gebhart/patrepeval huggingface dataset:
Improvement in the Palladium-Catalyzed Miyaura Borylation Reaction by Optimization of the Base: Scope and Mechanistic Study (2020)

Aryl boronic acids and esters are important building blocks in API synthesis. The palladium-catalyzed Suzuki-Miyaura borylation is the most common method for their preparation. This paper describes an improvement of the current reaction conditions. By using lipophilic bases such as potassium 2-ethyl hexanoate, the borylation reaction could be achieved at 35 °C in less than 2 h with very low palladium loading (0.5 mol %). A preliminary mechanistic study shows a hitherto unrecognized inhibitory effect by the carboxylate anion on the catalytic cycle, whereas 2-ethyl hexanoate minimizes this inhibitory effect. This improved methodology enables borylation of a wide range of substrates under mild conditions.
Impact of Mitochondrial Permeability on Endothelial Cell Immunogenicity in Transplantation (2018)

Static cold storage and warm reperfusion leads to a reduction in mitochondrial fitness in microvascular ECs due to mPTP opening. Further, mPTP opening promotes increased EC immunogenicity that can be prevented by NIM811 treatment.
Role of Nasal Casts for In Vitro Evaluation of Nasal Drug Delivery and Quantitative Evaluation of Various Nasal Casts (2020)

<b>Background:</b> Nasal casts may characterize intranasal drug deposition. <b>Methodology:</b> The Koken cast, described as 'anatomically correct', and the Optinose cast, derived from MRI of a healthy male during velum closure, were dimensionally compared and assessed for deposition assessment suitability. <b>Results:</b> Smallest vertical cross-sectional areas (valve region) for Koken and Optinose right/left: 2.55/2.75 and 1.18/1.18 cm<sup>2</sup>, respectively, versus a 'normative' mean (range) of 0.85 cm<sup>2</sup> (0.2-1.6 cm<sup>2</sup>). Intranasal volumes differed (computed tomography/water fill): Koken, 35.8/38.6 cm<sup>3</sup> and Optinose, 24.1/25.0 cm<sup>3</sup>, versus a 'normative' mean (range) of 26.4 cm<sup>3</sup> (20.9-31.1 cm<sup>3</sup>). <b>Conclusion:</b> Koken cast dimensions are larger than the normal range and the Optinose cast. The validity of casts for regulatory drug deposition studies is suspect.
Adenosine signalling in T‐cell activation favours development of IL‐17 positive cells with suppressive properties (2022)

Evidence suggests that the anti-inflammatory nucleoside adenosine can shape immune responses by shifting the regulatory (T<sub>reg</sub> )/helper (Th17) T-cell balance in favour of T<sub>reg</sub> . Since this observation is based on in vivo and in vitro studies mostly confined to murine models, we comprehensively analysed effects of adenosine on human T-cells. Proliferation, phenotype and cytokine production of stimulated T-cells were assessed by flow cytometry, multiplex assay and ELISA, gene expression profiling was determined by microarray. We found that the pan-adenosine agonist 5'-N-ethylcarboxamidoadenosine (NECA) skews human CD3<sup>+</sup> T-cell responses towards non-inflammatory Th17 cells. Addition of NECA during T-cell activation increased the development of IL-17<sup>+</sup> cells with a CD4<sup>+</sup> RORγt<sup>+</sup> phenotype and enhanced CD161 and CD196 surface expression. Remarkably, these Th17 cells displayed non-inflammatory cytokine and gene expression profiles including reduced Th1/Th17 transdifferentiation, a stem cell-like molecular signature and induced surface expression of the adenosine-producing ectoenzymes CD39 and CD73. Thus, T-cells cultured under Th17-inducing conditions together with NECA were capable of suppressing responder T-cells. Finally, genome-wide gene expression profiling revealed metabolic quiescence previously associated with non-pathogenic Th17 cells in response to adenosine signalling. Our data suggest that adenosine induces non-inflammatory Th17 cells in human T-cell differentiation, potentially through regulation of metabolic pathways.
Spin of single electron traps in silicon nanowire-based transistors (2005)

