gebhart/patrepeval huggingface dataset:
Protein Microgels from Amyloid Fibril Networks (2014)

Nanofibrillar forms of proteins were initially recognized in the context of pathology, but more recently have been discovered in a range of functional roles in nature, including as active catalytic scaffolds and bacterial coatings. Here we show that protein nanofibrils can be used to form the basis of monodisperse microgels and gel shells composed of naturally occurring proteins. We explore the potential of these protein microgels to act as drug carrier agents, and demonstrate the controlled release of four different encapsulated drug-like small molecules, as well as the component proteins themselves. Furthermore, we show that protein nanofibril self-assembly can continue after the initial formation of the microgel particles, and that this process results in active materials with network densities that can be modulated in situ. We demonstrate that these materials are nontoxic to human cells and that they can be used to enhance the efficacy of antibiotics relative to delivery in homogeneous solution. Because of the biocompatibility and biodegradability of natural proteins used in the fabrication of the microgels, as well as their ability to control the release of small molecules and biopolymers, protein nanofibril microgels represent a promising class of functional artificial multiscale materials generated from natural building blocks.
Effect of Polymer Clusters on the Stability of Liquid Crystal Alignment (2014)

Polymer clusters were formed on the surface of alignment films of liquid crystal cells by photo-polymerization of monomers (4,4′-dimethacryloyl-oxy-biphenyl (4,4′-DMOBPh) and 4,4′-diacryloyl-oxy-biphenyl (4,4′-DAOBPh)) that were dissolved in the liquid crystal (LC). The stability of the LC alignment was determined by measuring the difference in pretilt angle (Δtilt) before and after application of an alternate electric field of 60 Hz and 30 V for 50 hours. The Δtilt of the LC cell having the polymer clusters produced from the polymer of 4,4′-DMOBPh was smaller than that produced from the polymer of 4,4′-DAOBPh. This indicates that polymerizable groups affect the stability of the LC alignment.
Assessment of the Safety and Pharmacokinetics of Anidulafungin When Administered With Cyclosporine (2005)

Anidulafungin is a novel antifungal agent of the echinocandin class that is intended for the treatment of invasive fungal disease. It is likely that anidulafungin will be coadministered with cyclosporine. In vitro studies and clinical studies were performed to evaluate the effect of anidulafungin on cyclosporine metabolism and to investigate the safety and pharmacokinetics of anidulafungin when concomitantly administered with cyclosporine. The potential for anidulafungin to inhibit the metabolism of cyclosporine was evaluated by pooled human hepatic microsomal protein fractions in vitro, incubating 3H-cyclosporine with different concentrations of anidulafungin. The safety of coadministration and the effects of cyclosporine on the pharmacokinetics of anidulafungin were assessed in a multiple-dose, open-label clinical study of 12 healthy volunteers. Subjects received a 200-mg intravenous loading dose of anidulafungin, followed by a daily 100-mg intravenous maintenance dose on days 2 through 8. An oral solution of cyclosporine (Neoral oral solution; 100 mg/mL) 1.25 mg/kg was also administered to subjects twice daily on days 5 through 8. In the in vitro study, the addition of anidulafungin had no effect on cyclosporine metabolism by human hepatic microsomal protein fractions. In the clinical study, no dose-limiting toxicities or serious adverse events occurred. A small increase in anidulafungin concentrations and drug exposure (22%) was observed after 4 days of dosing with cyclosporine and was not considered to be clinically relevant. The results support the concomitant use of anidulafungin and cyclosporine without the need for dosage adjustments of either drug.
Current Sensing-Assisted Active Pixel Sensor for High-Speed CMOS Image Sensors (2015)

In this paper, we describe an active pixel CMOS image sensor that employs a current-sensing readout circuit. The readout uses a column-level current-sensing amplifier with negative feedback to increase current driving capability, which gives significantly faster settling time. A prototype 128 × 3 pixel sensor with a current gain of 10 was fabricated using standard 0.3-μm CMOS technology and demonstrated a reduction in settling time by a factor of 14 for both negative and positive voltage swings of the output node. The power consumption of the column-level readout amplifier is 110 μW.
Fabrication of Thin, Metallic Films along the Sidewalls of a Topographically Patterned Stamp and Their Application in Charge Printing (2005)

