÂ¼M).&lt;/p&gt;
Approche par rmn multinucleaire haute resolution solide et haute temperature de la reaction de clinkerisation (1996)

Le clinker, constituant essentiel du ciment portland, comporte quatre phases minerales principales qui sont les silicates di et tri calciques (c#2s et c#3s), l'aluminate tricalcique (c#3a) et l'alumino-ferrite de calcium (c#4af). Le clinker est obtenu par cuisson a haute temperature (environ 1400 a 1500c) d'un melange d'oxydes. Le premier chapitre presente une synthese bibliographique resumant les principaux axes de recherche developpes dans la litterature afin d'obtenir de nouvelles phases reactives et d'abaisser la temperature d'obtention du clinker en presence de sulfate et fluor. La resonance magnetique nucleaire (rmn) - principale technique retenue pour cette etude - est particulierement adaptee a la caracterisation des modifications structurales induites par les elements mineurs. Elle permet d'observer selectivement les elements et de decrire leur environnement immediat. Ce travail a necessite le developpement d'un montage rmn haute temperature specifiquement adapte a la gamme de temperature (400-1500c) afin d'etudier in situ les differentes etapes de la reaction de clinkerisation. Nous avons caracterise par rmn #2#9si les differentes phases polymorphes de c#2s et c#3s en temperature pour les composes purs et a temperature ambiante pour les echantillons stabilises par dopage. Nous avons decrit l'influence structurale des ajouts de sulfate et alumine sur la belite et de fluorine et alumine sur l'alite. Le desordre structural induit par les elements etrangers est une condition necessaire pour l'obtention de belite reactive vis a vis de l'eau. De plus, nous avons montre par rmn #1#7o la presence de chaux libre dans la structure de c#3s qui confirme l'accord existant entre stucture et proprietes en comparaison de la belite et de la chaux. Les differentes phases constituant les clinkers industriels presentent des signatures differenciees. Les ions al#3#+ en solution solide dans les silicates sont toujours en coordinence iv. Lors de la production du clinker, le fluor qui tend a former un cycle de matiere dans le four est responsable d'un appauvrissement de la teneur en c#3a. Afin de mieux apprehender la nature de la phase liquide formee au cours de la clinkerisation, nous avons decrit le mode d'action du fluor lors de la cuisson pour differentes compositions modeles et industrielles. En dernier lieu, nous avons observe in situ par rmn de #2#9si, #2#7al, #1#9f et de #1#7o la reaction de formation d'un clinker portland mineralise a partir d'un cru modele reconstitue.
Uncovering Latent Behaviors in Ant Colonies (2016)

Many biological systems exhibit collective behaviors that strengthen their adaptability to their environment, compared to more solitary species. Describing these behaviors is challenging yet necessary in order to understand these biological systems. We propose a probabilistic model that enables us to uncover the collective behaviors observed in a colony of ants. This model is based on the assumption that the behavior of an individual ant is a time-dependent mixture of latent behaviors that are specific to the whole colony. We apply this model to a large-scale dataset obtained by observing the mobility of nearly 1000 Camponotus fellah ants from six different colonies. Our results indicate that a colony typically exhibits three classes of behaviors, each characterized by a specific spatial distribution and a level of activity. Moreover, these spatial distributions, which are uncovered automatically by our model, match well with the ground truth as manually annotated by domain experts. We further explore the evolution of the behavior of individual ants and show that it is well captured by a second order Markov chain that encodes the fact that the future behavior of an ant depends not only on its current behavior but also on its preceding one.
Early fear memory defects are associated with altered synaptic plasticity and molecular architecture in the TgCRND8 Alzheimer's disease mouse model (2014)

