gebhart/patrepeval huggingface dataset:
Pioglitazone promotes survival and prevents hepatic regeneration failure after partial hepatectomy in obese and diabetic KK-Ay mice # (2009)

These findings indicated that pioglitazone improved hepatic regeneration failure in KK-A(y) mice. The mechanism underlying the effect of pioglitazone on regeneration failure most likely involves normalization of expression pattern of adipokines and subsequent cytokine responses during the early stage of PH.
Synthesis of 3-Carboxylated Indoles through a Tandem Process Involving Cyclization of 2-Ethynylanilines Followed by CO2 Fixation in the Absence of Transition Metal Catalysts (2012)

In this study, a facile synthesis of 3-carboxylated indoles involving a tandem-type cyclization of 2-ethynylanilines and subsequent CO2 fixation at the 3-position of the indole ring is realized. The reaction proceeds efficiently at 65 °C under 10 atm of CO2, giving rise to variously substituted 3-carboxylated indoles, generally in high yields. An inorganic base, such as K2CO3, is the only reagent required, and the addition of transition metal catalysts is not necessary. The method provides a novel, simple, and promising strategy for CO2 fixation in the research field of heterocyclic chemistry.
Bayesian Learning via Stochastic Gradient Langevin Dynamics (2011)

In this paper we propose a new framework for learning from large scale datasets based on iterative learning from small mini-batches. By adding the right amount of noise to a standard stochastic gradient optimization algorithm we show that the iterates will converge to samples from the true posterior distribution as we anneal the stepsize. This seamless transition between optimization and Bayesian posterior sampling provides an inbuilt protection against overfitting. We also propose a practical method for Monte Carlo estimates of posterior statistics which monitors a "sampling threshold" and collects samples after it has been surpassed. We apply the method to three models: a mixture of Gaussians, logistic regression and ICA with natural gradients. Copyright 2011 by the author(s)/owner(s).
Molecular Regulation of Contractile Smooth Muscle Cell Phenotype: Implications for Vascular Tissue Engineering (2010)

The molecular regulation of smooth muscle cell (SMC) behavior is reviewed, with particular emphasis on stimuli that promote the contractile phenotype. SMCs can shift reversibly along a continuum from a quiescent, contractile phenotype to a synthetic phenotype, which is characterized by proliferation and extracellular matrix (ECM) synthesis. This phenotypic plasticity can be harnessed for tissue engineering. Cultured synthetic SMCs have been used to engineer smooth muscle tissues with organized ECM and cell populations. However, returning SMCs to a contractile phenotype remains a key challenge. This review will integrate recent work on how soluble signaling factors, ECM, mechanical stimulation, and other cells contribute to the regulation of contractile SMC phenotype. The signal transduction pathways and mechanisms of gene expression induced by these stimuli are beginning to be elucidated and provide useful information for the quantitative analysis of SMC phenotype in engineered tissues. Progress in the development of tissue-engineered scaffold systems that implement biochemical, mechanical, or novel polymer fabrication approaches to promote contractile phenotype will also be reviewed. The application of an improved molecular understanding of SMC biology will facilitate the design of more potent cell-instructive scaffold systems to regulate SMC behavior.
Time-kill kinetics of oritavancin and comparator agents against Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium (2009)

Oritavancin displayed concentration-dependent killing of MSSA, MRSA, VRSA, VISA, VSE and VRE. Oritavancin was more rapidly bactericidal against all strains tested than were vancomycin, teicoplanin, linezolid or daptomycin at physiologically relevant concentrations. These data support the conclusion that oritavancin exerts concentration-dependent bactericidal activity on recent, drug-resistant isolates of S. aureus and enterococci.
Sequence-targeted chemical modifications of nucleic acids by complementary oligonucleotides covalently linked to porphyrins (1987)

Oligo-heptathymidylates covalently linked to porphyrins bind to complementary sequences and can induce local damages on the target molecule. In dark reactions, iron porphyrin derivatives exhibited various chemical reactivities resulting in base oxidation, crosslinking and chain scission reactions. Reactions induced by reductants, such as ascorbic acid, dithiothreitol or mercapto-propionic acid, led to very localised reactions. A single base was the target for more than 50% of the damages. Oxidising agents such as H2O2 and its alkyl derivatives induced reactions that extended to a wider range of altered bases. The specificity of the chemical modifications observed in these systems is discussed from a mechanistic point of view.
Validation of biomarkers in humans exposed to benzene: Urine metabolites (2000)

