gebhart/patrepeval huggingface dataset:
A network-based conditional genetic association analysis of the human metabolome (2018)

We found that compared to single-trait analysis, performing a genetic association analysis that includes biologically relevant covariates can either gain or lose power, depending on specific pleiotropic scenarios, for which we provide empirical examples. In the context of analyzed metabolomics data, the mechanistic network approach had more power compared to the data-driven approach. Nevertheless, we believe that our analysis shows that neither a prior-knowledge-only approach nor a phenotypic-data-only approach is optimal, and we discuss possibilities for improvement.
On-Column Surface-Enhanced Raman Spectroscopy Detection in Capillary Electrophoresis Using Running Buffers Containing Silver Colloidal Solutions (2000)

Direct on-column surface-enhanced Raman spectroscopy (SERS) detection is demonstrated in capillary electrophoresis (CE). Distinctive SERS spectra of two test compounds, riboflavin and Rhodamine 6G, are obtained in 100 microm i.d. fused-silica capillaries under CE conditions using running buffers that contain silver colloidal solutions. Detection is performed using an unmodified commercial Raman spectrometer in a confocal microscope mode of operation. The effects of laser power, wavelength, spectra acquisition time, silver colloidal concentration, and applied voltage (i.e., flow rate) on the quality of SERS spectra are evaluated. Using laser powers of 17 mW (at the sample) at 515 nm and employing 1 s spectral acquisition times, spectra with bands exhibiting signal-to-noise ratios greater than 10 could be obtained for 1.0 x 10(-6) M riboflavin and very low nanomolar concentrations of Rhodamine 6G. This was accomplished without optimization of silver colloidal solution compositions and by using a low-throughput spectrometer. Incorporation of the colloidal solutions into running buffers is shown to have little effect on the separation of the test compounds as monitored using a laser-induced fluorescence instrumental scheme. However, SERS spectra degrade if the capillary is not rinsed between experiments. Riboflavin and Rhodamine 6G spectra are obtained on-the-fly for actual CE separations. In the case of the latter solute, the injected quantity was approximately 90 amol.
The MARCH6-SQLE Axis Controls Endothelial Cholesterol Homeostasis and Angiogenic Sprouting (2020)

The endothelial monolayer forms a barrier between the lumen of blood vessels and the underlying tissues. Stable VE-cadherin-based adherens junctions are essential for maintaining this barrier, whereas their remodeling is required for angiogenesis in health and disease. Here, we position the ERAD-associated ubiquitin ligase MARCH6 as a determinant of angiogenic sprouting and barrier integrity through its ability to promote the degradation of the rate-limiting cholesterol biosynthetic enzyme squalene epoxidase (SQLE). Accordingly, MARCHF6 ablation in endothelial cells increases SQLE protein and cholesterol load. This leads to altered membrane order, disorganized adherens junctions, decreased endothelial barrier function, and impaired SQLE-dependent sprouting angiogenesis. Akin to MARCHF6 silencing, the overexpression of SQLE impairs angiogenesis. However, angiogenesis is also attenuated when SQLE is silenced, indicating that fine-tuning cholesterol biosynthesis is a determinant of healthy endothelial function. In summary, we propose a mechanistic link between regulation of cholesterol homeostasis by the MARCH6-SQLE axis and endothelial integrity and angiogenesis.
Pro HTML5 Programming (2011)

HTML5 is here, and with it, web applications have acquired power, ease, scalability, and responsiveness like never before. With this book, developers will learn how to use the latest cutting-edge HTML
Airway Management for Deep Sedation: Current Practice, Limitations, and Needs as Identified by Clinical Observation and Survey Results. (2020)

