gebhart/patrepeval huggingface dataset:
Structural Transition in an Ionic Liquid Controls CO2 Electrochemical Reduction (2015)

Broad-band multiplex vibrational sum-frequency generation spectroscopy (SFG) was used to study CO2 reduction on a polycrystalline Ag electrode with a room-temperature ionic liquid (RTIL) electrolyte, 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIM-BF4), with 0.3 mol % water. The Ag/RTIL/H2O system has been shown to reduce CO2 with low overpotential and, depending on water concentration, with Faradaic efficiency of nearly 100% (Rosen, B. A.; Salehi-Khojin, A.; Thorson, M. R.; Zhu, W.; Whipple, D. T.; Kenis, P. J. A.; Masel, R. I. Science 2011, 334, 643–644). The adsorbed CO created by CO2 reduction was probed with infrared (IR) pulses tuned to the CO stretch. Nonresonant (NR) SFG was used to probe the double layer. SFG showed that CO binds weakly to Ag at the CO2 reduction threshold of −1.33 V (vs Ag/AgCl), so CO does not poison the surface. At potentials equal to or more negative than the threshold, the curvature of the parabolic potential-dependent NR intensity significantly increased, and the Stark shift of adsorbed CO, a measure of the surface field, more than doubled. The curvature increase indicates a potential-driven structural transition in the RTIL within the double layer. This transition was a property of the RTIL itself since it occurred whether or not CO2 was present. Significantly, the RTIL transition and the increased surface field occurred precisely at the CO2 reduction threshold. Thus, we have demonstrated a close association between an electrochemically driven structural transition of the RTIL and low overpotential CO2 reduction.
Neural Ordinary Differential Equations (2018)

We introduce a new family of deep neural network models. Instead of specifying a discrete sequence of hidden layers, we parameterize the derivative of the hidden state using a neural network. The output of the network is computed using a black-box differential equation solver. These continuous-depth models have constant memory cost, adapt their evaluation strategy to each input, and can explicitly trade numerical precision for speed. We demonstrate these properties in continuous-depth residual networks and continuous-time latent variable models. We also construct continuous normalizing flows, a generative model that can train by maximum likelihood, without partitioning or ordering the data dimensions. For training, we show how to scalably backpropagate through any ODE solver, without access to its internal operations. This allows end-to-end training of ODEs within larger models.
Medication Errors Made by Elderly, Chronically Ill Patients (1962)

Medication Errors Made by Elderly, Chronically Ill Patients Doris Schwartz, Mamie Wang, Leonard Zeitz, and Mary E. W. Goss CopyRight https://doi.org/10.2105/AJPH.52.12.2018 Published Online: August 29, 2011
Towards a commercial process for the manufacture of genetically modified T cells for therapy (2015)

The recent successes of adoptive T-cell immunotherapy for the treatment of hematologic malignancies have highlighted the need for manufacturing processes that are robust and scalable for product commercialization. Here we review some of the more outstanding issues surrounding commercial scale manufacturing of personalized-adoptive T-cell medicinal products. These include closed system operations, improving process robustness and simplifying work flows, reducing labor intensity by implementing process automation, scalability and cost, as well as appropriate testing and tracking of products, all while maintaining strict adherence to Current Good Manufacturing Practices and regulatory guidelines. A decentralized manufacturing model is proposed, where in the future patients' cells could be processed at the point-of-care in the hospital.
Uptake of dextran‐coated monocrystalline iron oxides in tumor cells and macrophages (1997)

