gebhart/patrepeval huggingface dataset:
Kinetic and pharmacological properties of the M‐current in rodent neuroblastoma x glioma hybrid cells. (1992)

1. The M-like current IK(M,ng) in differentiated NG108-15 mouse neuroblastoma x rat glioma hybrid cells has been studied using tight-seal, whole-cell patch-clamp recording. 2. When calculated from steady-state current-voltage curves, the conductance underlying IK(M,ng) showed a Boltzmann dependence on voltage with half-activation voltage Vo = -44 mV (in 3 mM [K+]) and slope factor (a) = 8.1 mV/e-fold increase in conductance. In 12 mM [K+] Vo = -38 mV and a = 6.9 mV. The deactivation reciprocal time constant accelerated with hyperpolarization with slope factor 17 mV/e-fold voltage change. 3. The reversal potential for deactivation tail currents varied with external [K+] as if PNa/PK were 0.005. 4. Steady-state current was increased on removing external Ca2+. In the presence of external Ca2+, reactivation of IK(M, ng) after a hyperpolarizing step was delayed. This delay was preceded by an inward Ca2+ current, and coincided with an increase in intracellular [Ca2+] as measured with Indo-1 fluorescence. Elevation of intracellular [Ca2+] with caffeine also reduced IK(M, ng). 5. IK(M, ng) was inhibited by external divalent cations in decreasing order of potency (mM IC50 in parentheses): Zn2+ (0.011) greater than Cu2+ (0.018) greater than Cd2+ (0.070) greater than Ni2+ (0.44) greater than Ba2+ (0.47) greater than Fe2+ (0.69) greater than Mn2+ (0.86) greater than Co2+ (0.92) greater than Ca2+ (5.6) greater than Mg2+ (16) greater than Sr2+ (33). This was not secondary to inhibition of ICa since: (i) inhibition persisted in Ca(2+)-free solution; (ii) La3+ did not inhibit IK(M, ng) at concentrations which inhibited ICa; and (iii) organic Ca2+ channel blockers were ineffective. Inhibition comprised both depression of the maximum conductance and a positive shift of the activation curve. Addition of Ca2+ (10 microM free [Ca2+]) or Ba2+ (1 mM total [Ba2+]) to the pipette solution did not significantly change IK(M, ng). 6. IK(M, ng) was reduced by 9-amino-1,2,3,4-tetrahydroacridine (IC50 8 microM) and quinine (30 microM) but was insensitive to tetraethylammonium (IC50 greater than 30 mM), 4-aminopyridine (greater than 10 mM), apamin (greater than 3 microM) or dendrotoxin (greater than 100 nM). 7. IK(M, ng) was inhibited by bradykinin (1-10 microM) or angiotensin II (1-10 microM), but not by the following other receptor agonists: acetylcholine (10 mM), muscarine (10 microM), noradrenaline (100 microM), adrenaline (100 microM), dopamine (100 microM), histamine (100 microM), 5-hydroxytryptamine (10 microM), Met-enkephalin (1 microM), glycine (100 microM), gamma-aminobutyric acid (100 microM) or baclofen (500 microM).(ABSTRACT TRUNCATED AT 400 WORDS)
CRISPR/Cas9 Mediated Disruption of the Swedish APP Allele as a Therapeutic Approach for Early-Onset Alzheimer’s Disease (2018)