All metabolites, except BT, are good markers for benzene exposure at the observed levels; however, due to their high background, HQ, CAT, and phenol may not distinguish unexposed subjects from workers exposed to benzene at low ambient levels. S-PMA and t,t-MA are the most sensitive markers for low level benzene exposure.
Purification and characterization of 2,4-dichlorophenoxyacetate/alpha-ketoglutarate dioxygenase. (1993)

The Alcaligenes eutrophus 2,4-dichlorophenoxyacetate/alpha-ketoglutarate dioxygenase, encoded by the tfdA gene of plasmid pJP4, is an Fe(II)-dependent enzyme that catalyzes the conversion of 2,4-dichlorophenoxyacetate to 2,4-dichlorophenol and glyoxylate concomitant with the decomposition of alpha-ketoglutarate to form succinate and carbon dioxide (Fukumori, F., and Hausinger, R. P. (1993) J. Bacteriol. 175, 2083-2086). Using recombinant Escherichia coli cells that overexpress the tfdA gene, the thermolabile enzyme (stable only up to 30 degrees C) was purified to apparent homogeneity (specific activity of 16.9 mumol of substrate converted min-1 mg of protein-1) by a simple two-step procedure. The native protein has an apparent M(r) of 50,000 +/- 2,500, consistent with a homodimeric structure. Ferrous ion is absolutely required for activity and cannot be replaced by several other divalent cations tested. Ascorbic acid stimulates dioxygenase activity and reduces the rate of enzyme inactivation by a metal ion-mediated process. The enzyme exhibits maximum activity at pH 6.5-7, however, it is stable over a pH range of 6.5-11. Although capable of hydroxylating a wide range of phenoxyacetates and related compounds, the enzyme exhibits the greatest affinity (Km 17.5 +/- 1.0 microM) and highest catalytic efficiency for 2,4-dichlorophenoxyacetate. Similarly, alpha-ketoglutarate is the preferred co-substrate (Km 3.20 +/- 0.54 microM) for the enzyme, but it can utilize a range of other alpha-ketoacids with lower efficiency. Results from chemical modification studies are consistent with the presence of multiple essential histidine residues in the enzyme.
Cell–cell and intracellular lactate shuttles (2009)

Once thought to be the consequence of oxygen lack in contracting skeletal muscle, the glycolytic product lactate is formed and utilized continuously in diverse cells under fully aerobic conditions. 'Cell-cell' and 'intracellular lactate shuttle' concepts describe the roles of lactate in delivery of oxidative and gluconeogenic substrates as well as in cell signalling. Examples of the cell-cell shuttles include lactate exchanges between between white-glycolytic and red-oxidative fibres within a working muscle bed, and between working skeletal muscle and heart, brain, liver and kidneys. Examples of intracellular lactate shuttles include lactate uptake by mitochondria and pyruvate for lactate exchange in peroxisomes. Lactate for pyruvate exchanges affect cell redox state, and by itself lactate is a ROS generator. In vivo, lactate is a preferred substrate and high blood lactate levels down-regulate the use of glucose and free fatty acids (FFA). As well, lactate binding may affect metabolic regulation, for instance binding to G-protein receptors in adipocytes inhibiting lipolysis, and thus decreasing plasma FFA availability. In vitro lactate accumulation upregulates expression of MCT1 and genes coding for other components of the mitochondrial reticulum in skeletal muscle. The mitochondrial reticulum in muscle and mitochondrial networks in other aerobic tissues function to establish concentration and proton gradients necessary for cells with high mitochondrial densities to oxidize lactate. The presence of lactate shuttles gives rise to the realization that glycolytic and oxidative pathways should be viewed as linked, as opposed to alternative, processes, because lactate, the product of one pathway, is the substrate for the other.
Synthesis and Tyrosine Kinase Inhibitory Activity of a Series of 2-Amino-8H-pyrido[2,3-d]pyrimidines:  Identification of Potent, Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitors (1998)

