gebhart/patrepeval huggingface dataset:
Restoring Immune Function of Tumor-Specific CD4+ T Cells during Recurrence of Melanoma (2013)

Recurrent solid malignancies are often refractory to standard therapies. Although adoptive T cell transfer may benefit select individuals, the majority of patients succumb to their disease. To address this important clinical dilemma, we developed a mouse melanoma model in which initial regression of advanced disease was followed by tumor recurrence. During recurrence, Foxp3(+) tumor-specific CD4(+) T cells became PD-1(+) and represented >60% of the tumor-specific CD4(+) T cells in the host. Concomitantly, tumor-specific CD4(+) T effector cells showed traits of chronic exhaustion, as evidenced by their high expression of the PD-1, TIM-3, 2B4, TIGIT, and LAG-3 inhibitory molecules. Although blockade of the PD-1/PD-L1 pathway with anti-PD-L1 Abs or depletion of tumor-specific regulatory T cells (Tregs) alone failed to reverse tumor recurrence, the combination of PD-L1 blockade with tumor-specific Treg depletion effectively mediated disease regression. Furthermore, blockade with a combination of anti-PD-L1 and anti-LAG-3 Abs overcame the requirement to deplete tumor-specific Tregs. In contrast, successful treatment of primary melanoma with adoptive cell therapy required only Treg depletion or Ab therapy, underscoring the differences in the characteristics of treatment between primary and relapsing cancer. These data highlight the need for preclinical development of combined immunotherapy approaches specifically targeting recurrent disease.
Performance of 15 Miscanthus Genotypes at Five Sites in Europe (2001)

Miscanthus is a genus of high‐yielding perennial rhizomatous grasses with C 4 photosynthesis. Extensive field trials of Miscanthus spp. biomass production in Europe during the past decade have shown several limitations of the most widely planted clone, M . × giganteus Greef et Deu. A 3‐yr study was conducted at five sites in Europe (Sweden, Denmark, England, Germany, and Portugal) to evaluate adaptation and biomass production potential of four acquisitions of M . × giganteus (No. 1–4) and 11 other genotypes, including M. sacchariflorus (Maxim.) Benth. (No. 5), M. sinensis Andersson (No. 11–15), and hybrids (No. 6–10). At each site, three randomized blocks containing a 5‐ by 5‐m plot of each genotype were established (except in Portugal where there were two blocks) with micropropagated plants at 2 plants m −2 . In Sweden and Denmark, only M. sinensis and its hybrids satisfactorily survived the first winter following planting. Mean annual yields across all sites for all surviving genotypes increased each year from 2 t ha −1 dry matter following the first year of growth to 9 and 18 t ha −1 following the second and third year, respectively. Highest autumn yields at sites in Sweden, Denmark, England, and Germany were 24.7 ( M. sinensis hybrid no. 8), 18.2 ( M. sinensis hybrid no. 10), 18.7 ( M . × giganteus no. 3), and 29.1 t ha −1 ( M . × giganteus no. 4), respectively. In Portugal, where irrigation was used, the top‐yielding genotype produced 40.9 t ha −1 dry matter ( M. sinensis hybrid no. 7). Highest‐yielding genotypes in Sweden and Denmark were among the lowest yielding in Portugal and Germany, demonstrating strong genotype × environment interactions.
mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability (2021)

