gebhart/patrepeval huggingface dataset:
Signaling Node at TSC2 S1365 Potently Regulates T-Cell Differentiation and Improves Adoptive Cellular Cancer Therapy (2022)

Abstract MTORC1 integrates signaling from the immune microenvironment to regulate T-cell activation, differentiation, and function. TSC2 in the tuberous sclerosis complex potently regulates mTORC1 activation. CD8+ T-cells lacking TSC2 have constitutively enhanced mTORC1 activity and generate potent effector T cells; however sustained mTORC1 activation prevents generation of long-lived memory CD8+ T-cells. Here we show manipulating TSC2 at Ser1365 potently regulates activated but not basal mTORC1 signaling in T cells. Unlike non-stimulated TSC2 knockout cells, CD8+ T-cells expressing mutant TSC2-S1365A (SA) have normal basal mTORC1 activity. PKC and T-cell Receptor (TCR) stimulation induces TSC2 S1365 phosphorylation and preventing this with the SA mutation markedly increases mTORC1 activation and T-cell effector function. Consequently, CD8+ SA T-cells display greater effector responses while retaining their capacity to become long-lived memory T-cells. CD8+ SA T-cells also display enhanced effector function under hypoxic and acidic conditions. In murine and human solid-tumor models, CD8+ SA T-cells used as adoptive cell therapy have greater anti-tumor immunity than WT CD8+ T-cells. These findings reveal an upstream mechanism to regulate mTORC1 activity in T-cells. The TSC2-SA mutation enhances both T-cell effector function and long-term persistence/memory formation, supporting a novel approach to engineer better CAR-T cells to treat cancer.
Antiviral effect of α-glucosidase inhibitors on viral morphogenesis and binding properties of hepatitis C virus-like particles (2006)

Hepatitis C virus (HCV) infections are a major public-health concern. New antiviral drugs are needed urgently to complement and improve the efficacy of current chemotherapies. The morphogenesis of HCV represents an interesting, and still unexploited, novel molecular target. alpha-Glucosidase inhibitors derived from the glucose analogue deoxynojirimycin (DNJ) inhibit viral morphogenesis in cellulo via perturbation of the N-glycosylation pathway and hence the misfolding of viral glycoproteins that depend on certain N-glycans for correct folding. Due to the heavy N-glycosylation of HCV glycoproteins, it was hypothesized that such inhibitors would also affect HCV morphogenesis. To study the effect of alpha-glucosidase inhibitors on viral morphogenesis and binding properties, HCV virus-like particles (VLPs) were produced by using baculovirus loaded with HCV structural-protein genes. Here, it is demonstrated that, in the presence of these alpha-glucosidase inhibitors, viral glycoproteins synthesized and retained in the endoplasmic reticulum (i) contain unprocessed, triglucosylated N-glycans, (ii) are impaired in their interaction with calnexin and (iii) are at least partially misfolded. Moreover, it is shown that, although the production of VLPs is not affected by alpha-glucosidase inhibitors, these VLPs contain unprocessed, triglucosylated N-glycans and potentially misfolded glycoproteins. Finally, it is demonstrated that VLPs produced in the presence of alpha-glucosidase inhibitors have impaired binding properties to hepatoma cells. The inhibitors of morphogenesis studied here target steps of the HCV viral cycle that may prevent or delay viral resistance. These alpha-glucosidase inhibitors may prove to be useful molecules to fight HCV infection in combination protocols.
Sense Finger Dynamics in a ∑∆ Force-Feedback Gyroscope (2000)

This paper presents a gyroscope that uses ZA force-feedback for closed-loop Coriolis-acceleration sensing and l-bit digital output. The noise floor is approximately 3"lsldHz at atmospheric pressure. The effect of capacitive sense-finger resonance on the XA feedback loop is analyzed. In order to minimize quantization noise the resonant frequency of the sense fingers should be designed above J;/4, if the sense and feedback electrodes are separate. If the same electrodes are used for sensing and feedback, the finger resonance should be designed near f/6, where L. is the sampling frequency.
ABSTRACTS: 2 Mouse PAI‐1 promotes placentation by increasing foetal and maternal angiogenesis (2008)

