gebhart/patrepeval huggingface dataset:
Angular distribution of product internal states using laser fluorescence detection: The Ba+KCl reaction (1976)

The gas-phase reaction Ba+KCl→BaCl+K has been investigated under crossed beam conditions using laser fluorescence detection of the BaCl and K products. The angular distributions of individual BaCl vibrational states have been obtained. For low v, forward and backward peaks are observed; for high v, insufficient product translational energy is present to resolve separate peaks; and for all v, approximately 58% of the BaCl product is forward scattered. The reaction is interpreted as proceeding through an osculating complex. Although this complex is estimated to live one-half of a revolution, the energy partitioning is decidedly nonrandom. The peak of the vibrational product population occurs near v=7, and considerable rotational excitation is present.
Low-temperature processing of lead zirconate titanate thin films by 28 GHz microwave irradiation for MEMS application (2006)

Pb(Zr<sub>x</sub>Ti<sub>1-x</sub>)O<sub>3</sub> (PZT) thin films were coated on Pt/Ti/SiO<sub>2</sub>/Si substrates by a sol-gel method and then crystallized by 28 GHz microwave irradiation. The crystalline phases and microstructures as well as the electrical properties of the microwave-irradiated PZT films were investigated as a function of the elevated temperature generated by microwave irradiation. X-ray diffraction analysis indicated that the PZT films crystallized well into the perovskite phase at an elevated temperature of 480°C by microwave irradiation. Scanning electron microscopy images showed that the films had a granular grain structure and most of the grains were approximately 1.5 μm in size. With increasing the elevated temperature from 480°C to 600°C by microwave irradiation, the breadth of grain boundaries of the films became narrow and the remanent polarization of the films increased lightly. It is clear that microwave irradiation is effective for obtaining well-crystallized PZT films with good properties at low temperatures in a short time.
Neuro-symbolic Models for Interpretable Time Series Classification using Temporal Logic Description (2022)

Most existing Time series classification (TSC) models lack interpretability and are difficult to inspect. Interpretable machine learning models can aid in discovering patterns in data as well as give easy-to-understand insights to domain specialists. In this study, we present Neuro-Symbolic Time Series Classification (NSTSC), a neuro-symbolic model that leverages signal temporal logic (STL) and neural network (NN) to accomplish TSC tasks using multi-view data representation and expresses the model as a human-readable, interpretable formula. In NSTSC, each neuron is linked to a symbolic expression, i.e., an STL (sub)formula. The output of NSTSC is thus interpretable as an STL formula akin to natural language, describing temporal and logical relations hidden in the data. We propose an NSTSC-based classifier that adopts a decision-tree approach to learn formula structures and accomplish a multiclass TSC task. The proposed smooth activation functions enable the model to be learned in an end-to-end fashion. We test NSTSC on a real-world wound healing dataset from mice and benchmark datasets from the UCR time-series repository, demonstrating that NSTSC achieves comparable performance with the state-of-the-art models. Furthermore, NSTSC can generate interpretable formulas that match domain knowledge.
Synergistic nitroreductase/vanadium catalysis enables chemoselective nitro reductions to anilines in the absence of hydrogen gas (2022)

Anilines are valuable synthons in pharmaceuticals and agrochemicals. These compounds are generally produced by chemocatalytic reduction of the corresponding nitrobenzene precursors. However, known synthetic methods often lack sufficient activity or selectivity, which results in low yields or the formation of a variety of undesired side products. We envisaged a biocatalytic approach as a promising general platform for selective and mild nitroarene reduction. Herein, we report using nitroreductases in combination with vanadium salts for the quantitative reduction of nitroaromatics to their corresponding anilines. Substrate scope studies were performed with fourteen nitrobenzene and four nitropyridine compounds. In one example, the reaction was intensified to 27 ​g/L substrate loading at 25 ​mL scale, where chemoselective reduction of the nitro group was obtained with full conversion and more than 93% selectivity toward aniline product (isolated in 82% yield). These conditions demonstrate the first general enzymatic method for the reduction of nitroaromatics to anilines.
ProGen: Language Modeling for Protein Generation (2020)

