gebhart/patrepeval huggingface dataset:
New method of assessing cycle lengths in human atrial fibrillation (2013)

Measuring the mean cycle length (CL) of a rapidly beating heart is considered an efficient way to monitor arrhythmia such as atrial fibrillation (AF). Routinely, sequential CL mapping, using contact catheters in the atria, provides indications on the localization of regions involved in AF. In particular, this technique helps the practitioner, during ablation procedures, to identify some features of the arrhythmia, as, for instance, the driving atrium, or the fastest regions, or its complexity. In this study, we propose a non invasive mapping of CL (niCL), using phase information extracted from electrocardiographic imaging signals (ECGI). niCL mapping provides with a real time ablation planning to the bedside of patients, prior to ablation procedure. The results of this study validate the method in showing a direct correlation between endocavitory (inside the heart) measurements of CL (enCL) and niCL mapping.
Cost-effectiveness of nivolumab vs. ipilimumab/nivolumab vs. trifluridine/tipiracil or mFOLFOX6/cetuximab for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer. (2018)

e15134 Background: We use a decision analytic model to project the effectiveness and cost burden of microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) treatment in the era of immunotherapy. Methods: We simulated the treatment of hypothetical patients with MSI-H/dMMR mCRC in two scenarios: patients refractory to two lines of chemotherapy, or untreated. We compared nivolumab, ipilimumab/nivolumab, trifluridine/tipiracil (third-line) and mFOLFOX6/cetuximab (first-line) based on the CheckMate 142, RECOURSE, and CALGB/SWOG 80405 trials. Results: Ipilimumab/nivolumab was the most effective strategy in both third- and first-line settings, and both checkpoint inhibitor therapies were more effective than chemotherapy (Table 1). However, neither checkpoint inhibitor therapy was cost-effective compared to chemotherapy in the base case due to maintenance nivolumab drug cost. Ipilimumab/nivolumab could be the most cost-effective strategy in both settings if treatment duration were limited to two years. Conclusions: Checkpoint blockade is significantly more effective for MSI-H/dMMR mCRC compared to third- and first-line chemotherapy, but is not cost-effective in either setting due to drug costs. Decreases in duration of maintenance nivolumab could make ipilimumab/nivolumab cost-effective. THERAPY COST, US$| UNADJ.LYs| QALYs| ICER, US$/QALY Third-line therapy Base case Trifluridine/tipiracil 90,700 0.74 0.07 Nivolumab 1,113,400 8.21 6.76 153,000 Ipilimumab/nivolumab 1,519,200 10.69 9.25 162,700 Treatment limited to two years Trifluridine/tipiracil 90,700 0.74 0.07 Nivolumab 264,000 8.21 6.76 Weakly dominated Ipilimumab/nivolumab 298,900 10.69 9.25 22,700 First-line therapy Base case mFOLFOX6/cetuximab 388,400 2.72 1.63 Nivolumab 1,196,600 8.21 7.00 150,700 Ipilimumab/nivolumab 1,583,900 10.69 9.44 158,700 Treatment limited to 2 years mFOLFOX6/cetuximab 388,400 2.72 1.63 Strongly dominated Nivolumab 347,170 8.21 7.00 Ipilimumab/nivolumab 363,700 10.69 9.44 6,800 LY = life-years
Identifying the origination of liver metastasis using a hand-crafted computational pathology approach (2022)