Alzheimer's disease (AD) is a complex and slowly progressing dementing disorder that results in neuronal and synaptic loss, deposition in brain of aberrantly folded proteins, and impairment of spatial and episodic memory. Most studies of mouse models of AD have employed analyses of cognitive status and assessment of amyloid burden, gliosis, and molecular pathology during disease progression. Here we sought to understand the behavioral, cellular, ultrastructural, and molecular changes that occur at a pathological stage equivalent to the early stages of human AD. We studied the TgCRND8 mouse, a model of aggressive AD amyloidosis, at an early stage of plaque pathology (3 months of age) in comparison to their wildtype littermates and assessed changes in cognition, neuron and spine structure, and expression of synaptic glutamate receptor proteins. We found that, at this age, TgCRND8 mice display substantial plaque deposition in the neocortex and hippocampus and impairment on cued and contextual memory tasks. Of particular interest, we also observed a significant decrease in the number of neurons in the hippocampus. Furthermore, analysis of CA1 neurons revealed significant changes in apical and basal dendritic spine types, as well as altered expression of GluN1 and GluA2 receptors. This change in molecular architecture within the hippocampus may reflect a rising representation of inherently less stable thin spine populations, which can cause cognitive decline. These changes, taken together with toxic insults from amyloid-β protein, may underlie the observed neuronal loss.
Proteome Profiling of Human Cerebrospinal Fluid: Exploring the Potential of Capillary Electrophoresis with Surface Modified Capillaries for Analysis of Complex Biological Samples (2008)

A bottom-up proteomic approach, based on capillary electrophoresis (CE) in combination with matrix- assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-ToF/ToF MS), was used to analyze immunoaffinity depleted human cerebrospinal fluid (CSF) and compare it with a non-depleted sample. After enzymatic digestion and desalting, the tryptic peptides were separated by CE using PolyE-323 modified capillaries and fractionated off-line onto MALDI target plates for further analysis by MALDI-MS and MS/MS. The protein profile of the depleted sample was compared with non depleted CSF. Overall, 85 proteins were identified with 95% significance in both samples. The significance scores for proposed biomarkers, such as amyloid-like protein 1 precursor, could be increased up to 12 times after the depletion. Other proteins, often suggested to be related to neurodegenerative diseases, like amyloid beta A4 protein precursor, superoxide dismutase and apolipoprotein E precursor could only be found in the depleted CSF samples. The effect of a derivatization of tryptic peptides with 2- methoxy-4,5-dihydro-1H-imidazole reagent for protein identification with MS was also employed to increase the number of identified proteins and the sequence coverages. The results presented in this study illustrate the benefit of combining a sample pre-fractionation step and a label's ability to enhance the ionization efficiency with the potential of CE using PolyE-323 modified capillaries in the analysis of complex samples. The straight-forward approach that provides speed and simplicity resulting in high-resolution separations and low sample consumption represents an easily applicable separation technique that can serve as a complement to other currently existing analytical approaches needed in modern proteomic analysis of clinically relevant samples.
Molecular cloning of an extracellular aspartic proteinase fromRhizopus microsporusand evidence for its expression during infection (2002)

An extracellular aspartic proteinase (Rmap) from Rhizopus microsporus var. rhizopodiformis was detected in the culture supernatant of a fungal isolate from a case of rhinocerebral mucormycosis (case HA). The proteinase was purified to near homogeneity by ion exchange and affinity chromatography on pepstatin agarose. Based on its N-terminus the RMAP gene was cloned and found to code for 388 amino acids. The preproenzyme has an aminoterminal leader sequence of 65 amino acids, whereas the mature enzyme consists of 323 amino acids. The deduced amino-acid sequence of the preproenzyme was 82% homologous to an extracellular aspartic proteinase of Rhizopus niveus. Low stringency Southern blot analysis of R. microsporus DNA suggested the presence of other homologous genes. Expression of Rmap in Pichia pastoris was achieved, and the recombinant enzyme was active in the yeast culture supernatant. Both enzyme preparations exhibited a similar optimum of activity in the pH 2.5 region. Furthermore, Rmap was shown to activate bovine blood coagulation factor X at slightly acidic pH in vitro. Expression of the proteinase during mycosis was proven by a specific immune response of patient HA.
The VIP interface design system (2003)