Abstract Generative modeling for protein engineering is key to solving fundamental problems in synthetic biology, medicine, and material science. We pose protein engineering as an unsupervised sequence generation problem in order to leverage the exponentially growing set of proteins that lack costly, structural annotations. We train a 1.2B-parameter language model, ProGen, on ∼280M protein sequences conditioned on taxonomic and keyword tags such as molecular function and cellular component. This provides ProGen with an unprecedented range of evolutionary sequence diversity and allows it to generate with fine-grained control as demonstrated by metrics based on primary sequence similarity, secondary structure accuracy, and conformational energy.
Microorganisms (2012)

This chapter contains sections titled: Classification Structure Antibacterial targets Bacterial detection and identification Other than its mode of action, what factors determine the antibacterial activity of a drug? Bacterial resistance The ‘post-antibiotic age’? References Questions
Perivascular macrophages collaborate to facilitate chemotherapy resistance in cancer (2022)

Abstract A subset of tumor associated macrophages (TAMs) identified by their expression of the lymphatic vessel endothelial hyaluronan receptor-1 (Lyve-1) reside proximal to blood vasculature and contribute to disease progression. Using a spontaneous murine model of mammary adenocarcinoma ( MMTV-PyMT ), we show that Lyve-1 + TAMs, which co-express heme oxygenase-1, form coordinated multi-cellular ‘nest’ structures in the perivascular niche. We show that TAM nest formation is dependent on IL-6 and a communication axis involving CCR5 and its cognate ligands CCL3/4. We demonstrate that Lyve-1 + TAM nests are associated with CD8 + T-cell exclusion from the tumor and the resistance to immune-stimulating chemotherapeutics. This study highlights an unappreciated collaboration between TAMs and uncovers a spatially driven therapeutic resistance mechanism of these cells in cancer which can be therapeutically targeted.
The clinical features of anterior prostate cancers (2006)

APCs have lower Gleason grade and lower rates of extraprostatic extension, yet patients with anterior tumours have higher overall tumour volumes and higher PSM rates. Because current tools for detecting and staging prostate cancer can underestimate the extent of anterior prostate disease, improved methods are needed for localizing and characterizing anterior cancers.
Abstract 1021: Investigating the mechanism of PARP7 inhibition in type I interferon signaling by arrayed CRISPR screening (2021)

Abstract Genomic instability in cancer cells leads to cellular stress through the accumulation of aberrant nucleic acid species in the cytosol. We have shown that PARP7, a monoPARP, is a negative regulator of cytosolic nucleic acid sensing in cancer cells. RBN-2397 is a potent and selective PARP7 inhibitor that induces antitumor immunity in preclinical models and is currently being evaluated in a Phase I clinical trial. In our preclinical investigations, we found that in a subset of cancer cell lines, such as NCI-H1373, inhibition of PARP7 triggers Type I IFN release, STAT1 phosphorylation, and growth arrest. In contrast, other cell lines, for example, HARA, do not mount an IFN-response upon PARP7 inhibition, even though they are responsive to transfection of exogenous nucleic acids and PARP7 is expressed and enzymatically active. To investigate the underlying mechanism of PARP7 inhibition and to determine the drivers of the differential sensitivity across cell lines we performed arrayed CRISPR knockout screens, targeting approximately 240 genes in the nucleic acid sensing and IFN signaling pathways, in the presence and absence of PARP7 inhibition. Our arrayed screens confirmed multiple hits from a previous genome-wide pooled synthetic/lethal CRISPR dropout screen. For example, targeting genes in the cGAS/STING pathway conferred resistance to PARP7 inhibition in the NCI-H1373 responder cells, suggesting a critical dependence on this sensing pathway. In the PARP7 inhibitor-resistant HARA cells, deletion of components of innate immune-signaling (such as AIM2 and ADAR1), the NF-κB pathway, and genes involved in autophagy sensitized the cells to PARP7 inhibition. We further delineated the function of PARP7 by comparing the effects of the CRISPR perturbation across different cellular readouts such as STAT1 phosphorylation, IFN release, and proliferation. With our work, we shed light on the mechanism by which PARP7 acts as a critical suppressor of the innate immune response. Our findings demonstrate both redundancy and crosstalk between different nucleic acid-sensing pathways and may explain why some cell lines are resistant to PARP7 inhibition. Citation Format: Bin Gui, Ryan Abo, Patrick Flynn, Alvin Z. Lu, Jan-Rung Mo, Joseph M. Gozgit, Melissa M. Vasbinder, Zacharenia A. Varsamis, Andrew Santospago, Victoria M. Richon, Kevin W. Kuntz, Heike Keilhack, Timothy J. Mitchison, Mario Niepel. Investigating the mechanism of PARP7 inhibition in type I interferon signaling by arrayed CRISPR screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1021.
Focus issue on surface plasmon photonics introduction (2013)