We study anomalies in the Coulomb blockade spectrum of a quantum dot formed in a silicon nanowire. These anomalies are attributed to electrostatic interaction with charge traps in the device. A simple model reproduces these anomalies accurately and we show how the capacitance matrices of the traps can be obtained from the shape of the anomalies. From these capacitance matrices we deduce that the traps are located near or inside the wire. Based on the occurrence of the anomalies in wires with different doping levels we infer that most of the traps are arsenic dopant states. In some cases the anomalies are accompanied by a random telegraph signal which allows time resolved monitoring of the occupation of the trap. The spin of the trap states is determined via the Zeeman shift.
Inverse Optimization Techniques for Targeted Self-Assembly (2008)

This article reviews recent inverse statistical-mechanical methodologies that we have devised to optimize interaction potentials in soft matter systems that correspond to stable "target" structures. We are interested in finding the interaction potential, not necessarily pairwise additive or spherically symmetric, that stabilizes a targeted many-body system by generally incorporating complete configurational information. Unlike previous work, our primary interest is in the possible many-body structures that may be generated, some of which may include interesting but known structures, while others may represent entirely new structural motifs. Soft matter systems, such as colloids and polymers, offer a versatile means of realizing the optimized interactions. It is shown that these inverse approaches hold great promise for controlling self-assembly to a degree that surpasses the less-than-optimal path that nature has provided. Indeed, we envision being able to "tailor" potentials that produce varying degrees of disorder, thus extending the traditional idea of self-assembly to incorporate both amorphous and crystalline structures as well as quasicrystals. The notion of tailoring potentials that correspond to targeted structures is motivated by the rich fundamental statistical-mechanical issues and questions offered by this fascinating inverse problem as well as our recent ability to identify structures that have optimal bulk properties or desirable performance characteristics. Recent results have already led to a deeper basic understanding of the mathematical relationship between the collective structural behavior of many-body systems and their interactions, as well as optimized potentials that enable self-assembly of ordered and disordered particle configurations with novel structural and bulk properties.
Design and synthesis of novel derivatives of all-transretinoic acid demonstrate the combined importance of acid moiety and conjugated double bonds in its binding to PML–RAR-α oncogene in acute promyelocytic leukemia (2010)

The binding of all-trans retinoic acid (ATRA) to retinoid receptor-alpha (RAR-alpha) relieves transcriptional repression induced by the promyelocytic leukemia-retinoic acid receptor (PML-RAR) oncoprotein. The ATRA molecule contains a cyclohexenyl ring, a polyene chain containing conjugated double alkene bonds, and a terminal carboxyl group. To determine the contributions of these structural components of ATRA to its clinical efficacy, we synthesized three novel retinoids. These consisted of either a modified conjugated alkene backbone with an intact acid moiety (13a) or a modified conjugated alkene backbone and conversion of the acid group to either an ester (13b) or an aromatic amide (13c). Reporter assays demonstrated that compound 13a successfully relieved transcriptional repression by RAR-alpha, while 13b and 13c could not, demonstrating the critical role of the acid moiety in this binding. However, only ATRA was able to significantly inhibit the proliferation of APL cells while 13a, 13b, or 13c was not. Furthermore, only 13a led to partial non-significant differentiation of NB4 cells, demonstrating the importance of C9-C10 double bonds in differentiation induced CD11 expression. Our results demonstrate that both the acid moiety and conjugated double bonds present in the ATRA molecule are important for its biological activity in APL and have important implications for the design of future novel retinoids.
Paper-Based Analytical Device for Electrochemical Flow-Injection Analysis of Glucose in Urine (2012)

This article describes a new design for a paper-based electrochemical system for flow-injection analysis. Capillary wicking facilitates a gravity-driven flow of buffer solution continuously through paper and nitrocellulose, from a buffer reservoir at one end of the device to a sink at the other. A difference in height between the reservoir and the sink leads to a continuous and constant flow. The nitrocellulose lies horizontally on a working electrode, which consists of a thin platinum layer deposited on a solid support. The counter and reference electrodes are strategically positioned upstream in the buffer reservoir. A simple pipetting device was developed for reliable application of (sub)microliter volumes of sample without the need of commercial micropipets; this device did not damage the nitrocellulose membrane. Demonstration of the system for the determination of the concentration of glucose in urine resulted in a noninvasive, quantitative assay that could be used for diagnosis and monitoring of diabetes. This method does not require disposable test strips, with enzyme and electrodes, that are thrown away after each measurement. Because of its low cost, this system could be used in medical environments that are resource-limited.
Antioxidants reveal an inverted U‐shaped dose‐response relationship between reactive oxygen species levels and the rate of aging in Caenorhabditis elegans (2016)

