gebhart/patrepeval huggingface dataset:
Reversing T-cell exhaustion in immunotherapy: a review on current approaches and limitations (2021)

<b>Introduction</b>:T cell functions are altered during chronic viral infections and tumor development. This is mainly manifested by significant changes in T cells' epigenetic and metabolic landscapes, pushing them into an 'exhausted' state. Reversing this T cell exhaustion has been emerging as a 'game-changing' therapeutic approach against cancer and chronic viral infection.<b>Areas covered</b>:This review discusses the cellular pathways related to T cell exhaustion, and the clinical development and possible cellular targets that can be exploited therapeutically to reverse this exhaustion. We searched various databases (e.g. Google Scholar, PubMed, Elsevier, and other scientific database sites) using the keywords T cell exhaustion, T cell activation, co-inhibitory receptors, and reversing T cell exhaustion.<b>Expert opinion</b>:The discovery of the immune checkpoints pathways represents a significant milestone toward understanding and reversing T cell exhaustion. Antibodies that target these pathways have already demonstrated promising activities in reversing T cell exhaustion. Nevertheless, there are still many associated limitations. In this context, next-generation alternatives are on the horizon. This includes the use of small molecules to block the immune checkpoints' receptors, combining them with other treatments, and identifying novel, safer and more effective immunotherapeutic targets.
Passive cooling of Pellet Bed Reactor concepts for bimodal applications (1994)

A threedimensional transient heat conduction analysis of the Pellet Bed Reactor concepts for bimodal applications is performed to investigate the passive cooling capability of the reactor sectors, following a lossof-coolant accident (LOCA), and after shutdown. Results demonstrated that passive cooling of onc or two sectors of the reactor core following a LOCA is possible, while maintaining the reactor operating at a fraction of its nominal thermal power. It is also concluded that passive removal of decay heat can be achieved, while maintaining the maximum fuel temperature in the reactor core at or below 1600 K.
APPARATUS AND TECHNIQUE FOR COMPUTERIZED FLUOROSCOPIC INTRAVENOUS ANGIOGRAPMY (1980)

Ergun, D. L. M.S.; Shaw, C. G. M.S.; Kruger, R. A. Ph.D.; Lysel, M. Van M.S.; Mistretta, C. A. Ph.D.; Zarnstorff, W. Ph.D.; Strother, C. M. M.D.; Crummy, A. B. M.D.; Sackett, J. F. M.D.; Myerowitz, P. D. M.D.
Tripling Survival From Sudden Cardiac Arrest Via Early Defibrillation Without Traditional Education in Cardiopulmonary Resuscitation (2002)

Broad dissemination of AEDs for use by nonmedical volunteers enabled early defibrillation and tripled the survival rate for out-of-hospital SCA.
The effects of elevated CO2 concentration on competitive interaction between aceticlastic and syntrophic methanogenesis in a model microbial consortium (2014)

Investigation of microbial interspecies interactions is essential for elucidating the function and stability of microbial ecosystems. However, community-based analyses including molecular-fingerprinting methods have limitations for precise understanding of interspecies interactions. Construction of model microbial consortia consisting of defined mixed cultures of isolated microorganisms is an excellent method for research on interspecies interactions. In this study, a model microbial consortium consisting of microorganisms that convert acetate into methane directly (Methanosaeta thermophila) and syntrophically (Thermacetogenium phaeum and Methanothermobacter thermautotrophicus) was constructed and the effects of elevated CO2 concentrations on intermicrobial competition were investigated. Analyses on the community dynamics by quantitative RT-PCR and fluorescent in situ hybridization targeting their 16S rRNAs revealed that high concentrations of CO2 have suppressive effects on the syntrophic microorganisms, but not on the aceticlastic methanogen. The pathways were further characterized by determining the Gibbs free energy changes (ΔG) of the metabolic reactions conducted by each microorganism under different CO2 concentrations. The ΔG value of the acetate oxidation reaction (T. phaeum) under high CO2 conditions became significantly higher than -20 kJ per mol of acetate, which is the borderline level for sustaining microbial growth. These results suggest that high concentrations of CO2 undermine energy acquisition of T. phaeum, resulting in dominance of the aceticlastic methanogen. This study demonstrates that investigation on model microbial consortia is useful for untangling microbial interspecies interactions, including competition among microorganisms occupying the same trophic niche in complex microbial ecosystems.
<title>Determination of macroscopic optical properties of multilayer random media by remote sensing</title> (1991)