Thin, electrically conductive metallic films have been generated on the sidewalls of relief patterns on a poly(dimethylsiloxane) stamp using a combination of thin-film metal deposition and nanotransfer printing (see image). These conductive metal films generate patterns of charge in thin films of dielectrics using electrical microcontact printing. Sub-micrometer particles of polystyrene and iron oxide adhere specifically to the regions of charge.
Innenrücktitelbild: Mass Spectrometry Detection and Imaging of a Non‐Covalent Protein–Drug Complex in Tissue from Orally Dosed Rats (Angew. Chem. 36/2022) (2022)

Fliegende Elefanten und empfindliche Fracht. Die Elektrospray-Ionisierung von Proteinen wurde damit verglichen, molekulare Elefanten fliegen zu lassen. Helen J. Cooper und Mitarbeiter (e202202075) demonstrieren den massenspektrometrischen Nachweis und die Bildgebung eines in vivo erzeugten nicht-kovalenten Komplexes, der aus einem endogenen Protein und einem exogen verabreichten Wirkstoffmolekül besteht, direkt in Lebergewebe. Die Methode sollte bessere Einblicke in Protein-Wirkstoff-Komplexe zur Unterstützung der Wirkstoffentwicklung ermöglichen.
Ultrarapid Method for Coating Electrochemical Sensors with Antifouling Conductive Nanomaterials Enables Highly Sensitive Multiplexed Detection in Whole Blood (2021)

The commercialization of electrochemical (EC)-sensors for medical diagnostics is currently limited by their rapid fouling in biological fluids, and use of potential antifouling coatings is hindered by the complexity and cost of application methods. Here, a simple ultrafast (< 1 min) method is described for coating EC-sensors with cross-linked bovine serum albumin infused with conductive, pentaamine-functionalized, graphene particles that can be stored at room temperature for at least 20-weeks, which provides unprecedented sensitivity and selectivity for diagnostic applications. The antifouling coating is applied directly on-chip using rapid heating via simple dip-coating, which provides unprecedented high levels of electrode conductivity for up to 9-weeks in unprocessed biological samples. This method is leveraged to develop a multiplexed platform for detecting clinically relevant biomarkers including myocardial infarction and traumatic brain injury using only 15 µL of blood. Single-digit pg mL<sup>-1</sup> sensitivity is obtained within minutes in unprocessed human plasma and whole blood, which is faster and at least 50 times more sensitive than traditional enzyme-linked immunosorbent assays, and the signal generated is stable enough to be measured after 1 week of storage. The multiplexed EC-sensor platform is validated by analyzing 22 patient samples and demonstrating excellent correlation with reported clinical values.
Recent Applications of Covalent Chemical Probes for Investigating Drug Off-Target Engagement (2019)

Medicinal Chemistry Reviews is an outstanding 680 page volume providing timely and critical reviews of important topics in medicinal chemistry. It is provided free of charge to MEDI members in electronic format. Members can also order a print copy, for the cost of printing, shipping and handling
Guidelines and Benchmarks for Deployment of Deep Learning Models on Smartphones as Real-Time Apps (2019)

Deep learning solutions are being increasingly used in mobile applications. Although there are many open-source software tools for the development of deep learning solutions, there are no guidelines in one place in a unified manner for using these tools towards real-time deployment of these solutions on smartphones. From the variety of available deep learning tools, the most suited ones are used in this paper to enable real-time deployment of deep learning inference networks on smartphones. A uniform flow of implementation is devised for both Android and iOS smartphones. The advantage of using multi-threading to achieve or improve real-time throughputs is also showcased. A benchmarking framework consisting of accuracy, CPU/GPU consumption and real-time throughput is considered for validation purposes. The developed deployment approach allows deep learning models to be turned into real-time smartphone apps with ease based on publicly available deep learning and smartphone software tools. This approach is applied to six popular or representative convolutional neural network models and the validation results based on the benchmarking metrics are reported.
Zukunft des Schlafens (2015)

Wie werden wir in Zukunft schlafen? Und müssen wir das demnächst überhaupt noch? Mit diesen spannenden Fragen beschäftigen sich seit geraumer Zeit etliche kluge Köpfe. Neben der rein wissenschaftlichen Schlafforschung und Schlafmedizin gehören z.B. auch das Militär und die Wirtschaft zu den diesbezüglich vorpreschendsten Gruppen. Daneben interessieren sich seit jeher die gesamte Betten- und Matratzenindustrie für den Schlaf sowie neuerdings auch immer mehr Lifestyle-orientierte Dienstleister und Produzenten.
Removal of image intensifier veiling glare by mathematical deconvolution techniques (1985)