The APPswe (Swedish) mutation in the amyloid precursor protein (APP) gene causes dominantly inherited Alzheimer's disease (AD) as a result of increased β-secretase cleavage of the amyloid-β (Aβ) precursor protein. This leads to abnormally high Aβ levels, not only in brain but also in peripheral tissues of mutation carriers. Here, we selectively disrupted the human mutant APP<sup>SW</sup> allele using CRISPR. By applying CRISPR/Cas9 from Streptococcus pyogenes, we generated allele-specific deletions of either APP<sup>SW</sup> or APP<sup>WT</sup>. As measured by ELISA, conditioned media of targeted patient-derived fibroblasts displayed an approximate 60% reduction in secreted Aβ. Next, coding sequences for the APP<sup>SW</sup>-specific guide RNA (gRNA) and Cas9 were packaged into separate adeno-associated viral (AAV) vectors. Site-specific indel formation was achieved both in primary neurons isolated from APP<sup>SW</sup> transgenic mouse embryos (Tg2576) and after co-injection of these vectors into hippocampus of adult mice. Taken together, we here present proof-of-concept data that CRISPR/Cas9 can selectively disrupt the APP<sup>SW</sup> allele both ex vivo and in vivo-and thereby decrease pathogenic Aβ. Hence, this system may have the potential to be developed as a tool for gene therapy against AD caused by APPswe and other point mutations associated with increased Aβ.
Excipients used in lyophilization of small molecules (2016)

This review deals with the excipients used in various lyophilized formulations of small molecules. The role of excipients such as bulking agents, buffering agents, tonicity modifiers, antimicrobial agents, surfactants and co-solvents has been discussed. Additionally, a decision making process for their incorporation into the formulation matrix has been proposed. A list of ingredients used in lyophilized formulations marketed in USA has been created based on a survey of the Physician Desk Reference (PDR) and the Handbook on Injectable Drugs. Information on the recommended quantities of various excipients has also been provided, based on the details given in the Inactive Ingredient Guide (IIG).
BlitzNet: A Real-Time Deep Network for Scene Understanding (2017)

Real-time scene understanding has become crucial in many applications such as autonomous driving. In this paper, we propose a deep architecture, called BlitzNet, that jointly performs object detection and semantic segmentation in one forward pass, allowing real-time computations. Besides the computational gain of having a single network to perform several tasks, we show that object detection and semantic segmentation benefit from each other in terms of accuracy. Experimental results for VOC and COCO datasets show state-of-the-art performance for object detection and segmentation among real time systems.
Vertical-Gate Si/SiGe Double-HBT-Based Capacitorless 1T DRAM Cell for Extended Retention Time at Low Latch Voltage (2011)

A vertical-gate Si/SiGe double heterojunction bipolar transistor (VerDHBT)-based capacitorless 1T DRAM cell is proposed for improved storage performance with a fabrication feasibility through a selective epitaxy. It is verified through a TCAD device simulation for dc and transient characteristics of the proposed VerDHBT-based 1T DRAM. The off-state leakage current was significantly reduced, while the on-current was considerably increased with <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">S</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">IF</sub> / <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">B</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">mid</sub> / <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">D</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">IF</sub> = SiGe/SiGe/Si as the interfacial source/middle body/interfacial drain. A large hysteresis window for the “read 1” from the “read 0” and a long retention time at low latch voltage could be also obtained.
Epidemiological impact and disease burden of congenital cytomegalovirus infection in Europe (2009)

In Europe, congenital cytomegalovirus (CMV) infection is the leading cause of neurological disabilities in children, causing severe sequelae such as sensorineural hearing loss, neurodevelopmental delay or blindness. The infection causes high disease burden and costs. Nevertheless, there is little awareness of CMV among medical officials and the general public.
Hypervalent iodine in organic synthesis (1996)