Although several dextran-coated iron oxide preparations are in preclinical and clinical use, little is known about the mechanism of uptake into cells. As these particles have been shown to accumulate in macrophages and tumor cells, we performed cellular uptake and inhibition studies with a prototypical monocrystalline iron oxide nanoparticle (MION). MION particles were labeled with fluorescein isothiocyanate or radioiodinated and purified by gel permeation chromatography. Two preparations of MION particles were used in cell experiments: nontreated MION and plasma-opsonized MION purified by gradient density purification. As determined by immunoblotting, opsonization resulted in C3, vitronectin, and fibronectin association with MION. Incubation of cells with fluorescent MION showed active uptake of particles in macrophages both before and after opsonization. In C6 tumor cells, however, intracellular MION was only detectable in dividing cells. Quantitatively, 125I-labeled MION was internalized into cells with uptake values ranging from 17 ng (in 9L gliosarcoma) to 970 ng iron per million cells for peritoneal macrophages. Opsonization increased MION uptake into macrophages sixfold, whereas it increased the uptake in C6 tumor cells only twofold. Results from uptake inhibition assay suggest that cellular uptake of nonopsonized (dextran-coated) MION particles is mediated by fluid-phase endocytosis, whereas receptor-mediated endocytosis is presumably responsible for the uptake of opsonized (protein-coated) particles.
The balance of metagenomic elements shapes the skin microbiome in acne and health (2016)

Studies have emphasized the importance of disease-associated microorganisms in perturbed communities, however, the protective roles of commensals are largely under recognized and poorly understood. Using acne as a model disease, we investigated the determinants of the overall virulence property of the skin microbiota when disease- and health-associated organisms coexist in the community. By ultra-deep metagenomic shotgun sequencing, we revealed higher relative abundances of propionibacteria and Propionibacterium acnes phage in healthy skin. In acne patients, the microbiome composition at the species level and at P. acnes strain level was more diverse than in healthy individuals, with enriched virulence-associated factors and reduced abundance of metabolic synthesis genes. Based on the abundance profiles of the metagenomic elements, we constructed a quantitative prediction model, which classified the clinical states of the host skin with high accuracy in both our study cohort (85%) and an independent sample set (86%). Our results suggest that the balance between metagenomic elements, not the mere presence of disease-associated strains, shapes the overall virulence property of the skin microbiota. This study provides new insights into the microbial mechanism of acne pathogenesis and suggests probiotic and phage therapies as potential acne treatments to modulate the skin microbiota and to maintain skin health.
Chlorellosis in a Lamb (1973)

Bright green necrotic lesions were seen in the liver and hepatic lymph nodes of a slaughtered lamb. The lesions contained numerous organisms that had the morphology, staining properties, and mode of division typical of both Chlorella and Prototheca . The presence of pigment, presumably chlorophyll, suggests that the organisms were indeed Chlorella .
KARACİĞER METASTAZI İLE SEYREDEN MEDÜLLER TİROİD KARSİNOMU OLGU SUNUMU (2002)

Background.- Medullary thyroid carcinoma usually presents with palpable cervical lymphadenopathy, rapidly arising neck mass and local pain. Less frequently, dysphagia, dyspnea and dysphenia can be seen as a result of local invasion. However, especially in familial cases (MEN 2A, MEN 2B and nonMEN), chronic diarrhea can develop as the only symptom. Observation.- In the present study, we present a 25 year-old male patient with distant metastasis of medullary thyroid carcinoma. The diagnosis was confirmed after liver biopsy taken during diagnostic laparoscopy.* Anahtar Kelimeler: Medüller tiroid karsinomu, metastaz, ishal* Key words: Medullary thyroid carcinoma, metastasis diarrhea
Isolation of CpG islands from large genomic clones (1999)

Positional cloning is a powerful method for the identification of genes. Using genetic and physical mapping methods the genomic region within which a particular gene is located can relatively easily be narrowed down to a comparatively small area contained within cosmid, PAC or BAC clones. It is then a matter of identifying genes within these clones. Here we describe the appli-cation of a technique, which has been successfully used for the bulk purification of CpG islands from whole genomes, to the isolation of CpG island sequences from such clones. As CpG islands overlap transcription units they can be used to isolate full-length cDNAs for associated genes, either by probing cDNA libraries or by searching databases. CpG islands are linked with approximately 60% of human genes and because their isolation is independent of the expression profile of these genes this approach would complement other expression-based methods of gene identification. By applying this technique to a cosmid clone known to contain the PAX6 gene we successfully isolated the CpG island for this gene along with other CpG island-like sequences. Closer examination revealed that an extensive genomic region around the 5'-end of PAX6 is unusual with regard to methylation and GC content. CpG island sequences were also successfully isolated from a PAC clone carrying the MBD1 gene. These included the complete CpG island containing the first exon and regulatory sequences from MBD1.
Aggregation-induced CD effects in chiral poly(2,5-dialkoxy-1,4-phenylene)s (1998)