The liver is a common site for metastases for multiple cancer types – with adenocarcinoma being the most common subtype. Standard pathology assessments fail to identify a site of origin for three to five percent of these patients, who are then treated in an empirical manner.<sup>1</sup> Computational pathology is an ideal technology to improve diagnostic accuracy for metastatic cancers with a significant reduction in costs and increase in tissue preservation for future testing. Recently, Deep Learning (DL)-based algorithms have been developed to automatically identify the origination of metastases using only H&E-stained whole slide images as inputs.<sup>2</sup> However, immunohistochemical based analysis is time- and resource-intensive and tissue destructive, while the “black box” nature of the DL-based approach makes it difficult if not impossible to explain the biology behind the classifier’s decision. This pilot study demonstrates that an analysis of computer extracted quantitative cellular features from tumor epithelial nuclei, including a tumor nuclei morphological feature and graph feature as well as cytoplasm texture from H&E stained histology slides, can be used to identify the origination of liver metastasis. Since the primary source of liver metastasis is typically the colon, breast, pancreas, or esophagus,<sup>3</sup> a data set consisting of 120 patients with primary adenocarcinoma and matched liver metastases from the breast, colon, esophagus, and pancreas was constructed. A combination of supervised classification and unsupervised clustering was applied in order to identify the tumors’ origination using the above mentioned histomorphometric features from the data set. We evaluated the utility of histomorphometric features to identify the origination of the metastatic tumors in the liver using both supervised machine classifiers and unsupervised clustering. A Random Forest classifier achieved AUCs of 0.83, 0.63, 0.82, and 0.64 in classifying the primary or metastatic tumor from colon, esophagus, breast, and pancreas. The top performing features included local cellular diversity as well as cytoplasmic texture feature families. We further verified selected features using unsupervised methods such as UMAP, hierarchical clustering, and content-based image retrieving. Based off similarity measures calculated between image tiles in the primary and metastatic tissue, a heatmap corresponding to the WSIs for the primary tumor was constructed to highlight the sites representing potential points of origination of the metastases. Our preliminary results suggest that the site of origination for metastases in the context of primary breast tumors appears to be within the stroma.
Molecular cloning of a human β3‐adrenergic receptor cDNA (1993)

We report the molecular cloning of a beta 3-adrenergic receptor [beta 3-AR] cDNA from human brown adipose tissue. The cDNA-encoded protein is identical to the previously cloned beta 3-AR but with 6 additional amino acids at the C-terminus. The C-terminus is shared by the beta 3 receptors expressed in human neuroblastoma cells [SK-N-MC] [Mol. Pharmacol. 42 (1992) 964-970]. Furthermore, using a polymerase chain reaction strategy we have cloned and sequenced the beta 3-AR introns. Sequence analysis demonstrates that the human beta 3-AR gene comprises at least 3 exons and 2 introns and that the most abundant beta 3-AR transcripts encode a protein with an exon 3-derived C-terminus. Interestingly, although a similar organization has been found in rodent genes, the rat beta 3-AR transcripts encode a receptor with an exon 2-derived C-terminus.
Chromatin Immunoprecipitation (ChIP): Revisiting the Efficacy of Sample Preparation, Sonication, Quantification of Sheared DNA, and Analysis via PCR (2011)

The "quantitative" ChIP, a tool commonly used to study protein-DNA interactions in cells and tissue, is a difficult assay often plagued with technical error. We present, herein, the process required to merge multiple protocols into a quick, reliable and easy method and an approach to accurately quantify ChIP DNA prior to performing PCR. We demonstrate that high intensity sonication for at least 30 min is required for full cellular disruption and maximum DNA recovery because ChIP lysis buffers fail to lyse formaldehyde-fixed cells. In addition, extracting ChIP DNA with chelex-100 yields samples that are too dilute for evaluation of shearing efficiency or quantification via nanospectrophotometry. However, DNA extracted from the Mock-ChIP supernatant via the phenol-chloroform-isoamyl alcohol (PCIA) method can be used to evaluate DNA shearing efficiency and used as the standard in a fluorescence-based microplate assay. This enabled accurate quantification of DNA in chelex-extracted ChIP samples and normalization to total DNA concentration prior to performing real-time PCR (rtPCR). Thus, a quick ChIP assay that can be completed in nine bench hours over two days has been validated along with a rapid, accurate and repeatable way to quantify ChIP DNA. The resulting rtPCR data more accurately depicts treatment effects on protein-DNA interactions of interest.
The Use of Virtual Screening in ALK5 Kinase Inhibitor Discovery and Validation of Orally Active ALK5 Kinase Inhibitors in Oncology (2008)