Screening of a compound library led to the identification of 2-amino-6-(2,6-dichlorophenyl)-8-methylpyrido[2,3-d]pyrimidine (1) as a inhibitor of the platelet-derived growth factor receptor (PDGFr), fibroblast growth factor receptor (FGFr), and c-src tyrosine kinases (TKs). Replacement of the primary amino group at C-2 of 1 with a 4-(N,N-diethylaminoethoxy)phenylamino group yielded 2a, which had greatly increased activity against all three TKs. In the present work, variation of the aromatic group at C-6 and of the alkyl group at N-8 of the pyrido[2,3-d]pyrimidine core provided several analogues that retained potency, including derivatives that were biased toward inhibition of the TK activity of PDGFr. Analogues of 2a with a 3-thiophene or an unsubstituted phenyl group at C-6 were the most potent inhibitors. Compound 54, which had IC50 values of 31, 88, and 31 nM against PDGFr, FGFr, and c-src TK activity, respectively, was active in a variety of PDGF-dependent cellular assays and blocked the in vivo growth of three PDGF-dependent tumor lines.
Murine Models of Acute Leukemia: Important Tools in Current Pediatric Leukemia Research (2014)

Leukemia remains the most common diagnosis in pediatric oncology and, despite dramatic progress in upfront therapy, is also the most common cause of cancer-related death in children. Much of the initial improvement in outcomes for acute lymphoblastic leukemia (ALL) was due to identification of cytotoxic agents that are active against leukemia followed by the recognition that combination of these cytotoxic agents and prolonged therapy are essential for cure. Recent data demonstrating lack of progress in patients for whom standard chemotherapy fails suggests that the ability to improve outcome for these children will not be dramatically impacted through more intensive or newer cytotoxic agents. Thus, much of the recent research focus has been in the area of improving our understanding of the genetics and the biology of leukemia. Although in vitro studies remain critical, given the complexity of a living system and the increasing recognition of the contribution of leukemia extrinsic factors such as the bone marrow microenvironment, in vivo models have provided important insights. The murine systems that are used can be broadly categorized into syngeneic models in which a murine leukemia can be studied in immunologically intact hosts and xenograft models where human leukemias are studied in highly immunocompromised murine hosts. Both of these systems have limitations such that neither can be used exclusively to study all aspects of leukemia biology and therapeutics for humans. This review will describe the various ALL model systems that have been developed as well as discuss the advantages and disadvantages inherent to these systems that make each particularly suitable for specific types of studies.
Early Results of a Chemoimmunotherapy Regimen of Fludarabine, Cyclophosphamide, and Rituximab As Initial Therapy for Chronic Lymphocytic Leukemia (2005)

FCR produced a high CR rate in previously untreated CLL. Most patients had no detectable disease on flow cytometry at the end of therapy. Time to treatment failure analysis showed that 69% of patients were projected to be failure free at 4 years (95% CI, 57% to 81%).
A Structure-Activity Study of the Inhibition of HIV-1 Tat-Dependent Trans- Activation by Mixmer 2′- O -Methyl Oligoribonucleotides Containing Locked Nucleic Acid (LNA), α -L-LNA, or 2′-Thio-LNA Residues (2003)