The 6th International Conference on Surface Plasmon Photonics (SPP6) was held in Ottawa, Canada from May 26th to 31st, 2013. This independent series of biennial conferences is widely regarded as the premier series in the field, and the 6th edition maintained the tradition of excellence. This Focus Issue collects several papers related to research presented at SPP6, and although the number of papers it comprises is small compared to the total number of papers presented at the conference, the issue is representative and provides a good snapshot of the field at this point in time.
VISITOR: Visual Interactive State Sequence Exploration for Reinforcement Learning (2023)

Abstract Understanding the behavior of deep reinforcement learning agents is a crucial requirement throughout their development. Existing work has addressed the identification of observable behavioral patterns in state sequences or analysis of isolated internal representations; however, the overall decision‐making of deep‐learning RL agents remains opaque. To tackle this, we present VISITOR, a visual analytics system enabling the analysis of entire state sequences, the diagnosis of singular predictions, and the comparison between agents. A sequence embedding view enables the multiscale analysis of state sequences, utilizing custom embedding techniques for a stable spatialization of the observations and internal states. We provide multiple layers: (1) a state space embedding, highlighting different groups of states inside the state‐action sequences, (2) a trajectory view, emphasizing decision points, (3) a network activation mapping, visualizing the relationship between observations and network activations, (4) a transition embedding, enabling the analysis of state‐to‐state transitions. The embedding view is accompanied by an interactive reward view that captures the temporal development of metrics, which can be linked directly to states in the embedding. Lastly, a model list allows for the quick comparison of models across multiple metrics. Annotations can be exported to communicate results to different audiences. Our two‐stage evaluation with eight experts confirms the effectiveness in identifying states of interest, comparing the quality of policies, and reasoning about the internal decision‐making processes.
In SituRaman Spectroscopy for Cure Monitoring of Cationic Photopolymerizations of Divinyl Ethers (1996)

Cationic photopolymerizations of divinyl ethers photosensitized by anthracene was studied using in situ Raman spectroscopy. With careful experimental design, Raman spectroscopy was found to provide a sensitive and convenient method for studying the photopolymerization kinetics even though one of the reactants (the photosensitizer) is highly fluorescent. In illustrative experiments, reaction profiles of the double bond conversion vs. time were obtained by monitoring the Raman peaks at 1322 and 1622 cm−1 arising from the vinyl ether functionality. Similar reaction profiles were obtained using either of these peaks, whereas the intensity of a Raman signal at 1458 cm−1, arising from an unreactive ethyl ether functionality, was found to be independent of conversion. The final limiting conversion was found to increase with increasing reaction temperature with values ranging from 60 to 90%. As expected, the reaction rate was determined to be very dependent on both the initiation light intensity and the temperature of the reaction.
Activation-dependent expression of the blood group-related Lewis Y antigen on peripheral blood granulocytes (2000)

The expression of the difucosyl-lactosamine type 2 oligosaccharide Lewis Y (LeY) on peripheral blood cells was investigated. As assessed by the reactivity with the mouse anti-LeY monoclonal antibody (mAb) ABL 364 among circulating blood cells, the expression of the LeY oligosaccharide was uniquely restricted to granulocytes. Although the density of LeY expressed on resting granulocytes was weak, in vitro activation of granulocytes with fMLP induced a rapid and pronounced increase in granulocyte LeY expression. Analysis of CEA-related glycoproteins immunoprecipitated with anti-CD66 mAbs followed by immunoblotting with mAb ABL 364 showed that granulocyte LeY is attached to members of the CD66 cluster, in particular to the 160/90 kD glycoprotein recognized by anti-CD66 mAb CBL/gran 10. The activation-associated increase in LeY attached to CD66 adhesion molecules implicates a role of the LeY determinant in the cytoadhesive properties of granulocytes.
The Sézary syndrome: a malignant proliferation of helper T cells. (1976)

