gebhart/patrepeval huggingface dataset:
Phenotypic profiling of CFTR modulators in patient-derived respiratory epithelia (2017)

Pulmonary disease is the major cause of morbidity and mortality in patients with cystic fibrosis, a disease caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Heterogeneity in CFTR genotype-phenotype relationships in affected individuals plus the escalation of drug discovery targeting specific mutations highlights the need to develop robust in vitro platforms with which to stratify therapeutic options using relevant tissue. Toward this goal, we adapted a fluorescence plate reader assay of apical CFTR-mediated chloride conductance to enable profiling of a panel of modulators on primary nasal epithelial cultures derived from patients bearing different CFTR mutations. This platform faithfully recapitulated patient-specific responses previously observed in the "gold-standard" but relatively low-throughput Ussing chamber. Moreover, using this approach, we identified a novel strategy with which to augment the response to an approved drug in specific patients. In proof of concept studies, we also validated the use of this platform in measuring drug responses in lung cultures differentiated from cystic fibrosis iPS cells. Taken together, we show that this medium throughput assay of CFTR activity has the potential to stratify cystic fibrosis patient-specific responses to approved drugs and investigational compounds in vitro in primary and iPS cell-derived airway cultures.
Transcript of Live Discussion: The Cell Cycle in Alzheimer's Disease: Let's Unite Around Division1 (2003)

Welcome to today's chat on a fascinating hypothesis in Alzheimer's disease (AD). I am managing editor at the Alzheimer Research Forum and will be moderating today. Why do we not start by asking Inez Vincent to restate her hypothesis and say what is most needed now to further test it.
Cotylogaster occidentalis (Trematoda: Aspidogastrea): Scanning Electron Microscopic Observations of Sense Organs and Associated Surface Structures (1982)

Hon S. Ip, Sherwin S. Desser, Iris Weller, Cotylogaster occidentalis (Trematoda: Aspidogastrea): Scanning Electron Microscopic Observations of Sense Organs and Associated Surface Structures, Transactions of the American Microscopical Society, Vol. 101, No. 3 (Jul., 1982), pp. 253-261
Rehabilitation strategy for post-stroke recovery using an innovative elbow exoskeleton (2019)

Intensive and adaptive rehabilitation therapy is beneficial for post-stroke recovery. Three modes of rehabilitation are generally performed at different stages after stroke: external force-based control in the acute stage, assistive force-based rehabilitation in the midway of recovery and resistive force-based rehabilitation in the last stage. To achieve the above requirements, an innovative elbow exoskeleton has been developed to incorporate the three modes of rehabilitation in a single structure. The structure of the exoskeleton has been designed in such a way that the whole working region is divided into three where each region can provide a different mode of rehabilitation. Recovery rate can be varied for individuals since it depends on various parameters. To evaluate the rate of recovery, three joint parameters have been identified: range of angular movement, angular velocity and joint torque. These parameters are incorporated into the framework of planning a novel rehabilitation strategy, which is discussed in this article along with the structural description of the designed exoskeleton.
Synthesis and anti-HIV activity of dihydroisoxazole 6-chloropurine and adenine (1996)

Dihydroisoxazole 6-chloropurine and adenine were efficiently prepared via 1,3-dipolar cycloaddition reaction of a nitrile oxide with vinyl 6-chloropurine, and found to be moderately effective against HIV-1 in acutely infected primary human lymphocytes.
MFI-type (ZSM-5) zeolite-filled TiO2nanotubes for enhanced photocatalytic activity (2009)

The present work demonstrates enhanced photocatalytic activity for zeolite-filled TiO2 nanotubes. ZSM-5 zeolite nanocrystals were grown on and into a TiO2 nanotubular skeleton (TiNT/ZSM-5) by multi-step hydrothermal synthesis consisting of in situ seeding and multiple in situ crystallization (MISC). The resulting zeolite nanocrystals were in the range of a few nanometers and they adhere well to the nanotubular inner walls. After crystallization, the photocatalytic activity of this zeolite-filled nanotube catalyst system was compared with neat anatase TiO2 nanotube (TiNT) and with calcined ZSM-5 powder. The results show for TiNT/ZSM-5 a highly enhanced efficiency for the decomposition of acetophenone (used as an aromatic model organic pollutant).
Copolymerization kinetics of a model siloxane system (1997)