The goals of user interface management systems (UIMS) research are to reduce the high cost of implementing user interfaces and to increase the functionality of highly interactive, visually oriented user interfaces. The visual interface programming (VIP) system realizes the independence of the interface and computation functions of many programs and allows interface designers, whose expertise might lie in areas other than traditional computer programming, to construct interfaces independent of the development of other program components. The authors describe the structure of VIP and the principles that have guided its development.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Use of chemical probes to explore the toxicological potential of the K+/Cl− cotransporter (KCC) as a novel insecticide target to control the primary vector of dengue and Zika virus, Aedes aegypti (2018)

The majority of commercialized insecticides target the insect nervous system and therefore, neural proteins are well-validated targets for insecticide development. Considering that only a few neural targets are exploited for insecticidal action and the development of insecticide resistance has reduced the efficacy of current insecticidal classes, we sought to test the toxicological potential of the potassium-chloride cotransporter (KCC). In mammals, KCC proteins have seminal roles in shaping GABAergic signaling and inhibitory neurotransmission, thus ion transport through KCC is critical for proper neurotransmission. Therefore, we hypothesized that mosquito KCC represents a putative insecticide target site and that pharmacological inhibition of KCC constructs in Aedes aegypti will be lethal. To test this hypothesis, we developed a robust, cell-based fluorescence assay that enables in vitro characterization of small-molecules against Ae. aegypti KCC and performed a proof-of-concept study employing well characterized mammalian KCC modulators to determine the toxicological potential of Ae. aegypti KCC. The selective inhibitor of mammalian KCC, termed VU0463271, was found to be a potent inhibitor Ae. aegypti KCC and microinjection induced lethality in a concentration-dependent manner to susceptible and pyrethroid resistant strains. Importantly, an analog of VU0463271 was shown to be >40-fold less potent and did not induce toxicity, suggesting that the observed physiological effects and mortality are likely due to KCC inhibition. This proof-of-concept study suggests that Ae. aegypti KCC represents a putative target site for mosquitocide design that can mitigate the current mechanisms of insecticide resistance.
Dual-specificity splice sites function alternatively as 5′ and 3′ splice sites (2007)

As a result of large-scale sequencing projects and recent splicing-microarray studies, estimates of mammalian genes expressing multiple transcripts continue to increase. This expansion of transcript information makes it possible to better characterize alternative splicing events and gain insights into splicing mechanisms and regulation. Here, we describe a class of splice sites that we call dual-specificity splice sites, which we identified through genome-wide, high-quality alignment of mRNA/EST and genome sequences and experimentally verified by RT-PCR. These splice sites can be alternatively recognized as either 5' or 3' splice sites, and the dual splicing is conceptually similar to a pair of mutually exclusive exons separated by a zero-length intron. The dual-splice-site sequences are essentially a composite of canonical 5' and 3' splice-site consensus sequences, with a CAG|GURAG core. The relative use of a dual site as a 5' or 3' splice site can be accurately predicted by assuming competition for specific binding between spliceosomal components involved in recognition of 5' and 3' splice sites, respectively. Dual-specificity splice sites exist in human and mouse, and possibly in other vertebrate species, although most sites are not conserved, suggesting that their origin is recent. We discuss the implications of this unusual splicing pattern for the diverse mechanisms of exon recognition and for gene evolution.
Illuminating the norepinephrine transporter: fluorescent probes based on nisoxetine and talopram (2021)

The utilization of fluorescent ligands to study the monoamine transporters (MATs) has increased our knowledge of their function and distribution in live cell systems. In this study, we extend SAR for nisoxetine and talopram as parent compounds, to identify high affinity rhodamine-labeled fluorescent probes for the norepinephrine transporter (NET). Nisoxetine-based fluorescent probe <b>6</b> demonstrated high binding affinity (<i>K</i> <sub>i</sub> = 43 nM) for NET and an overall selectivity compared to the other transporters for dopamine (DAT; <i>K</i> <sub>i</sub> = 1540 nM) and serotonin (SERT; <i>K</i> <sub>i</sub> = 785 nM) in competitive radioligand binding assays. Using confocal microscopy, compound <b>6</b> was shown to stain both NET and SERT, but not DAT, at low nanomolar concentrations, in transporter-expressing cells.
3× 485-Gb/s WDM Transmission over 4800 km of ULAF and 12× 100-GHz WSSs Using CO-OFDM and Single Coherent Detection with 80-GS/s ADCs (2011)