Using deep sedation, adjunct airway devices such as oral or nasal airways are frequently required to maintain airway patency. Traditional oral airways (TOAs, made of rigid plastic) or nasal airways (made of pliable materials) can be associated with adverse effects, contributing to a trend of anesthesia providers placing nasal airways orally. A clinical observational study and an electronic provider survey were conducted to examine this emerging practice. The observation study objective was to investigate reported postoperative sore throat occurrence associated with use of either a nontraditional airway (nasal airway used orally) or TOA in deep sedation procedures (N = 243). Patients receiving nontraditional airways reported significantly less postoperative sore throat than those receiving TOAs (17% vs 40%, respectively; P < .001). These results prompted a broader exploration into airway practices of anesthesia providers via an electronic survey. Most respondents (n = 293) reported adverse effects, including gagging/coughing on insertion, oral cavity injury, and bleeding with TOAs. More than half (52.8%) reported using nasal airways orally. These results suggest a clinical void in current airway management options for deep sedation. Providers indicated the need for airway devices that provide a patent airway while mitigating adverse effects associated with commonly used airways.
Women in Academic Medicine: Measuring Stereotype Threat Among Junior Faculty (2015)

Innovative ST metrics can provide a more complete picture of academic medical center environments. While junior women faculty are susceptible to ST, they may not yet experience all of its consequences in their early careers. As such, ST metrics offer a tool for evaluating institutional initiatives to increase supportive environments for women in academic medicine.
p53 mutations and microsatellite instability in sporadic gastric cancer: when guardians fail. (1994)

Genetic instability may underlie the etiology of multistep gastric carcinogenesis. The altered microsatellites observed in tumors with the ubiquitous somatic mutation (USM) phenotype may represent the expression of such instability. Similarly, p53 mutations may allow the accumulation of genetic alterations caused by multiple mechanisms. In 40 sporadic gastric adenocarcinomas, nine tumors (22.5%) with p53 mutations in exons 5-8, and six tumors (15%) with the USM+ phenotype, were detected. None of the tumors had both alterations. The tumors with p53 mutations were predominantly in the proximal stomach whereas the USM+ tumors were predominantly in the distal stomach. The mutant p53 alleles were homogeneously distributed throughout the primary tumors, but usually absent from adjacent normal or dysplastic epithelium, indicating that p53 mutations are typically acquired before the bulk of clonal expansion. The loss of mutant p53 alleles during progression was also rarely observed in metastatic foci. Altered microsatellites were homogeneously present in the USM+ primary and metastatic tumors and one synchronous tubular adenoma, but were not detected in adjacent normal and metaplastic epithelium. These findings also demonstrate that the USM+ phenotype is expressed before the bulk of clonal expansion. In most (5 of 6) USM+ tumors, the sizes of the altered microsatellites differed between regions, indicating that the instability usually persists during clonal expansion. These findings indicate that both p53 mutations and the USM+ phenotype are present prior to the bulk of tumor growth and therefore may contribute to, rather than be a late consequence of, malignant transformation.
Field Implementation of Proppant Slugs to Avoid Premature Screen-Out of Hydraulic Fractures with Adequate Proppant Concentration (1993)

ABSTRACT Premature screen-outs and/or low proppant concentration are the most likely cause of failure in hydraulic fracturing treatments. Although commonly blamed on a variety of presumed problems—most typically the treating fluid, or large-scale reservoir conditions, such as permeability or stress profile—the true source of most problems has been uncovered only recently by careful analysis of treatment data. The source is referred to as near-wellbore tortuosity, but it can variously arise from deviatoric stress, natural fractures and/or perforation-dominated creation of complex fracture patterns in the wellbore vicinity. Numerous theories have been formulated to deal with near-wellbore screen-outs and, especially for oriented wellbores from Arctic or offshore platforms, various perforation strategies have been postulated and/or implemented. In contrast to the idealizations and costs associated with those theories and strategies, this paper presents simple cheap solutions that are less sensitive to the wellbore environment This novel strategy involves injection of proppant slugs into the near-wellbore region and, when necessary, immediate shut-ins upon small slugs, with three important results: the response of the near well-bore region can be measured and characterized; a large part of the near-wellbore tortuosity can be removed, by simplifying the near-wellbore fracture pattern; and the true nature of the large-scale reservoir response can be determined, e.g. from the greatly modified pressure fall-off obtained after placing slugs near the wellbore. The paper reports the concept and implementation, in a number of commercial fracturing environments, in both gas and oil reservoirs, with both foam and liquid-gel jobs. These show the effective removal of tortuosity varying from 20 to 200 bars and associated elevation of allowable proppant concentrations.
A taxonomy for English nouns and verbs (1981)

