gebhart/patrepeval huggingface dataset:
Integrating Combinatorial Lipid Nanoparticle and Chemically Modified Protein for Intracellular Delivery and Genome Editing (2018)

The use of protein to precisely manipulate cell signaling is an effective approach for controlling cell fate and developing precision medicine. More recently, programmable nucleases, such as CRISPR/Cas9, have shown extremely high potency for editing genetic flow of mammalian cells, and for treating genetic disorders. The therapeutic potential of proteins with an intracellular target, however, is mostly challenged by their low cell impermeability. Therefore, a developing delivery system to transport protein to the site of action in a spatiotemporal controlled manner is of great importance to expand the therapeutic index of the protein. In this Account, we first summarize our most recent advances in designing combinatorial lipid nanoparticles with diverse chemical structures for intracellular protein delivery. By designing parallel Michael addition or ring-opening reaction of aliphatic amines, we have generated a combinatorial library of cationic lipids, and identified several leading nanoparticle formulations for intracellular protein delivery both in vitro and in vivo. Moreover, we optimized the chemical structure of lipids to control lipid degradation and protein release inside cells for CRISPR/Cas9 genome-editing protein delivery. In the second part of this Account, we survey our recent endeavor in developing a chemical approach to modify protein, in particular, coupled with the nanoparticle delivery platform, to improve protein delivery for targeted diseases treatment and genome editing. Chemical modification of protein is a useful tool to modulate protein function and to improve the therapeutic index of protein drugs. Herein, we mostly summarize our recent advances on designing chemical approaches to modify protein with following unique findings: (1) chemically modified protein shows selective turn-on activity based on the specific intracellular microenvironment, with which we were able to protein-based targeted cancer therapy; (2) the conjugation of hyaluronic acid (HA) to protein allows cancer cell surface receptor-targeted delivery of protein; (3) the introduction of nonpeptidic boronic acid into protein enabled cell nucleus targeted delivery; this is the first report that a nonpeptidic signal can direct protein to subcellular compartment; and (4) the fusion of protein with negatively supercharged green fluorescent protein (GFP) facilitates the self-assembly of protein with lipid nanoparticle for genome-editing protein delivery. At the end of the Account, we give a perspective of expanding the chemistry that could be integrated to design biocompatible lipid nanocarriers for protein delivery and genome editing in vitro and in vivo, as well as the chemical approaches that we can harness to modulate protein activity in live cells for targeted diseases treatment.
Mechanisms of enhancement of neurite regeneration in vitro following a conditioning sciatic nerve lesion (1998)

To examine the mechanisms responsible for the more rapid nerve regeneration observed after a previous (conditioning) nerve injury, adult rats were subjected to a midthigh sciatic nerve transection by using one of three protocols designed to facilitate or restrict nerve regeneration: 1) ligation, in which transected axons were prevented from regenerating; 2) cut, in which transected axons were permitted to extend into peripheral target tissue but were separated from the denervated peripheral nerve stump; and 3) crush, in which axons could regenerate normally through the denervated distal nerve tract. The affected dorsal root ganglia (DRG) were subsequently removed, dissociated, and cultured for up to 3 days, and the timing of neurite initiation, rate of outgrowth, and arborization pattern of previously injured neurons were compared with control DRG. Our results indicate that conditioning lesions have at least four distinct and differentially regulated effects on neuronal morphogenesis: 1) conditioning lesions promote earlier neurite initiation, 2) prior nerve injury decreases the ability of neurons to extend long neurites following a second axotomy, 3) exposure to the environment of a denervated peripheral nerve stimulates greater initial rates of neurite outgrowth, and 4) conditioning lesions reduces initial neuritic branching frequency, resulting in straighter neurites whose growth cones extend further distances from their cell bodies. The primary effect of all conditioning lesions on cultured DRG neurons appeared to be to advance the timing of morphogenesis, resulting in conditioning-lesioned neurons that exhibited characteristics consistent with control neurons that had been cultured for an additional day or more. A secondary effect of conditioning lesions on neurite outgrowth rates was dependent on the local environment of the axons prior to culturing.
Open-source three-dimensional printing of biodegradable polymer scaffolds for tissue engineering (2014)

