gebhart/patrepeval huggingface dataset:
Barcode Sequencing Screen IdentifiesSUB1as a Regulator of Yeast Pheromone Inducible Genes (2016)

Abstract The yeast pheromone response pathway serves as a valuable model of eukaryotic mitogen-activated protein kinase (MAPK) pathways, and transcription of their downstream targets. Here, we describe application of a screening method combining two technologies: fluorescence-activated cell sorting (FACS), and barcode analysis by sequencing (Bar-Seq). Using this screening method, and pFUS1-GFP as a reporter for MAPK pathway activation, we readily identified mutants in known mating pathway components. In this study, we also include a comprehensive analysis of the FUS1 induction properties of known mating pathway mutants by flow cytometry, featuring single cell analysis of each mutant population. We also characterized a new source of false positives resulting from the design of this screen. Additionally, we identified a deletion mutant, sub1Δ, with increased basal expression of pFUS1-GFP. Here, in the first ChIP-Seq of Sub1, our data shows that Sub1 binds to the promoters of about half the genes in the genome (tripling the 991 loci previously reported), including the promoters of several pheromone-inducible genes, some of which show an increase upon pheromone induction. Here, we also present the first RNA-Seq of a sub1Δ mutant; the majority of genes have no change in RNA, but, of the small subset that do, most show decreased expression, consistent with biochemical studies implicating Sub1 as a positive transcriptional regulator. The RNA-Seq data also show that certain pheromone-inducible genes are induced less in the sub1Δ mutant relative to the wild type, supporting a role for Sub1 in regulation of mating pathway genes. The sub1Δ mutant has increased basal levels of a small subset of other genes besides FUS1, including IMD2 and FIG1, a gene encoding an integral membrane protein necessary for efficient mating.
Anti-Human Immunodeficiency Virus Activity, Cross-Resistance, Cytotoxicity, and Intracellular Pharmacology of the 3′-Azido-2′,3′-Dideoxypurine Nucleosides (2009)

Although the approved nucleoside reverse transcriptase (RT) inhibitors (NRTI) are integral components of therapy for human immunodeficiency virus type 1 (HIV-1) infection, they can have significant limitations, including the selection of NRTI-resistant HIV-1 and cellular toxicity. Accordingly, there is a critical need to develop new NRTI that have excellent activity and safety profiles and exhibit little or no cross-resistance with existing drugs. In this study, we report that the 3'-azido-2',3'-dideoxypurine nucleosides (ADPNs) 3'-azido-2',3'-dideoxyadenosine (3'-azido-ddA) and 3'-azido-2',3'-dideoxyguanosine (3'-azido-ddG) exert potent antiviral activity in primary human lymphocytes and HeLa and T-cell lines (50% inhibitory concentrations [IC50s] range from 0.19 to 2.1 microM for 3'-azido-ddG and from 0.36 to 10 microM for 3'-azido-ddA) and that their triphosphate forms are incorporated as efficiently as the natural dGTP or dATP substrates by HIV-1 RT. Importantly, both 3'-azido-ddA and 3'-azido-ddG retain activity against viruses containing K65R, L74V, or M184V (IC50 change of <2.0-fold) and against those containing three or more thymidine analog mutations (IC50 change of <3.5-fold). In addition, 3'-azido-ddG does not exhibit cytotoxicity in primary lymphocytes or epithelial or T-cell lines and does not decrease the mitochondrial DNA content of HepG2 cells. Furthermore, 3'-azido-ddG is efficiently phosphorylated to 3'-azido-ddGTP in human lymphocytes, with an intracellular half-life of the nucleoside triphosphate of 9 h. The present data suggest that additional preclinical studies are warranted to assess the potential of ADPNs for treatment of HIV-1 infection.
Preparation of carbocyclic, phosphonate analogues of cyclic adenosine monophosphate (cAMP) (1997)

Compounds 2 and 5 have been synthesised and cyclised to form the cyclic 3′,5′-adenosine monophosphate (cAMP) analogues 3, 6 and 7. In a complementary exercise, cyclopentadiene has been converted into the phosphonic acid 16 in six steps. Compound 16 has been deprotected and cyclised to form the cyclic 3′,5′-adenosine monophosphate (cAMP) analogues 18 and 19.
Nanosized and metastable molybdenum oxides as negative electrode materials for durable high-energy aqueous Li-ion batteries (2021)