The definition texts of a machine-readable pocket dictionary were analyzed to determine the disambiguated word sense of the kernel terms of each word sense being defined. The resultant sets of word pairs of defined and defining words were then computationally connected into two taxonomic semilattices ("tangled hierarchies") representing some 24,000 noun nodes and 11,000 verb nodes. The study of the nature of the "topmost" nodes in these hierarchies, and the structure of the trees reveal information about the nature of the dictionary's organization of the language, the concept of semantic primitives and other aspects of lexical semantics. The data proves that the dictionary offers a fundamentally consistent description of word meaning and may provide the basis for future research and applications in computational linguistic systems.
Post-synthetic transamination at position N4 of cytosine in oligonucleotides assembled with routinely used phosphoramidites (2020)

The commercially available and cheap nucleotide phosphoramidites are routinely used for the oligonucleotide (ODN) assembly. T, isobutyryl-dG (<sup>iBu</sup>dG), benzoyl-dA (<sup>Bz</sup>dA), acetyl-dC (<sup>Ac</sup>dC) and benzoyl-dC (<sup>Bz</sup>dC) derivatives are sufficient to produce orthogonally protected ODNs. Clean and efficient (ca. 30%-70% yield) post-synthetic amination of an ODN assembled with such phosphoramidites was selectively achieved at the N4 position of a singly introduced <sup>Bz</sup>dC. Such a method represents a novel and cheap strategy for the user-friendly post-modification of oligonucleotides at the internal position.
Phythochemical analysis of Uncaria products commercially available in Hungary (2008)

In the last few decades the number of products containing Asian, South-American and African plants has been steadily increasing on the European market. A significant proportion of these products contain plants which have not been widely studied and are not integrated in the evidence based phytotherapy. Proposed indications often lack sufficient scientific evidence and in many cases are not in line with the original traditional application of the plant.
Antiproliferative activity of carotenoid pigments produced by extremophile bacteria (2019)

Various microorganisms are able to synthesize pigments, which usually present antioxidant properties. The aim of this work was to evaluate the antiproliferative activity of bacterial pigments against cancer cells Neuro-2a, Saos-2 and MCF-7. Pigments were obtained from <i>Deinococcus</i> sp. UDEC-P1 and <i>Arthrobacter</i> sp. UDEC-A13. Both bacterial strains were isolated from cold environments (Patagonia and Antarctica, respectively). Pigments were purified and analyzed by HPLC. Antiproliferative activity was evaluated by 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT) assay. Deinoxanthin carotenoid obtained from <i>Deinococcus</i> sp. UDEC-P1 was able to reduce significatively the viability of Saos-2 (37.1%), while no effect was observed against MCF-7 and Neuro-2a. Pigments obtained from <i>Arthrobacter</i> sp. UDEC-A13 showed a significant viability reduction of three tumour cells (20.6% Neuro-2a, 26.3% Saos-2 and 13.2% MCF-7). Therefore, carotenoid pigments produced by extremophilic bacteria <i>Deinococcus</i> sp. UDEC-P1 and <i>Arthrobacter</i> sp. UDEC-A13 could be proposed as novel complementary compounds in anticancer chemotherapy.
Circulating bacterial DNA as a tool towards noninvasive biomarkers for colorectal adenocarcinoma and adenoma. (2019)