_We have investigated the chiroptical properties of novel PPPs containing chiral side chains. The synthesis of poly(2,5-bis[2-(S)-methylbutoxy]-1,4-phenylene) (BMB-PPP) has been successfully achieved in a Suzuki-type aryl—aryl cross coupling (Mn: 9700, Dp: 40, PPP calibration). The very good solubility of BMB-PPP allows for a detailed study of its chiroptical properties. Our studies demonstrate that the bisignated CD spectra of BMB-PPP are associated with an intermolecular aggregation phenomenon. BMB-PPP shows remarkably high dissymmetry factors both in poor solvent/good solvent mixtures and in the solid state (Δε/ε up to 0.01). BMB-PPP exhibits an intense blue photoluminescence in solution, and in the solid state. In addition, the first execution of the so-called “sergeant and soldier” principle for a chiral-substituted, conjugated polymer is described.
Small molecule clearance in ultrafiltration/diafiltration in relation to protein interactions: Study of citrate binding to a Fab (2008)

Ultrafiltration/diafiltration (UFDF) is commonly utilized in the purification of recombinant proteins to concentrate and buffer exchange the product. It is often the final step in the purification process, placing the protein in its final formulation and clearing small molecules introduced in upstream purification steps. This article presents a case study of reduced small molecule clearance in ultrafiltration/diafiltration of an antigen-binding fragment of a monoclonal antibody. Citrate, a commonly utilized small molecule in downstream processes, is shown to have reduced clearance due to specific interactions with the protein product. The study presents process solutions and utilizes a simple model to characterize clearance of small molecules which exhibit interactions with product protein.
Quantitative On-Line Analysis of Physiological Data for Lesion Placement in Pallidotomy (2000)

A computerized method of determining the focal point of electrical activity in the pallidum of parkinsonian patients was developed using on-line quantitative physiological data analysis. Thirty patients in a series of 70 were studied in depth. Neuronal activity was recorded from the pallidum using a semi-microelectrode. The signal is inspected visually while its average power, characteristic frequency and complexity are computed. The target locus was indicated by the highest level of global activity in the vicinity of the electrode (signal power maximum), maximal signal complexity and minimal characteristic frequency. Most often, the vertical coordinate required correction. The postoperative clinical and imaging results have indicated the effectiveness of this method.
Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo. (1995)

The NPXY sequence is highly conserved among integrin beta subunit cytoplasmic tails, suggesting that it plays a fundamental role in regulating integrin-mediated function. Evidence is provided that the NPXY structural motif within the beta 3 subunit, comprising residues 744-747, is essential for cell morphological and migratory responses mediated by integrin alpha v beta 3 in vitro and in vivo. Transfection of CS-1 melanoma cells with a cDNA encoding the wild-type integrin beta 3 subunit, results in de novo alpha v beta 3 expression and cell attachment, spreading, and migration on vitronectin. CS-1 cells expressing alpha v beta 3 with mutations that disrupt the NPXY sequence interact with soluble vitronectin or an RGD peptide, yet fail to attach, spread, or migrate on immobilized ligand. The biological consequences of these observations are underscored by the finding that CS-1 cells expressing wild-type alpha v beta 3 acquire the capacity to form spontaneous pulmonary metastases in the chick embryo when grown on the chorioallantoic membrane. However, migration-deficient CS-1 cells expressing alpha v beta 3 with mutations in the NPXY sequence lose this ability to metastasize. These findings demonstrate that the NPXY motif within the integrin beta 3 cytoplasmic tail is essential for alpha v beta 3-dependent post-ligand binding events involved in cell migration and the metastatic phenotype of melanoma cells.
Signal Peptide-Dependent Protein Transport in Bacillus subtilis : a Genome-Based Survey of the Secretome (2000)