We demonstrate WDM transmission of three 485-Gb/s CO-OFDM channels with 16-QAM subcarrier-modulation, each received by a single coherent detection step. Transmission over 48 100-km ULAF spans and 12 wavelength-selective-switches with 4-b/s/Hz net spectral-efficiency is achieved.
miR-146b antagomir–treated human Tregs acquire increased GVHD inhibitory potency (2016)

CD4(+)CD25(+)FoxP3(+) thymic-derived regulatory T cells (tTregs) are indispensable for maintaining immune system equilibrium. Adoptive transfer of tTregs is an effective means of suppressing graft-versus-host disease (GVHD) in murine models and in early human clinical trials. Tumor necrosis factor receptor-associated factor 6 (TRAF6), an ubiquitin-conjugating enzyme that mediates nuclear factor κB (NF-κB) activation, plays an essential role in modulating regulatory T cell survival and function. MicroRNAs (miRNAs) are noncoding RNAs, which mediate RNA silencing and posttranscriptional gene repression. By performing comprehensive TaqMan Low Density Array miRNA assays, we identified 10 miRNAs differentially regulated in human tTreg compared with control T cells. One candidate, miR-146b, is preferentially and highly expressed in human naive tTregs compared with naive CD4 T cells. miRNA prediction software revealed that TRAF6 was the one of the top 10 scored mRNAs involved tTreg function with the highest probability as a potential miR-146b target. Antagomir-mediated knockdown of miRNA-146b, but not another miRNA-146 family member (miRNA-146a), enhanced TRAF6 expression. TRAF6, in turn, increases NF-κB activation, which is essential for tTreg function as well as Foxp3 protein and antiapoptotic gene expression, and downregulates proapoptotic gene expression. miR-146b knockdown increased the nuclear localization and expression of genes regulated by NF-κB, which was associated with enhanced tTreg survival, proliferation, and suppressive function measured in vitro and in vivo. TRAF6 inhibition had the opposite effects. We conclude that an miR-146b-TRAF6-NF-κB-FoxP3 signaling pathway restrains regulatory T cell survival, proliferation, and suppressor function. In vitro exposure of human tTregs to miR-146b antagomirs can be exploited to improve the clinical efficacy of human adoptive tTreg transfer in a GVHD setting.
Quality-aware millimeter-wave device-to-device multi-hop routing for 5G cellular networks (2014)

Millimeter-wave (mm-wave) transmission is a promising method for increasing capacity in next-generation cellular systems. However, since mm-wave signals are too weak to (i) do long-distance communication and (ii) survive in non-line-of-sight situations, multi-hop relaying is required. We thus study in this paper a multi-hop routing protocol at mm-wave (38 GHz and 28GHz) frequencies. Due to the great and steadily increasing importance of video streaming in cellular applications, we pay special attention to the maximization of video transmission quality, which makes the optimization problem different from the usual sum-rate maximization. Specifically, we develop a protocol that optimizes the “sum quality” of the transmission of different video streams, subject to constraints (minimum quality) of separate streams. We take the unique properties of mm-waves (sparse angular power spectrum, leading to low interference) into account in our method. Extensive simulation results show the superiority of our approach compared to max-min flow routing which is widely used in QoS-sensitive applications.
Pyrolysis‐mass spectrometry of the phenolic constituents of plant cell walls (1984)