The development of inherently safe energy devices is a key challenge, and aqueous Li-ion batteries draw large attention for this purpose. Due to the narrow electrochemical stable potential window of aqueous electrolytes, the energy density and the selection of negative electrode materials are significantly limited. For achieving durable and high-energy aqueous Li-ion batteries, the development of negative electrode materials exhibiting a large capacity and low potential without triggering decomposition of water is crucial. Herein, a type of a negative electrode material (i.e., Li <i><sub>x</sub></i> Nb<sub>2/7</sub>Mo<sub>3/7</sub>O<sub>2</sub>) is proposed for high-energy aqueous Li-ion batteries. Li <i><sub>x</sub></i> Nb<sub>2/7</sub>Mo<sub>3/7</sub>O<sub>2</sub> delivers a large capacity of ∼170 mA ⋅ h ⋅ g<sup>-1</sup> with a low operating potential range of 1.9 to 2.8 versus Li/Li<sup>+</sup> in 21 m lithium bis(trifluoromethanesulfonyl)amide (LiTFSA) aqueous electrolyte. A full cell consisting of Li<sub>1.05</sub>Mn<sub>1.95</sub>O<sub>4</sub>/Li<sub>9/7</sub>Nb<sub>2/7</sub>Mo<sub>3/7</sub>O<sub>2</sub> presents high energy density of 107 W ⋅ h ⋅ kg<sup>-1</sup> as the maximum value in 21 m LiTFSA aqueous electrolyte, and 73% in capacity retention is achieved after 2,000 cycles. Furthermore, hard X-ray photoelectron spectroscopy study reveals that a protective surface layer is formed at the surface of the negative electrode, by which the high-energy and durable aqueous batteries are realized with Li <i><sub>x</sub></i> Nb<sub>2/7</sub>Mo<sub>3/7</sub>O<sub>2</sub> This work combines a high capacity with a safe negative electrode material through delivering the Mo-based oxide with unique nanosized and metastable characters.
Simian Virus 40 Small t Antigen Mediates Conformation-Dependent Transfer of Protein Phosphatase 2A onto the Androgen Receptor (2005)

The tumor antigens simian virus 40 small t antigen (ST) and polyomavirus small and medium T antigens mediate cell transformation in part by binding to the structural A subunit of protein phosphatase 2A (PP2A). The replacement of B subunits by tumor antigens inhibits PP2A activity and prolongs phosphorylation-dependent signaling. Here we show that ST mediates PP2A A/C heterodimer transfer onto the ligand-activated androgen receptor (AR). Transfer by ST is strictly dependent on the agonist-activated conformation of AR, occurs within minutes of the addition of androgen to cells, and can occur in either the cytoplasm or the nucleus. The binding of ST changes the conformation of the A subunit, and ST rapidly dissociates from the complex upon PP2A A/C heterodimer binding to AR. PP2A is transferred onto the carboxyl-terminal half of AR, and the phosphatase activity is directed to five phosphoserines in the amino-terminal activation function region 1, with a corresponding reduction in transactivation. Thus, ST functions as a transfer factor to specify PP2A targeting in the cell and modulates the transcriptional activity of AR.
Installation of Minimal Tetrazines through Silver-Mediated Liebeskind–Srogl Coupling with Arylboronic Acids (2019)

Described is a general method for the installation of a minimal 6-methyltetrazin-3-yl group via the first example of a Ag-mediated Liebeskind-Srogl cross-coupling. The attachment of bioorthogonal tetrazines on complex molecules typically relies on linkers that can negatively impact the physiochemical properties of conjugates. Cross-coupling with arylboronic acids and a new reagent, 3-((<i>p</i>-biphenyl-4-ylmethyl)thio)-6-methyltetrazine (b-Tz), proceeds under mild, PdCl<sub>2</sub>(dppf)-catalyzed conditions to introduce minimal, linker-free tetrazine functionality. Safety considerations guided our design of b-Tz which can be prepared on decagram scale without handling hydrazine and without forming volatile, high-nitrogen tetrazine byproducts. Replacing conventional Cu(I) salts used in Liebeskind-Srogl cross-coupling with a Ag<sub>2</sub>O mediator resulted in higher yields across a broad library of aryl and heteroaryl boronic acids and provides improved access to a fluorogenic tetrazine-BODIPY conjugate. A covalent probe for MAGL incorporating 6-methyltetrazinyl functionality was synthesized in high yield and labeled endogenous MAGL in live cells. This new Ag-mediated cross-coupling method using b-Tz is anticipated to find additional applications for directly introducing the tetrazine subunit to complex substrates.
Studies on the chemistry of 2,3,5,6‐tetrahydro‐6‐phenylimidazo[2,l‐b]‐thiazole. III. . Reaction with isocyanates and isothiocyanates (1977)