Foreword. Preface. General Considerations. Preparative Methods for Hypervalent Iodine Reagents. (Diacetoxyiodo)benzene. [Bis(acyloxy)iodo]arenes. Iodosylbenzene. (Difluoroiodo)-and (dichloroiodo)arenes. [Hydroxy(tosyloxy)iodo]benzene and Its Analogues. Diaryliodonium Salts. Phenyliodonium Salts with an Aliphatic Moiety. Phenyliodonium Zwitterions. Reagents of Iodine (V). Some Further Reagents of Iodine (lll). Index of Compounds and Methods. Subject Index. Foreword. Preface. General Considerations: Introduction. A Note on Classes and Nomenclature. Bonding and Structure in Hypervalent Iodine. Reactivity Patterns. Practical Aspects. General References. Preparative Methods for Hypervalent Iodine Reagents: [Bis(acyloxy)iodo]arenes. (Difluoroiodo)- and (dichloroiodo)arenes. Iodosylarenes. [Hydroxy(iosyloxy)iodo]benzene and its Analogues. Reagents of Iodine (V). (Diacetoxyiodo)benzene: Acetoxylation. Transformations of Carbonyl Compounds. Phenolic Oxidation. Oxidation of Nitrogen Compounds. Hypervalent iodine Reagents in Combination with Azido Compounds. DIB and Sodium Azide in Combination with Other Reagents. Transformations of Alkynes Involving Thiophenols and Diphenyl Diselenide. Miscellaneous Reactions. [Bis(acyloxy)iodo]arenes: Part A: Reactions with [bis(trifluoroacetoxy)iodo]benzene. Transformations of Alkynes. Transformations of Ketones. Phenolic Oxidation. Oxidation of Nitrogen Compounds. Transfomration of Sulfur Compounds. Miscellaneous Transformations. Part B: Reactions with [bis(acyloxy)iodo]arenes. Oxidations. Homolytic Alkylation and Arylation. Iodosylbenzene: Reactions with Unsaturated Compounds. Reactions with Alcohols and Carbonyl Compounds. Reactions with NitrogenCompounds. Reactions with Sulfur and Other Compounds. (Difluoroiodo)-and (dichloroiodo)arenes: Chlorination. Remote Functionalism, of Steroids. Fluorination. Further Transformations. [Hydroxy(tosyloxy)iodo]benzene and Its Analogues: Reactionswith Alkenes and Allenes. Reactions with Alkynes and Alcohols. Reactions with Keto Compounds. Reactions with Nitrogen, Sulfur, and Other compounds. Diaryliodonium Salts: Preparative Methods. Carbon-Carbon Bond-Forming Reactions. Arylation of Heteroatoms. Phenyliodonium Salts with an Aliphatic Moiety: Preparative Methods. Reactivity of Perfluoroalkyl Phenyliodonium Salts. Reactivity of Other Iodonium Salts. Phenyliodonium Zwitterions: Preparation. Reactivity of Iodine-Carbon Ylides. Reactivity of Iodine-Nitrogen Ylides. Reactivity of 1,4-dipoles. Reagents of Iodine)V_: Reactions with Iodylarenes. Reactions with Dess-Martin Reagent and o-iodylbenzoic Acid. Some Further Reagents of Iodine (III): o-Iodosylbenzoic Acid and Its Derivatives. Reagents with Iodine-Oxygen Bonds. Reagents with Iodine-Nitrogen Bonds. Index of Compounds and Methods. Subject Index.
Enhanced antitumor activity of combined pretargeted radioimmunotherapy and paclitaxel in medullary thyroid cancer xenograft. (2002)