The HIV-1 trans-activation responsive element (TAR) RNA stem-loop interacts with the HIV trans-activator protein Tat and other cellular factors to stimulate transcriptional elongation from the viral long terminal repeat (LTR). Inhibitors of these interactions block full-length transcription and, hence, would potentially inhibit HIV replication. We have studied structure-activity relationships in inhibition of trans-activation by steric block 2'-O-methyl (OMe) oligonucleotides chimeras (mixmers) containing locked nucleic acid (LNA) units. Inhibition was measured both in Tat-dependent in vitro transcription from an HIV-1 DNA template directed by HeLa cell nuclear extract and in a robust HeLa cell reporter assay that involves use of stably integrated plasmids to express firefly luciferase Tat dependently and Renilla luciferase Tat-independently. OMe oligonucleotides with optimally 40%-50% LNA units and a minimum of 12 residues in length were active in the cellular assay when delivered with cationic gemini surfactant GS11 at 50% inhibitory concentrations of 230 +/- 40 nM, whereas activity in the in vitro transcription assay was observed down to 9 residues. No cellular activity was observed for OMe oligonucleotides of 12 or 16 residues, which was shown to be due to poor cellular uptake. Both 12-mer mixmers containing alpha -L-LNA or 2'-thio-LNA (S-LNA) were also active in in vitro transcription and the former in cellular reporter inhibition assays, demonstrating that the property of promotion of cellular uptake by LNA is not due to specific sugar conformational effects. Covalent conjugates of OMe/LNA chimeras with Kaposi-fibroblast growth factor (K-FGF) or Transportan peptides failed to enter HeLa cells without a delivery agent but were fully active when delivered by cationic gemini surfactant, showing that in principle, peptide conjugation does not interfere with cellular activity. Thus, OMe/LNA mixmers are powerful reagents for use as steric block inhibitors of gene expression regulated by protein-RNA interactions within HeLa cell nuclei.
Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat (2019)

Psilocin and psilocybin showed no antidepressant-like effect in the FSL rats, despite a positive effect in humans. This suggests that other animal models of depression and other behavioural tests may be more appropriate for translational studies in the effects of psilocybin.
Computational Model Predicts a Role for ERG Current in Repolarizing Plateau Potentials in Dopamine Neurons: Implications for Modulation of Neuronal Activity (2007)

Blocking the small-conductance (SK) calcium-activated potassium channel promotes burst firing in dopamine neurons both in vivo and in vitro. In vitro, the bursting is unusual in that spiking persists during the hyperpolarized trough and frequently terminates by depolarization block during the plateau. We focus on the underlying plateau potential oscillation generated in the presence of both apamin and TTX, so that action potentials are not considered. We find that although the plateau potentials are mediated by a voltage-gated Ca(2+) current, they do not depend on the accumulation of cytosolic Ca(2+), then use a computational model to test the hypothesis that the slowly voltage-activated ether-a-go-go-related gene (ERG) potassium current repolarizes the plateaus. The model, which includes a material balance on calcium, is able to reproduce the time course of both membrane potential and somatic calcium concentration, and can also mimic the induction of plateau potentials by the calcium chelator BAPTA. The principle of separation of timescales was used to gain insight into the mechanisms of oscillation and its modulation using nullclines in the phase space. The model predicts that the plateau will be elongated and ultimately result in a persistent depolarization as the ERG current is reduced. This study suggests that the ERG current may play a role in burst termination and the relief of depolarization block in vivo.
A Mouse Geneticist’s Practical Guide to CRISPR Applications (2014)

CRISPR/Cas9 system of RNA-guided genome editing is revolutionizing genetics research in a wide spectrum of organisms. Even for the laboratory mouse, a model that has thrived under the benefits of embryonic stem (ES) cell knockout capabilities for nearly three decades, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 technology enables one to manipulate the genome with unprecedented simplicity and speed. It allows generation of null, conditional, precisely mutated, reporter, or tagged alleles in mice. Moreover, it holds promise for other applications beyond genome editing. The crux of this system is the efficient and targeted introduction of DNA breaks that are repaired by any of several pathways in a predictable but not entirely controllable manner. Thus, further optimizations and improvements are being developed. Here, we summarize current applications and provide a practical guide to use the CRISPR/Cas9 system for mouse mutagenesis, based on published reports and our own experiences. We discuss critical points and suggest technical improvements to increase efficiency of RNA-guided genome editing in mouse embryos and address practical problems such as mosaicism in founders, which complicates genotyping and phenotyping. We describe a next-generation sequencing strategy for simultaneous characterization of on- and off-target editing in mice derived from multiple CRISPR experiments. Additionally, we report evidence that elevated frequency of precise, homology-directed editing can be achieved by transient inhibition of the Ligase IV-dependent nonhomologous end-joining pathway in one-celled mouse embryos.
Screen Printing of Highly Loaded Silver Inks on Plastic Substrates Using Silicon Stencils (2015)