3045 Background: The gut microbiota is closely associated with the progression of colorectal neoplasia. While most metagenomics studies utilized fecal samples, circulating bacteria DNA in colorectal adenocarcinoma (ADC) or adenoma (ADM) patients remain unexplored. This study aimed to characterize microbiota DNA in plasma samples and build a machine-learning model for ADC and ADM early detection. Methods: In this proof-of-concept study, we performed whole genome sequencing (~30X) of plasma samples from 25 ADC patients, 10 ADM patients, and 22 healthy controls (HC). Significant biomarkers were identified in the discovery cohort (12 ADC and 11 HC) and built into a random-forest model which was tested in the validation cohort (13 ADC and 11 HC). These biomarkers were further examined in ADM and tested for abundance difference with ADC and HP. Results: In the discovery cohort, 111 species had increased relative abundance in ADC compared to HC and 165 species had decreased relative abundance. Alteration in several species such as Flavobacterium and Ruminococcus torques were consistent with previously published results in faecal and gut microbiome samples. The random forest-recursive feature elimination model selected 28 significant species from the discovery cohort (mean AUC = 0.98, repeated 2-fold cross-validation) and yielded an AUC of 1 in the validation cohort. Interestingly, most biomarker species in ADM patients, with abundance intermediate between ADC and HC, were distinguished from HC. To further test the clinical utility of this model, sequencing data were randomly down-sampled to 1X and the model performance remained robust (AUC = 1) at distinguishing ADC and ADM from HC. Conclusions: This study is the first effort to characterize circulating bacteria DNA in patients with ADC and ADM. Our findings revealed significant difference in relative abundance of several bacterial species between ADC, ADM and HC. A predictive model constructed with selected microbial features accurately distinguished ADC and ADM from HC. Circulating bacteria biomarkers represent potential non-invasive tools for early diagnosis of colorectal neoplasia.
Enasidenib in mutant-IDH2 relapsed or refractory acute myeloid leukemia (R/R AML): Results of a phase I dose-escalation and expansion study. (2017)

7004 Background: Recurrent mutations in isocitrate dehydrogenase 2 (m IDH2) occur in 8-15% of AML pts. mIDH2 proteins synthesize an oncometabolite, 2-hydroxyglutarate (2HG), causing DNA and histone hypermethylation and blocked myeloid differentiation. Enasidenib (AG-221) is an oral, selective, small-molecule inhibitor of mIDH2 protein. Methods: This phase 1/2 study assessed the maximum tolerated dose (MTD), pharmacokinetic and pharmacodynamic profiles, safety, and clinical activity of enasidenib in pts with m IDH2 myeloid malignancies. Safety for all pts and efficacy outcomes for R/R AML pts from the phase 1 dose-escalation and expansion phases are reported. Results: In all, 239 pts received enasidenib. In the dose-escalation (n=113), the MTD was not reached at doses up to 650 mg daily. Median 2HG reductions from baseline were 92%, 90%, and 93% for pts receiving &lt;100 mg, 100 mg, and &gt;100 mg daily, respectively. Enasidenib 100 mg QD was chosen for the expansion phase (n=126) based on PK/PD profiles and demonstrated efficacy. Median number of enasidenib cycles was 5 (range 1–25). Grade 3-4 drug-related investigator reported AEs included indirect hyperbilirubinemia (12%) and IDH-inhibitor-associated differentiation syndrome (ie, retinoic acid syndrome; 7%). For R/R AML pts, overall response rate (ORR) was 40.3%, including 34 (19.3%) complete remissions (CR; Table). Response was associated with cellular differentiation, typically with no evidence of aplasia. Median overall survival (OS) for R/R AML pts was 9.3 months (mos). For pts who attained CR, OS was 19.7 mos. Pts who had received ≥2 prior AML regimens (n=94; 53%) had median OS of 8.0 mos. Conclusions: Enasidenib was well tolerated, induced CRs, and was associated with OS of &gt;9 mos in pts who had failed prior AML therapies. Differentiation of myeloblasts, not cytotoxicity, appears to drive the clinical efficacy of enasidenib. Clinical trial information: NCT01915498. [Table: see text]
Is routine measurement of amylase concentration in drainage fluid necessary after total gastrectomy for gastric cancer? (2011)

Drainage fluid inspection can provide accurate diagnosis of PF formation, similar to D-AMY measurement, suggesting that routine D-AMY measurement is probably not necessary in every patient.
Local Phasor-Based Control of DER Inverters for Voltage Regulation on Distribution Feeders (2020)