The fabrication of scaffolds for tissue engineering requires elements of customization depending on the application and is often limited due to the flexibility of the processing technique. This investigation seeks to address this obstacle by utilizing an open-source three-dimensional printing (3DP) system that allows vast customizability and facilitates reproduction of experiments. The effects of processing parameters on printed poly(ε-caprolactone) scaffolds with uniform and gradient pore architectures have been characterized with respect to fiber and pore morphology and mechanical properties. The results demonstrate the ability to tailor the fiber diameter, pore size, and porosity through modification of pressure, printing speed, and programmed fiber spacing. A model was also used to predict the compressive mechanical properties of uniform and gradient scaffolds, and it was found that modulus and yield strength declined with increasing porosity. The use of open-source 3DP technologies for printing tissue-engineering scaffolds provides a flexible system that can be readily modified at a low cost and is supported by community documentation. In this manner, the 3DP system is more accessible to the scientific community, which further facilitates the translation of these technologies toward successful tissue-engineering strategies.
Pressure-Pair-Based Floor Localization System Using Barometric Sensors on Smartphones (2019)

As smartphone technology advances and its market penetration increases, indoor positioning for smartphone users is becoming an increasingly important issue. Floor localization is especially critical to indoor positioning techniques. Numerous research efforts have been proposed for improving the floor localization accuracy using information from barometers, accelerometers, Bluetooth Low Energy (BLE), and Wi-Fi signals. Despite these existing efforts, no approach has been able to determine what floor smartphone users are on with near 100% accuracy. To address this problem, we present a novel pressure-pair based method called FloorPair, which offers near 100% accurate floor localization. The rationale of FloorPair is to construct a relative pressure map using highly accurate relative pressure values from smartphones with two novel features: first, we marginalized the uncertainty from sensor drifts and unreliable absolute pressure values of barometers by paring the pressure values of two floors, and second, we maintained high accuracy over time by applying an iterative optimization method, making our method sustainable. We evaluated the validity of the FloorPair approach by conducting extensive field experiments in various types of buildings to show that FloorPair is an accurate and sustainable floor localization method.
Quantitative cardiac <sup>31</sup>P spectroscopy at 3 Tesla using adiabatic pulses (2009)

Cardiac phosphorus magnetic resonance spectroscopy (MRS) with surface coils promises better quantification at 3 Tesla (T) from improved signal-to-noise ratios and spectral resolution compared with 1.5 T. However, Bloch equation and field analyses at 3T show that for efficient quantitative MRS protocols using small-angle adiabatic (BIR4/BIRP) pulses the excitation-field is limited by radiofrequency (RF) power requirements and power deposition. When BIR4/BIRP pulse duration is increased to reduce power levels, T2-decay can introduce flip-angle dependent errors in the steady-state magnetization, causing errors in saturation corrections for metabolite quantification and in T1s measured by varying the flip-angle. A new dual-repetition-time (2TR) T1 method using frequency-sign-cycled adiabatic-half-passage pulses is introduced to alleviate power requirements, and avoid the problem related to T2 relaxation during the RF pulse. The 2TR method is validated against inversion-recovery in phantoms using a practical transmit/receive coil set designed for phosphorus MRS of the heart at depths of 9-10 cm with 4 kW of pulse power. The T1s of phosphocreatine (PCr) and adenosine triphosphate (gamma-ATP) in the calf-muscle (n=9) at 3 T are 6.8+/-0.3 s and 5.4+/-0.6 s, respectively. For heart (n=10) the values are 5.8+/-0.5 s (PCr) and 3.1+/-0.6 s (gamma-ATP). The 2TR protocol measurements agreed with those obtained by conventional methods to within 10%.
Thermodynamic Behavior of FeCl3-H2O and HCl-FeCl3-H2O Systems – A Pitzer Model at 25 °C (2013)