Reactive oxygen species (ROS) are potentially toxic, but they are also signaling molecules that modulate aging. Recent observations that ROS can promote longevity have to be reconciled with the numerous claims about the benefits of antioxidants on lifespan. Here, three antioxidants [N-acetylcysteine (NAC), vitamin C, and resveratrol (RSV)] were tested on Caenorhabditis elegans mutants that alter drug uptake, mitochondrial function, and ROS metabolism. We observed that like pro-oxidants, antioxidants can both lengthen and shorten lifespan, dependent on concentration, genotypes, and conditions. The effects of antioxidants thus reveal an inverted U-shaped dose-response relationship between ROS levels and lifespan. In addition, we observed that RSV can act additively to both NAC and paraquat, to dramatically increase lifespan. This suggests that the effect of compounds that modulate ROS levels can be additive when their loci of action or mechanisms of action are sufficiently distinct.
Recombinant Adeno-Associated Virus-Mediated Editing of the G551D Cystic Fibrosis Transmembrane Conductance Regulator Mutation in Ferret Airway Basal Cells (2022)

Mutations in the cystic fibrosis transmembrane conductance regulator (<i>CFTR</i>) gene cause cystic fibrosis (CF), a chronic disease that affects multiple organs, including the lung. We developed a CF ferret model of a scarless G551→D substitution in <i>CFTR</i> (<i>CFTR</i><sup>G551D-KI</sup>), enabling approaches to correct this gating mutation in CF airways via gene editing. Homology-directed repair (HDR) was tested in Cas9-expressing CF airway basal cells (Cas9-GKI) from this model, as well as reporter basal cells (Y66S-Cas9-GKI) that express an integrated nonfluorescent Y66S-EGFP (enhanced green fluorescent protein) mutant gene to facilitate rapid assessment of HDR by the restoration of fluorescence. Recombinant adeno-associated virus (rAAV) vectors were used to deliver two DNA templates and sgRNAs for dual-gene editing at the <i>EGFP</i> and <i>CFTR</i> genes, followed by fluorescence-activated cell sorting of <i>EGFP</i><sup>Y66S</sup>-corrected cells. When gene-edited airway basal cells were polarized at an air-liquid interface, unsorted and <i>EGFP</i><sup>Y66S</sup>-corrected sorted populations gave rise to 26.0% and 70.4% CFTR-mediated Cl<sup>-</sup> transport of that observed in non-CF cultures, respectively. The consequences of gene editing at the <i>CFTR</i><sup>G551D</sup> locus by HDR and nonhomologous end joining (NHEJ) were assessed by targeted gene next-generation sequencing (NGS) against a specific amplicon. NGS revealed HDR corrections of 3.1% of G551 sequences in the unsorted population of rAAV-infected cells, and 18.4% in the <i>EGFP</i><sup>Y66S</sup>-corrected cells. However, the largest proportion of sequences had indels surrounding the CRISPR (clustered regularly interspaced short palindromic repeats) cut site, demonstrating that NHEJ was the dominant repair pathway. This approach to simultaneously coedit at two genomic loci using rAAV may have utility as a model system for optimizing gene-editing efficiencies in proliferating airway basal cells through the modulation of DNA repair pathways in favor of HDR.
Retrotransposon insertion as a novel mutational cause of spinal muscular atrophy (2022)

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder resulting from biallelic alterations of the SMN1 gene: deletion, gene conversion or, in rare cases, intragenic variants. The disease severity is mainly influenced by the copy number of SMN2 , a nearly identical gene, which produces only low amounts of full-length (FL) mRNA. Here we describe the first example of retrotransposon insertion as a pathogenic SMN1 mutational event. The 50-year-old patient is clinically affected by SMA type III with a diagnostic odyssey spanning nearly 30 years. Despite a mild disease course, he carries a single SMN2 copy. Using Exome Sequencing and Sanger sequencing, we characterized a SVA-F retrotransposon inserted in SMN1 intron 7. Using RT-PCR and RNASeq experiments on lymphoblastoid cell lines, we documented the dramatic decrease of FL transcript production in the patient compared to subjects with the same SMN1 and SMN2 copy number, thus validating the pathogenicity of this SVA insertion. We characterized the mutant FL-SMN1-SVA transcript and showed that it is subject to degradation by nonsense-mediated mRNA decay. The stability of the SMN-SVA protein may explain the mild course of the disease. This observation exemplifies the role of retrotransposons in human genetic disorders.
Trace amines: Identification of a family of mammalian G protein-coupled receptors (2001)