Introduction: Murine placentation is associated with trophoblast cells invasion of the maternal endometrium and extensive maternal and foetal angiogenesis. Both processes involve proteases‐dependent extracellular matrix remodelling. Among the protease inhibitors, plasminogen activator inhibitor‐1 (PAI‐1) is transiently produced by spongiotrophoblasts and trophoblast giant cells at days 10.5‐11.5 day post‐coitum (dpc). Although accumulating evidence demonstrates the key role of PA‐1 in pathological angiogenesis, its function during placental vascularisation remains to be elucidated. PAI‐1 knockout mice are fertile and the litter sizes are normal. We have therefore analysed the consequence of PAI‐1 deficiency on murine placentation. Material and Methods: We have studied the possible role of PAI‐1 by quantitating the placental vessel density, the relative thickness of the labyrinth, decidua and spongiotrophoblast at day 10.5, 12.5 and 14.5 dpc in mice deficient for PAI‐1 or in control mice. An original method of computer‐assisted image analysis allowed us to quantify alterations of several placental compartments identified with specific monoclonal antibodies (keratin, desmin, fibrinogen and MECA‐32). To investigate the differentially expressed genes, we performed laser capture microdissection (LCM), followed by genome‐wide expression profiling using high‐density oligonucleotides microarray analysis (GeneChip Mouse Genome 430 2.0 Array, Affymetrix). Data were analysed using Ingenuity Pathways Analysis (Ingenuity Systems ® , http://www.ingenuity.com ). Results: At 10.5 and 12.5 dpc, an abnormal placental morphology was observed in both labyrinth and spongiotrophoblast layers in PAI‐1‐/‐ mice. Lack of PAI‐1 resulted in a transient decreased maternal and fetal vascularisation of the placenta that caused (1) an enhancement in the decidua/labyrinth and labyrinth/spongiotrophoblast thickness ratios, (2) a significant increase of trophoblast density. Normalization of placental morphology occurred by day 14.5 dpc in PAI‐1 deficient mice. Statistical analysis of microarrays revealed 706 genes differentially expressed between PAI‐1 deficient and normal mice in the labyrinth zone at 10.5 dpc. At 14.5 dpc, only 205 genes are differentially expressed. Using Ingenuity Pathways Analysis, most of those genes were found to be associated to lipid metabolism, cellular growth and proliferation. Conclusion: Despite a transient PAI‐1 requirement for optimal placental angiogenesis, this gene does not appear to be essential for trophoblast invasion and placentation.
Fabrication of Current Collectors and Binder‐Free Electrodes on Separators Used in Lithium‐Ion Batteries (2020)

Abstract We report the fabrication of a composite electrode through the deposition of electrode materials directly onto a separator to avoid the use of a metallic current collector. In addition to being an active electrode material, this method employs only graphene as both a carbon additive and a binder. A major achievement is the elimination of heavy and inactive current collector, harmful solvents, and resistive binder. The deposition of the composite film electrode was applied through the filtrated dispersion of a redox active material and graphene through a separator (Celgard), which is commonly used in battery. The electronic conductivity of LiFePO 4 /Celgard electrodes was ∼10 times higher than that of conventional electrodes spread onto an aluminum current collector. The electrochemical performances of LiFePO 4 /C (LFP) and Li 4 Ti 5 O 12 (LTO) half‐cells fabricated according to this process and a conventional method were compared. A clear improvement in the electrochemical performance for electrodes fabricated using the new method was observed, particularly at high C‐rates. LiFePO 4 /Celgard electrodes deliver specific capacities of up to 125 mAh.g −1 electrode corresponding to more than 6 times the gravimetric capacity of an LFP electrode coated on Al foil. A LiFePO 4 /Li 4 Ti 5 O 12 full cell made using film electrodes deposited on a Celgard membrane shows stable specific capacities during the cycling at various C‐rates and delivers a specific capacity of 106 mAh.g −1 electrode at a C/10 rate.
Die Steuerung des Stealth‐Effekts von Nanoträgern durch das Verständnis der Proteinkorona (2016)

