gebhart/patrepeval huggingface dataset:
A multi‐pronged investigation into the effect of glucose starvation and culture duration on fed‐batch CHO cell culture (2015)

In this study, omics-based analysis tools were used to explore the effect of glucose starvation and culture duration on monoclonal antibody (mAb) production in fed-batch CHO cell culture to gain better insight into how these parameters can be controlled to ensure optimal mAb productivity and quality. Titer and N-glycosylation of mAbs, as well as proteomic signature and metabolic status of the production cells in the culture were assessed. We found that the impact of glucose starvation on the titer and N-glycosylation of mAbs was dependent on the degree of starvation during early stationary phase of the fed-batch culture. Higher degree of glucose starvation reduced intracellular concentrations of UDP-GlcNAc and UDP-GalNAc, but increased the levels of UDP-Glc and UDP-Gal. Increased GlcNAc and Gal occupancy correlated well with increased degree of glucose starvation, which can be attributed to the interplay between the dilution effect associated with change in specific productivity of mAbs and the changed nucleotide sugar metabolism. Herein, we also show and discuss that increased cell culture duration negatively affect the maturation of glycans. In addition, comparative proteomics analysis of cells was conducted to observe differences in protein abundance between early growth and early stationary phases. Generally higher expression of proteins involved in regulating cellular metabolism, extracellular matrix, apoptosis, protein secretion and glycosylation was found in early stationary phase. These analyses offered a systematic view of the intrinsic properties of these cells and allowed us to explore the root causes correlating culture duration with variations in the productivity and glycosylation quality of monoclonal antibodies produced with CHO cells.
Mapping the Proteoform Landscape of Five Human Tissues (2022)

A functional understanding of the human body requires structure-function studies of proteins at scale. The chemical structure of proteins is controlled at the transcriptional, translational, and post-translational levels, creating a variety of products with modulated functions within the cell. The term “proteoform” encapsulates this complexity at the level of chemical composition. Comprehensive mapping of the proteoform landscape in human tissues necessitates analytical techniques with increased sensitivity and depth of coverage. Here, we took a top-down proteomics approach, combining data generated using capillary zone electrophoresis (CZE) and nanoflow reversed-phase liquid chromatography (RPLC) hyphenated to mass spectrometry to identify and characterize proteoforms from human lung, heart, spleen, small intestine, and kidney. CZE and RPLC provided complementary post-translational modification (PTM) and proteoform selectivity, thereby enhancing overall proteome coverage when used in combination. Of the 11,466 proteoforms identified in this study, 7,373 (64%) were not reported previously. Large differences in protein- and proteoform-level were readily quantified, with initial inferences about proteoform biology operative in the analyzed organs. Differential proteoform regulation of defensins, glutathione transferases, and sarcomeric proteins across tissues generate hypotheses about how they function and are regulated in human health and disease.
Organogenesis of Kidney and Endocrine Pancreas (2007)

Growing new organs in situ by implanting developing animal organ primordia (organogenesis) represents a novel solution to the problem of limited supply for human donor organs that offers advantages relative to transplanting embryonic stem (ES) cells or xenotransplantation of developed organs. Successful transplantation of organ primordia depends on obtaining them at defined windows during embryonic development within which the risk of teratogenicity is eliminated, growth potential is maximized, and immunogenicity is reduced. We and others have shown that renal primordia transplanted into the mesentery undergo differentiation and growth, become vascularized by blood vessels of host origin, exhibit excretory function and support life in otherwise anephric hosts. Renal primordia can be transplanted across isogeneic, allogeneic or xenogeneic barriers. Pancreatic primordia can be transplanted across the same barriers undergo growth, and differentiation of endocrine components only and secrete insulin in a physiological manner following mesenteric placement. Insulin-secreting cells originating from embryonic day (E) 28 (E28) pig pancreatic primordia transplanted into the mesentery of streptozotocin-diabetic (type 1) Lewis rats or ZDF diabetic (type 2) rats or STZ-diabetic rhesus macaques engraft without the need for host immune-suppression. Our findings in diabetic macaques represent the first steps in the opening of a window for a novel treatment of diabetes in humans.
On the Capability of QoE Improvement Based on the Adjustment of RLC Parameters (2020)