The multifunctional cytokine, TGF-β, is often overexpressed in human tumors and in preclinical studies has been demonstrated to have autocrine and paracrine protumor activities including immune evasion, invasiveness, epithelial to mesenchymal transition, angiogenesis, tumor-stromal interactions, survival, induction of tumor interstitial pressure, and decreased drug penetration. These findings suggest that antagonism of the TGF-β pathway may be of benefit in the treatment of cancer. One attractive target, the type I TGF-β receptor (ALK5) has an intracellular serine/threonine kinase, which is required for TGF-β signaling and is amenable to inhibition by small molecule, ATP binding site-targeted kinase inhibitors. We utilized the growing understanding of the interactions between kinases and their ATP binding site inhibitors to pursue a number of focused lead discovery strategies. In one of those, we developed a novel shape-based pharmacophore model and discovered a potent, selective ALK5 inhibitor, HTS466284. ALK5 inhibitors obtained from several focused lead discovery strategies were optimized for oral bioavailability and in vivo activity resulting in the development of orally active ALK5 inhibitors such as SM16, which show potent antitumor activity in rodent tumor models.
Cover Picture: Diphenylacetylene‐Linked Peptide Strands Induce Bidirectional β‐Sheet Formation (Angew. Chem. Int. Ed. 14/2014) (2014)

β-Sheets, key secondary structural elements of folded proteins, are commonly involved in therapeutically important protein–protein interactions and are a critical constituent of amyloid deposits in many neurodegenerative conditions. In their Communication on page 3650 ff., A. D. Hamilton, S. Thompson, et al. reveal a strategy for mediating these interactions through the use of a tetrasubstituted diphenylacetylene to induce the formation of β-sheet structures in two directions (illustration by Dr. Karl Harrison).
Crystalline-Oriented Beta-Sialon:Eu2+Deposits Fabricated by Electrophoretic Deposition (EPD) within Strong Magnetic Field (2014)

Electrophoretic deposition (EPD) assisted with a horizontally-setup strong magnetic field (12 T) was utilized to fabricate the deposits of the β-sialon:Eu2+ phosphor. The direction of the magnetic field was perpendicular to that of the electric field. The deposits were fabricated by aligning the β-sialon:Eu2+ particles along the higher magnetic-susceptibility c-crystal axis (a, b-crystal plane), therefore making the oriented deposits consist of the phosphor particles present dominant appearances of the side faces (a, b-plane). Particularly, longer depositing time gave rise to higher orientation degree. Photoluminescence (PL) intensities of the deposits oriented along a, b-plane were significantly improved by comparing with those of the randomly-oriented samples; especially, the 12.4%-fold improvement of the PL intensity was obtained at 150 s depositing time. This fabrication technique of the oriented phosphor deposit may be potentially used to prepare the flat LEDs, with more brightness, instead of conventional methods.
Supercapacitors operated at extremely low environmental temperatures (2021)

This review describes recent advances relating to the optimization of electrode and electrolyte materials for use in SC cells that can operate at extremely low temperatures.
Acoustic resonance phase locked photoacoustic spectrometer (2023)

A photoacoustic spectroscopy method and apparatus for maintaining an acoustic source frequency on a sample cell resonance frequency comprising: providing an acoustic source to the sample cell to generate a photoacoustic signal, the acoustic source having a source frequency; continuously measuring detection phase of the photoacoustic signal with respect to source frequency or a harmonic thereof; and employing the measured detection phase to provide magnitude and direction for correcting the source frequency to the resonance frequency.
A Novel Renewable Thermoplastic Polyacetal by Polymerization of Glycolaldehyde Dimer, a Major Product of the Fast Pyrolysis of Cellulosic Feedstock (2015)