Using 29Si NMR, we monitor the copolymerization of trimethylethoxysilane and dimethyldiethoxysilane (model compounds for more complex sol-gel copolymer systems) in a batch reactor. Under the chosen conditions, the extents of self- and cross-condensation reactions are readily determined. Using a nonideal polycondensation kinetic model, we show that the copolymerization rate coefficient for a pair of sites of differing functionality is bounded by their homopolymerization rate coefficients, lying closer to the larger one. This reactivity pattern generates a heterogeneous monomer distribution in the copolymerization products. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 1293–1302, 1997
S-Nitroso-L-Cysteine Stereoselectively Blunts the Deleterious Effects of Fentanyl on Breathing While Augmenting Antinociception in Freely-Moving Rats (2022)

Endogenous and exogenously administered S-nitrosothiols modulate the activities of central and peripheral systems that control breathing. We have unpublished data showing that the deleterious effects of morphine on arterial blood-gas chemistry (i.e., pH, pCO<sub>2</sub>, pO<sub>2</sub>, and sO<sub>2</sub>) and Alveolar-arterial gradient (i.e., index of gas exchange) were markedly diminished in anesthetized Sprague Dawley rats that received a continuous intravenous infusion of the endogenous S-nitrosothiol, S-nitroso-L-cysteine. The present study extends these findings by showing that unanesthetized adult male Sprague Dawley rats receiving an intravenous infusion of S-nitroso-L-cysteine (100 or 200 nmol/kg/min) markedly diminished the ability of intravenous injections of the potent synthetic opioid, fentanyl (10, 25, and 50 μg/kg), to depress the frequency of breathing, tidal volume, and minute ventilation. Our study also found that the ability of intravenously injected fentanyl (10, 25, and 50 μg/kg) to disturb eupneic breathing, which was measured as a marked increase of the non-eupneic breathing index, was substantially reduced in unanesthetized rats receiving intravenous infusions of S-nitroso-L-cysteine (100 or 200 nmol/kg/min). In contrast, the deleterious effects of fentanyl (10, 25, and 50 μg/kg) on frequency of breathing, tidal volume, minute ventilation and non-eupneic breathing index were fully expressed in rats receiving continuous infusions (200 nmol/kg/min) of the parent amino acid, L-cysteine, or the D-isomer, namely, S-nitroso-D-cysteine. In addition, the antinociceptive actions of the above doses of fentanyl as monitored by the tail-flick latency assay, were enhanced by S-nitroso-L-cysteine, but not L-cysteine or S-nitroso-D-cysteine. Taken together, these findings add to existing knowledge that S-nitroso-L-cysteine stereoselectively modulates the detrimental effects of opioids on breathing, and opens the door for mechanistic studies designed to establish whether the pharmacological actions of S-nitroso-L-cysteine involve signaling processes that include 1) the activation of plasma membrane ion channels and receptors, 2) selective intracellular entry of S-nitroso-L-cysteine, and/or 3) S-nitrosylation events. Whether alterations in the bioavailability and bioactivity of endogenous S-nitroso-L-cysteine is a key factor in determining the potency/efficacy of fentanyl on breathing is an intriguing question.
Packaging guest proteins into the encapsulin nanocompartment from Rhodococcus erythropolis N771 (2014)

The encapsulin nanocompartment from Rhodococcus erythropolis N771 (Reencapsulin) was expressed and purified in wild-type and C-terminally His-tagged forms. Negative-stained transmission electron microscopy, field-flow fractionation combined with multi-angle light scattering and dynamic light scattering analyses showed that 60 Reencapsulin monomers were assembled as a spherical particle with a diameter of 28 nm. Heterogeneous guest proteins such as EGFP and firefly luciferase were packaged into the internal cavity of the Reencapsulin nanocompartment by fusing the C-terminal 37-amino-acid sequence of the R. erythropolis N771 DypB peroxidase to the C-terminus. Reencapsulin has the potential to package target proteins in its internal cavity and/or display them on its external surface, making it a feasible carrier for nanotechnology applications.
Natural iminosugar derivatives of 1-deoxynojirimycin inhibit glycosylation of hepatitis viral envelope proteins. (2007)