The constant evolution in mobile communications networks have led operators to seek new techniques to optimize their mobile networks with the objective of satisfying the expectations of the users. In this way, traditional optimization techniques based on improving radio indicators, have given way to new techniques based on improving the quality of experience (QoE) perceived by users. This paper is focused on analyzing the impact of the adjustment of radio link control (RLC) layer configuration parameters on the QoE perceived by the users of two different types of services. Firstly, an evaluation of the QoE experienced by the user of a real-time video streaming service with respect to the transmission buffer size of the RLC layer in unacknowledged mode (UM) has been carried out. Secondly, the QoE perceived by the user of a file transfer service in relation to the variation of the configuration parameters of the RLC layer in acknowledged mode (AM) has been evaluated. The study, which has been carried out in a simulated cellular environment, has been performed for different system bandwidth values, thus proving the relationship between the QoE perceived by the users, the optimal RLC configuration parameters values and the available bandwidth.
PPARβ regulates vitamin A metabolism-related gene expression in hepatic stellate cells undergoing activation (2003)

Activation of cultured hepatic stellate cells correlated with an enhanced expression of proteins involved in uptake and storage of fatty acids (FA translocase CD36, Acyl-CoA synthetase 2) and retinol (cellular retinol binding protein type I, CRBP-I; lecithin:retinol acyltransferases, LRAT). The increased expression of CRBP-I and LRAT during hepatic stellate cells activation, both involved in retinol esterification, was in contrast with the simultaneous depletion of their typical lipid-vitamin A (vitA) reserves. Since hepatic stellate cells express high levels of peroxisome proliferator activated receptor beta (PPARbeta), which become further induced during transition into the activated phenotype, we investigated the potential role of PPARbeta in the regulation of these changes. Administration of L165041, a PPARbeta-specific agonist, further induced the expression of CD36, B-FABP, CRBP-I, and LRAT, whereas their expression was inhibited by antisense PPARbeta mRNA. PPARbeta-RXR dimers bound to CRBP-I promoter sequences. Our observations suggest that PPARbeta regulates the expression of these genes, and thus could play an important role in vitA storage. In vivo, we observed a striking association between the enhanced expression of PPARbeta and CRBP-I in activated myofibroblast-like hepatic stellate cells and the manifestation of vitA autofluorescent droplets in the fibrotic septa after injury with CCl4 or CCl4 in combination with retinol.
1012 Effect of annealing temperature on the texture in wire of Ti-Nb-Al superelastic alloy (2008)

Texture of wire of Ti-24mok%Nb-3mol%Al biomedical shape memory alloy was investigated by electron backscatter diffraction pattern (EBSP) and X-ray diffraction (XRD) analysis. The alloy is parent β(bcc) phase at room temperature and exhibits superelasticity. An ingot was fabricated by Ar arc-melting and homogenized at 1273K for 7.2ks in vacuum and then quenched into water. The ingot was cold-drawn with a reduction in cross-section about 90% and a wire with a cross-sectional diameter of 1mm was successfully obtained. The solution-treatments at 873K, 973K, 1073K, and 1173K for 3.6ks were made to evaluate the effect of annealing temperature on the recrystallization texture. The fiber texture of <102>_β was formed in the wire which was solution-treated at 873K and as-rolled one. The texture was broaden and approached to the <110>_β fiber texture with the increase in the solution-treatment temperature. The wire is used in a bending mode in the practical use and superelastic deformation in tension and compression along the wire-direction is necessary. The maximum transformation strains of the β-α"(C-orthorhombic) thermoelastic martensitic transformation are +2.6% and -2.1% along <102>_β whereas they are +2.9% and -0.8% in the <110>_β fiber texture. <102>_β texture is, therefore, favorable for the wire material in this alloy.
Carbon Nanotube Sensor Passivation Mitigates Inflammatory Response in Microglia (2020)