In this paper, we present the first reported synthesis of poly(2,5-dihydroxy-1,4-dioxane) (PDHDO), a novel renewable thermoplastic polyacetal prepared by polymerization of glycolaldehyde dimer, namely 2,5-dihydroxy-1,4-dioxane (DHDO) via a catalytic process. The monomer can be obtained in high purity and large quantities from the fast pyrolysis of lignocellulosic feedstock at a cost that has been estimated to be competitive with that of petrochemical monomers such as ethylene or ethylene glycol. This novel polyacetal is expected to hydrolyze back to the monomer in the environment. Glycolaldehyde is present in soy and browning sauces, is a natural metabolite, and is found in the environment where it is easily oxidized. Thus, this new renewable thermoplastic could potentially be cost competitive with petrochemical polyolefins and is expected not to present issues of persistency or bio-accumulation.
Dexamethasone premedication suppresses vaccine-induced immune responses against cancer (2020)

Glucocorticosteroids (GCS) have an established role in oncology and are administered to cancer patients in routine clinical care and in drug development trials as co-medication. Given their strong immune-suppressive activity, GCS may interfere with immune-oncology drugs. We are developing a therapeutic cancer vaccine, which is based on a liposomal formulation of tumor-antigen encoding RNA (RNA-LPX) and induces a strong T-cell response both in mice as well as in humans. In this study, we investigated <i>in vivo</i> in mice and in human PBMCs the effect of the commonly used long-acting GCS Dexamethasone (Dexa) on the efficacy of this vaccine format, with a particular focus on antigen-specific T-cell immune responses. We show that Dexa, when used as premedication, substantially blunts RNA-LPX vaccine-mediated immune effects. Premedication with Dexa inhibits vaccine-dependent induction of serum cytokines and chemokines and reduces both the number and activation of splenic conventional dendritic cells (cDC) expressing vaccine-encoded antigens. Consequently, priming of functional effector T cells and therapeutic activity is significantly impaired. Interestingly, responses are less impacted when Dexa is administered post-vaccination. Consistent with this observation, although many inflammatory cytokines are reduced, IFNα, a key cytokine in T-cell priming, is less impacted and antigen expression by cDCs is intact. These findings warrant special caution when combining GCS with immune therapies relying on priming and activation of antigen-specific T cells and suggest that careful sequencing of these treatments may preserve T-cell induction.
WandZBoson Production inpp¯Collisions ats=1.8TeV (1995)

The inclusive cross sections times leptonic branching ratios for $W$ and $Z$ boson production in $p\overline{p}$ collisions at $\sqrt{s}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}1.8$ TeV were measured using the D0 detector at the Fermilab Tevatron collider: ${\ensuremath{\sigma}}_{W}B(W\ensuremath{\rightarrow}e\ensuremath{\nu})\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}2.36\ifmmode\pm\else\textpm\fi{}0.07\ifmmode\pm\else\textpm\fi{}0.13\mathrm{nb}$, ${\ensuremath{\sigma}}_{W}B\left(W\ensuremath{\rightarrow}\ensuremath{\mu}\ensuremath{\nu}\right)\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}2.09\ifmmode\pm\else\textpm\fi{}0.23\ifmmode\pm\else\textpm\fi{}0.11\mathrm{nb}$, ${\ensuremath{\sigma}}_{Z}B\left(Z\ensuremath{\rightarrow}{e}^{+}{e}^{\ensuremath{-}}\right)\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}0.218\ifmmode\pm\else\textpm\fi{}0.011\ifmmode\pm\else\textpm\fi{}0.012\mathrm{nb}$, and ${\ensuremath{\sigma}}_{Z}B\left(Z\ensuremath{\rightarrow}{\ensuremath{\mu}}^{+}{\ensuremath{\mu}}^{\ensuremath{-}}\right)\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}0.178\ifmmode\pm\else\textpm\fi{}0.030\ifmmode\pm\else\textpm\fi{}0.009\mathrm{nb}$. The first error is the combined statistical and systematic uncertainty, and the second reflects the uncertainty in the luminosity. For the combined electron and muon analyses we find ${\ensuremath{\sigma}}_{W}B(W\ensuremath{\rightarrow}l\ensuremath{\nu})/{\ensuremath{\sigma}}_{Z}B(Z\ensuremath{\rightarrow}{l}^{+}{l}^{\ensuremath{-}})\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}10.90\ifmmode\pm\else\textpm\fi{}0.49$. Assuming standard model couplings, this result is used to determine the width of the $W$ boson, $\ensuremath{\gamma}(W)\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}2.044\ifmmode\pm\else\textpm\fi{}0.093\mathrm{GeV}$.
Development and Optimization of an Electrospraying Device for the Continuous Collection of Nano- and Microparticles~!2009-12-01~!2010-01-29~!2010-04-14~! (2010)