A silkworm (Bombyx mori L.) extract known to contain naturally occurring iminosugars, including 1-deoxynojirimycin (1-DNJ) derived from the mulberry tree (Morus alba L.), was evaluated in surrogate HCV and HBV in vitro assays. Antiviral activity of the silkworm extract and one of its purified constituents, 1-DNJ, was demonstrated against bovine viral diarrhea virus (BVDV) and GB virus-B (GBV-B), both members of the Flaviviridae family, and against woodchuck hepatitis virus (WHV) and hepatitis B virus (HBV), both members of the Hepadnaviridae family of viruses. The silkworm extract exhibited a 1,300 fold greater antiviral effect against BVDV in comparison to purified 1-DNJ. Glycoprotein processing of BVDV envelope proteins was disrupted upon treatment with the naturally derived components. The glycosylation of the WHV envelope proteins was affected largely by treatment with the silkworm extract than with purified 1-DNJ as well. The mechanism of action for this therapy may lie in the generation of defective particles that are unable to initiate the next cycle of infection as demonstrated by inhibition of GBV-B in vitro. We postulate that the five constituent iminosugars present in the silkworm extract contribute, in a synergistic manner, toward the antiviral effects observed for the inhibition of intact maturation of hepatitis viral particles and may complement conventional therapies. These results indicate that pre-clinical testing of the natural silkworm extract with regards to the efficacy of treatment against viral hepatitis infections can be evaluated in the respective animal models, in preparation for clinical trials in humans.
Vascular–Parenchymal Cross-Talk Promotes Lung Fibrosis through BMPR2 Signaling (2023)

<b>Rationale:</b> Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by progressive lung scarring. IPF-related pulmonary vascular remodeling and pulmonary hypertension (PH) result in a particularly poor prognosis. <b>Objectives:</b> To study the pathogenesis of vascular remodeling in fibrotic lungs and its contribution to progression of fibrosis. <b>Methods:</b> We used an experimental model of lung fibrosis associated with PH by transient overexpression of active TGF-β1 (transforming growth factor-β1). Samples from patients with fibrotic lung diseases were analyzed in depth using immunostaining, gene expression, and gene mutations. <b>Measurements and Main Results:</b> We found a reduction in endothelial cells (ECs) and activation of vascular smooth muscle cells (VSMCs) in fibrotic lungs. Coculturing fibroblasts with VSMCs or ECs from fibrotic lungs induced fibrotic phenotypes in fibroblasts. IPF fibroblasts induced EC death and activation of VSMCs in coculture systems. Decreased concentrations of BMPR2 (bone morphogenic protein receptor 2) and its signaling were observed in ECs and VSMCs from fibrotic lungs in both rats and humans. On fibroblasts treated with media from VSMCs, BMPR2 suppression in VSMCs led to fibrogenic effects. Tacrolimus activated BMPR2 signaling and attenuated fibrosis and PH in rodent lungs. Whole-exome sequencing revealed rare mutations in PH-related genes, including <i>BMPR2</i>, in patients with IPF undergoing transplantation. A unique missense <i>BMPR2</i> mutation (p.Q721R) was discovered to have dysfunctional effects on BMPR2 signaling. <b>Conclusions:</b> Endothelial dysfunction and vascular remodeling in PH secondary to pulmonary fibrosis enhance fibrogenesis through impaired BMPR2 signaling. Tacrolimus may have value as a treatment of advanced IPF and concomitant PH. Genetic abnormalities may determine the development of PH in advanced IPF.
<title>Optoelectronic interconnect architecture of parallel modified signed-digit adder and subtractor</title> (1995)

In this paper, a space-position-logic-encoding scheme is proposed, which not only makes best use of the convenience of binary logic operation, but is also suitable for the trinary property of modified signed-digit numbers. Based on the space-position-logic-encoding scheme, a fully parallel modified signed-digit adder and subtracter is built by use of optoelectronic switch and microstructure interconnect technologies. Thus an effective combination of a parallel algorithm and a parallel architecture is implemented. Finally, both simulation results and experimental results are provided.
Online intensification of search around solutions of interest for multi/many-objective optimization (2020)