A significant antitumor effect associated with moderate toxicity was obtained previously with anticarcinoembryonic antigen x antidiethylene-triaminepentaacetic acid (DTPA)-indium F6-734 bispecific antibody and iodine-131-labeled DTPA-indium bivalent hapten in an animal model of medullary thyroid cancer (MTC). The purpose of this study was to determine whether the cytotoxic agents doxorubicin and paclitaxel, also known as radiosensitizers, improve efficacy of pretargeted radioimmunotherapy (RIT) in experimental MTC. Nude mice bearing TT MTC xenograft were treated with F6-734 and iodine-131-labeled DTPA-indium bivalent hapten injected 48 h apart with or without doxorubicin or paclitaxel. The maximum tolerated dose (MTD) of RIT was 92.5 MBq (as determined previously) and that of doxorubicin and paclitaxel 200 and 1000 micrograms, respectively. A control group received no treatment. Animal weight, hematotoxicity, tumor volume, and serum calcitonin were monitored for 5 months. Tumor growth inhibition induced by drugs alone, RIT alone, or combined therapy was characterized by measuring relative tumor volume 20, 40, and 60 days after treatment to detect additivity or synergism. Mean tumor volume doubling time (MTVDT) was 13 +/- 4 days in the control group, 15 +/- 8 days in the group treated with the MTD of doxorubicin, and 32 +/- 13 days in the group treated with the MTD of paclitaxel. After RIT alone at 92.5 MBq, MTVDT was 86 +/- 22 days. After RIT at 74 MBq (80% of MTD), MTVDT was 56 +/- 10 days. MTVDT was not significantly different from this value after RIT plus doxorubicin, 60 +/- 16 days (65 and 100% of the respective single-agent MTDs). Combination of RIT with paclitaxel (65 and 100% of the respective single-agent MTDs) prolonged the suppression of tumor growth. One complete response was observed, and MTVDT was 114 +/- 44 days. This value was significantly longer than the value obtained with RIT alone at 74 MBq (P < 0.05) or with RIT combined with doxorubicin (P < 0.02). The change in serum calcitonin levels paralleled those in tumor volume. Analysis of dose-response curves at days 20 and 40 showed additivity between RIT and paclitaxel, and analysis at day 60 suggested a synergistic effect. In conclusion, addition of doxorubicin did not improve RIT efficacy, whereas paclitaxel improved RIT efficacy significantly without increasing toxicity.
Anomalous path detection with hardware support (2005)

Embedded systems are being deployed as a part of critical infrastructures and are vulnerable to malicious attacks due to internet accessibility. Intrusion detection systems have been proposed to protect computer systems from unauthorized penetration. Detecting an attack early on pays off since further damage is avoided and in some cases, resilient recovery could be adopted. This is especially important for embedded systems deployed in critical infrastructures such as Power Grids etc. where a timely intervention could save catastrophes. An intrusion detection system monitors dynamic program behavior against normal program behavior and raises an alert when an anomaly is detected. The normal behavior is learnt by the system through training and profiling.However, all current intrusion detection systems are purely software based and thus suffer from large performance degradation due to constant monitoring operations inserted in application code. Due to the potential performance overheads, software based solutions cannot monitor program behavior at a very fine level of granularity, thus leaving potential security holes as shown in the literature. Another important drawback of such methods is that they are unable to detect intrusions in near real time and the time lag could prove disastrous in real time embedded systems. In this paper, we propose a hardware-based approach to verify program execution paths of target applications dynamically and to detect anomalous executions. With hardware support, our approach offers multiple advantages over software based solutions including minor performance degradation, much stronger detection capability (a larger variety of attacks get detected) and zero-latency reaction upon an anomaly for near real time detection and thus much better security.
On-Line Prediction of Motor Shaft Misalignment Using Fast Fourier Transform Generated Spectra Data and Support Vector Regression (2006)

Shaft alignment prediction is essential for the development of effective coupling and rotating equipment maintenance systems. In this paper, we present a modified support vector regression (SVR) approach for shaft alignment predictions based on fast Fourier transform generated spectra data. The modified SVR approach uses data-dependent parameters in order to reduce computation time and achieve better predictions. The spectra data used is characterized by a large number of descriptors and very few data points. The strengths of SVR for shaft misalignment prediction include its ability to represent data in high-dimensional space through kernel functions. We reduce the dimension of the data using a multivariate AIC criterion in order to guarantee that the selected spectra are response dependent. We compare the performance of SVR with two of the most popular techniques used in condition monitoring, partial least squares, and principal components regression. Our results show that we can improve the performance of shaft misalignment prediction using SVR and the approach compares very favorably with partial least squares and principal components regression approaches. Also, we present a quantitative measure, shaft misalignment monitoring index, which can be used to facilitate easy identification of the alignment condition and as input to maintenance systems design.
Gene Transfection in High Serum Levels: Case Studies with New Cholesterol Based Cationic Gemini Lipids (2013)