Non-covalent functionalization of single-walled carbon nanotubes (SWCNTs) has enabled advances in biomolecule imaging. In particular, modification of SWCNTs with select sequences of single-stranded DNA (ssDNA) produces near infrared optically active sensors for neurotransmitters such as dopamine, enabling high spatiotemporally resolved optical recording of synaptic and extrasynaptic signaling. However, the carbon lattice surface of SWCNT induces activation of the innate immune system, leading to an inflammatory response. Activation of microglia, the brain’s resident immune cells, is of particular relevance to imaging neuromodulation. Here, we show that non-covalent ssDNA-SWCNT nanosensor passivation with a PEGylated phospholipid can mitigate microglial activation while maintaining the nanosensor’s response towards dopamine. To do so, we screen a candidate library of PEGylated biomolecules, nonionic surfactants, and block copolymers against their ability to mitigate the microglial immune response as measured by transcriptomic analysis. We find that PEGylated phospholipids are capable of adsorption to ssDNA-SWCNTs without significant ssDNA displacement, with moderate reduction in nonspecific protein adsorption. These trends are recapitulated by a reduction in inflammatory response of SIM-A9 microglial cells, marked by lowered expression of cytokines CXCL2 and IL-6, mitigated morphological change, and decreased cytotoxicity. Taken together, these results suggest noncovalent passivation improves biocompatibility of DNA-SWNCT nanosensors and provides the groundwork for implementing similar passivation methods for other optical probes of this class.
Nucleotide Regulation of Growth Hormone-Releasing Factor Binding to Rat Pituitary Receptors* (1989)

The specific binding of a GRF radioligand, [His1,125I-Tyr10,Nle27]hGRF-1-32NH2, to rat pituitary homogenates is reduced by the addition of GTP and its nonhydrolyzable analogs 5'-guanylylimidodiphosphate (GppNHp) and guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S). GDP and cAMP had no effect while the nonhydrolyzable ATP analogs 5'-adenylylimidodiphosphate and adenosine 5'-O-(3-thiotriphosphate) did elicit a significant reduction in GRF binding. The effect of GppNHp was half-maximal at 0.2 microM, and the maximum inhibition achieved was 85%. The effect of 0.1 microM GppNHp on GRF competitive displacement experiments indicated a significant reduction in affinity for the ligand (Kd = 0.51 +/- 0.11 nM in the absence of GppNHp and 2.1 +/- 1.1 nM in its presence) without an effect on receptor number. The GRF radioligand dissociates slowly from its receptor (t1/2 = 250 +/- 50 min), but the addition of 0.1 microM GppNHp converts approximately half of the receptors present to a more rapidly dissociating form (t1/2 = 9 +/- 10 min). These results are consistent with existing models for receptor-G-protein interactions, and thus, we conclude that transduction of the GRF response across the cell membrane involves a guanine nucleotide-binding protein, presumably Gs.
Learning a latent manifold of odor representations from neural responses in piriform cortex (2018)

A major difficulty in studying the neural mechanisms underlying olfactory perception is the lack of obvious structure in the relationship between odorants and the neural activity patterns they elicit. Here we use odor-evoked responses in piriform cortex to identify a latent manifold specifying latent distance relationships between olfactory stimuli. Our approach is based on the Gaussian process latent variable model, and seeks to map odorants to points in a low-dimensional embedding space, where distances between points in the embedding space relate to the similarity of population responses they elicit. The model is specified by an explicit continuous mapping from a latent embedding space to the space of high-dimensional neural population firing rates via nonlinear tuning curves, each parametrized by a Gaussian process. Population responses are then generated by the addition of correlated, odor-dependent Gaussian noise. We fit this model to large-scale calcium fluorescence imaging measurements of population activity in layers 2 and 3 of mouse piriform cortex following the presentation of a diverse set of odorants. The model identifies a low-dimensional embedding of each odor, and a smooth tuning curve over the latent embedding space that accurately captures each neuron's response to different odorants. The model captures both signal and noise correlations across more than 500 neurons. We validate the model using a cross-validation analysis known as co-smoothing to show that the model can accurately predict the responses of a population of held-out neurons to test odorants.
LEMAC: LTF-EPFL Miniature Atomic Clock : current status (2022)

