gebhart/patrepeval huggingface dataset:
Scalable Production of Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Under Serum-/Xeno-Free Conditions in a Microcarrier-Based Bioreactor Culture System (2020)

Mesenchymal stromal cells (MSC) hold great promise for tissue engineering and cell-based therapies due to their multilineage differentiation potential and intrinsic immunomodulatory and trophic activities. Over the past years, increasing evidence has proposed extracellular vesicles (EVs) as mediators of many of the MSC-associated therapeutic features. EVs have emerged as mediators of intercellular communication, being associated with multiple physiological processes, but also in the pathogenesis of several diseases. EVs are derived from cell membranes, allowing high biocompatibility to target cells, while their small size makes them ideal candidates to cross biological barriers. Despite the promising potential of EVs for therapeutic applications, robust manufacturing processes that would increase the consistency and scalability of EV production are still lacking. In this work, EVs were produced by MSC isolated from different human tissue sources [bone marrow (BM), adipose tissue (AT), and umbilical cord matrix (UCM)]. A serum-/xeno-free microcarrier-based culture system was implemented in a Vertical-Wheel<sup>TM</sup> bioreactor (VWBR), employing a human platelet lysate culture supplement (UltraGRO<sup>TM</sup>-PURE), toward the scalable production of MSC-derived EVs (MSC-EVs). The morphology and structure of the manufactured EVs were assessed by atomic force microscopy, while EV protein markers were successfully identified in EVs by Western blot, and EV surface charge was maintained relatively constant (between -15.5 ± 1.6 mV and -19.4 ± 1.4 mV), as determined by zeta potential measurements. When compared to traditional culture systems under static conditions (T-flasks), the VWBR system allowed the production of EVs at higher concentration (i.e., EV concentration in the conditioned medium) (5.7-fold increase overall) and productivity (i.e., amount of EVs generated per cell) (3-fold increase overall). BM, AT and UCM MSC cultured in the VWBR system yielded an average of 2.8 ± 0.1 × 10<sup>11</sup>, 3.1 ± 1.3 × 10<sup>11</sup>, and 4.1 ± 1.7 × 10<sup>11</sup> EV particles (<i>n</i> = 3), respectively, in a 60 mL final volume. This bioreactor system also allowed to obtain a more robust MSC-EV production, regarding their purity, compared to static culture. Overall, we demonstrate that this scalable culture system can robustly manufacture EVs from MSC derived from different tissue sources, toward the development of novel therapeutic products.
De novo protein identification in mammalian sperm using high-resolution in situ cryo-electron tomography (2022)

Abstract Understanding molecular mechanisms of cellular pathways requires knowledge of the identities of participating proteins, their cellular localization and their 3D structures. Contemporary workflows typically require multiple techniques to identify target proteins, track their localization using fluorescence microscopy, followed by in vitro structure determination. To identify mammal-specific sperm proteins and understand their functions, we developed a visual proteomics workflow to directly address these challenges. Our in situ cryo-electron tomography and subtomogram averaging provided 6.0 Å resolution reconstructions of axonemal microtubules and their associated proteins. The well-resolved secondary and tertiary structures allowed us to computationally match, in an unbiased manner, novel densities in our 3D reconstruction maps with 21,615 AlphaFold2-predicted protein models of the mouse proteome. We identified Tektin 5, CCDC105 and SPACA9 as novel microtubule inner proteins that form an extensive network crosslinking the lumen of microtubule and existing proteins. Additional biochemical and mass spectrometry analyses helped validate potential candidates. The novel axonemal sperm structures identified by this approach form an extensive interaction network within the lumen of microtubules, suggesting they have a role in the mechanical and elastic properties of the microtubule filaments required for the vigorous beating motions of flagella.
A Continuous Fault Countermeasure for AES Providing a Constant Error Detection Rate (2010)