In practical multi/many-objective optimization problems, a decision maker is often only interested in a handful of solutions of interest (SOI) instead of the entire Pareto Front (PF). It is therefore of significant research interest to design algorithms that can automatically detect SOIs and search around them instead of attempting to find the entire PF. However, this is challenging for a number of reasons. First and foremost, the interpretation of the underlying measures in terms of quantifying trade-off information for SOIs is not straightforward. Scalability is also an issue for most of such existing measures. Additionally, for many-objective algorithms that rely on decomposition, adaptation of reference directions and appropriate means to scale the objectives to maintain solution density around SOIs is not trivial. Lastly, constraints and decision-space are often overlooked in the existing studies but are important for practical applications. In this work, we present a simple approach to identify SOIs, using normalized net gain over nadir point and angle of influence. We illustrate the utility of the measure for offline and online identification of SOIs using a range of unconstrained and constrained benchmarks and practical design problems spanning up to 5 objectives. We also show further analysis in decision-space for an application problem to aid decision-making in practical scenarios.
Unprecedented Epimerization of an Azithromycin Analogue: Synthesis, Structure and Biological Activity of 2′-Dehydroxy-5″-Epi-Azithromycin (2022)

Certain macrolide antibiotics, azithromycin included, possess anti-inflammatory properties that are considered fundamental for their efficacy in the treatment of chronic inflammatory diseases, such as diffuse pan-bronchiolitis and cystic fibrosis. In this study, we disclose a novel azithromycin analog obtained via Barton-McCombie oxidation during which an unprecedented epimerization on the cladinose sugar occurs. Its structure was thoroughly investigated using NMR spectroscopy and compared to the natural epimer, revealing how the change in configuration of one single stereocenter (out of 16) profoundly diminished the antimicrobial activity through spatial manipulation of ribosome binding epitopes. At the same time, the anti-inflammatory properties of parent macrolide were retained, as demonstrated by inhibition of LPS- and cigarette-smoke-induced pulmonary inflammation. Not surprisingly, the compound has promising developable properties including good oral bioavailability and a half-life that supports once-daily dosing. This novel anti-inflammatory candidate has significant potential to fill the gap in existing anti-inflammatory agents and broaden treatment possibilities.
Measurement of prompt charged-particle production in $pp$ collisions at $\sqrt{s} = 13\,\mathrm{TeV}$ (2021)

The differential cross-section of prompt inclusive production of long-lived charged particles in proton-proton collisions is measured using a data sample recorded by the LHCb experiment at a centre-of-mass energy of $ \sqrt{s} $ = 13 TeV. The data sample, collected with an unbiased trigger, corresponds to an integrated luminosity of 5.4 nb$^{−1}$. The differential cross-section is measured as a function of transverse momentum and pseudorapidity in the ranges p$_{T}$ ∈ [80, 10 000) MeV/c and η ∈ [2.0, 4.8) and is determined separately for positively and negatively charged particles. The results are compared with predictions from various hadronic-interaction models.[graphic not available: see fulltext]
Interleukin 2-mediated Conversion of Ovarian Cancer-associated CD4+ Regulatory T Cells Into Proinflammatory Interleukin 17-producing Helper T Cells (2009)

Epithelial ovarian cancer (EOC) is a highly inflammatory malignancy, characterized by the presence, at the tumor site, of regulatory T cells (Treg) that suppress antitumor immunity. Recently, a new lineage of CD4+ T cells producing the proinflammatory cytokine interleukin (IL)-17 [T helper (TH) 17] has been identified as a major player in some autoimmune diseases. The role of TH17 cells in cancer, however, and their relationship with coexisting Treg populations, whose differentiation is partially controlled by the same mediators (ie, transforming growth factor-beta), are yet unclear. Here, we show that EOC-associated/infiltrating lymphocytes derived by culturing tumor samples in the presence of IL-2 contain significant frequencies of TH17 cells, coproducing interferon-gamma (IFN)-gamma and tumor necrosis factor (TNF)-alpha, which represent, in some cases, up to 40% of total CD4+ T cells. TH17 cells were also detected ex vivo, but at lower proportions than in cultured tumor-infiltrating lymphocytes/tumor-associated lymphocytes, and were confined to the CD4+CD25- fraction. Remarkably, analysis of EOC-associated conventional CD4CD25 T cell and Treg populations isolated ex vivo from tumor samples by cell sorting and cultured with tumor-associated CD3- cells in the presence of IL-2 revealed that EOC Treg stimulated under these conditions were rapidly converted into TH17 cells, down-regulated FOXP3 expression, and lost their suppressive capacity. Thus, although the impact of TH17 cells on the evolution of EOC remains to be established, our data suggest that local IL-2 treatment in ovarian cancer may result in the conversion of tumor-associated Treg into TH17 cells, relieve Treg-mediated suppression, and contribute to enhance antitumor immunity.
Vasodilators in the Treatment of Heart Failure (1977)