One of the most salient features of Bacillus subtilis and related bacilli is their natural capacity to secrete a variety of proteins into their environment, frequently to high concentrations. This has led to the commercial exploitation of bacilli as major "cell factories" for secreted enzymes. The recent sequencing of the genome of B. subtilis has provided major new impulse for analysis of the molecular mechanisms underlying protein secretion by this organism. Most importantly, the genome sequence has allowed predictions about the composition of the secretome, which includes both the pathways for protein transport and the secreted proteins. The present survey of the secretome describes four distinct pathways for protein export from the cytoplasm and approximately 300 proteins with the potential to be exported. By far the largest number of exported proteins are predicted to follow the major "Sec" pathway for protein secretion. In contrast, the twin-arginine translocation "Tat" pathway, a type IV prepilin-like export pathway for competence development, and ATP-binding cassette transporters can be regarded as "special-purpose" pathways, through which only a few proteins are transported. The properties of distinct classes of amino-terminal signal peptides, directing proteins into the various protein transport pathways, as well as the major components of each pathway are discussed. The predictions and comparisons in this review pinpoint important differences as well as similarities between protein transport systems in B. subtilis and other well-studied organisms, such as Escherichia coli and the yeast Saccharomyces cerevisiae. Thus, they may serve as a lead for future research and applications.
Local delivery of the topoisomerase I inhibitor camptothecin sodium prolongs survival in the rat intracranial 9L gliosarcoma model (1995)

Camptothecin, a naturally occurring inhibitor of the DNA-replicating enzyme topoisomerase I, demonstrated promising anti-tumor activity in pre-clinical testing; however, because of unexpected toxicity and low anti-tumor effects in the initial clinical trials, further testing was discontinued. We hypothesized that local controlled delivery of camptothecin sodium would achieve effective concentrations in brain tumors without the observed systemic side effects, thereby allowing this novel drug to be used to treat patients with malignant gliomas. To test this hypothesis, we evaluated the sensitivity of rat glioma lines and established human glioma lines to camptothecin in vitro. We found that the LD90 for the established rat and human lines was 0.3 to 1.4 microM after a 1 hr exposure and decreased to less than 0.1 microM after continuous exposure for 7 days. We loaded camptothecin into a controlled-release polymer (ethylene-vinyl acetate co-polymer; EVAc) and showed by high-pressure liquid chromatography that controlled release occurred over at least 21 days. We then tested camptothecin against 9L gliosarcoma, implanted into the brain of Fischer 344 rats. Five days after tumor implantation, animals were treated with camptothecin delivered either systemically or locally by release from EVAc. Local controlled delivery by the polymer significantly extended survival: 59% of the treated animals were long-term survivors (> 120 days) compared to 0% of controls. Systemic administration did not extend survival compared to controls. We compared the efficacy of camptothecin delivered locally with a polymer to camptothecin injected directly into the tumor. Camptothecin increased survival only when delivered locally by polymer.
Mechanisms and Kinetics for Sorption of CO2 on Bicontinuous Mesoporous Silica Modified with n-Propylamine (2011)

We studied equilibrium adsorption and uptake kinetics and identified molecular species that formed during sorption of carbon dioxide on amine-modified silica. Bicontinuous silicas (AMS-6 and MCM-48) were postsynthetically modified with (3-aminopropyl)triethoxysilane or (3-aminopropyl)methyldiethoxysilane, and amine-modified AMS-6 adsorbed more CO(2) than did amine-modified MCM-48. By in situ FTIR spectroscopy, we showed that the amine groups reacted with CO(2) and formed ammonium carbamate ion pairs as well as carbamic acids under both dry and moist conditions. The carbamic acid was stabilized by hydrogen bonds, and ammonium carbamate ion pairs formed preferably on sorbents with high densities of amine groups. Under dry conditions, silylpropylcarbamate formed, slowly, by condensing carbamic acid and silanol groups. The ratio of ammonium carbamate ion pairs to silylpropylcarbamate was higher for samples with high amine contents than samples with low amine contents. Bicarbonates or carbonates did not form under dry or moist conditions. The uptake of CO(2) was enhanced in the presence of water, which was rationalized by the observed release of additional amine groups under these conditions and related formation of ammonium carbamate ion pairs. Distinct evidence for a fourth and irreversibly formed moiety was observed under sorption of CO(2) under dry conditions. Significant amounts of physisorbed, linear CO(2) were detected at relatively high partial pressures of CO(2), such that they could adsorb only after the reactive amine groups were consumed.
Bond-specific chemistry: OD:OH product ratios for the reactions H+HOD(100) and H+HOD(001) (1991)