Many implementations of cryptographic algorithms have shown to be susceptible to fault attacks. To detect manipulations, countermeasures have been proposed. In the case of AES, most countermeasures deal with the non-linear and the linear part separately, which either leaves vulnerable points at the interconnections or causes different error detection rates across the algorithm. In this paper, we present a way to achieve a constant error detection rate throughout the whole algorithm. The use of extended AN+B codes together with redundant table lookups allows to construct a countermeasure that provides complete protection against adversaries who are able to inject faults of byte size or less. The same holds for adversaries who skip an instruction. Other adversaries are detected with a probability of more than 99%.
Novel Methodology to Investigate the Effect of Radiation Dose to Heart Substructures on Overall Survival (2020)

The maximum dose to the combined cardiac region encompassing the right atrium, right coronary artery, and ascending aorta was found to have the greatest effect on patient survival. A maximum equivalent dose in 2-Gy fractions of 23 Gy was identified for consideration as a dose limit in future studies.
Data from: Quantitative comparisons of block thresholds and onset responses for charge-balanced kilohertz frequency waveforms (2020)

Objective: There is growing interest in delivering kilohertz frequency (KHF) electrical signals to block conduction in peripheral nerves for treatment of various diseases. Previous studies used different KHF waveforms to achieve block, and it remains unclear how waveform affects nerve block parameters. Approach: We quantified the effects of waveform on KHF block of the rat tibial nerve in vivo and in computational models. We compared block thresholds and onset responses across current-controlled sinusoids and charge-balanced rectangular waveforms with different asymmetries and duty cycles. Main Results: Sine waves had higher block thresholds than square waves, but used less power at block threshold. Block threshold had an inverse relationship with duty cycle of rectangular waveforms irrespective of waveform asymmetry. Computational model results were consistent with relationships measured in vivo, although the models underestimated the effect of duty cycle on increasing thresholds. The axonal membrane substantially filtered waveforms, the filter transfer function was strikingly similar across waveforms, and filtering resulted in post-filtered rms block thresholds that were approximately constant across waveforms in silico and in vivo. Onset response was not consistently affected by waveform shape, but onset was smaller at amplitudes well above block threshold. Therefore, waveforms with lower block thresholds (e.g., sine waves or square waves) could be more readily increased to higher amplitudes relative to block threshold to reduce onset response. We also observed a reduction in onset responses across consecutive trials after initial application of supra-block threshold amplitudes. Significance: Waveform had substantial effects on block thresholds, and the amplitude relative to block threshold had substantial effects on onset response. These data inform choice of waveform in subsequent studies and clinical applications, enhance effective use of block in therapeutic applications, and facilitate the design of parameters that achieve block with minimal onset responses.
Phosphorothioate modified oligonucleotide–protein interactions (2020)

Antisense oligonucleotides (ASOs) interact with target RNAs via hybridization to modulate gene expression through different mechanisms. ASO therapeutics are chemically modified and include phosphorothioate (PS) backbone modifications and different ribose and base modifications to improve pharmacological properties. Modified PS ASOs display better binding affinity to the target RNAs and increased binding to proteins. Moreover, PS ASO protein interactions can affect many aspects of their performance, including distribution and tissue delivery, cellular uptake, intracellular trafficking, potency and toxicity. In this review, we summarize recent progress in understanding PS ASO protein interactions, highlighting the proteins with which PS ASOs interact, the influence of PS ASO protein interactions on ASO performance, and the structure activity relationships of PS ASO modification and protein interactions. A detailed understanding of these interactions can aid in the design of safer and more potent ASO drugs, as illustrated by recent findings that altering ASO chemical modifications dramatically improves therapeutic index.
Water-resistant, hydrophobic UVB-shielding films from water-borne nanostructured latexes (2013)