Abstract In den letzten zehn Jahren haben polymere Nanoträger immer mehr Interesse und Verwendung in medizinischen Anwendungen gefunden. Besonders beim Einsatz als Wirkstoff‐Träger lassen sich mit Nanoträgern viele Hindernisse der medikamentösen Therapie überwinden. Ihre Anwendung wird jedoch durch die komplexe Zusammensetzung der Partikelabdeckung mit Blutproteinen (“Proteinkorona”) erschwert. Diese Proteinkorona macht Vorhersagen über die zelluläre Interaktion, Biodistribution und Toxizität nahezu unmöglich. Vor allem die unspezifische Aufnahme der Nanoträger ist ein wesentliches Hindernis bei der klinischen Anwendung. Dieser Kurzaufsatz gibt einen Überblick über unseren Kenntnisstand auf diesem Gebiet; der Fokus liegt dabei auf Oberflächenfunktionalisierungen, die die unspezifische Aufnahme reduzieren (“Stealth‐Effekt”). Erörtert werden auch Möglichkeiten zur weiteren Verbesserung von Nanoträgern.
Structure of the Flow Field of a Nonpremixed Gas Jet Flame in Cross-Flow (1997)

Experimental studies on nonpremixed turbulent flames in cross flow are necessary as the current analytical and numerical tools are unable to provide acceptable quantitative information about their complex flow fields. This study, which complements the results of a previous study by the authors on the flame structure in the stabilization region of a partially lifted turbulent diffussion flame in cross-flow (TDFCF), presents the measured turbulence quantities in the flow field of the same flame. Results include mean velocities in the cross-stream and spanwise directions, the vertical and horizontal components of fluctuating components of velocity, Reynolds stress, power spectra, and autocorrelations useful for developing and validating theoretical models of TDFCF in the moderate momentum flux ratio range
Rat and guinea pig pancreatic acini possess both VIP1and VIP2receptors, which mediate enzyme secretion (2000)

Pancreatic acini from most species possess vasoactive intestinal peptide (VIP) receptors. Recently, two subtypes of VIP receptors, VIP(1)-R and VIP(2)-R, were cloned. Which subtype exists on pancreatic acini or mediates secretion is unclear. To address this, we examined pancreatic acini from both rat and guinea pig. VIP(1)-R and VIP(2)-R mRNA were identified in dispersed acini from both species by Northern blot analysis and in rat by Southern blot analysis. With the use of the VIP(2)-R-selective ligand Ro-25-1553 in both species, inhibition of binding of (125)I-labeled VIP to acini showed a biphasic pattern with a high-affinity component (10%) and a second representing 90%. The VIP(1)-R-selective ligand, [Lys(15),Arg(16),Leu(27)]VIP-(1-7)-GRF-(8-27), gave a monophasic pattern. Binding of Ro-25-1553 was better fit by a two-site model. In both rat and guinea pig acini, the dose-response curve of Ro-25-1553 for stimulation of enzyme secretion was biphasic, with a high-affinity component of 10-15% of the maximal secretion and a low-affinity component accounting for 85-90%. At low concentrations (10 nM) of Ro-25-1553 and [Lys(15),Arg(16), Leu(27)]VIP-(1-7)-GRF(8-27), which only occupy VIP receptors, a 4-fold and a 56-fold increase in cAMP occurred, respectively. These results show that both VIP(1)-R and VIP(2)-R subtypes exist on pancreatic acini of rat and guinea pig, their activation stimulates enzyme secretion by a cAMP-mediated mechanism, and the effects of VIP are mediated 90% by activation of VIP(1)-R and 10% by VIP(2)-R. Because VIP has a high affinity for both VIP-R subtypes, its effect on pancreatic acini is mediated by two receptor subtypes, which will need to be considered in future studies of the action of VIP in the pancreas.
Expanding the biosynthetic repertoire of plant type III polyketide synthases by altering starter molecule specificity (2002)

Type III polyketide synthases (PKS) generate an array of natural products by condensing multiple acetyl units derived from malonyl-CoA to thioester-linked starter molecules covalently bound in the PKS active site. One strategy adopted by Nature for increasing the functional diversity of these biosynthetic enzymes involves modifying polyketide assembly by altering the preference for starter molecules. Chalcone synthase (CHS) is a ubiquitous plant PKS and the first type III PKS described functionally and structurally. Guided by the three-dimensional structure of CHS, Phe-215 and Phe-265, which are situated at the active site entrance, were targeted for site-directed mutagenesis to diversify CHS activity. The resulting mutants were screened against a panel of aliphatic and aromatic CoA-linked starter molecules to evaluate the degree of starter molecule specificity in CHS. Although wild-type CHS accepts a number of natural CoA thioesters, it does not use N-methylanthraniloyl-CoA as a substrate. Substitution of Phe-215 by serine yields a CHS mutant that preferentially accepts this CoA-thioester substrate to generate a novel alkaloid, namely N-methylanthraniloyltriacetic acid lactone. These results demonstrate that a point mutation in CHS dramatically shifts the molecular selectivity of this enzyme. This structure-based approach to metabolic redesign represents an initial step toward tailoring the biosynthetic activity of plant type III PKS.
Jensen's inequality (2008)

