gebhart/patrepeval huggingface dataset:
Multiparameter Peptide Optimization toward Stable Triple Agonists for the Treatment of Diabetes and Obesity (2020)

Abstract Historically, peptide optimization has mainly focused on pharmacological activity. Physicochemical properties have often been evaluated late in discovery, potentially providing molecules with suboptimal stability properties. Often, such issues cannot be overcome by formulation approaches but need additional optimization cycles for a redesign of the peptide. Here, early rational multiparameter optimization of exendin‐4 based agonists is described toward i) a balanced triple activity profile at the glucagon‐like peptide 1, glucagon, and gastric inhibitory polypeptide receptors for the treatment of diabetes and obesity and in parallel ii) robust physicochemical properties for 1‐daily subcutaneous application in a multiple‐dose pen device. In depth evaluation of an optimized candidate shows an excellent profile with respect to its physicochemical properties and pharmacokinetic/pharmacodynamic (PD) behavior in minipigs and monkeys.
Analysis of self-correcting active pixel sensors (2005)

This paper evaluates the operation of self-correcting active pixel sensors presented in [6] using both Signal-to-Noise Ratio and Dynamic Range figures. The evaluation is based on a simplified Active Pixel Sensing (APS) model. We show that in the absence of stuck faults (i.e., no errors) the performance of the system suffers from considerable degradation especially at low illumination (i.e., typical indoor scenes). We use the same model to quantify the number of defective pixels under which self correction is beneficial and evaluate the quality of the resultant image
Sulfur Containing Stable Unsubstituted Heptacene Analogs (2011)

Heptacene and higher polyacenes have been sought for their high degree of charge carrier mobility in thin film transistors. Such acenes are, however, extremely unstable in ambient conditions. Approaches to obtain stable heptacenes include introduction of suitable substituents, of heteroatoms, or both. Methods to synthesize stable linear and a nonlinear unsubstituted heptacene analogs are discussed. No changes in the UV-visible absorption spectra in solution over time for these materials indicate higher oxidative stability compared to analogous polyacenes.
Enhanced jun Gene Expression Is an Early Genomic Response to Transforming Growth Factor β Stimulation (1989)

Transforming growth factor beta (TGF beta) is a multifunctional polypeptide that regulates proliferation, differentiation, and other functions of many cell types. The pathway of TGF beta signal transduction in cells is unknown. We report here that an early effect of TGF beta is an enhancement of the expression of two genes encoding serum- and phorbol ester tumor promoter-regulated transcription factors: the junB gene and the c-jun proto-oncogene, respectively. This stimulation was observed in human lung adenocarcinoma A549 cells which were growth inhibited by TGF beta, AKR-2B mouse embryo fibroblasts which were growth stimulated by TGF beta, and K562 human erythroleukemia cells, which were not appreciably affected in their growth by TGF beta. The increase in jun mRNA occurred with picomolar TGF beta concentrations within 1 h of TGF beta stimulation, reached a peak between 1 and 5 h in different cells, and declined gradually to base-line levels. This mRNA response was followed by a large increase in the biosynthesis of the c-jun protein (AP-1), as shown by metabolic labeling and immunoprecipitation analysis. However, differential and cell type-specific regulation appeared to determine the timing and magnitude of the response of each jun gene in a given cell. In AKR-2B and NIH 3T3 cells, only junB was induced by TGF beta, evidently in a protein synthesis-independent fashion. The junB response to TGF beta was maintained in c-Ha-ras and neu oncogene-transformed cells. Thus, one of the earliest genomic responses to TGF beta may involve nuclear signal transduction and amplification by the junB and c-jun transcription factors in concert with c-fos, which is also induced. The differential activation of the jun genes may explain some of the pleiotropic effects of TGF beta.
Bacteria/blood/material interactions. I. Injected and preseeded slime‐forming Staphylococcus epidermidis in flowing blood with biomaterials (1995)