A drawback of the current mRNA-lipid nanoparticle (LNP) COVID-19 vaccines is that they have to be stored at (ultra)low temperatures. Understanding the root cause of the instability of these vaccines may help to rationally improve mRNA-LNP product stability and thereby ease the temperature conditions for storage. In this review we discuss proposed structures of mRNA-LNPs, factors that impact mRNA-LNP stability and strategies to optimize mRNA-LNP product stability. Analysis of mRNA-LNP structures reveals that mRNA, the ionizable cationic lipid and water are present in the LNP core. The neutral helper lipids are mainly positioned in the outer, encapsulating, wall. mRNA hydrolysis is the determining factor for mRNA-LNP instability. It is currently unclear how water in the LNP core interacts with the mRNA and to what extent the degradation prone sites of mRNA are protected through a coat of ionizable cationic lipids. To improve the stability of mRNA-LNP vaccines, optimization of the mRNA nucleotide composition should be prioritized. Secondly, a better understanding of the milieu the mRNA is exposed to in the core of LNPs may help to rationalize adjustments to the LNP structure to preserve mRNA integrity. Moreover, drying techniques, such as lyophilization, are promising options still to be explored.
Generation of a cytotoxic T‐lymphocyte response using a Salmonella antigen‐delivery system (1990)

We have constructed a general-use vector for the cloning and stable expression of foreign genes in the chromosome of attenuated Salmonella typhimurium. Using this chromosomal expression vector (CEV), we expressed the circumsporozoite (CS) gene of the mouse malaria Plasmodium yoelii in an aroA S. typhimurium strain. Mice immunized with CS-expressing Salmonella recombinants mount a CS-specific cytotoxic T-lymphocyte (CTL) response. This is the first demonstration that attenuated Salmonella can elicit a specific CTL response to a foreign protein in mice. The ability to easily and stably express foreign genes from the Salmonella chromosome and the generation of specific CTL greatly expands the potential of Salmonella as an antigen-delivery system.
Text Detection, Tracking and Recognition in Video: A Comprehensive Survey (2016)

The intelligent analysis of video data is currently in wide demand because a video is a major source of sensory data in our lives. Text is a prominent and direct source of information in video, while the recent surveys of text detection and recognition in imagery focus mainly on text extraction from scene images. Here, this paper presents a comprehensive survey of text detection, tracking, and recognition in video with three major contributions. First, a generic framework is proposed for video text extraction that uniformly describes detection, tracking, recognition, and their relations and interactions. Second, within this framework, a variety of methods, systems, and evaluation protocols of video text extraction are summarized, compared, and analyzed. Existing text tracking techniques, tracking-based detection and recognition techniques are specifically highlighted. Third, related applications, prominent challenges, and future directions for video text extraction (especially from scene videos and web videos) are also thoroughly discussed.
Epidermal Growth Factor (1979)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
<title>Error image in error diffusion</title> (1992)

The concept of an error image is defined for the error diffusion algorithm. Ordinarily hidden from view, the error image is a visual representation of the internally generated errors from which the algorithm derives its name. In this paper, it is shown that the error image contains a linear component of the input image, which induces edge enhancement in the output error diffusion image. Examples are shown for three different error weight distributions: a 1-D one- ahead distribution, the standard 4-element distribution, and a 12-element error distribution. The amount of edge enhancement in the corresponding algorithm is shown to vary with the amount of input image information present in the error image.
Positive Feedback and Noise Activate the Stringent Response Regulator Rel in Mycobacteria (2008)

Phenotypic heterogeneity in an isogenic, microbial population enables a subset of the population to persist under stress. In mycobacteria, stresses like nutrient and oxygen deprivation activate the stress response pathway involving the two-component system MprAB and the sigma factor, SigE. SigE in turn activates the expression of the stringent response regulator, rel. The enzyme polyphosphate kinase 1 (PPK1) regulates this pathway by synthesizing polyphosphate required for the activation of MprB. The precise manner in which only a subpopulation of bacterial cells develops persistence, remains unknown. Rel is required for mycobacterial persistence. Here we show that the distribution of rel expression levels in a growing population of mycobacteria is bimodal with two distinct peaks corresponding to low (L) and high (H) expression states, and further establish that a positive feedback loop involving the mprAB operon along with stochastic gene expression are responsible for the phenotypic heterogeneity. Combining single cell analysis by flow cytometry with theoretical modeling, we observe that during growth, noise-driven transitions take a subpopulation of cells from the L to the H state within a "window of opportunity" in time preceding the stationary phase. It is these cells which adapt to nutrient depletion in the stationary phase via the stringent response. We find evidence of hysteresis in the expression of rel in response to changing concentrations of PPK1. Hysteresis promotes robustness in the maintenance of the induced state. Our results provide, for the first time, evidence that bistability and stochastic gene expression could be important for the development of "heterogeneity with an advantage" in mycobacteria and suggest strategies for tackling tuberculosis like targeting transitions from the low to the high rel expression state.
Mechanisms of resistance to EGFR-targeted drugs: lung cancer (2016)