SummaryWe present the latest development of our in-house miniature atomic clock (LEMAC). The clock scheme is based on the continuous wave (CW) optical-microwave double resonance (DR) interrogation. Significant efforts have been put in a newly designed miniature microwave loop-gap resonator (LGR), laser locking scheme, and integrated Physics Package design. In its final state, our clock is expected to show a short-term stability performance of &#x03C3;<inf>y</inf>(&#x03C4;)&#x003C;1 &#x00D7; 10<sup>&#x2212;11</sup> &#x03C4;<sup>&#x2212;1/2</sup> in terms of Allan deviation, for an insulated (magnetic and thermal) resonator volume &#x003C;20 cm<sup>3</sup>.
Blockchain Timestamping Architecture Version 6 (BTAv6) (2017)

A method for timestamping, anchoring and certification of a virtually unlimited amount of data in one or more blockchains, focusing on scalability and cost-effectiveness while ensuring existence, integrity and ownership by using cryptographic proofs that are independently verifiable by anyone in the world without disclosure of the original data and without the intervention of the certifying party.
Analysis of dense cellular networks with stretched exponential path loss (2017)

Distance-based attenuation is a critical aspect of wireless communications. As opposed to the ubiquitous power-law path loss model, this paper proposes a stretched exponential path loss model that is suitable for short-range communication. In this model, the signal power attenuates over a distance r as e <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-αrβ</sup> , where α, β are tunable parameters. We integrate this path loss model into a downlink cellular network with base stations modeled by a Poisson point process, and derive expressions for the coverage probability and area spectral efficiency. Although the most general result for coverage probability has a double integral, several special cases are given where the coverage probability has a compact or even closed form. We show that coverage probability collapses to zero for high base station densities. We next prove that the area spectral efficiency is non-decreasing with the base station density and converges to a constant for high densities.
CONTRIBUTION OF NEUROGENIC AND MYOGENIC FACTORS TO THE CONTRACTILE ACTIVITY OF THE GUINEA‐PIG DISTAL COLON IN VIVO AND <i>IN VITRO</i> (1985)

The response of the guinea-pig distal colon to distension and drugs expected to interfere with neural control of contractile activity were investigated in urethane anaesthetized animals and compared to results obtained in the isolated preparation. Under urethane anaesthesia bout 50% of the unloaded preparations had no detectable contractile activity. However these preparations contracted in response to topical acetylcholine. Saline distension induced the appearance of a phasic contractile activity in 'quiescent' preparations and enhanced amplitude of contractions in previously active ones. Atropine (1 mg/kg i.v.) reduced tone and transiently suppressed phasic contractile activity of the distal colon. When phasic contractile activity resumed a second dose of atropine had no further inhibitory effect. Topical physostigmine (20 micrograms in 0.1 ml) produced a marked and long lasting increase in tone paralleled by a marked enhancement in amplitude of the phasic contractile activity. These excitatory effects of topical physostigmine were suppressed by intravenous atropine (1 mg/kg). Hexamethonium (20 mg/kg i.v.) produced a sudden and transient increase in tone and suppressed DMPP (0.1 mg/kg i.v.) but not noradrenaline (2 micrograms/kg i.v.) induced relaxations. Propranolol (2 mg/kg i.v.) or phentolamine (0.5 mg/kg i.v.) transiently increased tone of the guinea-pig distal colon and suppressed noradrenaline induced relaxations. DMPP induced relaxations were reduced by propranolol plus phentolamine. Topical tetrodotoxin (50 micrograms in 0.1 ml) had an overall slight excitatory effect on phasic contractile activity of the in vivo preparation. The effects of i.v. atropine, hexamethonium, phentolamine or propranolol on tone and spontaneous activity were prevented by pretreatment with tetrodotoxin. Isolated segments of guinea-pig distal colon exhibited a fairly regular spontaneous phasic contractile activity whose amplitude was increased by stretching of the preparation. Atropine (3 microM) produced a transient inhibition while hexamethonium (40 microM) had no effect on spontaneous contractile activity. Tetrodotoxin (0.5 microM) had both inhibitory and excitatory effects on tone and spontaneous activity of the preparation. At steady state amplitude of contractions was enhanced (15-30% increase) by tetrodotoxin. DMPP (1-100 microM) first induced a phasic contraction and then suppressed transiently the spontaneous activity of the isolated preparation.(ABSTRACT TRUNCATED AT 400 WORDS)
Autophagic flux blockage by accumulation of weakly basic tenovins leads to elimination of B-Raf mutant tumour cells that survive vemurafenib (2018)