Several measurement and analysis schemes have been explored, using simulated data, in an effort to identify new strategies for the determination of the macroscopic optical properties of multilayer random media. Several simple algorithms are described which are capable of identifying the values of important parameters such as the total cross- section, (summation)t, the ratio of the absorption to total-cross section, (summation)a/(summation)t, and depth of subsurface boundaries in two- and three- layer media. The albedo values of the media varied for 0.9 to 0.99 and the superficial layer had an absorptivity either greater or less than the subsurface layers. A novel feature of the algorithms is a comparison of the responses of coupled pairs of detectors. Their utility stems from the fact that variations in the orientation and location of collimated detectors permit the selective interrogation of subsurface regions in dense scattering media.
Vibronic coupling. VII. Magnetic circular dichroism of trimers, aromatic hydrocarbons, and porphyrins (1973)

Vibronic wavefunctions for trimers are used to calculate the A and B parameters characteristic of MCD spectra. In the weak-coupling limit both the A and the B parameters are zero for s = 0 states and nonzero for s = ±1 states. In the strong-coupling limit, the vibrationally induced 0–1 transition has nonzero A and B parameters, but the spectrum is dominated by the B term. Vibronic wavefunctions for cyclic polyenes are used to calculate the A and B parameters for the electronically forbidden, vibronically allowed 0–1 transitions in closed-shell aromatics and porphyrins. In 4n +2-atomic systems, the 0–1 transition for the B1u state has a small A term, vibronic in nature, and a B term that dominates the spectrum. The parameters are calculated for benzene, 18-annulene, coronene, and triphenylene. In the E2n−1 electronic state of a 4n-atomic system with 4n+2 electrons, there are two vibronic states that are made allowed by excitation of one quantum of either of two nontotally symmetric vibrations. There is a novel magnetic interaction between these two vibronic states. A model 16-membered polyene is used to calculate the A and B parameters for the metal and free-base porphyrins. In the metal porphyrins, the two A parameters are of opposite sign and each is of opposite sign to its corresponding B parameter. The MCD spectrum for each of the two 0–1 transitions in the Q state of the metal porphyrins is dominated by the A term. The free-base spectrum is also discussed. This simple and intuitive model gives calculated values that compare well with the experimental ones.
Species-Specific Bacteria Identification Using Differential Mobility Spectrometry and Bioinformatics Pattern Recognition (2005)

As bacteria grow and proliferate, they release a variety of volatile compounds that can be profiled and used for speciation, providing an approach amenable to disease diagnosis through quick analysis of clinical cultures as well as patient breath analysis. As a practical alternative to mass spectrometry detection and whole cell pyrolysis approaches, we have developed methodology that involves detection via a sensitive, micromachined differential mobility spectrometer (microDMx), for sampling headspace gases produced by bacteria growing in liquid culture. We have applied pattern discovery/recognition algorithms (ProteomeQuest) to analyze headspace gas spectra generated by microDMx to reliably discern multiple species of bacteria in vitro: Escherichia coli, Bacillus subtilis, Bacillus thuringiensis, and Mycobacterium smegmatis. The overall accuracy for identifying volatile profiles of a species within the 95% confidence interval for the two highest accuracy models evolved was between 70.4 and 89.3% based upon the coordinated expression of between 5 and 11 features. These encouraging in vitro results suggest that the microDMx technology, coupled with bioinformatics data analysis, has potential for diagnosis of bacterial infections.
Effect of NC-1300-0-3 on Healing of Acetic Acid-Induced Gastric Ulcers in Rats (1993)