The Sézary syndrome is a frequently lethal disease characterized by circulating malignant cells of thymus-derived (T)-cell origin. The capacity of circulating malignant lymphocytes from patients with this syndrome to synthesize immunoglobulins and to function as helper or suppressor cells regulating immunoglobulin synthesis by bone marrow-derived (B) lymphocytes was determined. Peripheral blood lymphocytes from normal individuals had geometric mean immunoglobulin synthetic rates of 4,910 ng for IgM, 1,270 ng for IgA, and 1,625 ng for IgG per 2 X 10(6) cells in culture with pokeweed mitogen for 7 days. Purified normal B cells had geometric mean synthetic rates of 198 ng for IgM, 145 ng for IgA, and 102 ng for IgG. Leukemic cells from patients with the Sézary syndrome produced essentially no immunoglobulins. Adding normal T cells to normal B cells restored their immunoglobin producing capacity. Leukemic cells from four of five patients tested had a similar capacity to help immunoglobulin synthesis by purified normal B cells. Additionally, Sézary cells from one patient studied induced a nearly 10-fold increase in IgA synthesis by lymphocytes from a child with ataxia telangiectasia and selective IgA deficiency. Furthermore, these Sézary cells induced more than a 500-fold increase in IgG and IgA synthesis by lymphocytes from a child with Nezelof's syndrome. When Sézary cells were added to normal unfractionated lymphocytes, they did not suppress immunoglobulin biosynthesis. In addition, unlike the situation observed when large numbers of normal T cells were added to purified B cells, there was no depression of immunoglobulin synthesis at very high malignant T-cell to B-cell ratios. These data support the view that Sézary T cells do not express suppressor cell activity. The results presented in this paper suggest that neoplastic lymphocytes from the majority of patients with the Sézary syndrome originate from a subset of T cells programmed exclusively for helper-like interactions with B cells in their production of immunoglobulin molecules.
Rapid dynamics of general transcription factor TFIIB binding during preinitiation complex assembly revealed by single-molecule analysis (2016)

Transcription of protein-encoding genes in eukaryotic cells requires the coordinated action of multiple general transcription factors (GTFs) and RNA polymerase II (Pol II). A "step-wise" preinitiation complex (PIC) assembly model has been suggested based on conventional ensemble biochemical measurements, in which protein factors bind stably to the promoter DNA sequentially to build a functional PIC. However, recent dynamic measurements in live cells suggest that transcription factors mostly interact with chromatin DNA rather transiently. To gain a clearer dynamic picture of PIC assembly, we established an integrated in vitro single-molecule transcription platform reconstituted from highly purified human transcription factors and complemented it by live-cell imaging. Here we performed real-time measurements of the hierarchal promoter-specific binding of TFIID, TFIIA, and TFIIB. Surprisingly, we found that while promoter binding of TFIID and TFIIA is stable, promoter binding by TFIIB is highly transient and dynamic (with an average residence time of 1.5 sec). Stable TFIIB-promoter association and progression beyond this apparent PIC assembly checkpoint control occurs only in the presence of Pol II-TFIIF. This transient-to-stable transition of TFIIB-binding dynamics has gone undetected previously and underscores the advantages of single-molecule assays for revealing the dynamic nature of complex biological reactions.
Adenylyl Cyclase 6 Mediates Inhibition of TNF in the Inflammatory Reflex (2018)