Most of the speciation models of aqueous electrolyte systems are based on the “ion pairing and complexing approach”. They are only suitable for aqueous solutions with ionic strengths lower than about 1 eq.kgw-1. For highly saline solutions, an approach based on “specific-ion interactions” (the so-called “Pitzer approach”) provides much more accurate results. Various thermodynamic databases supporting the “Pitzer approach” exist, but they are often inconsistent and poorly documented. The number of chemical elements is limited because of the difficulties inherent to producing relevant experimental data for wide ranges of temperature, ionic strength, pH, and for low solubility metals and hydroxides, and also because of the difficulty in evaluation of consistent and accurate values for interaction parameters. This study presents a new set of parameters using the standard Pitzer formalism that is able to model the behavior of Fe-rich solutions and solid-liquid equilibria in binary FeCl3-H2O and mixed HCl-FeCl3-H2O systems at 25 °C. The new binary and mixing interaction parameters are adjusted in order to fit various independent experimental activity (water activity, osmotic coefficients) and ferric chloride salts solubility data. This work allows updating and improving thermodynamic databases for Fe(III) systems in order to simulate the complex geochemical behaviour of solutions and gas-brine-rock interactions in various applications in the geosciences or industrial processes.
Characterization and 400‐MHz <sup>1</sup>H‐NMR analysis of urinary fucosyl glycoasparagines in fucosidosis (1991)

Fucosyl glycoasparagines accumulating in the urine of a patient with fucosidosis were isolated using reverse-phase HPLC. Structural analysis of 25 glycoasparagines was carried out by combination of methylation and 400-MHz 1H-NMR spectroscopy analyses. The compounds represent different steps in the incomplete catabolism of N-glycosidically linked glycans, as the result of an alpha-L-fucosidase deficiency. All of the glycoasparagines possess a fucose residue alpha-1,6-linked to the GlcNAc 1 residue attached to asparagine. Fucose residues on the peripheral branches were linked either alpha-1,3 to GlcNAc residues (X determinant) or alpha-1,2 to galactose residues (H determinant). The present study allows precise assignments of the NMR parameters for most of the fucosyl linkages occurring in N-glycosidically linked glycans of the N-acetyllactosamine type.
Sams Teach Yourself PHP, MySQL and Apache All in One (2008)

Sams Teach Yourself PHP, MySQL and Apache All in One Fourth Edition Julie C. Meloni Starter Kit CD-ROM includes a complete starter kit for Windows, Linux, and Mac OS X In just a short time, you can learn how to use PHP, MySQL, and Apache together to create dynamic, interactive websites and applications using the three leading open-source web development technologies. Using a straightforward, step-by-step approach, each lesson in this book builds on the previous ones, enabling you to learn the essentials of PHP scripting, MySQL databases, and the Apache web server from the ground up. Regardless of whether you run Linux, Windows, or Mac OS X, the enclosed CD includes a complete starter kit that lets you install all the software you need to set up a stable environment for learning, testing, and production. Learn how to Install, configure, and set up the PHP scripting language, the MySQL database system, and the Apache Web server Get these technologies to work together to create a dynamic, database-backed website Interact with MySQL using PHP Work with forms and files Create a web-based discussion forum or mailing list Add a storefront and shopping cart to your site Optimize your MySQL databases Fine-tune the Apache servers performance Restrict access to your applications Set up a secure web server Julie C. Meloni is the technical director for i2i Interactive, a multimedia company located in Los Altos, California. She has been developing web-based applications since the early days of the web, and is the author of several books and articles on web-based programming languages and database topics, including Sams Teach Yourself MySQL in 24 Hours. CD-ROM Includes A complete PHP, MySQL, and Apache starter kit for Windows, Linux, or Mac OS X. Category:Web Development Covers:PHP 5.2, MySQL 5, Apache 2.2 User Level:Beginning
Influence of Oxygen Ion Conduction on Nitric Oxide Decomposition (1994)

Ba 2 In 2 O 5 , Ba 2 Y 4 O 9 , and BaLa 2 O 4 having brownmillerite‐related structures were synthesized. Ionic conductivity and catalytic activity following the reduction of NO to N 2 were also investigated, both of which increased at the order‐disorder transition temperature for oxygen vacancies of these compounds. It was made clear that the catalytic activity of NO decomposition reaction increased with a decrease in the order–disorder transition temperature. Moreover, it was found that ionic conductivity contributed to the catalytic activity of NO reduction to N 2 .
η<sup>6</sup>-Cycloparaphenylene Transition Metal Complexes: Synthesis, Structure, Photophysical Properties, and Application to the Selective Monofunctionalization of Cycloparaphenylenes (2015)