We introduce a new control paradigm termed Phasor-Based Control (PBC) to coordinate Distributed Energy Resources (DER) for improved voltage regulation and other objectives. PBC is a multi-layer control framework where the state of the distribution grid is represented by voltage phasors, and Phasor Measurement Units (PMUs) measure the state at critical points in the distribution grid. In the PBC paradigm, a supervisory controller (S-PBC) sets phasor targets which local controllers track. In this paper, we propose a Proportional Integral (PI) implementation for the local control layer (LPBC), to regulate real and reactive power output of distributed inverters to track a voltage phasor target computed by the supervisory layer. We tune the PI controller gains offline with a genetic algorithm that yields better performance than the Ziegler-Nichols method. We benchmark the proposed L-PBC controller against droop volt-var control (DVVC) and observe improved voltage regulation in simulation on the IEEE 13 node unbalanced test feeder (IEEE 13NF). By means of numerical simulation we observe the response of the L-PBC controllers to small and large grid disturbances. Simulations on larger feeders, IEEE 123-node and 647-node, demonstrate challenges with tuning controllers in setups with different amounts of power-voltage coupling.
ADAMTS4-specific MR probe to assess aortic aneurysms in vivo using synthetic peptide libraries (2022)

The incidence of abdominal aortic aneurysms (AAAs) has substantially increased during the last 20 years and their rupture remains the third most common cause of sudden death in the cardiovascular field after myocardial infarction and stroke. The only established clinical parameter to assess AAAs is based on the aneurysm size. Novel biomarkers are needed to improve the assessment of the risk of rupture. ADAMTS4 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 4) is a strongly upregulated proteoglycan cleaving enzyme in the unstable course of AAAs. In the screening of a one-bead-one-compound library against ADAMTS4, a low-molecular-weight cyclic peptide is discovered with favorable properties for in vivo molecular magnetic resonance imaging applications. After identification and characterization, it's potential is evaluated in an AAA mouse model. The ADAMTS4-specific probe enables the in vivo imaging-based prediction of aneurysm expansion and rupture.
Using Sentinel-1 Ocean Data for Mapping Sea Surface Currents Along the Southern Norwegian Coast (2019)

In this paper, the capability of Sentinel-1 data to map ocean surface currents in the Skagerrak Sea, with a focus on the Norwegian Coastal Current (NCC), is investigated. Post-processing methods for removing artefacts in the data and improving of the geophysical interpretation are suggested. Scalloping is one major artefact, which significantly degrades the quality of the velocity maps. Two methods, in spatial and spectral domain, for correcting this effect are proposed. It is also found that the radial velocity provided in the Sentinel-1 ocean data is biased, hence land is used as a reference to correct for the absolute and inter-beam bias. Finally, the retrieved (corrected) velocity is compared to a regional ocean circulation model (ROMS). It is shown that there is a good agreement between the ocean model and the retrieved velocity with values of ≈ 0.8 m/s in the core of the NCC.
Explosive-seam welding seals large pressure vessels (1977)

Simple single-step operation hermetically seals aluminum, brass, steel, copper, and titanium vessels.
Excitation of Ions by High-Harmonic Frequency Components in Paul and Penning Traps and Ion Guides. I. Selective Simultaneous Dipolar Excitation of High Charge States with Clipped Sinusoidal and Non-Harmonic Waveforms in a Linear Quadrupole Ion Guide (2004)

This article presents a method for simultaneous excitation of multiple high charge states of a molecular ion in Paul or Penning trap. Using a linear quadrupolar ion guide we validate the method by using a variety of time- domain excitation waveforms with high harmonics of the first charge state's resonant frequency. The proposed way of inducing harmonics is the deliberate distortion of the excitation waveform from its sinusoidal form. In order to facilitate interference of the harmonics, a superposition of two sinusoids different by a frequency factor of two is used. The simplest form of distortion - amplitude restriction - of such waveform produces interference of the harmonics and results in selective excitation of charge states. Multiple protonation states of melittin were used as a model in this study.
Critical parameters for the partial coalescence of a droplet (2007)

The partial coalescence of a droplet onto a planar liquid-liquid interface is investigated experimentally by tuning the viscosities of both liquids. The problem mainly depends on four dimensionless parameters: The Bond number (gravity vs surface tension), the Ohnesorge numbers (viscosity in both fluids vs surface tension), and the density relative difference. The ratio between the daughter droplet size and the mother droplet size is investigated as a function of these dimensionless numbers. Global quantities such as the available surface energy of the droplet have been measured during the coalescence. The capillary waves propagation and damping are studied in detail. The relation between these waves and the partial coalescence is discussed. Additional viscous mechanisms are proposed in order to explain the asymmetric role played by both viscosities.