Macrophage cytokine production is regulated by neural signals, for example in the inflammatory reflex. Signals in the vagus and splenic nerves are relayed by choline acetyltransferase<sup>+</sup> T cells that release acetylcholine, the cognate ligand for alpha7 nicotinic acetylcholine subunit-containing receptors (α7nAChR), and suppress TNF release in macrophages. Here, we observed that electrical vagus nerve stimulation with a duration of 0.1-60 s significantly reduced systemic TNF release in experimental endotoxemia. This suppression of TNF was sustained for more than 24 h, but abolished in mice deficient in the α7nAChR subunit. Exposure of primary human macrophages and murine RAW 264.7 macrophage-like cells to selective ligands for α7nAChR for 1 h <i>in vitro</i> attenuated TNF production for up to 24 h in response to endotoxin. Pharmacological inhibition of adenylyl cyclase (AC) and knockdown of adenylyl cyclase 6 (AC6) or c-FOS abolished cholinergic suppression of endotoxin-induced TNF release. These findings indicate that action potentials in the inflammatory reflex trigger a change in macrophage behavior that requires AC and phosphorylation of the cAMP response element binding protein (CREB). These observations further our mechanistic understanding of neural regulation of inflammation and may have implications for development of bioelectronic medicine treatment of inflammatory diseases.
Ion Tunneling in Polymeric Solid Electrolytes for Batery and Electrochromic Display in the Dry State (1988)

Abstract Polymeric solid electrolytes which show bi-or single-ionic tunneling were prepared, and their unique ion conduction was applied for the design of some devices. Poly [(oligooxyethylene) methacrylatel] /MX hybrids and poly [(oligooxyethylene) methacrylate-co-methacrylic acid alkali metal salts] were prepared as typical models of those tunneling systems. These showed ionic conductivities above 10−5 and 10−7 S/cm at room temperature, respectively. An all-solid-state electrochromic display and a dry battery were prepared with these polymeric solid electrolytes. The all-solid-state electrochromic display showed excellent coloring and bleaching response by 1–3 V. The all-solid-state battery showed V oc = 3.1 V stability for over 2 weeks. Their characteristics as well as their mechanism are also reported.
Engineering Hyperthermostability into a GH11 Xylanase Is Mediated by Subtle Changes to Protein Structure (2008)

Understanding the structural basis for protein thermostability is of considerable biological and biotechnological importance as exemplified by the industrial use of xylanases at elevated temperatures in the paper pulp and animal feed sectors. Here we have used directed protein evolution to generate hyperthermostable variants of a thermophilic GH11 xylanase, EvXyn11. The Gene Site Saturation Mutagenesis (GSSM) methodology employed assesses the influence on thermostability of all possible amino acid substitutions at each position in the primary structure of the target protein. The 15 most thermostable mutants, which generally clustered in the N-terminal region of the enzyme, had melting temperatures (Tm) 1-8 degrees C higher than the parent protein. Screening of a combinatorial library of the single mutants identified a hyperthermostable variant, EvXyn11TS, containing seven mutations. EvXyn11TS had a Tm approximately 25 degrees C higher than the parent enzyme while displaying catalytic properties that were similar to EvXyn11. The crystal structures of EvXyn11 and EvXyn11TS revealed an absence of substantial changes to identifiable intramolecular interactions. The only explicable mutations are T13F, which increases hydrophobic interactions, and S9P that apparently locks the conformation of a surface loop. This report shows that the molecular basis for the increased thermostability is extraordinarily subtle and points to the requirement for new tools to interrogate protein folding at non-ambient temperatures.
Effects of short‐term and prolonged infusions of somatostatin on endocrine pancreas, body weight and food intake in rats (1980)

Infusion of cyclic somatostatin (700 mg/kg/min) for 4 h in rat fed and libitum suppressed basal insulin but not glucagon release. It was accompanied by hypoglycemia during the first hour whereas, at the end of the infusion, hyperglycemia was present. The same dose of somatostatin applied 60 min prior to and during a 30 min load of glucose or arginine significantly inhibited their effects on insulin and glucagon release. In contrast, when this dose of somatostatin was given during a 24 h period by the i.v. route it did not inhibit glucose induced insulin release though circulating somatostatin levels were constantly and markedly elevated. Furthermore, in rats continuously infused with somatostatin for 4 days, no effect was found either on plasma concentrations of glucose, insulin, glucagon, growth hormone and cyclic AMP, or on body weight gain, food consumption or water intake. The pancreases of these animals showed normal concentrations of insulin and glucagon and a normal nuclear area of D-cells. Our experiments demonstrate that, in short-term experiments in rats, somatostatin influences insulin and glucagon release as well as glucose homeostasis. Furthermore, they suggest that during prolonged i.v. administration of somatostatin, rats develop mechanisms counteracting the effect of the peptide, e.g., peripheral tachyphylaxis.