The synthesis, structure, photophysical properties, and reactivity of cycloparaphenylenes (CPPs) coordinated to group 6 transition metal fragments are described. The η(6)-coordination of [9]CPP or [12]CPP with M(CO)6 (M = Cr, Mo, W) afforded the corresponding [n]CPP-M(CO)3 complexes (n = 9, 12; M = Cr, Mo, W). In the (1)H NMR spectra of these complexes, characteristic upfield-shifted singlet signals corresponding to the four hydrogen atoms attached to the coordinated C6H4 ring of the CPPs were observed at 5.4-5.9 ppm. The complex [9]CPP-Cr(CO)3 could be successfully isolated in spite of its instability. X-ray crystallographic analysis and computational studies of [9]CPP-Cr(CO)3 revealed that chromium-CPP coordination occurs at the convex surface of [9]CPP both in the solid state and in solution. TD-DFT calculations suggested that the emerging high-wavenumber absorption peak upon coordination of [9]CPP to Cr(CO)3 should be assigned to a weak HOMO-LUMO transition. Moreover, by using the complex [9]CPP-Cr(CO)3, a rapid and highly monoselective CPP functionalization has been achieved. The established one-pot method, consisting of complexation, deprotonation, nucleophilic substitution, and decomplexation steps, yielded silyl-, boryl-, and methoxycarbonyl-substituted CPPs in up to 93% yield relative to reacted starting material.
Enantioselective carbon‐‐hydrogen insertion is an effective and efficient methodology for the synthesis of (<b><i>r</i></b>)‐(‐)‐baclofen (2002)

A highly enantioselective methodology for the synthesis of the GABA(B) receptor agonist (R)-(-)-baclofen is described. This synthesis begins with p-chlorophenethyl alcohol and involves a catalytic carbon-hydrogen insertion reaction of a chiral dirhodium(II) carboxamidate with the corresponding diazoacetate (81% yield, 95% ee). Subsequent steps convert the intermediate gamma-lactone to (R)- (-)-baclofen in a 60% overall yield. The amount of catalyst required for the C-H insertion transformation is only 0.5 mol%.
Role of staphylococcal enterotoxin A in a fatal case of endocarditis (2003)

A young female with no identifiable risk factors developed rapid, overwhelming Staphylococcus aureus endocarditis. Despite rapid sterilization of the blood and the mitral valve with optimal antimicrobials, she had persistent septic shock. In order to investigate this, the toxin-producing capacity of the infecting strain and the patient's ability to produce antibodies were determined. The strain produced high levels of both alpha-toxin and staphylococcal enterotoxin A (SEA), whilst the patient responded with modestly high levels of antibodies to alpha-toxin and low-normal levels to SEA. The patient was most probably susceptible to the actions of SEA and developed a toxic-shock-syndrome-like disease that further aggravated her valvular dysfunction. This case illustrates that optimal antimicrobial therapy alone is not sufficient treatment in patients with persistent toxic shock and that there is a need to evaluate immunomodulatory strategies in such patients.
Autonomous Power Generating System with Multi-Level Converters (2006)

Paper presents a novel topology of autonomous power generating system with a diesel engine and a permanent magnet synchronous generator (DE/PMSG) in configuration with the multi-level converters. The star-connected three-phase back-to-back topology with a five-level diode-clamped rectifier (5LDCR) and a five-level diode-clamped inverter (5LDCI) supplies a three phase output load. The proposed multi-level current mode control technique represented in dq frame and subsequently converted to abc frame provide an effective solution to voltage imbalance problem in a DC link network. The proposed balancing method is applied to "back-to-back" operational mode only. In case of operation from the interfaced battery energy storage (BES), the balancing problem does not exist because individual DC-DC converters (SU/SD) stabilize voltages across four capacitors in the DC link network. Importantly, the gen-set is able to operate with an asymmetrical, a nonlinear and an impact load in three phases and it provides the power factor correction on the generator side
Why Superhydrophobic Surfaces Are Not Always Icephobic (2012)

We discuss mechanical forces that act upon a water droplet and a piece of ice on a rough solid surface and the difference between dewetting and ice fracture. The force needed to detach a water droplet depends on contact angle (CA) hysteresis and can be reduced significantly in the case of a superhydrophobic surface. The force needed to detach a piece of ice depends on the receding CA and the initial size of interfacial cracks. Therefore, even surfaces with very high receding CA may have strong adhesion to ice if the size of the cracks is small.
Source and Channel Coding for Quasi-Static Fading Channels (2006)