Abstract 2,3,5,6‐Tetrahydro‐ b ‐phenylimidazo[2,l ‐b‐ ]thiazole reacts with aryl isothiocyanates to give dipolar 1:1 adducts. The adducts are relatively unstable and, in solution, exist in equilibrium with starting materials. The reaction with aryl and alkyl isocyanates, however, leads to cyclic 2:1 adducts, while sulphonyl and acyl isocyanates give stable dipolar 1:1 adducts. J. Chem. Soc. , 14, 989 (1977)
High performance wire‐array silicon solar cells (2010)

Abstract Nano/micro‐wire silicon solar cells, consisting of wire‐arrays of radial p – n junction structures, are expected to offer performance enhancement at lower costs, using smaller volumes of low carrier lifetime, cheaper silicon. Using inexpensive microsphere‐lithography‐based fabrication that is scalable to large areas, we have demonstrated wire‐array solar cells that outperform the control cell. Key to the design of these cells is the impact of various parameters, such as wire diameter and junction depth, that influences the competing effects of light trapping ability of the wire‐array, quantum efficiency, and series resistance of the resulting device. Using capacitance measurements we can identify two possible types of junction structure in a wire‐array solar cell: radial and planar. We show that the former is the prerequisite for performance‐enhancing wire‐array solar cells. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Abstract 3669: Autocrine interleukin/STAT3 signaling in breast implant-associated T cell anaplastic large cell lymphoma cell lines suggests a mechanism for tumor progression and effective therapy (2012)

Abstract Recently, over 80 cases of anaplastic large-cell kinase (ALK)-negative, T-cell, anaplastic, non-Hodgkin lymphomas (T-ALCL) have been identified worldwide in patients with textured saline and silicone breast implants. These breast implant-associated T-ALCL cases are striking for their homogeneous clinical presentation and pathology that is distinct from established classes of ALCL. In order to understand the nature of this newly emerged clinical entity, we have established three new cell lines, designated T cell Breast Lymphoma (TLBR) -1, -2, and -3, from patient primary tumor biopsy specimens. Characterization of these pre-clinical models confirmed fidelity to the original tumor biopsy specimens and highlighted unique features that may aid the development of effective treatments for these cancers. Gene expression analysis demonstrated significant up-regulation of survivin and down-regulation of pro-apoptotic genes (BID, BAK, BBC3) by all TLBR cell lines relative to healthy donor T cells. This preliminary finding prompted examination of upstream regulators of cell survival in T cells, namely the interleukin signaling associated with the JAK/STAT pathway. TLBR cell lines were found to secrete high levels of IL-6 and IL-10, and were strongly positive for the cognate receptors. The TLBR cell lines also showed elevated levels of STAT3 and pSTAT3 by immunoblotting techniques, along with a simultaneous reduction in expression of the pSTAT3 phosphatase, SHP-1. These results implicate an unregulated autocrine STAT3 pathway present in the TLBR cell lines that strongly contributes to their tumorigenesis. Assays of various inhibitors of this pathway support this hypothesis since targeting of STAT3 with the tyrosine kinase inhibitor, Sunitinib, led to dramatic in vitro cell death in all TLBR cell lines. More specific inhibition of STAT3 with S3I-201 had comparable results with Sunitinib. Furthermore, IL-6 neutralization by a monoclonal antibody or SHP-1 restoration by 5-azacytidine treatment also demonstrated moderate efficacy in inhibiting TLBR cell line growth in vitro. These discoveries strongly suggest the use of these reagents in the clinical treatment of Breast Implant Associated T-ALCL. The TLBR cell lines closely resemble the primary breast implant-associated lymphomas from which they were derived, and as such provide valuable preclinical models to study the unique biology and provide clinicians with improved knowledge for treatment and diagnosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3669. doi:1538-7445.AM2012-3669
Inverse Design of Solid-state Quantum Emitter Single-photon Sources (2022)

We demonstrate a new, multi-objective inverse design strategy for single-photon sources based on single quantum emitters, and show that it can produce comparable performance, with more favorable trade-offs, than conventional design based on pre-existing nanophotonic geometries.
Towards regeneration: the evolution of medicine from fighting to building (2018)