E4177, 3-[(2'-carboxybiphenyl-4-yl)methyl]-2-cyclopropyl-7-methyl-3H- imidazo[4,5-b]pyridine, was characterized by in vitro autoradiography and by examining functional antagonism upon angiotensin II (Ang II)-induced contraction of isolated vessels. In rat adrenal cortex and liver, E4177 competitively inhibited the specific binding of 125I-[Sar1,Ile8]Ang II, with IC50 being (5.2 +/- 1.0) x 10(-8) M for the adrenal cortex and (1.2 +/- 0.3) x 10(-7) M for the liver. These IC50 values were similar to those for losartan, which showed an IC50 of (6.0 +/- 0.9) x 10(-8) M for the adrenal cortex and (1.3 +/- 0.5) x 10(-7) M for the liver. In contrast, E4177 and losartan had little effect on the binding to rat adrenal medulla where AT2-receptors predominate. These results indicate that E4177 is AT1-specific as is losartan. E4177 and losartan competitively antagonized the Ang II-induced contraction of human and rabbit arterial strips without any agonistic action. The obtained IC50 values indicated that E4177 was twice as potent as losartan in human arteries and three times more so in rabbit aortic strips. Responses to norepinephrine, serotonin, histamine or KCl were not affected by E4177. In addition, E4177 (10(-5) M) had no effect on angiotensin-converting enzyme activity. These data indicate that E4177 is a potent AT1 Ang II-receptor antagonist that may be clinically useful for the treatment of cardiovascular diseases such as hypertension.
Transgenic quail to dynamically image amniote embryogenesis (2015)

Embryogenesis is the coordinated assembly of tissues during morphogenesis through changes in individual cell behaviors and collective cell movements. Dynamic imaging, combined with quantitative analysis, is ideal for investigating fundamental questions in developmental biology involving cellular differentiation, growth control and morphogenesis. However, a reliable amniote model system that is amenable to the rigors of extended, high-resolution imaging and cell tracking has been lacking. To address this shortcoming, we produced a novel transgenic quail that ubiquitously expresses nuclear localized monomer cherry fluorescent protein (chFP). We characterize the expression pattern of chFP and provide concrete examples of how Tg(PGK1:H2B-chFP) quail can be used to dynamically image and analyze key morphogenetic events during embryonic stages X to 11.
Vitality, perceived social support and disease activity determine the performance of social roles in recently diagnosed multiple sclerosis: A longitudinal analysis (2008)

Vitality, the perceived amount of social support, and disease activity, i.e. the T2-weighted supratentorial lesion load, determine the performance of social roles in the early stages of multiple sclerosis.
Transient response improvement in isolated DC-DC converter with current injection circuit (2005)

Converter transient response is mainly limited by filter LC delay time, controller delay time and propagation delay time. It is a tradeoff between efficiency and transient response in the design. In isolated DC/DC converter, the bandwidth of opto-coupler has an extra strong effect on the system bandwidth improvement. This paper presents current injection method, switching mode current injection circuit only engaged in transient periods operating in high frequency at the secondary side to improve the bandwidth for better dynamic response while the main topology can operate in lower frequency for good efficiency. Simple voltage control for fixed switching frequency and stable operation, instead of hysteretic control, is carried out for current injection circuit. Finally, experimental results are given to verify the theoretical analysis.
Simultaneous quantification of histone acetylation, methylation and ubiquitination at multiple sites by LC/MS/MS‐MRM (2010)

Histone post‐translational modifications (PTMs) plays a vital role in directing the fate of gene silencing in the direction of either normal cell development and differentiation or aberrant permanent silencing/activation of cancer‐related genes. To accurately quantify histone modifications in one specific cell line or cancer tissue becomes essential for the study of epigenetic alteration in diseases. Currently, Western‐blot is widely used to assess global histone modifications while ChIP or ChIP‐on‐Chip is used for the analysis of histone modifications at a specific gene location. Mass spectrometry has been recently emerged as a new and amazing tool for qualitative and quantitative analysis of histone modifications. Here, we report an LC/MS/MS‐MRM method for simultaneous quantification of histone acetylation, methylation and ubiquitination at multiple sites using an Agilent triple quadrupole mass spectrometer. The limit of quantification of H2B ubiquitination is 7.3 ng/ml, or 0.15 ng on the column (20 μl of injection volume), for the tryptic ubiquitinated H2B peptide. The dynamic range of quantification is 4~5 order of magnitude. Using this method, we find that H2B ubiquitination in leukemia cell line‐U937 is at least two times of that in leukemia cell line‐HL60, and that the ubiquitination is regulated by AF10 protein. In brain tissue of a person with Amyloid‐positive Alzheimer Disease (AD), histone H3 acetylation and H3 K79 methylation is 40% higher than in the brain tissue of a person with Amyloid‐negative AD or a person without AD.
High Frequency LiNbO3 Bulk Wave Resonator (2019)