Tyramine, beta-phenylethylamine, tryptamine, and octopamine are biogenic amines present in trace levels in mammalian nervous systems. Although some "trace amines" have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Using a degenerate PCR approach, we have identified 15 G protein-coupled receptors (GPCR) from human and rodent tissues. Together with the orphan receptor PNR, these receptors form a subfamily of rhodopsin GPCRs distinct from, but related to the classical biogenic amine receptors. We have demonstrated that two of these receptors bind and/or are activated by trace amines. The cloning of mammalian GPCRs for trace amines supports a role for trace amines as neurotransmitters in vertebrates. Three of the four human receptors from this family are present in the amygdala, possibly linking trace amine receptors to affective disorders. The identification of this family of receptors should rekindle the investigation of the roles of trace amines in mammalian nervous systems and may potentially lead to the development of novel therapeutics for a variety of indications.
Self-Amplifying RNA Vaccines Give Equivalent Protection against Influenza to mRNA Vaccines but at Much Lower Doses (2017)

New vaccine platforms are needed to address the time gap between pathogen emergence and vaccine licensure. RNA-based vaccines are an attractive candidate for this role: they are safe, are produced cell free, and can be rapidly generated in response to pathogen emergence. Two RNA vaccine platforms are available: synthetic mRNA molecules encoding only the antigen of interest and self-amplifying RNA (sa-RNA). sa-RNA is virally derived and encodes both the antigen of interest and proteins enabling RNA vaccine replication. Both platforms have been shown to induce an immune response, but it is not clear which approach is optimal. In the current studies, we compared synthetic mRNA and sa-RNA expressing influenza virus hemagglutinin. Both platforms were protective, but equivalent levels of protection were achieved using 1.25 μg sa-RNA compared to 80 μg mRNA (64-fold less material). Having determined that sa-RNA was more effective than mRNA, we tested hemagglutinin from three strains of influenza H1N1, H3N2 (X31), and B (Massachusetts) as sa-RNA vaccines, and all protected against challenge infection. When sa-RNA was combined in a trivalent formulation, it protected against sequential H1N1 and H3N2 challenges. From this we conclude that sa-RNA is a promising platform for vaccines against viral diseases.
New, Functionalized Ionic Liquids from Michael‐Type Reactions — A Chance for Combinatorial Ionic Liquid Development. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Supplementary Tables 8 - 15 from Genetically Defined Subsets of Human Pancreatic Cancer Show Unique <i>In Vitro</i> Chemosensitivity (2023)

&lt;p&gt;PDF file, 127K, S8 IC50s of DPC4/SMAD4 isogenic cells tested with Cisplatin, Irinotecan and Gemcitabine; S9 Correlation analysis between IC50s of Cisplatin, Irinotecan and Gemcitabine and TGFB pathway activity of DPC4 isogenic cells; S10 Genes whose expression levels were correlated with chemosensitivity in pancreatic cancer cell lines; S11 Combination indices (CI) for csplatin+irinotecan combination in DPC4 isogenic cell lines; S12 IC50s of TP53 isogenic colon cancer cell lines tested with Parp1 inhibitor and Triptolide; S13 Comparisons of gene mutation statuses of cell lines having IC50&lt;200nM with those having IC50&gt;10000nM for Parp1 inhibitor; S14 Genes with significantly different gene expression in cell cycle and DNA damage pathway and other DNA damage repair genes without significant difference between TP53 defective PC cell lines having IC50&lt;200nM and those having IC50&gt;10000nM for Parp1 inhibitor; S15 P16/CDKN2A deleted PC cells rank ordered by their sensitivity to gemcitabine and MMC investigated for association with CDKN2B, DMRTA1, MTAP and TUSC1 in pancreatic cancer cells.&lt;/p&gt;
Mapping irradiation hybrids to cosmid and yeast artificial chromosome libraries by direct hybridization of Alu-PCR products (1991)