Hydrophobic structured latexes prepared by multi-step emulsion polymerization provide the means for the preparation of films with good mechanical properties without the use of coalescing aids. We demonstrate using the UVB-filter 2-ethylhexyl-4-methoxycinnamate (EMC) that a lipophilic substance can be entrapped in the core–shell latexes during their synthesis. Three VOC-free latexes were prepared using the amino acid based surfactant sodium lauroylsarcosinate as an emulsifier containing 0.7, 1.4, 1.9% w/w EMC corresponding to 2.0, 3.6, 4.9% w/w of the UVB-filter in the cast films. The non-loaded latex and its respective film were also prepared without using any coalescing agent. EMC was found to be stable under the polymerization conditions. All the latexes presented similar hydrodynamic diameters regardless of their cargo content. Dynamic mechanical analysis evidenced the compartmentalized structure of the films and a decrease of the glass transition temperatures corresponding to each compartment with increasing the EMC content. Tensile strength experiments manifested smaller stress at break and enlarged strain at break values for increasing the EMC content. All the films loaded with the UVB-filter were found to completely block UVB radiation even after a one month-long soaking in water and a four day long sun exposure. This opens a novel way of skin and wound protection against UVB radiation.
eOS - the dawn of the resource economy (2005)

Summary form only given. We believe that achieving the benefits of a resource economy, which supports the execution of services wherever and whenever is most convenient, cost-effective, and trustworthy, represents the next big computer systems research opportunity. That is, the emphasis in the operating research community should move away from extracting a few more percentage points of speed from individual computing resources, and focus instead on how to size, provision, and manage those resources to serve the needs of a rapidly diversifying set of services. HP Laboratories are embarking on a major endeavor to pursue this, and are actively seeking research partners to collaborate with us.
Kinematics of the Low-Level Jet (1968)

Winds and vertical velocities are examined in ten southerly low-level jets and then averaged in coordinate systems centered on the jet. The jet at 0600 CST is strongly supergeostrophic but is reflected in both geostrophic and ageostrophic components of the wind. Air is typically rising downstream from the wind maximum and sinking just upstream from the jet core. This orientation of vertical velocities provides a possible explanation for the high frequency of nocturnal thunderstorms in the midwest.
Short circuit localization on integrated circuits using magnetic microscopy techniques coupled to simulations (2009)

International audience
Elucidating the Immune-Related Mechanisms by Which Probiotic Strain Lactobacillus casei BL23 Displays Anti-tumoral Properties (2019)

We have recently described antitumor properties of <i>Lactobacillus casei</i> BL23 strain in both a mouse allograft model of human papilloma virus (HPV)-induced cancer and dimethylhydrazine-associated colorectal cancer. However, the mechanisms underlying these beneficial effects are still unknown. Interestingly, <i>in vitro</i> cellular models show that this bacterium is able to stimulate the production of high levels of IL-2. Because this cytokine has well-known antitumor properties, we decided to explore its role in the anti-cancer effects of BL23 using the HPV-induced cancer model. We found a negative correlation between IL-2 and tumor size confirming the necessity of IL-2 to protect from tumor development. Then, we blocked IL-2 synthesis using neutralizing monoclonal antibodies in mice that were challenged with lethal levels of tumor cells; this led to a significant reduction in the protective abilities of BL23. Next, we used a genetically modified strain of <i>Lactococcus lactis</i> to deliver exogenous IL-2 to the system, and in doing so, we were able to partially mimic the antitumor properties of BL23. Additionally, we showed the systemic role of T-cells in tumor protection through a negative correlation between tumor size and T-cells subpopulations and an increasement of BL23-specific local Foxp3 levels in tumor-bearing mice. Finally, we observed a negative correlation between tumor size and NK+ cells, but local recruitment of NK cells and cytotoxic activity appeared specific to BL23 treatment. Taken together, our data suggest that IL-2 signaling pathway plays an important role in the anti-tumoral effects of probiotic strain <i>L. casei</i> BL23. These results encourage further investigation in the use of probiotic strains for potential therapeutic applications to clinical practice, in particular for the treatment of colorectal cancer. Furthermore, our approach could be extended and applied to other potential beneficial microorganisms, such as gut microbiota, in order to better understand the crosstalk between microbes and the host.
Compiling issues for supercomputers (1988)