International audience
A FERROELECTRIC BASED PASSIVE RFID TAG FOR UHF (860–960 MHz) BAND (2007)

ABSTRACT For a longer working distance between passive tags and the reader, the ferroelectric based technologies are proposed in UHF (860–960 MHz) band transponder. The small ferroelectric capacitor layout area with a stacked capacitor structure over circuit region and a large dielectric permittivity of 250 to 500 and small 1T1C cell array layout area with simple 2T2C based reference scheme allow small chip size. The low operation voltage of 1.5 V to 2.0 V without high voltage boosting scheme also contribute to small power consumption and low cost.
Beyond interference avoidance: Distributed sub-network scheduling in wireless networks with local views (2013)

In most wireless networks, nodes have only limited local information about the network state, which includes connectivity and channel state information. With limited local information about the network, each node's knowledge is mismatched, therefore they must make distributed decisions. In this paper, we pose the following question - if every node has network state information only about a small neighborhood, how and when should nodes choose to transmit? While scheduling answers the above question for point-to-point physical layers which are designed for an interference-avoidance paradigm, we look for answers in cases when interference can be embraced by advanced code design, as suggested by results in network information theory. To make progress on this challenging problem, we propose a distributed algorithm which achieves rates higher than interference-avoidance based link scheduling, especially if each node knows more than one hop of network state information.
Human-tracking systems using pyroelectric infrared detectors (2006)

We design and develop a low-cost pyroelectric detector-based IR motion-tracking system. We study the characteristics of the detector and the Fresnel lenses that are used to modulate the visibility of the detectors. We build sensor clusters in different configurations and demonstrate their use for human motion tracking.
Spermatozoan Metabolism as a Non-Traditional Model for the Study of Huntington’s Disease (2022)

Huntington's Disease (HD) is a fatal autosomal dominant neurodegenerative disease manifested through motor dysfunction and cognitive deficits. Decreased fertility is also observed in HD animal models and HD male patients, due to altered spermatogenesis and sperm function, thus resulting in reduced fertilization potential. Although some pharmaceuticals are currently utilized to mitigate HD symptoms, an effective treatment that remedies the pathogenesis of the disease is yet to be approved by the FDA. Identification of genes and relevant diagnostic biomarkers and therapeutic target pathways including glycolysis and mitochondrial complex-I-dependent respiration may be advantageous for early diagnosis, management, and treatment of the disease. This review addresses the HD pathway in neuronal and sperm metabolism, including relevant gene and protein expression in both neurons and spermatozoa, indicated in the pathogenesis of HD. Furthermore, zinc-containing and zinc-interacting proteins regulate and/or are regulated by zinc ion homeostasis in both neurons and spermatozoa. Therefore, this review also aims to explore the comparative role of zinc in both neuronal and sperm function. Ongoing studies aim to characterize the products of genes implicated in HD pathogenesis that are expressed in both neurons and spermatozoa to facilitate studies of future treatment avenues in HD and HD-related male infertility. The emerging link between zinc homeostasis and the HD pathway could lead to new treatments and diagnostic methods linking genetic sperm defects with somatic comorbidities.
Identification of Amino Acid Residues in Influenza A Virus PA-X That Contribute to Enhanced Shutoff Activity (2019)

The influenza virus protein PA-X modulates the host immune responses and viral pathogenicity through suppression of host protein expression. The endonuclease active site in the N-terminal region, the basic amino acid cluster in the C-terminal PA-X-specific region, and N-terminal acetylation of PA-X by NatB are important for the shutoff activity of PA-X. Here, we focused on the shutoff activity of PA-X derived from the A/California/04/2009 and A/WSN/33 viruses because these two PA-X proteins differ in their shutoff activity. Mutagenesis analysis revealed that proline and serine at positions 28 and 65, respectively, play a central role in this difference. Furthermore, we found that P28 and S65 also affect the shutoff activity of PA-X derived from other influenza virus subtypes. These data demonstrate that P28 and S65 contribute to enhanced shutoff activity of PA-X.
Functional signaling pathway analysis of lung adenocarcinomas identifies novel therapeutic targets for KRAS mutant tumors (2015)