Blood-material interactions were studied using in vitro recirculation with human blood, slime-forming Staphylococcus epidermidis, and cardiovascular materials. Staphylococcus epidermidis, under preseeded or injected conditions, adhered to nonsmooth materials and elevated plasma levels of fibrinopeptide A (FpA) and C3a in the presence of all materials. Increased white blood cell (WBC) and platelet adhesion and thrombospondin and platelet factor 4 (PF4) release were noted for respective materials in the presence of injected bacteria. Materials that adhered significant quantities of injected S. epidermidis exhibited low levels of adsorbed proteins. Materials with high levels of preseeded S. epidermidis showed high levels of adsorbed proteins. Adhesion of preseeded bacteria and blood plasma elevations of C3a and FpA were lowest on semicrystalline polymer substrates, intermediate on halogenated substrates, and highest on amorphous substrates. In the presence of injected bacteria, WBCs and platelets adhered at earlier recirculation times to amorphous substrates than to semicrystalline substrates.
Conception de nouvelles nanotechnologies pour le traitement du cancer (2004)

L'administration de principes actifs à activité antitumorale par voie intraveineuse présente souvent des problèmes d'effets secondaires liés à une insuffisante spécificité et à une instabilité in vivo des molécules utilisées. L'objectif de cette thèse a donc été d'étudier la vectorisation des principes actifs à activité anticancéreuse sous forme de nouveaux systèmes colloïdaux, soit en réalisant un ciblage actif de nanoparticules biodégradables à rémanence vasculaire prolongée ( furtives') avec un agent de reconnaissance (acide folique), soit en formulant des vecteurs constitués de prodrogues lipophiles d'anticancéreux pour leur stabilisation in vivo. Le but final est, dans les deux cas, d'améliorer l'efficacité de l'administration de molécules antitumorales par voie intraveineuse
Active microrheology and simultaneous visualization of sheared phospholipid monolayers (2011)

Two-dimensional films of surface-active agents-from phospholipids and proteins to nanoparticles and colloids-stabilize fluid interfaces, which are essential to the science, technology and engineering of everyday life. The 2D nature of interfaces present unique challenges and opportunities: coupling between the 2D films and the bulk fluids complicates the measurement of surface dynamic properties, but allows the interfacial microstructure to be directly visualized during deformation. Here we present a novel technique that combines active microrheology with fluorescence microscopy to visualize fluid interfaces as they deform under applied stress, allowing structure and rheology to be correlated on the micron-scale in monolayer films. We show that even simple, single-component lipid monolayers can exhibit viscoelasticity, history dependence, a yield stress and hours-long time scales for elastic recoil and aging. Simultaneous visualization of the monolayer under stress shows that the rich dynamical response results from the cooperative dynamics and deformation of liquid-crystalline domains and their boundaries.
The heme moiety of cytochrome c is an autoreactive Ir gene-restricted T cell epitope. (1988)

In these studies, we have shown that the heme moiety of cyt c is a dominant T cell epitope that induces a large proliferative response in lymph node T cells derived from SJL and B10.A mice when presented on either unfixed or fixed syngeneic APCs. Not only is this vigorous response observed for cyt c-primed T cell populations but also for populations obtained from naive SJL or B10.A mice. The reactivity to the heme moiety falls under strict MHC restriction, in that it is present only in murine strains bearing either the I-Ak or I-As molecule and can be blocked by antibodies specific for these class II molecules. Therefore, these findings require that the current models describing the nature of T cell epitopes be extended to include nonpeptide molecules. Furthermore, as the heme moiety is ubiquitous throughout the organism, although sequestered within proteins, the existence of heme-reactive T cell populations in unprimed animals provides another example of the existence of self-reactive T cell clones.
D$v$/D$t$-Control Methods for the SiC JFET/Si MOSFET Cascode (2012)

Switching devices based on SiC offer outstanding performance with respect to operating frequency, junction temperature, and conduction losses enabling significant improvement of the performance of converter systems. There, the cascode consisting of a MOSFET and a JFET has additionally the advantage of being a normally off device and offering a simple control via the gate of the MOSFET. Without d <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">v</i> /d <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</i> -control, however, the transients for hard commutation reach values of up to 45kV/μs, which could lead to electromagnetic interference problems. Especially in drive systems, problems could occur, which are related to earth currents (bearing currents) due to parasitic capacitances. Therefore, new d <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">v</i> /d <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</i> -control methods for the SiC JFET/Si MOSFET cascode as well as measurement results are presented in this paper. Based on this new concepts, the outstanding performance of the SiC devices can be fully utilized without impairing electromagnetic compatibility.
Effect of a Methyl-Protecting Group on the Adsorption of Pyrrolidine on Si(100)-2 × 1 (2001)