Abstract Cell walls of plant parts of maize, barley, Italian ryegrass, wheat bran, lucerne and red clover were subjected to low voltage pyrolysis‐mass spectrometry. The ion intensity at m/z 120, which is characteristic of p ‐coumaric acid, was significantly correlated (r=0.99) with the p ‐coumaric acid content of the walls; the ion intensity at m/z 150, characteristic of ferulic acid, was present in the spectra of the graminaceous walls. Factor analysis of the pyrolysis‐mass spectra indicated that some, at least, of the p ‐coumaric and ferulic acid constituents of the walls are bound to pentosans, and suggested that not all the aromatic constituents of the walls are bound to polysaccharides.
Dimensional Analysis of Laughter in Female Conversational Speech (2019)

How do people hear laughter in expressive, unprompted speech? What is the range of expressivity and function of laughter in this speech, and how can laughter inform the recognition of higher-level expressive dimensions in a corpus? This paper presents a scalable method for collecting natural human description of laughter, transforming the description to a vector of quantifiable laughter dimensions, and deriving baseline classifiers for the different dimensions of expressive laughter. Then, it explores the impact of leveraging nuances of laughter in the recognition of higher-level, general expressive dimensions, discovered in the same way, such as genuine happiness, sarcasm, nervous reflection, and more. The performance of the low-level laughter classifiers is presented, along with the performance of the high-level laughter-aware and laughter-unaware classifiers.
Compartmentalization of the proteasome-interacting proteins during sperm capacitation (2019)

Ubiquitination is a stable, reversible posttranslational modification of target proteins by covalent ligation of the small chaperone protein ubiquitin. Most commonly ubiquitination targets proteins for degradation/recycling by the 26S proteasome in a well-characterized enzymatic cascade. Studies using human and non-human mammalian spermatozoa revealed the role of the ubiquitin-proteasome system (UPS) in the regulation of fertilization, including sperm-zona pellucida (ZP) interactions as well as the early events of sperm capacitation, the remodeling of the sperm plasma membrane and acrosome, and for the acquisition of sperm fertilizing ability. The present study investigated the activity of UPS during in vitro capacitation of fresh boar spermatozoa in relation to changes in sperm proteome. Parallel and sequential treatments of ejaculated and capacitated spermatozoa under proteasome permissive/inhibiting conditions were used to isolate putative sperm proteasome-associated sperm proteins in a compartment-specific manner. A differential proteomic approach employing 1D PAGE revealed differences in accumulated proteins at the molecular weights of 60, 58, 49, and 35 kDa, and MS analysis revealed the accumulation of proteins previously reported as proteasome co-purifying proteins, as well as some novel proteins. Among others, P47/lactadherin, ACRBP, ADAM5, and SPINK2 (alias SAAI) were processed by the proteasome in a capacitation dependent manner. Furthermore, the capacitation-induced reorganization of the outer acrosomal membrane was slowed down in the presence of proteasomal inhibitors. These novel results support the proposed role of UPS in sperm capacitation and open several new lines of inquiry into sperm capacitation mechanism.
Doppler-free two-photon laser excitation of the vacuum ultraviolet absorption spectrum of CO (1978)

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A Detrimental Role for IL‐10 During Host Immune Responses to Influenza Virus Infection (2008)

IL‐10 is an important anti‐inflammatory molecule that can cause immunosuppression, leading to long‐term viral persistence during chronic infection of mice with viruses such as lymphocytic choriomeningitis virus. However, its specific role during acute viral infections has not been documented. We now report that IL‐10 appears to also play a detrimental role during host responses to acute influenza virus infection since absence of IL‐10 led to improved viral clearance, weight recovery and survival rate in influenza‐infected mice. There were similar levels of CD4 + and CD8 + T cell recruitment into the lungs of infected WT and IL‐10 −/− mice, and depletion of CD8 + T cells did not significantly influence viral clearance in IL‐10 −/− mice. Although viral infected IL‐10 −/− mice exhibited different kinetics of neutrophil recruitment compared to WT mice, neutrophil depletion did not hamper viral clearance. On the other hand, H1N1‐specific antibody levels in BALF were slightly increased in viral infected IL‐10 −/− mice compared to WT mice. The mechanism of IL‐10 mediated suppression of host recovery from influenza virus infection is under further investigation. (Supported by NIH grant RO1 AI 41715)