Despite the improvement in clinical outcomes derived by the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumours harbour EGFR-activating mutations, prognosis remains unfavourable because of the occurrence of either intrinsic or acquired resistance. We reviewed the published literature and abstracts of oral and poster presentations from international conferences addressing EGFR-TKIs resistance mechanisms discovered in preclinical models and in patients with NSCLC. The molecular heterogeneity of lung cancer has several implications in terms of possible mechanisms of either intrinsic or acquired resistance to EGFR-targeted inhibitors. Several mechanisms of resistance have been described to EGFR-TKIs, such as the occurrence of secondary mutation (T790M, C797S), the activation of alternative signalling (Met, HGF, AXL, Hh, IGF-1R), the aberrance of the downstream pathways (AKT mutations, loss of PTEN), the impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism) and histological transformation. Although some of the mechanisms of resistance have been identified, much additional information is needed to understand and overcome resistance to EGFR-TKI agents. The majority of resistance mechanisms described are the result of a selection of pre-existing clones; thus, studies on the mechanisms by which subclonal alterations have an impact on tumour biology and influence cancer progression are extremely important in order to define the best treatment strategy.
An Endoglycosidase with Alternative Glycan Specificity Allows Broadened Glycoprotein Remodelling (2012)

Protein endoglycosidases are useful for biocatalytic alteration of glycans on protein surfaces, but the currently limited selectivity of endoglycosidases has prevented effective manipulation of certain N-linked glycans widely found in nature. Here we reveal that a bacterial endoglycosidase from Streptococcus pyogenes , EndoS, is complementary to other known endoglycosidases (EndoA, EndoH) used for current protein remodeling. It allows processing of complex-type N-linked glycans +/- core fucosylation but does not process oligomannose- or hybrid-type glycans. This biocatalytic activity now addresses previously refractory antibody glycoforms.
A Novel, General Method for the Synthesis of Nitrile Oxides:  Dehydration of O-Silylated Hydroxamic Acids (2000)

[reaction: see text] O-Silylated hydroxamic acids serve as stable, readily accessible, crystalline precursors to nitrile oxides when treated with trifluoromethanesulfonic anhydride and triethylamine. Under these mild conditions in the presence of olefins O-silylated hydroxamic acids afford isoxazoline cycloadducts. This procedure represents a novel, general method for the one-step generation of nitrile oxides, which complements existing protocols.
Antiviral activity of a chemically stabilized 2‐5A analog upon microinjection into HeLa cells (1986)

2-5A[ppp(A2'p)n5'A] has been implicated as a mediator in the antiviral action of interferon. Its direct evaluation as an indicator of virus replication is hampered by two limitations: its inability to penetrate intact cells, and its rapid intracellular degradation by (2'-5')phosphodiesterase. These problems could be overcome by using a microinjection technique whereby a phosphodiesterase-resistant analog of 2-A, in which the 2'-terminals adenosine residue is replaced by 2-(9-adenyl)-6-hydroxy-methyl-4-hexylmorpholine, was injected into individual HeLa cells before infection with mengovirus or vesicular stomatitis virus (VSV). This comparative assay with two representatives of different virus classes in a single experimental system pointed to the high sensitivity of VSV to inhibition by 2-5A oligonucleotides, in contrast with the low sensitivity of mengovirus. Microinjection of the hexylmorpholine 2-5A analog led to a much greater reduction in mengovirus yield than did microinjection of 2-5A itself.
Enantioselective Synthesis ofS-Equol from Dihydrodaidzein by a Newly Isolated Anaerobic Human Intestinal Bacterium (2005)