The room-temperature adsorption of pyrrolidine and its methyl-protected analogue, N-methylpyrrolidine, on the Si(100)-2 × 1 surface has been investigated using multiple internal reflection Fourier transform infrared spectroscopy and ab initio quantum chemistry calculations. For both compounds, initial adsorption occurs by barrierless formation of a dative bond between the nitrogen lone pair and the electrophilic atom of the Si dimer. However, while pyrrolidine proceeds to chemisorb dissociatively through N−H bond cleavage, methylpyrrolidine is shown to be trapped in its dative-bonded precursor state at room temperature due to a substantial barrier for N−CH3 cleavage. Additionally, the saturation coverage of methylpyrrolidine on Si is seen to be significantly less than that of pyrrolidine, due likely to both steric factors and charge-transfer effects.
Microporous Carbon Nanoplates from Regenerated Silk Proteins for Supercapacitors (2013)

Novel carbon-based microporous nanoplates containing numerous heteroatoms (H-CMNs) are fabricated from regenerated silk fibroin by the carbonization and activation of KOH. The H-CMNs exhibit superior electrochemical performance, displaying a specific capacitance of 264 F/g in aqueous electrolytes, a specific energy of 133 Wh/kg, a specific power of 217 kW/kg, and a stable cycle life over 10000 cycles.
On $C^0$-genericity of distributional chaos (2020)

Let $M$ be a compact smooth manifold without boundary. Based on results by Good and Meddaugh (2020), we prove that a strong distributional chaos is $C^0$-generic in the space of continuous self-maps (resp. homeomorphisms) of $M$. The results contain answers to questions by Li et al. (2016) and Moothathu (2011) in the zero-dimensional case. A related counter-example on the chain components under shadowing is also given.
Toughness assessment of elastomeric polypropylene (ELPP) by the essential work of the fracture method (1998)

The essential work of the fracture (EWF) method was employed to determine the fracture performance of thermoplastic polypropylene (PP) elastomers. Three types of elastomeric polypropylene (ELPP) of homo- and copolymer nature based on different catalysts were involved in this study. Tests were carried out in both I and III fracture modes to check the applicability of the EWF approach for such elastomers. It was found that the trouser tearing test (mode III) overestimates both the specific essential (we) and plastic work (wp) terms when the tearing resistance of the ELPP is higher than the resistance to tensile loading. With decreasing crystallinity (i.e., by decreasing length of the stereoregular chain segments of the block copolymers or increased content of comonomer) we increased, whereas in respect to wp,, an opposite tendency was found. This was interpreted by possible changes in the thermoreversible network structure of the ELPP in which crystalline domains act as network knot points in the amorphous PP matrix. © 1998 John Wiley & Sons, Inc. J. Appl. Polym. Sci. 70: 873–881, 1998
Wnt signaling in triple negative breast cancer is associated with metastasis (2013)

Background&#13;\n&#13;\nTriple Negative subset of (TN) Breast Cancers (BC), a close associate of the basal-like subtype (with limited discordance) is an aggressive form of the disease which convey unpredictable, and poor prognosis due to limited treatment options and lack of proven effective targeted therapies.&#13;\n&#13;\nMethods&#13;\n&#13;\nWe conducted an expression study of 240 formalin-fixed, paraffin-embedded (FFPE) primary biopsies from two cohorts, including 130 TN tumors, to identify molecular mechanisms of TN disease.&#13;\n&#13;\nResults&#13;\n&#13;\nThe annotation of differentially expressed genes in TN tumors contained an overrepresentation of canonical Wnt signaling components in our cohort and others. These observations were supported by upregulation of experimentally induced oncogenic Wnt/β-catenin genes in TN tumors, recapitulated using targets induced by Wnt3A. A functional blockade of Wnt/β-catenin pathway by either a pharmacological Wnt-antagonist, WntC59, sulidac sulfide, or β-catenin (functional read out of Wnt/β-catenin pathway) SiRNA mediated genetic manipulation demonstrated that a functional perturbation of the pathway is causal to the metastasis- associated phenotypes including fibronectin-directed migration, F-actin organization, and invasion in TNBC cells. A classifier, trained on microarray data from β-catenin transfected mammary cells, identified a disproportionate number of TNBC breast tumors as compared to other breast cancer subtypes in a meta-analysis of 11 studies and 1,878 breast cancer patients, including the two cohorts published here. Patients identified by the Wnt/β-catenin classifier had a greater risk of lung and brain, but not bone metastases.&#13;\n&#13;\nConclusion&#13;\n&#13;\nThese data implicate transcriptional Wnt signaling as a hallmark of TNBC disease associated with specific metastatic pathways.
Scalable, effective, and rapid decontamination of SARS-CoV-2 contaminated N95 respirators using germicidal ultraviolet C (UVC) irradiation device (2021)