X-ray images acquired with an image intensifier detector system suffer from veiling glare, a low-frequency degradation described by a point spread function (PSF). The PSF has two experimentally determined parameters unique to a given image intensifier. This information is utilized to deconvolve the degradation from digitally acquired images. Results demonstrate a significant increase in contrast ratio of high-contrast objects after deconvolution and image restoration.
Abstract P009: Differential Redox Signaling In Urine Derived Renal Proximal Tubule Cells Isolated From Inverse Salt Sensitive Vs Salt Resistant Clinical Study Participants (2020)

Increased morbidity and mortality occurs in some individuals consuming low sodium diets. We demonstrated that single nucleotide polymorphisms (SNPs) in the dopamine type 2 receptor (D2R) as well as lower expression of cellular and plasma membrane D2R are associated with inverse salt sensitivity (ISS, a paradoxical increase in blood pressure while on the low sodium diet). Urine derived human renal proximal tubule cells (RPTC) were cultured from 3 separate ISS and 3 salt resistant (SR, resists blood pressure change on both low and high sodium diets) participants. D2R reduces cellular redox signaling so we hypothesized that an aberrant redox state occurs in ISS and SR RPTC exposed to different NaCl concentrations. RPTC incubated in 90 mM NaCl (low salt - LS) for 2 hours in both ISS and SR RPTCs had a significant reduction of monochlorobimane (mBCl - reduced glutathione indicator) compared to 140 mM NaCl (normal salt -NS) (SR -7.1± 2.1% and ISS -9.7 ± 1.6% vs NS, n=12, p&lt;0.05, t-test). Only ISS RPTC had a significant increase in mBCl fluorescence in 190 mM NaCl (ISS +7.0 ± 2.5% vs NS, n=12, p&lt;0.05, t-test) and mBCl fluorescence was not affected by incubation with losartan (angiotensin type 1 receptor inhibitor). 3-Aminobenzamide (3AB, 1 mM) inhibits Parp1 (poly[ADP-ribose] synthase), a protein necessary for the transcriptional repressor CTCF insulator function. 3AB reversed the lower mBCl fluorescence only in the SR RPTC, suggesting that reducing CTCF insulator function only affects D2R wild type cells. mBCl fluorescence in ISS RPTC showed a greater reduction by LOS vs SR RPTC (ISS -49.3 ± 1.5% vs SR -37.3 ± 4.8%, n=12, p&lt;0.05, t-test), which was blocked by nemonapride (NEM, 1 uM, D2R antagonist) and further reduced the mBCl fluorescence only in the SR RPTC. Whether these differences in salt sensitivities are due to differential effects of CTCF insulator function at the homozygous variant or wild type D2R warrants further studies.
Chemie der Übergangsmetall‐Heterocyclen‐Komplexe, I. Über eine elektrophile Pyrrolyl‐Eliminierung aus Azacymantren (1979)

Abstract Tricarbonyl(η 5 ‐pyrrolyl)mangan ( 2 )ergibt bei der Reaktion mit Diphenylketen in siedendem Tetrahydrofuran/Wasser den Dreikern‐Komplex 4 sowie N ‐(Diphenylacetyl)pyrrol ( 3 ). Die Konfiguration von 4 als Komplex vom Typ fac ‐(CO) 3 Mn(L 1 ) 2 L 2 (L 1 = 2 ; L 2 = Diphenylacetato‐ O ) ist aus den NMR‐Spektren ableitbar und für den kristallinen Zustand durch Röntgenstrukturanalyse gesichert. ‐ Der neuartige N ‐Azacymantren‐Komplex (η 5 ‐C 5 H 5 )Mn(CO) 2 [(s̀‐C 4 H 4 N)Mn(CO) 3 ] ( 6 ) läßt sich durch gezielten Ligandenaustausch an (η 5 ‐C 5 H 5 )Mn(CO) 3 ( 1 ) synthetisieren. Aufgrund der IR‐ und NMR‐Daten besitzt 2 in seiner Eigenschaft als einzähniger Stickstoffligand ein hohes s̀‐Donor/π‐Akzeptor‐Verhältnis.
A 1 GHz GaAs CCD with capacitive gates and high transfer efficiency (2003)