From laser-induced fluorescence measurements, the OD:OH product branching ratio is determined to be greater than 25:1 for the reaction H+HOD(001) and less than 1:8 for the reaction H+HOD(100). Fast H atoms are generated by the photolysis of HI at 266 nm and the HOD is excited to a specific vibronic state using an optical parametric oscillator. Here HOD(001) and HOD(100) correspond to O–H and O–D local-mode stretch fundamentals, respectively. Within our signal-to-noise level, reaction occurs exclusively with the extended hydrogen atom of HOD in each case.
A Bayesian Population PK–PD Model of Ispinesib-induced Myelosuppression (2006)

The goal of the present analysis is to fit a Bayesian population pharmacokinetic pharmacodynomic (PK-PD) model to characterize the relationship between the concentration of ispinesib and changes in absolute neutrophil counts (ANC). Ispinesib, a kinesin spindle protein (KSP) inhibitor, blocks assembly of a functional mitotic spindle, leading to G2/M arrest. A first time in human, phase I open-label, non-randomized, dose-escalating study evaluated ispinesib at doses ranging from 1 to 21 mg/m(2). PK-PD data were collected from 45 patients with solid tumors. The pharmacokinetics of ispinesib were well characterized by a two-compartment model. A semimechanistic model was fit to the ANC. The PK and PD data were successfully modelled simultaneously. This is the first presentation of simultaneously fitting a PK-PD model to ANC using Bayesian methods. Bayesian methods allow for the use of prior information for some system-related parameters. The model may be used to examine different schedules, doses, and infusion times.
Virtual instrumentation: a survey of standards and their interrelation (2002)

Many standards exist in the field of instrumentation. The ever increasing scale of integration of processing power with instrumentation has opened ways to extend and transform the functionality of instruments in software, i.e. create a virtual instrument. Controlling and standardizing this virtual instrument requires a multi-level definition. In this paper we review some of the most relevant developments in this field.
Compilation and analysis of eukaryotic POL II promoter sequences (1986)

A representative set of 168 eukaryotic POL II promoters has been compiled from the EMBL library and subjected to computer signal search analysis. Application of this technique to E. coli promoters as a control ensemble revealed the well known consensus sequences at -35 and -10 which indicates that the methods are adequate to approach problems of this kind. The results obtained from the eukaryotic promoter set can be summarized as follows: Common sequence features are confined to a region between -50 and +10 relative to the transcriptional initiation site. The only well conserved consensus sequence is TATAAA, centered at -28. A weak motif, CA followed preferentially by pyrimidines, surrounds the cap-site. Two pentanucleotides which have been shown by experiments to stimulate transcription of certain genes, GGGCG and CCAAT, are moderately over-represented in the upstream region (between -129 and -50). However, they occur at highly variable distances from the initiation site.
Substrate specificity of the protein tyrosine phosphatases. (1993)

The substrate specificity of a recombinant protein tyrosine phosphatase (PTPase) was probed using synthetic phosphotyrosine-containing peptides corresponding to several of the autophosphorylation sites in epidermal growth factor receptor (EGFR). The peptide corresponding to the autophosphorylation site, EGFR988-998, was chosen for further study due to its favorable kinetic constants. The contribution of individual amino acid side chains to the binding and catalysis was ascertained utilizing a strategy in which each amino acid within the undecapeptide EGFR988-998 (DADEpYLIPQQG) was sequentially substituted by an Ala residue (Ala-scan). The resulting effects due to singular Ala substitution were assessed by kinetic analysis with two widely divergent homogeneous PTPases. A "consensus sequence" for PTPase recognition may be suggested from the Ala-scan data as DADEpYAAPA, and the presence of acidic residues proximate to the NH2-terminal side of phosphorylation is critical for high-affinity binding and catalysis. The Km value for EGFR988-998 decreased as the pH increased, suggesting that phosphate dianion is favored for substrate binding. The results demonstrate that chemical features in the primary structure surrounding the dephosphorylation site contribute to PTPase substrate specificity.