Particulate respirators such as N95s are an essential component of personal protective equipment (PPE) for front-line workers. This study describes a rapid and effective UVC irradiation system that would facilitate the safe re-use of N95 respirators and provides supporting information for deploying UVC for decontamination of SARS-CoV-2 during the COVID-19 pandemic. To assess the inactivation potential of the proposed UVC germicidal device as a function of time by using 3 M 8211-N95 particulate respirators inoculated with SARS-CoV-2. A germicidal UVC device to deliver tailored UVC dose was developed and test coupons (2.5 cm<sup>2</sup>) of the 3 M-N95 respirator were inoculated with 10<sup>6</sup> plaque-forming units (PFU) of SARS-CoV-2 and were UV irradiated. Different exposure times were tested (0-164 s) by fixing the distance between the lamp and the test coupon to 15.2 cm while providing an exposure of at least 5.43 mWcm<sup>-2</sup>. Primary measure of outcome was titration of infectious virus recovered from virus-inoculated respirator test coupons after UVC exposure. Other measures included the method validation of the irradiation protocol, using lentiviruses (biosafety level-2 agent) and establishment of the germicidal UVC exposure protocol. An average of 4.38 × 10<sup>3</sup> PFU ml<sup>-1</sup> (SD 772.68) was recovered from untreated test coupons while 4.44 × 10<sup>2</sup> PFU ml<sup>-1</sup> (SD 203.67), 4.00 × 10<sup>2</sup> PFU ml<sup>-1</sup> (SD 115.47), 1.56 × 10<sup>2</sup> PFU ml<sup>-1</sup> (SD 76.98) and 4.44 × 10<sup>1</sup> PFU ml<sup>-1</sup> (SD 76.98) was recovered in exposures 2, 6, 18 and 54 s per side respectively. The germicidal device output and positioning was monitored and a minimum output of 5.43 mW cm<sup>-2</sup> was maintained. Infectious SARS-CoV-2 was not detected by plaque assays (minimal level of detection is 67 PFU ml<sup>-1</sup>) on N95 respirator test coupons when irradiated for 120 s per side or longer suggesting 3.5 log reduction in 240 s of irradiation, 1.3 J cm<sup>-2</sup>. A scalable germicidal UVC device to deliver tailored UVC dose for rapid decontamination of SARS-CoV-2 was developed. UVC germicidal irradiation of N95 test coupons inoculated with SARS-CoV-2 for 120 s per side resulted in 3.5 log reduction of virus. These data support the reuse of N95 particle-filtrate apparatus upon irradiation with UVC and supports use of UVC-based decontamination of SARS-CoV-2 during the COVID-19 pandemic.
Single-cell image analysis reveals over-expression of organic anion transporting polypeptides (OATPs) in human glioblastoma tissue (2022)

Here, we demonstrate, for the first time, the protein expression of four OATPs in human GBM tissue, including upregulation within the tumor microenvironment by myeloid cells and tumor vasculature, and isoform-specific upregulation within hypoxic niches.
Determination of Probability of Causative Pathogen in Infectious Keratitis Using Deep Learning Algorithm of Slit-Lamp Images (2021)

Abstract Corneal opacities are an important cause of blindness, and its major etiology is infectious keratitis. Slit-lamp examinations are commonly used to determine the causative pathogen; however, their diagnostic accuracy is low even for experienced ophthalmologists. To characterize the “face” of an infected cornea, we have adapted a deep learning architecture used for facial recognition and applied it to determine a probability score for a specific pathogen causing keratitis. To record the diverse features and mitigate the uncertainty, batches of probability scores of 4 serial images taken from many angles or fluorescence staining were learned for score and decision level fusion using a gradient boosting decision tree. A total of 4306 slit-lamp images and 312 images obtained by internet publications on keratitis by bacteria, fungi, acanthamoeba, and herpes simplex virus (HSV) were studied. The created algorithm had a high overall accuracy of diagnosis, e.g., the accuracy/area under the curve (AUC) for acanthamoeba was 97.9%/0.995, bacteria was 90.7%/0.963, fungi was 95.0%/0.975, and HSV was 92.3%/0.946, by group K-fold validation, and it was robust to even the low resolution web images. We suggest that our hybrid deep learning-based algorithm be used as a simple and accurate method for computer-assisted diagnosis of infectious keratitis.
Theoretical Modeling of Low‐Energy Electronic Absorption Bands in Reduced Cobaloximes (2014)