Accurate and fast methods for computing data dependencies are vital to the efficiency of vectorizing and parallelizing compilers. Program transformations employed by these compilers are effective only if dependencies are computed as accurately as possible. In this paper we consider two issues for supercomputer compilers. First, we discuss in detail exact and inexact tests for computing data dependencies and focus on the linearization scheme. We then discuss a program transformation call loop spreading which allows us to execute in parallel adjacent loops with interloop dependencies.
Online video tracking using collaborative convolutional networks (2016)

Recently, convolutional neural network (CNN) models have achieved great success in many vision tasks. However, few attempts have been made to explore CNN for online model-free object tracking without time-consuming offline training. In this paper, we propose an online convolutional network (OC-N) for visual object tracking. To make the network less dependent on labeled data, K-means is employed to learn multistage filter banks for hierarchical feature learning. To preserve more spatial information for tracking, down-sampling and pooling operations are eliminated, which enables our system more sensitive to spatial variations. A regression model is adopted as the output layer of OCN to predict the position changes of the target. To deal with the stability-plasticity dilemma, two OCNs with different update rates are integrated to construct an ensemble framework. Experiments on challenging benchmark video sequences demonstrate that the proposed tracker outperforms several state-of-the-art methods.
BaTiO3-LiF ceramics fired at low temperature. (1989)

Sintering temperature of BaTiO3 is reduced by addition of LiF, increasing the Ba/Ti ratio and decreasing the starting particle size of BaTiO3. Li and F are contained not only in BaTiO3 grains, but also in grain baundaries. The quantity of them decreased by increasing firing temperature, because of vaporizatin of LiF, and also is dependent on the Ba/Ti ratio which affects the reaction mechanism in firing process.
Supramolecular interactions in the solid state (2015)

In the last few decades, supramolecular chemistry has been at the forefront of chemical research, with the aim of understanding chemistry beyond the covalent bond. Since the long-range periodicity in crystals is a product of the directionally specific short-range intermolecular interactions that are responsible for molecular assembly, analysis of crystalline solids provides a primary means to investigate intermolecular interactions and recognition phenomena. This article discusses some areas of contemporary research involving supramolecular interactions in the solid state. The topics covered are: (1) an overview and historical review of halogen bonding; (2) exploring non-ambient conditions to investigate intermolecular interactions in crystals; (3) the role of intermolecular interactions in morphotropy, being the link between isostructurality and polymorphism; (4) strategic realisation of kinetic coordination polymers by exploiting multi-interactive linker molecules. The discussion touches upon many of the prerequisites for controlled preparation and characterization of crystalline materials.
Heat Shock Proteins Regulate Inflammation by Both Molecular and Network Cross-Reactivity (2005)

Heat shock proteins were initially identified as heterogeneous families of stress-induced proteins characterised by their chaperone activity [1]. Subsequently, they were identified as immunodominant antigens recognised by the host immune system following microbial infection [2] or during the course of autoimmune disease [3–6]. Recently, the role of heat shock proteins as endogenous activators of the innate and adaptive immune system has been unveiled [7]. In this chapter we discuss the relevance of heat shock proteins and their immune activities to the regulation of inflammation and autoimmune disease. We shall see that the regulatory activities of heat shock proteins on inflammation involve two types of cross-reactivity: molecular cross-reactivity exists between microbial and self-heat shock proteins and network cross-reactivity exists between different self-heat shock proteins.
Chemokine signaling in cancer-stroma communications (2021)