Tenovin-6 is the most studied member of a family of small molecules with antitumour activity in vivo. Previously, it has been determined that part of the effects of tenovin-6 associate with its ability to inhibit SirT1 and activate p53. However, tenovin-6 has also been shown to modulate autophagic flux. Here we show that blockage of autophagic flux occurs in a variety of cell lines in response to certain tenovins, that autophagy blockage occurs regardless of the effect of tenovins on SirT1 or p53, and that this blockage is dependent on the aliphatic tertiary amine side chain of these molecules. Additionally, we evaluate the contribution of this tertiary amine to the elimination of proliferating melanoma cells in culture. We also demonstrate that the presence of the tertiary amine is sufficient to lead to death of tumour cells arrested in G1 phase following vemurafenib treatment. We conclude that blockage of autophagic flux by tenovins is necessary to eliminate melanoma cells that survive B-Raf inhibition and achieve total tumour cell kill and that autophagy blockage can be achieved at a lower concentration than by chloroquine. This observation is of great relevance as relapse and resistance are frequently observed in cancer patients treated with B-Raf inhibitors.
A three-dimensional model of the gas cell atomic frequency standard (1989)

Initial calculations from a three-dimensional (3-D) model of the gas cell atomic frequency standard are discussed. In particular, a recent suggestion that the short-term stability of a gas cell standard might be improved by varying the microwave power is considered. Though the authors' results generally support the previous conclusion, they show that the degree of sensitivity is less than that predicted by one-dimensional (1-D) gas-cell frequency-standard model. This difference in predicted sensitivity is a manifestation of the three-dimensional model's more accurate treatment of the clock-cavity microwave field distribution. The more accurate treatment is highlighted by the three-dimensional model's determination of isoefficiency contours (contours showing spatial regions in the clock cavity that have equal efficiency for producing clock signal), and noting their spatial dependence on microwave power.
Achieving Ultra High Freshness in Real-Time Monitoring and Decision Making with Incremental Decoding (2021)

Real-time monitoring and remote control of stochastic systems have attracted considerable attention due to their potential in task-oriented communications and industrial Internet of Things (IIoT). How to achieve ultra high-freshness in real-time monitoring and remote control becomes a challenging problem. In this paper, we are interested in the freshness oriented source coding with incremental decoding. This is contrast to con-ventional source encoding/decoding, in which a random sample is estimated after its entire codeword is received. Incremental decoding, however, allows the real-time estimation of a random sample once a new bit or channel coding block is decoded in the physical layer. Its source codebook is then optimized, based on which we further conceive a real-time decision policy. Our policies minimize the average mean square error (MSE) or decision cost by judiciously designed codebook for source encoding. Numerical results show that the incremental decoding substantially reduces the MSE and decision cost in real-time monitoring.
Physiological function of water channels as affected by salinity in roots of paprika pepper (1999)

The sap flow (Jv) and the osmotic pressure‐dependent hydraulic conductance (L 0 ) of detached exuding root systems from paprika pepper plants (cv. Albar) were measured. Plants stressed with NaCl (30 m M ) and with six times the macronutrients of the Hoagland nutrient solution (6×HNS) were compared with controls grown in complete Hoagland nutrient solution. Jv of +NaCl and +6×HNS plants decreased markedly, but recovered to values similar to those of controls after removal of the treatments. Hydraulic conductance L 0 was always less in NaCl plants than in controls and 6×HNS. A total increase in the ion concentration of the xylem (except Na + and Cl − ) was observed with both treatments. In control and 6×HNS plants, HgCl 2 treatment (50 μ M ) caused a sharp decline in L 0 to values similar to those of NaCl‐stressed roots, but were restored by treating with 5 m M dithiothreitol (DTT). However, in NaCl roots only a slight effect of Hg 2+ and DTT was observed. In each treatment, there was no difference in the flux of K + into the xylem after HgCl 2 and DTT application. The results suggest that NaCl decreased L 0 of the roots by reducing either the activity or abundance of Hg‐sensitive water channels. The putative reduction in water‐channel function of NaCl‐treated plants did not seem to be due to the osmotic effect.