The reduced Co(I) states of cobaloximes are powerful nucleophiles that play an important role in the hydrogen-evolving catalytic activity of these species. In this work we analyze the low-energy electronic absorption bands of two cobaloxime systems experimentally and use a variety of density functional theory and molecular orbital ab initio quantum chemical approaches. Overall we find a reasonable qualitative understanding of the electronic excitation spectra of these compounds but show that obtaining quantitative results remains a challenging task.
Synthesis of high sensitivity C-reactive protein in Beas2B cells and nasal epithelial cells of patients with cystic fibrosis (2023)

Introduction High sensitivity C-reactive protein (hsCRP) has an upcoming role in predicting pulmonary inflammation and clinical disease progression in lung diseases. HsCRP may predict clinical disease activity and risk of pulmonary exacerbations in adult cystic fibrosis (CF) patients. Furthermore, hsCRP can be synthesized by airway epithelial cells in patients with chronic obstructive pulmonary disease (COPD). Preliminary analysis of 32 CF patients showed a strong correlation of hsCRP with proinflammatory cytokines and lung clearance index (LCI). Our aim was to investigate the role of airway epithelium as a source of systemic hsCRP levels in CF patients.
Piezoelectric Nanocavity Interface for Strong Coupling between a Superconducting Circuit, Phonon, and Spin (2023)

We introduce a hybrid tripartite quantum system for strong coupling between a semiconductor spin, a mechanical phonon, and a microwave excitation of a superconducting circuit. Consisting of a piezoelectric resonator with an integrated diamond strain concentrator, this system achieves microwave-acoustic and spin-acoustic coupling rates of approximately megahertz or greater, allowing simultaneous ultrahigh cooperativities (approximately ${10}^{3}$ and approximately ${10}^{2}$, respectively). From finite-element modeling and master-equation simulations, we estimate superconducting-circuit-to-spin quantum state transfer fidelities exceeding 0.95 on the basis of separately demonstrated device parameters. We anticipate that this device will enable hybrid quantum architectures that leverage the advantages of both superconducting circuits and solid-state spins for information processing, memory, and networking.
Measurement and Analysis of Static Pressure Field in a Torque Converter Turbine (1995)

In this paper, the static pressure field and performance parameters of a torque converter turbine are measured, analyzed, and interpreted under three speed ratio conditions (0, 0.6, and 0.8). A proven measurement technique was developed for the steady-state measurement of static pressures in the turbine. Results show that: 1) the static pressure field is generally poor at the core section; 2) centrifugal force has the dominant effect on the static pressure drop in the turbine at SR = 0.6 and SR = 0.8; and 3) the static pressure loss due to viscous effects and due to the diffusion of the relative velocity is very pronounced at SR = 0.
Validation of the culture assisting robot in the media changing process for cell processing (2022)

Currently, in the field of regenerative medicine, cell processing is being manually performed. Such a process is labor intensive and expensive, and its efficiency needs to be enhanced. Recently, automatic cell culture apparatus equipped with a vertical articulated robot have been proposed. However, automation of all cell processing tasks complicates the system. This study develops a simple and rational cell processing system by combining the tasks performed by a robot and human. In a previous study, we improved the efficiency of discarding and injecting tasks using a robot arm in the media changing process. In this study, we report the results of the validation of the cell culture assisting robot that facilitates the improvement of the efficiency of discarding and injecting tasks. Our experimental results revealed the feasibility of a cell culture assisting robot that can be used in a safety cabinet. By installing the apparatus, discarding and injecting processes can be performed in parallel, which takes less than half the time compared with the manual process. The total time of the discarding and injecting processes for 40 flasks was 17 min 26 s. In addition, the risk of dripping can be reduced using this apparatus.