Cancer is a multi-faceted disease in which spontaneous mutation(s) in a cell leads to the growth and development of a malignant new organ that if left undisturbed will grow in size and lead to eventual death of the organism. During this process, multiple cell types are continuously releasing signaling molecules into the microenvironment, which results in a tangled web of communication that both attracts new cell types into and reshapes the tumor microenvironment as a whole. One prominent class of molecules, chemokines, bind to specific receptors and trigger directional, chemotactic movement in the receiving cell. Chemokines and their receptors have been demonstrated to be expressed by almost all cell types in the tumor microenvironment, including epithelial, immune, mesenchymal, endothelial, and other stromal cells. This results in chemokines playing multifaceted roles in facilitating context-dependent intercellular communications. Recent research has started to shed light on these ligands and receptors in a cancer-specific context, including cell-type specificity and drug targetability. In this review, we summarize the latest research with regards to chemokines in facilitating communication between different cell types in the tumor microenvironment.
Identification of volatile compounds from fruits aroma and citrus essential oils and their effect on oviposition of Ceratitis capitata (Diptera: Tephritidae) (2023)

Ceratitis capitata (Wiedemann), also known as the Mediterranean fruit fly, is one of the most serious pests for several fresh fruit commodities causing extensive fruit losses worldwide. The response of C. capitata adults to fruit and nonfruit volatiles has been extensively studied. However, the linkage between fruit volatiles and the female ovipositional choice has not been fully elucidated. The present study focused on identifying the volatile organic compounds emitted by detached intact fresh fruits (oranges, lemons, bergamots, and apples) and citrus essential oils and evaluate their effect on Mediterranean fruit fly oviposition. There were more than 130 and 45 volatiles compounds detected in fruits odors and citrus essential oils, respectively. The volatile profile of fruits was dominated either from terpenes and terpenoids or from esters of butanoic, hexanoic, and octanoic acids while limonene was by far the most abundant compound in all citrus essential oils. Oviposition of C. capitata was strongly affected by volatiles emanated from both intact fruit and the citrus essential oils. Regarding the volatiles of the intact fruits, the odor of sweet orange elicited strong oviposition responses to females, while bergamot had the least stimulatory effect on oviposition. Bergamot oil also elicited the least oviposition stimulation compared to sweet orange and lemon essential oils. Our discussion elaborates on the role of fruit volatiles on host finding behavior and fruit susceptibility to C. capitata infestation and includes possible practical implication of the above findings.
Carcinoid Tumors of the Extrahepatic Bile Ducts (2000)

The authors report seven patients with carcinoid tumors of the extrahepatic bile ducts (EHBDs). All patients were women, with an average age at diagnosis of 49.8 years (range, 37-67 yrs). The most common presenting symptom was painless jaundice with or without pruritus. Although one patient had peptic ulcer disease before the onset of obstructive jaundice, none had systemic endocrine manifestations. These neoplasms were most often located in the common bile duct. Grossly, the carcinoid tumors were usually nodular and poorly demarcated, and ranged from 1.1 to 2.7 cm in size. Only one of the neoplasms was polypoid. Microscopically, the tumors had a trabecular or nesting pattern with occasional tubule formation, and were composed of relatively small cells with granular chromatin. All of the neoplasms expressed chromogranin and two expressed synaptophysin. Three expressed serotonin and two of the three were also immunoreactive for pancreatic polypeptide or somatostatin. Two tumors were focally positive for gastrin and one of these two tumors was also positive for serotonin and pancreatic polypeptide. All seven carcinoid tumors showed no immunoreactivity for p53, and assays for p53 loss of heterozygosity analysis were negative in two, suggesting that p53 mutations do not play a role in the pathogenesis of EHBD carcinoids. A mutation in codon 12 of K-ras was found in one carcinoid tumor whereas two of two showed immunoreactivity for Dpc4 protein. In view of the small number of carcinoids studied, the importance of these findings in the pathogenesis of these tumors is unclear. Ultrastructural examination of three of the tumors revealed numerous membrane-bound, round neurosecretory granules. Clinically, these lesions had an indolent course. Even in the presence of lymph node metastases (noted in two patients), all of the patients remained disease free 2 to 11 years (average follow up, 6.6 yrs) after segmental resection or pancreaticoduodenectomy (Whipple's procedure). Because carcinoid tumors of the EHBD are of low malignant potential, they should be separated from the more common adenocarcinomas in this location.