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Study on Crest Factor Controlled Multi-Tone Signal for Analog RF Circuit Testing (2020)

In this paper, we have examined two crest factor controlled multi-tone signal generation algorithms: modified Newman and Fibonacci sequence initial phase setting methods. We have found with simulation that the former can realize relatively wide crest factor control range but the waveform quality degrades as the crest factor increases, compared to the latter. These algorithms can be used, such as for effective test of the transmission characteristics of OFDM systems, where the frequency dependent nonlinearity cannot be ignored.
Modeling, Fault Detection, and Fault Isolation for Cold-gas Propulsion Systems (2022)

Cold-gas thrusters are a common choice for the propulsion system of smaller satellites. This paper studies the problem of modeling, fault detection, and fault isolation of a typical cold-gas thruster system. First, the laws of the conservation of mass, energy, and momentum are employed to develop a dynamical model of the thruster system. Then, the dominant sources of uncertainty affecting this model are investigated. Based on the developed model and the structure of uncertainties, a suitable fault-detection and isolation (FDI) technique is selected from the literature and is tailored to the problem at hand. The performance of the FDI technique applied to a cold-gas thruster system is assessed in common fault scenarios. It is shown that the proposed technique is able to robustly detect and isolate these common faults without triggering false positives due to uncertainties and disturbances.
Cluster of Asphaltene Nanoaggregates by DC Conductivity and Centrifugation (2014)

A model of the dominant molecular and stable colloidal structures of asphaltenes has been proposed, the Yen–Mullins model. The formation of clusters of asphaltene nanoaggregates in toluene was reported elsewhere to occur at a concentration of a few grams per liter with a cluster aggregation number of approximately 8 (Mullins, O. C. Energy Fuels 2010, 24, 2179−2207). Here, we measure the DC-conductivity signal of toluene as a function of asphaltene concentration obtaining support for the critical clustering concentration (CCC) of a roughly 1.7 g/L in toluene. In addition, the small change in the Stokes drag at the CCC indicates that the cluster aggregation number is small, less than 10. The temperature variation of the CCC is measured to be small and within error, suggesting that cluster formation is entropically driven. Centrifugation experiments were also performed on asphaltene–toluene solutions at different concentrations. These experiments confirmed that a significant change in asphaltene aggregation occurs in the concentration range of the CCC. The CCC values from centrifugation and DC-conductivity measurements are roughly the same. The centrifugation experiments confirm a cluster size of ∼5 nm corroborating the small aggregation number found in the DC-conductivity experiments. These results add to the growing body of literature validating the Yen–Mullins model.
What is the right addressing scheme for India? (2018)

Computer generated addresses are coming to your neighborhood because most places in the world do not have an assigned meaningful street address. In India, 80% of the addresses are written with respect to a landmark which typically lies between 50-1500 meters of the actual address; such addresses make geolocating very challenging. Accuracy in geolocation is critical for emergency services to navigate quickly to reach you and for logistics industries to improve on-time performance and efficient routing of the package coming to your house. In this paper, we explore suggested addressing schemes for India, to determine what use cases and potential technologies will have the best adoption and therefore, greatest impact.
CCAAT/ enhancer‐binding protein β activation by capsaicin contributes to the regulation of CYP1A1 expression, mediated by the aryl hydrocarbon receptor (2011)

Capsaicin alone weakly induced CYP1A1 expression, and 3-MC-induced CYP1A1 levels were suppressed by capsaicin. Activation of C/EBPβ and inhibition of 3-MC-induced AhR transactivation by capsaicin contributed to the suppression of CYP1A1 expression. Capsaicin has a potential chemopreventive effect through inhibiting induction of CYP1A1 by poly aryl hydrocarbons.
The Role of Regulatory Genes During Maize Domestication: Evidence From Nucleotide Polymorphism and Gene Expression (2008)