Little is known about the complex signaling architecture of KRAS and the interconnected RAS-driven protein-protein interactions, especially as it occurs in human clinical specimens. This study explored the activated and interconnected signaling network of KRAS mutant lung adenocarcinomas (AD) to identify novel therapeutic targets.Thirty-four KRAS mutant (MT) and twenty-four KRAS wild-type (WT) frozen biospecimens were obtained from surgically treated lung ADs. Samples were subjected to Laser Capture Microdissection and Reverse Phase Protein Microarray analysis to explore the expression/activation levels of 150 signaling proteins along with co-activation concordance mapping. An independent set of 90 non-small cell lung cancers (NSCLC) was used to validate selected findings by immunohistochemistry (IHC).Compared to KRAS WT tumors, the signaling architecture of KRAS MT ADs revealed significant interactions between KRAS downstream substrates, the AKT/mTOR pathway, and a number of Receptor Tyrosine Kinases (RTK). Approximately one-third of the KRAS MT tumors had ERK activation greater than the WT counterpart (p<0.01). Notably 18% of the KRAS MT tumors had elevated activation of the Estrogen Receptor alpha (ER-α) (p=0.02).This finding was verified in an independent population by IHC (p=0.03).KRAS MT lung ADs appear to have a more intricate RAS linked signaling network than WT tumors with linkage to many RTKs and to the AKT-mTOR pathway. Combination therapy targeting different nodes of this network may be necessary to treat this group of patients. In addition, for patients with KRAS MT tumors and activation of the ER-α, anti-estrogen therapy may have important clinical implications.
Advillin acts upstream of phospholipase C ϵ1 in steroid-resistant nephrotic syndrome (2017)

Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of chronic kidney disease. Here, we identified recessive mutations in the gene encoding the actin-binding protein advillin (AVIL) in 3 unrelated families with SRNS. While all AVIL mutations resulted in a marked loss of its actin-bundling ability, truncation of AVIL also disrupted colocalization with F-actin, thereby leading to impaired actin binding and severing. Additionally, AVIL colocalized and interacted with the phospholipase enzyme PLCE1 and with the ARP2/3 actin-modulating complex. Knockdown of AVIL in human podocytes reduced actin stress fibers at the cell periphery, prevented recruitment of PLCE1 to the ARP3-rich lamellipodia, blocked EGF-induced generation of diacylglycerol (DAG) by PLCE1, and attenuated the podocyte migration rate (PMR). These effects were reversed by overexpression of WT AVIL but not by overexpression of any of the 3 patient-derived AVIL mutants. The PMR was increased by overexpression of WT Avil or PLCE1, or by EGF stimulation; however, this increased PMR was ameliorated by inhibition of the ARP2/3 complex, indicating that ARP-dependent lamellipodia formation occurs downstream of AVIL and PLCE1 function. Together, these results delineate a comprehensive pathogenic axis of SRNS that integrates loss of AVIL function with alterations in the action of PLCE1, an established SRNS protein.
Prevention of the Angiogenic Switch in Human Breast Cancer (2009)

Abstract : Our studies over the past 5 years have focused on investigating the mechanisms that regulate the angiogenic switch in primary breast cancers and progression towards metastasis, as well as development of novel therapies that target these processes. While it is well accepted that initiation of cancer requires activation of an oncogene and/or loss of tumor suppressors, tumor progression to neoplasia and subsequent tumor mass expansion require activation of the angiogenic switch (1). To determine the mechanisms that regulate the angiogenic switch, we utilized multiple approaches including screens to identify genes that may be causal in triggering this switch, investigation of the role of the breast cancer susceptibility gene (BRCA1) in regulating angiogenic proteins, and identifying soluble factors produced by non-metastatic breast cancer cells that are critical in suppressing the growth of metastatic lesions. To examine the efficacy of novel therapies for breast cancer with anti-angiogenic activity, we focused on two specific anti-angiogenic therapies, a novel oral formulation of the fumagillin analogue TNP-470 called Lodamin and a recombinant peptide consisting of the first 27 amino acids in the endogenous angiogenesis inhibitor endostatin. We evaluated the efficacy of these two novel anti-angiogenic agents on the growth of human breast cancer in immunocompromised mice and confirmed their primary mechanism of action. The results from these studies have advanced our understanding of how the angiogenic switch may be regulated in breast cancer and provide insight into novel targets and signaling pathways for both primary breast tumorigenesis and more advanced metastatic disease.