The development, fabrication and testing of a compact electrospray device are presented with the dual goal of increasing yields and total particle amounts by orders of magnitude and retaining the monodispersity of the generated polymeric particles. A new and optimized electrospraying device producing 285 mg/24h monodisperse micro-sized particles with a yield of 79.2% was developed and tested. The new design allowed continuous particle production and collection. By optimization of the chamber design, high velocities in combination with reduced turbulences led to increasing yields. In comparison to a simple electrospraying configuration, the new device enabled collection 14.25 times more particles in 24h. Besides this significant increase in particle amounts and numbers, collection effectiveness increased as well. While a basic electrospraying device allowed collection of only 34.7% of the generated particles, the yields determined for the new device were 79.2%. We report a 2.28 times increase in effectiveness combined with the potential to generate continuously particles with enhanced productivity while maintaining monodispersity of the particles. This modified electrospraying device may facilitate the production of micro-and nano-sized particles for biomedical and pharmaceutical applications in relevant amounts and reduced losses inside the device.
A signal-noise separation algorithm for the estimation of respiratory rate from breath sound (2011)

Breathing is an involuntary action by the human body, and irregularities in breathing suggests possible respiratory disorders. Respiratory rate is an important parameter for breath sound analysis, and many papers have been published on how respiratory rate can be measured accurately and non-invasively. However, relatively fewer papers deal with breath sound based respiratory rate estimation. This paper proposes a signal-noise separation algorithm for estimating the respiratory rate from the breath sound. The estimation accuracy, in terms of mean square error, of the proposed algorithm has been evaluated using data collected from patients of the National University Hospital (NUH), for both low noise and high noise environments.
<i>P</i>. <i>berghei</i> infections of mosquitoes expressing <i>TEP1r</i> under the <i>Vg</i> promoter. (2017)