A high-performance GaAs charge-coupled device (CCD) structure that has charge transfer efficiency (CTE) greater than 0.999 at 1 GHz is reported. This device is the highest performance capacitive gate GaAs CCD yet reported. A method of improving CTE in capacitive-gate CCDs by recessing the gap regions is described, and preliminary experimental results are presented. Use of an AlGaAs cap layer, resulting in a four order of magnitude reduction in Schottky gate leakage current, is described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Short-term Load Forecasting with Deep Boosting Transfer Regression (2022)

With the increasing popularity of electric vehicles and the growing trend of working from home, electricity consumption in the residential sector is expected to continue to grow rapidly over the next few years. As a consequence, short-term residential load forecasting is becoming even more vital for the reliability and sustainability of the smart grid. Although deep learning models have shown impressive success in different areas including short-term electric load forecasting, such models require a large amount of training data. For many real-world load forecasting cases, we may not have enough training data to learn a reliable forecasting model. In this paper, we address this challenge through the use of boosting-based transfer learning with multiple sources. We first train a set of deep regression models on source houses that can provide relatively abundant data. We then transfer these learned models via the boosting framework to support data-scarce target houses. The transfer process is selective and customized for each target house to minimize the potential for negative transfer. Experimental results, based on real-world residential data sets, show that the proposed method can significantly improve forecasting accuracy.
Multifunctional Antibody Agonists Targeting Glucagon‐like Peptide‐1, Glucagon, and Glucose‐Dependent Insulinotropic Polypeptide Receptors (2016)

Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), glucagon (GCG) receptor (GCGR), and glucose-dependent insulinotropic polypeptide (GIP, also known as gastric inhibitory polypeptide) receptor (GIPR), are three metabolically related peptide hormone receptors. A novel approach to the generation of multifunctional antibody agonists that activate these receptors has been developed. Native or engineered peptide agonists for GLP-1R, GCGR, and GIPR were fused to the N-terminus of the heavy chain or light chain of an antibody, either alone or in pairwise combinations. The fusion proteins have similar in vitro biological activities on the cognate receptors as the corresponding peptides, but circa 100-fold longer plasma half-lives. The GLP-1R mono agonist and GLP-1R/GCGR dual agonist antibodies both exhibit potent effects on glucose control and body weight reduction in mice, with the dual agonist antibody showing enhanced activity in the latter.
Multiharmonic tracking using marginalized particle filters (2008)

Man-made and natural systems often generate signals with multi-harmonic components, and the accurate estimation of the harmonically related components of these signals is critical for various applications. The posterior distribution of frequency estimates for this class of signal is multi-model--posing a challenge for frequency tracking algorithms which may lock onto a super or sub harmonic of the fundamental frequency. We propose a multi-harmonic tracker based on a sequential Monte Carlo method (SMCM) which can account for the multi-modality of the posterior distribution to track the harmonically related components of a signal more accurately than a tracker based on local linearization. We compare the SMCM multi-harmonic tracker with the extended Kalman filter (EKF) multi-harmonic tracker by applying them to real biomedical signals including electrocardiograms (ECG) and arterial blood pressure (ABP) signals. The results clearly show the superior performance of the proposed multi-harmonic tracker over the EKF tracker.
Engineered Biosynthesis of Aklanonic Acid Analogues (2005)

Aklanonic acid, an anthraquinone natural product, is a common advanced intermediate in the biosynthesis of several antitumor polyketide antibiotics, including doxorubicin and aclacinomycin A. Intensive semisynthetic and biosynthetic efforts have been directed toward developing improved analogues of these clinically important compounds. The primer unit of such polyfunctional aromatic polyketides is an attractive site for introducing novel chemical functionality, and attempts have been made to modify the primer unit by precursor-directed biosynthesis or protein engineering of the polyketide synthase (PKS). We have previously demonstrated the feasibility of engineering bimodular aromatic PKSs capable of synthesizing unnatural hexaketides and octaketides. In this report, we extend this ability by preparing analogues of aklanonic acid, a decaketide, and its methyl ester. For example, by recombining the R1128 initiation module with the dodecaketide-specific pradimicin PKS, the isobutyryl-primed analogue of aklanonic acid (YT296b, 10) and its methyl ester (YT299b, 12) were prepared. In contrast, elongation modules from dodecaketide-specific spore pigment PKSs were unable to interact with the R1128 initiation module. Thus, in addition to revealing a practical route to new anthracycline antibiotics, we also observed a fundamental incompatibility between antibiotic and spore pigment biosynthesis in the actinomycetes bacteria.
Two-Phase Synthesis of Monodisperse Silica Nanospheres with Amines or Ammonia Catalyst and Their Controlled Self-Assembly (2011)