DURING the last few years, there has been a great deal of interest in vasodilator therapy in cases of acute and chronic heart failure. Better understanding of cardiac physiology and development of bedside hemodynamic monitoring techniques using flowdirected catheters have provided impetus to evaluate different physiologic and pharmacologic interventions in acutely ill patients. Most patients with congestive heart failure have elevation of the left ventricular filling pressure (LVFP) and low cardiac output. Elevated LVFP (index of blood volume) is a compensatory phenomenon in the early stage of heart failure to maintain cardiac output. This beneficial effect may later result in excessive myocardial oxygen demand, decreased coronary flow, and symptoms of pulmonary congestion. Similarly, arterial constriction occurring initially in heart failure may be appropriate to maintain circulation to vital organs, but may eventually result in a decrease in cardiac output because of the elevated systemic vascular resistance.<sup>1</sup> Experimental evidence shows
Foldable electrified ultralight vehicles as key component for sustainable traffic chains (2016)

Foldable ultralight electric vehicles (E-ULV) are a promising key component for future sustainable traffic chains for urban regions with mountainous topography. While typical E-Bikes are hard to use in the rush-hour of metropolitan public transport association vehicles, these - actually not available - E-ULV are a real innovation for the “last miles”. This paper presents electric drive add-on kits for foldable scooters and very light foldable bikes as well as their possible cost in case of a market launch. The E-ULV had been tested in small fleets on public roads and turned out shift car kilometers to the public transport system effectively.
Selenium-Based Solid-Phase Synthesis of Benzopyrans I: Applications to Combinatorial Synthesis of Natural Products (2000)

Eine praktikable neue Strategie für die Festphasensynthese und die kombinatorische Chemie: Harzgebundene 2,2-Dimethylbenzopyran-Bausteine wurden durch eine neuartige Methode aufgebaut, bei der ein Selen-funktionalisierter polymerer Träger im Zuge einer Cycloaddition beladen wird („Cycloloading”︁, siehe Schema). Diese Synthesebausteine lassen sich weiter funktionalisieren, und nach oxidativer Abspaltung vom Harz erhält man kleine kombinatorische Bibliotheken verschiedener Naturstoffe und synthetischer Analoga.
Rates of local procedural-related structural injury following clipping or coiling of anterior communicating artery aneurysms (2015)

Background Surgical clipping and endovascular coiling yield similar functional outcomes for the treatment of saccular aneurysms of the anterior communicating (ACOM) artery. However, surgical treatment may be associated with greater rates of cognitive impairment due to injury of adjacent structures. We aimed to quantify the rates of injury (infarction/hemorrhage) for both clipping and coiling of ACOM aneurysms. Methods This was a retrospective dual-center radiological investigation of a consecutive series of patients with ruptured and unruptured ACOM aneurysms treated between January 2011 and October 2014. Post-treatment CT or MRI was assessed for new ischemic or hemorrhagic injury. Injury relating to the primary hemorrhage or vasospasm was differentiated. Univariate analysis using χ 2 tests and multivariate analysis using binary logistic regression was used. Results 66 patients treated with clipping were compared with 93 patients treated with coiling. 32/66 (48.5%) patients in the clipping group suffered treatment-related injury (31 ischemic, 1 hemorrhagic) compared with 4/93 (4.4%) patients in the coiling group (3 ischemic, 1 hemorrhagic) (p&lt;0.0001). For patients with subarachnoid hemorrhage, the multivariate OR for infarction for clipping over coiling was 24.42 (95% CI 5.84 to 102.14), p&lt;0.0001. The most common site of infarction was the basal forebrain (28/66 patients, 42.4%), with bilateral infarction in 4. There was injury of the septal/subcallosal region in 12/66 patients (18%). Conclusions Clipping of ACOM aneurysms is associated with significantly higher rates of structural injury than coiling, and this may be a reason for superior cognitive outcomes in patients treated with coiling in previously published studies.
Effects of convolution on chaotic signals (1992)

Because chaotic signals are potentially useful both in describing physical phenomena and in engineering applications, signal processing algorithms exploiting their unique characteristics are of interest. The authors consider issues pertaining to processing signals in convolutional distortion. Specifically, they discuss the effects of convolutional distortion on two parameters commonly used in the description of chaotic signals-the Lyapunov exponents and the fractal dimension of the attractor. In addition, a blind deconvolution technique based on minimizing a nonlinear prediction error for data generated by one-dimensional chaotic maps is presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>