We should retreat from metaphors of war in medicine and look to regenerative medicine in its broadest sense, say <b>Ian Hargraves and colleagues</b> with a focus on rebuilding both bodies and lives
On the automata size for Presburger arithmetic (2004)

Automata provide an effective mechanization of decision procedures for Presburger arithmetic. However, only crude lower and upper bounds are known on the sizes of the automata produced by this approach. In this paper, we prove that the number of states of the minimal deterministic automaton for a Presburger arithmetic formula is triple exponentially bounded in the length of the formula. This upper bound is established by comparing the automata for Presburger arithmetic formulas with the formulas produced by a quantifier elimination method. We also show that this triple exponential bound is tight (even for nondeterministic automata). Moreover, we provide optimal automata constructions for linear equations and inequations.
Applications of ALD MnO to electrochemical water splitting (2015)

Atomic layer deposition (ALD) is an attractive method to deposit uniform catalytic films onto high surface area electrodes. One interesting material for ALD synthesis is MnOx, a promising earth-abundant catalyst for the oxygen evolution reaction (OER). It has previously been shown that catalysts beginning as MnO synthesized using ALD on smooth glassy carbon (s-GC) electrodes and Mn2O3 obtained upon annealing MnO on s-GC are active OER catalysts. Here, we use ALD to deposit MnO on high surface area GC (HSA-GC) substrates, forming an active catalyst on a geometric surface area basis. We then characterize three types of catalysts, HSA-GC MnO, s-GC MnO, and annealed MnO (Mn2O3), using cyclic voltammetry (CV), scanning electron microscopy (SEM), and ex situ X-ray absorption spectroscopy (XAS). We show that under OER conditions, all three catalysts oxidize to similar surface states with a mixture of Mn(3+)/Mn(4+) and that MnOx surface area effects can account for the observed differences in the catalytic activity. We also demonstrate the need for a high surface area support for high OER activity on a geometric basis.
ChemInform Abstract: Linear Coordinative Bonding at Oxygen: A Spectroscopic and Structural Study of Phosphine Oxide‐Group 13 Lewis Acid Adducts. (1990)

Abstract Adducts such as (I) are studied by multinuclear NMR spectroscopy in CH 2 Cl 2 solution and by X‐ray crystallography of the three compounds (I) (for all space group R3, Z = 6).
Identification and characterization of AckA-dependent protein acetylation in Neisseria gonorrhoeae (2017)

Neisseria gonorrhoeae, the causative agent of gonorrhea, has a number of factors known to contribute to pathogenesis; however, a full understanding of these processes and their regulation has proven to be elusive. Post-translational modifications (PTMs) of bacterial proteins are now recognized as one mechanism of protein regulation. In the present study, Western blot analyses, with an anti-acetyl-lysine antibody, indicated that a large number of gonococcal proteins are post-translationally modified. Previous work has shown that Nε-lysine acetylation can occur non-enzymatically with acetyl-phosphate (AcP) as the acetyl donor. In the current study, an acetate kinase mutant (1291ackA), which accumulates AcP, was generated in N. gonorrhoeae. Broth cultures of N. gonorrhoeae 1291wt and 1291ackA were grown, proteins extracted and digested, and peptides containing acetylated-lysines (K-acetyl) were affinity-enriched from both strains. Mass spectrometric analyses of these samples identified a total of 2686 unique acetylation sites. Label-free relative quantitation of the K-acetyl peptides derived from the ackA and wild-type (wt) strains demonstrated that 109 acetylation sites had an ackA/wt ratio>2 and p-values <0.05 in at least 2/3 of the biological replicates and were designated as "AckA-dependent". Regulated K-acetyl sites were found in ribosomal proteins, central metabolism proteins, iron acquisition and regulation proteins, pilus assembly and regulation proteins, and a two-component response regulator. Since AckA is part of a metabolic pathway, comparative growth studies of the ackA mutant and wt strains were performed. The mutant showed a growth defect under aerobic conditions, an inability to grow anaerobically, and a defect in biofilm maturation. In conclusion, the current study identified AckA-dependent acetylation sites in N. gonorrhoeae and determined that these sites are found in a diverse group of proteins. This work lays the foundation for future studies focusing on specific acetylation sites that may have relevance in gonococcal pathogenesis and metabolism.
Lightweight high-brightness helmet-mounted head-up display system (2016)