A significant progress has recently been made in the synthesis of monodisperse silica nanoparticles less than 30 nm in diameter by using basic amino acids (e.g., lysine) as a base catalyst for hydrolysis of silicon alkoxide. Alternatively, a more versatile and economical amino acid-free method has been developed to synthesize uniform silica nanospheres (SNSs) with low polydispersity (<12%) in liquid-liquid biphasic systems containing tetraethoxysilane (TEOS), water, and primary amine (or ammonia) under precisely controlled pH conditions (pH 10.8-11.4). The diameter of the SNSs determined from scanning electron microscopy (SEM) can be tuned from ∼12 to ∼36 nm by simply changing the initial pH of the aqueous phase in the reaction mixtures. Furthermore, the as-synthesized sol was taken as the starting material for studying the influences of the type of base catalysts on the solvent evaporation-induced three-dimensional (3D) self-assembly of SNSs. X-ray diffraction (XRD) and nitrogen adsorption-desorption are used to characterize the degree of packing of the resulting 3D arrays. The assembled SNSs with large interparticle mesopores with the diameter of ca. 8.1 nm and low packing fraction of ca. 66.1% are observed upon solvent evaporation of as-synthesized sol in the presence of primary amine. This indicates that SNSs are loosely packed, compared with the packing fraction of 74% for a face-centered cubic array of ideal hard spheres. In contrast, with the aid of an organic buffer or lysine as additives, the assembly of SNSs having smaller mesopores (ca. 3.9 nm) and higher packing fraction of 70.5-71.5% are achieved. It is suggested that the chemical additives with the ability to maintain relatively strong repulsive interaction until the final stage of evaporation play a vital role in the fabrication of well-ordered SNSs arrays.
Data from Expression of CD14, IL10, and Tolerogenic Signature in Dendritic Cells Inversely Correlate with Clinical and Immunologic Response to TARP Vaccination in Prostate Cancer Patients (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Despite the vast number of clinical trials conducted so far, dendritic cell (DC)-based cancer vaccines have mostly shown unsatisfactory results. Factors and manufacturing procedures essential for these therapeutics to induce effective antitumor immune responses have yet to be fully characterized. We here aimed to identify DC markers correlating with clinical and immunologic response in a prostate carcinoma vaccination regimen.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; We performed an extensive characterization of DCs used to vaccinate 18 patients with prostate carcinoma enrolled in a pilot trial of T-cell receptor gamma alternate reading frame protein (TARP) peptide vaccination (NCT00908258). Peptide-pulsed DC preparations (114) manufactured were analyzed by gene expression profiling, cell surface marker expression and cytokine release secretion, and correlated with clinical and immunologic responses.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; DCs showing lower expression of tolerogenic gene signature induced strong antigen-specific immune response and slowing in PSA velocity, a surrogate for clinical response. These DCs were also characterized by lower surface expression of CD14, secretion of IL10 and MCP-1, and greater secretion of MDC. When combined, these four factors were able to remarkably discriminate DCs that were sufficiently potent to induce strong immunologic response.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; DC factors essential for the activation of immune responses associated with TARP vaccination in prostate cancer patients were identified. This study highlights the importance of in-depth characterization of DC vaccines and other cellular therapies, to understand the critical factors that hinder potency and potential efficacy in patients. &lt;i&gt;Clin Cancer Res; 23(13); 3352–64. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Volume visualization using two projections (2003)

Describes a method for producing image volumes from only two orthogonally oriented projections. A merging technique is re-introduced and methods for visualizing composite image volumes using linear ray summing and nonlinear maximum intensity approaches are compared. A right cylinder phantom and a clinical angiogram served as the authors' image subjects. Projections were made of the composite volumes and the resulting visual content was observed and reported. These projections can be made from any viewing orientation.