A newly isolated rod-shaped, gram-negative anaerobic bacterium from human feces, named Julong 732, was found to be capable of metabolizing the isoflavone dihydrodaidzein to S-equol under anaerobic conditions. The metabolite, equol, was identified by using electron impact ionization mass spectrometry, (1)H and (13)C nuclear magnetic resonance spectroscopy, and UV spectral analyses. However, strain Julong 732 was not able to produce equol from daidzein, and tetrahydrodaidzein and dehydroequol, which are most likely intermediates in the anaerobic metabolism of dihydrodaidzein, were not detected in bacterial culture medium containing dihydrodaidzein. Chiral stationary-phase high-performance liquid chromatography eluted only one metabolite, S-equol, which was produced from a bacterial culture containing a racemic mixture of dihydrodaidzein. Strain Julong 732 did not show racemase activity to transform R-equol to S-equol and vice versa. Its full 16S rRNA gene sequence (1,429 bp) had 92.8% similarity to that of Eggerthella hongkongenis HKU10. This is the first report of a single bacterium capable of converting a racemic mixture of dihydrodaidzein to enantiomeric pure S-equol.
An energy-based method for location of power system oscillation source (2012)

An energy-based method to locate oscillation sources in power systems is proposed. The energy is identical to the transient energy. The amount of energy is consistent with the oscillation amplitude, and then the component producing energy has negative contribution to the damping and is considered as the oscillation source. The consistency of energy dissipation with damping torque of a generator is proved. A method to compute energy flow in the network based on wide area measurement system data and independent of energy functions is proposed. The energy dissipation or production of a component in the system can be obtained from the net energy flow. The components producing energy are oscillation sources and emergency control actions should be taken on them. The method is validated by simulations and actual oscillation incidents analyses.
Vinorelbine and cisplatin (CIVIC regimen) for the treatment of metastatic breast carcinoma after failure of anthracycline- and/or paclitaxel-containing regimens (1998)

The CIVIC regimen is effective and has acceptable tolerance in patients with metastatic breast carcinoma refractory to previous anthracycline- and/or paclitaxel-containing chemotherapy. Four cycles were found to provide the best toxicity-efficacy ratio.
The effects of a ground shield on spiral inductors fabricated in a silicon bipolar technology (2002)

The frequency dependence of the model parameters of patterned ground shield (PGS) inductors in large part is explained as a consequence of modeling a distributed system with a lumped model. Using an n/sup +/-buried/n-well PGS, the peak Q is improved by /spl sim/25% with small changes of L and C/sub p/. Having a PGS does not significantly improve isolation between inductors.
The orphan nuclear receptor Rev-erbα: a transcriptional link between circadian rhythmicity and cardiometabolic disease (2007)

These findings identify Rev-erbalpha as a modulator of cardiovascular risk factors and as a determinant of the circadian regulation of metabolic pathways. Moreover, Rev-erbalpha crosstalks with other nuclear receptors which influence atherosclerosis susceptibility. Rev-erbalpha may thus serve to integrate metabolic and circadian signals.
Learning from Models. (1997)