We present a compact binocular head-up display for integration in a motorcycle helmet. A 2D MEMS-mirror reflecting laser beams enables the formation of a bright image superimposed on the user vision by means of retinal scanning. A 3d-printed prototype including the required optical components is presented and characterized. It fits the morphology of most users thanks to several degrees of freedom accessible to the user for fine-tuning.
Dysregulation of kallikrein-related peptidases in renal cell carcinoma: potential targets of miRNAs (2010)

Renal cell carcinoma (RCC) accounts for 3% of all adult malignancies and currently no diagnostic marker exists. Kallikrein-related peptidases (KLKs) have been implicated in numerous cancers including ovarian, prostate, and breast carcinoma. KLKs 5, 6, 10, and 11 have decreased expression in RCC when compared to normal kidney tissue. Our bioinformatic analysis indicated that the KLK 1, 6, and 7 genes have decreased expression in RCC. We experimentally verified these results and found that decreased expression of KLKs 1 and 3 were significantly associated with the clear cell RCC subtype (p<0.001). An analysis of miRNAs differentially expressed in RCC showed that 61 of the 117 miRNAs that were reported to be dysregulated in RCC were predicted to target KLKs. We experimentally validated two targets using two independent approaches. Transfection of miR-224 into HEK-293 cells resulted in decreased KLK1 protein levels. A luciferase assay demonstrated that hsa-let-7f can target KLK10 in the RCC cell line ACHN. Our results, showing differential expression of KLKs in RCC, suggest that KLKs could be novel diagnostic markers for RCC and that their dysregulation could be under miRNA control. The observation that KLKs could represent targets for miRNAs suggests a post-transcriptional regulatory mechanism with possible future therapeutic applications.
Direct measurements and numerical simulations of gas charging in microelectromechanical system capacitive switches (2012)

Gas breakdown in microelectromechanical system capacitive switches is demonstrated using high resolution current measurements and by particle-in-cell/Monte Carlo collision (PIC/MCC) simulations. Measurements show an electric current through a 3 μm air gap increasing exponentially with voltage, starting at 60 V. PIC/MCC simulations with Fowler-Nordheim [Proc. R. Soc. London, Ser. A 119, 173 (1928)] field emission reveal self-sustained discharges with significant ion enhancement and a positive space charge. The effective ion-enhanced field emission coefficient increases with voltage up to about 0.3 with an electron avalanche occurring at 159 V. The measurements and simulations demonstrate a charging mechanism for microswitches consistent with earlier observations of gas pressure and composition effects on lifetime.
Direct coupling of VCSELs to plastic optical fibers using guide holes patterned in a thick photoresist (2002)

We report a simple passive alignment method to couple plastic optical fibers (POFs) to vertical-cavity surface-emitting lasers (VCSELs) for use in parallel optical interconnects. Polymer guide holes were fabricated directly on the top of VCSELs by means of standard photolithography using SU-8 epoxy-based thick photoresist. Perfluorinated graded-index POFs were inserted and fixed in the guide holes to provide butt-coupled packaging modules. For a VCSEL of 15-μm diameter and a POF of 124-μm core diameter, coupling efficiencies were obtained between about 80% and 50%, depending on drive current. The standard deviation of the efficiency at a drive current of 10 mA was 5.9% for a 1 × 5 array.
Depression of Synaptic Transmission by Vascular Endothelial Growth Factor in Adult Rat Hippocampus and Evidence for Increased Efficacy after Chronic Seizures (2005)

In addition to its potent effects on vasculature, it has become clear that vascular endothelial growth factor (VEGF) has effects on both neurons and glia, and recent studies suggest that it can be neuroprotective. To determine potential mechanisms underlying this neuroprotection, recombinant human VEGF was bath applied to adult rat hippocampal slices, and both extracellular and intracellular recordings were used to examine intrinsic properties and synaptic responses of hippocampal principal neurons. Initial studies in area CA1 showed that VEGF significantly reduced the amplitude of responses elicited by Schaffer collateral stimulation, without influencing membrane properties. Similar effects occurred in CA3 pyramidal cells and dentate gyrus granule cells when their major glutamatergic afferents were stimulated. Because VEGF expression is increased after seizures, effects of VEGF were also examined in rats with recurrent spontaneous seizures. VEGF reduced spontaneous discharges in slices from these rats but had surprisingly little effect on epileptiform discharges produced by disinhibition of slices from control rats. These results demonstrate a previously unknown effect of VEGF on neuronal activity and also demonstrate a remarkable potency in the epileptic brain. Based on this, we suggest that VEGF or VEGF-related targets could provide useful endpoints to direct novel therapeutic strategies for epilepsy.