A direct hybridization protocol is described for screening cosmid and yeast artificial chromosome libraries with pools of Alu-PCR products from somatic cell or irradiation hybrids. This method eliminates purification, cloning and analysis of each individual Alu-PCR product before library screening. A series of human X chromosome irradiation hybrids were mapped by this method, using a cosmid reference library for comparisons between overlapping hybrids to identify interesting clones for further analysis.
Batterie al litio per dispositivi biomedicali (2006)

Gli avanzamenti della ricerca nel campo delle batterie al litio primarie e secondarie, sotto la pressante richiesta di mercato, hanno contribuito enormemente alla miniaturizzazione dei dispositivi biomedicali ed alla loro impiantabilità. In questo articolo viene data una breve panoramica su alcune batterie che hanno permesso lo sviluppo di dispositivi biomedicali sempre più sofisticati e che per questo motivo giocano una parte essenziale e determinante nel miglioramento della qualità della vita.
Effects of Picornavirus Proteinases on Host Cell Transcription (2014)

Poliovirus (PV) is known to shut off both host cell transcription and translation. It is believed that the shutoff of host cell transcription in PV-infected cells increases the pool of free ribonucleotides that the PV-encoded RNA-dependent RNA polymerase (Pol) uses to transcribe and replicate the viral genomic RNA. In support of this theory, PV first shuts off Pol I-mediated transcription in the cell that accounts for greater than 50% of all host cell transcription. The authors have used in vitro transcription systems for understanding the mechanism by which PV shuts off host cell transcription catalyzed by RNA Pol I, II, and III. Infection of susceptible cells with PV results in rapid and dramatic changes in macromolecular metabolism, including the shutoff of host cell transcription. Early attempts to identify the cellular components of the transcriptional machinery inactivated by picornavirus infection focused on the polymerases. To examine whether 3Cpro is sufficient to cause inhibition of host cell transcription seen in virus-infected cells, 3Cpro was cloned into the eukaryotic expression vector pCDNA. The role of the 3C protease in host cell transcription shutoff is clear from both genetic and biochemical analyses. PV is an RNA virus, which replicates in the cytoplasm of infected cells. To shut off host cell transcription, one or more viral gene products must enter the nucleus of the infected host cell. The viral precursor 3CD has protease activity and is able to autocatalyze the formation of 3C and 3D polypeptides.
Dynamic Gain Excursion Suppression in High-Speed Automatically Gain Controlled EDFAs Using an Optical Delay Line (2001)

We have studied the dynamic behavior of high-speed automatically gain controlled erbium-doped fiber amplifiers pumped at 980 nm. Employing an optical delay line in the amplifiers, the maximum dynamic gain excursions can be reduced.
When Unseen Domain Generalization is Unnecessary? Rethinking Data Augmentation (2019)

Recent advances in deep learning for medical image segmentation demonstrate expert-level accuracy. However, in clinically realistic environments, such methods have marginal performance due to differences in image domains, including different imaging protocols, device vendors and patient populations. Here we consider the problem of domain generalization, when a model is trained once, and its performance generalizes to unseen domains. Intuitively, within a specific medical imaging modality the domain differences are smaller relative to natural images domain variability. We rethink data augmentation for medical 3D images and propose a deep stacked transformations (DST) approach for domain generalization. Specifically, a series of n stacked transformations are applied to each image in each mini-batch during network training to account for the contribution of domain-specific shifts in medical images. We comprehensively evaluate our method on three tasks: segmentation of whole prostate from 3D MRI, left atrial from 3D MRI, and left ventricle from 3D ultrasound. We demonstrate that when trained on a small source dataset, (i) on average, DST models on unseen datasets degrade only by 11% (Dice score change), compared to the conventional augmentation (degrading 39%) and CycleGAN-based domain adaptation method (degrading 25%); (ii) when evaluation on the same domain, DST is also better albeit only marginally. (iii) When training on large-sized data, DST on unseen domains reaches performance of state-of-the-art fully supervised models. These findings establish a strong benchmark for the study of domain generalization in medical imaging, and can be generalized to the design of robust deep segmentation models for clinical deployment.