Modern economics is dominated by modelling. For professional economists and students alike, the practice of economics is based around the activity of building and manipulating models of the economy. Even at the earliest stage of study, the use of models forms the basic method of instruction. Economists learn from this modelling method. But what do they learn? What is the process? And what conditions need to be fulfilled for such learning to take place? In order to see what models do, and how they can teach us things, we have to understand the details of their construction and usage. To explore these questions, this essay takes as case study material two models of the monetary system by Irving Fisher (1867–1947), one of the pioneers of scientific model building in economics. IRVING FISHER AND HIS CONTEXTS The contemporary economic view of money ‘Money’, and in particular the economic laws and government responsibilities which governed its value, formed the most important economic question in America in the 1890s, the time when Irving Fisher took up economics seriously. The institutional arrangements for controlling money were bitterly fought over in the political arena, forming a key element in the presidential and congressional elections of 1892 and more so in 1896, when the farmers rallied behind the political slogan that they were being ‘crucified on a cross of gold’. These arguments necessarily entailed discussions of monetary theory and beliefs about economic laws, and many reputable American economists wrote books about the theory, institutional and empirical aspects of money in the period of the 1890s and 1900s.
Reversible and irreversible cross-linking of immunoglobulin heavy chains through their carbohydrate residues (1990)

After periodate oxidation and incubation with a dihydrazide, cross-linking of the two heavy chains of immunoglobulins G from several species proceeds specifically through their oligosaccharides. We have used malonic acid dihydrazide, adipic acid dihydrazide and dithiodipropionic acid dihydrazide. The last compound is introduced in this work as a cleavable-carbohydrate-specific cross-linker. It was found that in rabbit and human immunoglobulins the degree of cross-linking was strongly dependent on the oxidation conditions but only very weakly dependent on the concentration and size of the dihydrazides. Papain cleavage of the cross-linked rabbit IgG indicated that the cross-linking occurred predominantly, if not exclusively, in the Fc region, probably through the two glycans linked to Asn-297 in the CH2 domain of each of the two heavy chains. The immunoglobulins from sheep, pig, goat and guinea pig show a comparable cross-linking pattern, indicating that the sugar chains from these immunoglobulins have a spatial structure closely related to that of rabbit and human IgG. When dithiodipropionic acid dihydrazide was used as the cross-linker, the cross-link could be cleaved by mercaptoethanol.
Enhanced Cellular Uptake and Transport of Polyclonal Immunoglobulin G and Fab After Their Cationization (2000)

Antibodies are poorly transported across cell membranes and biological barriers in vivo. Cationization of antibody molecules by the derivatization of surface carboxyl groups generating primary amino groups could represent a strategy for intracellular antibody delivery. Before cationization of polyclonal colchicine-specific IgG and Fab, using hexamethylenediamine the isoelectric point (pl) of native IgG and Fab (nIgG and nFab) was in the range of 5.9 9.0 and 8.7-9.3, respectively. The pI of cationized IgG and Fab (cIgG and cFab) were both higher at 8.7, 10.3 and 9.5 -11, respectively. The affinity and specificity of both IgG and Fab were not modified by cationization. When HL 60 cells were incubated with the native or cationized 125I-BSA. -IgG and -Fab, the maximal cellular uptake of clgG and cFab was 3.2 and 2.4 times higher than that of nIgG and nFab at an extracellular concentration of 500 ng/ml. Results also indicated that the uptake was dose- and temperature-dependent suggesting absorptive-mediated endocytosis of cationized antibodies by HL 60 cells. Confocal microscopy analysis indicated that the cationized antibodies were present in the plasma membranes and cytoplasm of HL 60 cells. Finally, a study with bovine arterial endothelial monolayer cells showed that the transport of cIgG and cFab through the monolayer cells was 3.3- and 4.3-fold higher for 125I-cIgG and 125I-cFab than those of the corresponding native forms.
Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML (2017)

In 2017, 4 drugs received US Food and Drug Administration marketing approval for acute myeloid leukemia (AML) treatment: targeted therapies for mutant <i>FLT3</i> and <i>IDH2</i>, a liposomal cytarabine-daunorubicin formulation for therapy-related AML and AML with myelodysplasia-related changes, and resurgence of an antibody-drug conjugate designed to target CD33. Promising results also emerged for the BCL-2 inhibitor venetoclax combined with low-intensity therapy in older patients unfit for intensive chemotherapy. This quintet of new drugs is likely to reshape the therapeutic landscape of AML.