We consider transmission of a continuous amplitude source over a quasi-static Rayleigh fading channel. We analyze three different source and channel coding strategies in terms of overall expected distortion (ED). Our goal is to maximize the distortion exponent (Delta), which is the exponential decay rate of ED with increasing SNR. In each case, by adjusting the system parameters we find the best Delta as a function of the bandwidth expansion. We also find an upper bound for Delta and illustrate how this upper bound can be achieved for all bandwidth expansions even with reasonably simple strategies. Although we focus on a Gaussian source for brevity, we demonstrate that our results can be extended to more general source distributions
Continuous Vectorcardiography in Patients with Chest Pain Indicative of Acute Ischemic Heart Disease (1992)

To assess the clinical usefulness of continuous on-line vectorcardiography (VCG), we studied 61 patients admitted to the coronary care unit (CCU) with chest pain, supposedly ischemic. Continuous VCG was performed for 24 h, monitoring QRS vector difference (QRS-VD), ST-change vector magnitude (STC-VM) and ST vector magnitude (ST-VM) measured 20 and 60 ms after the termination of the QRS complex. The patients were divided into four groups based on the final diagnosis; group A, 15 patients with normal exercise tests and extracardiac causes of chest pain; group B, 15 patients with unstable angina; group C, 15 patients with non-Q-wave myocardial infarction (MI); group D, 16 patients with Q-wave MI. Treatment was given according to a normal routine. Of 31 patients with MI, 16 received treatment with streptokinase. Groups A and B showed no significant permanent changes in QRS-VD, STC-VM or ST-VM. However, group B showed a higher occurrence of transient episodes (duration: 2 min-6 h) of a significant change of QRS-VD by > 15 microVs and of STC-VM, ST-VM 20 and ST-VM 60 by > 0.1 mV. Groups C and D showed both permanent changes and transient episodes for the studied vector parameters. Transient episodes were significantly fewer in group D than in group B. In patients with MI, the permanent change of vector parameters evolved more rapidly and reached a plateau earlier in those treated with streptokinase (QRS-VD: 178 +/- 82 vs. 293 +/- 100 min, p < 0.001; ST-VM 20: 142 +/- 75 vs. 293 +/- 89 min, p < 0.005). The magnitude of the end value for QRS-VD correlated with infarct size estimated by the maximal value of creatine kinase (r = 0.89; p < 0.001). We conclude that in patients admitted to the CCU with chest pain, continuous VCG monitoring early differentiates patients suffering from ischemic heart disease (IHD) from patients without IHD. It also differentiates patients with unstable angina from patients with MI.
Membrane Targeted Anticancer Drugs: Potent Inducers of Apoptosis and Putative Radiosensitisers (2003)

In the last two decades, cellular membranes have been identified as novel targets for antineoplastic drugs. Two classes of synthetic phospholipid analogues: the alkyllysophospholipids (ALP) with the prototypical 1-O-Octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (Et-18-OCH3, Edelfosine), as well as the alkylphosphocholines (APC) with the prototypical hexadecylphosphocholine (HePC, Miltefosine), have been identified targeting cellular membranes and exerting potent antineoplastic effects in cell culture and animal models. In contrast to most of the chemotherapeutic agents in clinical use, APC and ALP primarily interfere with cellular membranes without direct interaction with the DNA. They modulate membrane permeability and fluidity, membrane lipid composition, metabolism of phospholipids and proliferation signal transduction. Interestingly, similar to DNA-damaging drugs, ALP and APC induce apoptotic cell death. Furthermore, combination experiments with cytotoxic drugs or radiation revealed a synergistic effect in leukaemic and brain tumour cell lines. These findings together with the observations that ALP and APC selectively kill malignant cells, that they lack bone marrow toxicity and even exert growth stimulatory effects on hematopoietic progenitor cells make ALP and APC a promising tool for novel approaches in cancer chemotherapy. In this contribution, novel findings on the mechanism of action, apoptotic signalling pathways and putative radiosensitising effects of ALP and APC were reviewed, with a special focus on erucylphosphocholine (ErPC), the prototype of the novel intravenously applicable APC derivatives.
Breast Cancer Subtypes and the Risk of Local and Regional Relapse (2010)

Luminal A tumors are associated with a low risk of local or regional recurrence. Molecular subtyping of breast tumors using a six-marker immunohistochemical panel can identify patients at increased risk of local and regional recurrence.