Screen printing is a potential technique for mass-production of printed electronics; however, improvement in printing resolution is needed for high integration and performance. In this study, screen printing of highly loaded silver ink (77 wt %) on polyimide films is studied using fine-scale silicon stencils with openings ranging from 5 to 50 μm wide. This approach enables printing of high-resolution silver lines with widths as small as 22 μm. The printed silver lines on polyimide exhibit good electrical properties with a resistivity of 5.5×10(-6) Ω cm and excellent bending tolerance for bending radii greater than 5 mm (tensile strains less than 0.75%).
Description, performance, and calibration of a charge-coupled-device camera (1980)

A description is given of the SAO CCD camera using the 100 x 100 Fairchild chip operated in a direct imaging mode, together with extensive data on its performance in the laboratory and at the telescope. Short descriptions of the cryogenic, electronic, computer control, and optical systems are presented. Laboratory measurements of the correction for the nonuniformity in sensitivity, linearity, system noise, quantum efficiency, and dark current are discussed. Calibrations of the positions and magnitudes of standard stars in clusters and the surface brightness of a standard galaxy are analyzed. These measurements illustrate the effectiveness of the camera as a photometric detector and also calibrate the parameters of the system.
Inflammatory Monocyte Mobilization Decreases Patient Survival in Pancreatic Cancer: A Role for Targeting the CCL2/CCR2 Axis (2013)

Inflammatory monocyte recruitment is critical to pancreatic cancer progression, and targeting CCR2 may be an effective immunotherapeutic strategy in this disease.
ADP-ribosyl protein lyase. Purification, properties, and identification of the product. (1984)

ADP-ribosyl protein lyase, formerly termed ADP-ribosyl histone-splitting enzyme (Okayama, H., Honda, M., and Hayaishi, O. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 2254-2257), was purified approximately 4,000-fold from rat liver and characterized. The purified enzyme exhibited a single protein band at the position of Mr = 83,000 upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme split the bond between ADP-ribose and histone H2B or H1, and also acted on ADP-ribosyl pentapeptide (Pro-(ADP-ribosyl)Glu-Pro-Ala-Lys) of H2B but not its deadenylylated derivative, phosphoribosyl pentapeptide. The enzyme cleaved the bond between histone and mono(ADP-ribose), but hardly cleaved the bond with oligo- or poly(ADP-ribose). The enzymatic product was close to, but not identical with, ADP-ribose. The terminal ribose residue, obtained by hydrolysis of the split product by snake venom phosphodiesterase and alkaline phosphatase, was identified as 3-deoxy-D-glycero-pentos-2-ulose by the following gas chromatography-mass spectrometric analyses: 1) the reduced sugar was a mixture of 3-deoxy-threo- and 3-deoxy-erythro-pentitol, and 2) the deuterated reduced sugar was identical with that derived from synthetic 3-deoxy-D-glycero-pentos-2-ulose. This result indicated that the direct product was 5'-ADP-3"-deoxypent-2"-enofuranose, a dehydrated form of ADP-ribose, and that the enzyme is a lyase and not a hydrolase.
Anti-melanoma effects of R24, a monoclonal antibody against GD3 ganglioside (1997)

R24, a mouse monoclonal antibody against GD3 ganglioside, is potent at mediating in vitro effector functions such as human complement-mediated cytotoxicity and antibody-dependent cellular cytotoxicity, and can block melanoma tumor growth in animal models. Because of these properties and the fact that GD3 is abundantly expressed on virtually all melanomas but is found on few normal tissues, R24 has been tested in a series of clinical trials in patients with metastatic melanoma. As a single agent, R24 can induce responses in patients treated with metastatic melanoma. Overall, there have been 10 responders out of 103 patients reported; two responses have been complete responses. Responses have largely occurred in patients treated with intermediate doses of R24 and have included complete responses. Combining R24 with either cytotoxic drugs or cytokines has not increased this response rate, although one trial with R24 and interleukin-2 resulted in a 43% response rate and merits further investigation. Local-regional treatments R24 (intratumor injections, regional limb perfusion, intrathecal administration) have also been attempted in a small number of patients and responses have been described. Taken together, multiple centers have reported responses in patients with metastatic melanoma treated with R24.