&lt;p&gt;&lt;b&gt;a&lt;/b&gt;. &lt;i&gt;P&lt;/i&gt;. &lt;i&gt;berghei&lt;/i&gt; infection of &lt;i&gt;TEP1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;Δct2&lt;/i&gt;&lt;/sup&gt; mutant mosquitoes rescued with transgenic &lt;i&gt;TEP1&lt;/i&gt;r. Shown are the number of live parasites (green circles) and melanized parasites (black circles) in the midguts of mosquitoes 7 days after infection. Control mosquitoes are &lt;i&gt;TEP1&lt;/i&gt; mutant alone (&lt;i&gt;TEP1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;Δct2&lt;/i&gt;&lt;/sup&gt;) and transgenic mosquitoes expressing &lt;i&gt;GFP&lt;/i&gt; instead of &lt;i&gt;TEP1r&lt;/i&gt; (&lt;i&gt;Vg-GFP&lt;/i&gt;). &lt;b&gt;b&lt;/b&gt;. &lt;i&gt;P&lt;/i&gt;. &lt;i&gt;berghei&lt;/i&gt; infection of &lt;i&gt;TEP1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;ΔT&lt;/i&gt;&lt;/sup&gt; mutant mosquitoes compared to &lt;i&gt;TEP1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;ΔT&lt;/i&gt;&lt;/sup&gt; rescued with transgenic &lt;i&gt;TEP1&lt;/i&gt;r (&lt;i&gt;TEP1&lt;/i&gt;&lt;sup&gt;&lt;i&gt;ΔT&lt;/i&gt;&lt;/sup&gt;&lt;i&gt;;Vg-TEP1r)&lt;/i&gt;. &lt;b&gt;c.&lt;/b&gt; &lt;i&gt;P&lt;/i&gt;. &lt;i&gt;berghei&lt;/i&gt; infection of transgenic mosquitoes expressing &lt;i&gt;TEP1r&lt;/i&gt; in a wild type &lt;i&gt;TEP1s&lt;/i&gt; background. Live (green circles) and melanized (black circles) parasites are compared in wild type (&lt;i&gt;TEP1s&lt;/i&gt;) and transgenic (&lt;i&gt;TEP1s;Vg-TEP1r&lt;/i&gt;) mosquitoes. &lt;b&gt;d&lt;/b&gt;. &lt;i&gt;P&lt;/i&gt;. &lt;i&gt;berghei&lt;/i&gt; infection of transgenic &lt;i&gt;TEP1r&lt;/i&gt; mosquitoes in wild type &lt;i&gt;TEP1s&lt;/i&gt; background after &lt;i&gt;TEP1&lt;/i&gt; allele-specific knockdown. Compared are transgenic mosquitoes treated with &lt;i&gt;dsLacZ&lt;/i&gt;, &lt;i&gt;dsTEP1s&lt;/i&gt; and &lt;i&gt;dsTEP1r&lt;/i&gt;, 3 days prior to infection. For all &lt;i&gt;P&lt;/i&gt;. &lt;i&gt;berghei&lt;/i&gt; infections, experiments were performed at least 3 times, representative experiments are shown. The raw numbers of parasites and calculated &lt;i&gt;p values&lt;/i&gt; for all infections are provided in &lt;a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006113#ppat.1006113.s002" target="_blank"&gt;S2 Table&lt;/a&gt;.&lt;/p&gt;
Highly efficient transparent organic light-emitting diodes by ion beam assisted deposition-prepared indium tin oxide cathode (2007)

The authors have investigated the effects of indium tin oxide (ITO) deposited by ion beam assisted e-beam evaporation on the performance of polymer light-emitting diodes. ITO was evaporated as a cathode onto a thin Mg:Ag layer by an e-beam process, and its performance as a transparent cathode was subsequently compared to that of Mg:Ag and sputtering-prepared ITO. Polymer devices’ luminance and efficiency were improved by more than ten times by ion beam assisted deposition (IBAD)-prepared ITO deposition, with little observable damage to the organic layer. Implementation of the IBAD process resulted in the reduction of the interfacial energy barrier which induced band bending. Furthermore, outcoupling with ITO resulted in enhanced luminance.
Residence Time Distribution of Steady and Pulsed Flow in a Parallel‐Plate Channel with Staggered Fins (2011)

Abstract The residence time distribution (RTD) in a parallel‐plate channel with staggered fins for both steady and pulsed flow conditions was experimentally determined. Dispersion and tank‐in‐series models were also adopted to characterize the system. The process fluid was water and the experiments were performed at room temperature. A steady Reynolds number Re ranging from 100 to 1000 was studied. The pulsating flow was generated using a frequency f of 6–20 Hz and an amplitude A of 0–2.3 mm. A pulse injection of sodium chloride solution was used as a tracer and the response in the form of electrical conductivity was measured at the outlet stream. The flow in the staggered finned channel approaches nearly plug‐flow behavior with either higher steady‐flow velocity or superposition of oscillation at low Re.
Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: a cross-sectional study (2023)

German Clinical Trials Register (DRKS00007966, 04/05/2015).