We investigated DNA sequence variation in 72 candidate genes in maize landraces and the wild ancestor of maize, teosinte. The candidate genes were chosen because they exhibit very low sequence diversity among maize inbreds and have sequence homology to known regulatory genes. We observed signatures of selection in 17 candidate genes, indicating that they were potential targets of artificial selection during domestication. In addition, 21 candidate genes were identified as potential targets of natural selection in teosinte. A comparison of the proportion of selected genes between our regulatory genes and genes unfiltered for their potential function (but also with very low sequence diversity among maize inbreds) provided some weak evidence that regulatory genes are overrepresented among selected genes. We detected no significant association between the positions of genes identified as potential targets of selection during domestication and quantitative trait loci (QTL) responsible for maize domestication traits. However, a subset of these genes, those identified by sequence homology as kinase/phosphatase genes, significantly cluster with the domestication QTL. We also analyzed expression profiles of genes in distinct maize tissues and observed that domestication genes are expressed on average at a significantly higher level than neutral genes in reproductive organs, including kernels.
Synthesis of SN30000, Tables S1-S4, and Figures S1-S6 from Pharmacokinetic/Pharmacodynamic Modeling Identifies SN30000 and SN29751 as Tirapazamine Analogues with Improved Tissue Penetration and Hypoxic Cell Killing in Tumors (2023)

Synthesis of SN30000, Tables S1-S4, and Figures S1-S6 from Pharmacokinetic/Pharmacodynamic Modeling Identifies SN30000 and SN29751 as Tirapazamine Analogues with Improved Tissue Penetration and Hypoxic Cell Killing in Tumors
Supervision and motion planning for a mobile manipulator interacting with humans (2008)

Human Robot collaborative task achievement requires adapted tools and algorithms for both decision making and motion computation. The human presence as well as its behavior must be considered and actively monitored at the decisional level for the robot to produce synchronized and adapted behavior. Additionally, having a human within the robot range of action introduces security constraints as well as comfort considerations which must be taken into account at the motion planning and control level. This paper presents a robotic architecture adapted to human robot interaction and focuses on two tools: a human aware manipulation planner and a supervision system dedicated to collaborative task achievement.
Angiopoietin-like 4 (ANGPTL4, Fasting-induced Adipose Factor) Is a Direct Glucocorticoid Receptor Target and Participates in Glucocorticoid-regulated Triglyceride Metabolism (2009)

Glucocorticoids are important regulators of lipid homeostasis, and chronically elevated glucocorticoid levels induce hypertriglyceridemia, hepatic steatosis, and visceral obesity. The occupied glucocorticoid receptor (GR) is a transcription factor. However, those genes regulating lipid metabolism under GR control are not fully known. Angiopoietin-like 4 (ANGPTL4, fasting-induced adipose factor), a protein inhibitor of lipoprotein lipase, is synthesized and secreted during fasting, when circulating glucocorticoid levels are physiologically increased. We therefore tested whether the ANGPTL4 gene (Angptl4) is transcriptionally controlled by GR. We show that treatment with the synthetic glucocorticoid dexamethasone increased Angptl4 mRNA levels in primary hepatocytes and adipocytes (2-3-fold) and in the livers and white adipose tissue of mice (approximately 4-fold). We tested the mechanism of this increase in H4IIE hepatoma cells and found that dexamethasone treatment increased the transcriptional rate of Angptl4. Using bioinformatics and chromatin immunoprecipitation, we identified a GR binding site within the rat Angptl4 sequence. A reporter plasmid containing this site was markedly activated by dexamethasone, indicative of a functional glucocorticoid response element. Dexamethasone treatment also increased histone H4 acetylation and DNase I accessibility in genomic regions near this site, further supporting that it is a glucocorticoid response element. Glucocorticoids promote the flux of triglycerides from white adipose tissue to liver. We found that mice lacking ANGPTL4 (Angptl4(-/-)) had reductions in dexamethasone-induced hypertriglyceridemia and hepatic steatosis, suggesting that ANGPTL4 is required for this flux. Overall, we establish that ANGPTL4 is a direct GR target that participates in glucocorticoid-regulated triglyceride metabolism.
Formation and suppression of a newly discovered secondary EOS event in HBM test systems (2004)

A previously undetected trailing pulse from HBM testers was found to create unexpected gate oxide failures on new technologies. This secondary pulse, which is EOS in nature, is caused by the discharge relay and the parasitics of the charge circuit. This paper investigates this critical phenomenon and establishes the tester improvements to safely suppress the trailing pulse effects.