-OH groups present on the cationic headgroups in combination with oxyethylene linkers on cholesterol based geminis, gave an optimized combination of new genera of gemini lipids possessing high transfection efficiency even in presence of very high percentage of serum. This property makes them preferential transfection reagents for possible in vivo studies.
Apoptotic Cell Death Triggered by Nitric Oxide in Pancreatic β-Cells (1995)

Nitric oxide (NO) is believed to be an effector molecule that mediates interleukin (IL)-1 beta-induced destruction and dysfunction of pancreatic beta-cells. We have demonstrated that both exogenous NO and NO generated endogenously by IL-1 beta brought about apoptosis of isolated rat pancreatic islet cells as well as pancreatic beta-cell tumor-derived cell line HIT. This apoptosis was characterized by cleavage of DNA into nucleosomal fragments of 180-200 bp and morphologically by nuclear shrinkage, chromatic condensation, and apoptotic body formation. The IL-1 beta-induced internucleosomal DNA cleavage occurred in a time- and dose-dependent manner. Actinomycin D, cycloheximide, and nitric oxide synthase inhibitors inhibited the DNA cleavage, which was correlated with the amount of NO produced, indicating that NO produced by HIT cells themselves could mediate the apoptosis. Furthermore, in the presence of tumor necrosis factor (TNF)-alpha, large amounts of NO were produced by IL-1 beta and DNA cleavage occurred more noticeably, although TNF-alpha alone did not generate NO. Streptozotocin (STZ), a diabetogenic reagent containing a nitroso moiety, also released NO and induced internucleosomal DNA cleavage in HIT cells. These results suggest that NO-induced internucleosomal DNA cleavage is an important initial step in the destruction and dysfunction of pancreatic beta-cells induced by inflammatory stimulation or treatment with STZ.
Redox Regulation of Cancer Metastasis: Molecular Signaling and Therapeutic Opportunities (2014)

Cancer metastasis is the major cause of cancer-related mortality. Accumulated evidence has shown that high-metastasis potential cancer cells have more reactive oxygen species (ROS) accumulation compared with low-metastasis potential cancer cells. ROS can function as second messengers to regulate multiple cancer metastasis-related signaling pathways via reversible oxidative posttranslational modifications of cysteine in key redox-sensitive proteins, which leads to the structural and functional change of these proteins. Because ROS can promote cancer metastasis, therapeutic strategies aiming at inducing/reducing cellular ROS level or targeting redox sensors involved in metastasis hold great potential in developing new efficient approaches for anticancer therapy. In this review, we summarize recent findings on regulation of tumor metastasis by key redox sensors and describe the potential of targeting redox signaling pathways for cancer therapy.
Antimicrobial peptides: The ancient arm of the human immune system (2010)

The production of peptides and small proteins with microbicidal activity collectively called antimicrobial peptides (AMPs) is commonly considered to be a primitive mechanism of immunity and has been extensively studied in insects and other non-vertebrate organisms. In addition, a variety of AMPs present in amphibian skin secretion has been well characterised. There is now increasing evidence that AMPs play a crucial role in human immunity as well. Virtually all human tissues and cells typically exposed to microbes are able to produce AMPs. Important AMPs belonging to two structurally distinct classes, known as the defensins and the cathelicidins, are mainly produced by epithelial cells and neutrophils. AMPs significantly contributing to the chemical skin barrier are represented by dermcidin, psoriasin and RNase 7. The antimicrobial activity of saliva largely depends on histidine-rich AMPs known as histatins. Many more, in part less well-known AMPs and AMP-like proteins exist that exhibit various additional functions, apart from their antimicrobial properties. Among them, the neutrophil granule proteins azurocidin and cathepsin G are members of a family of serine-protease homologues called serprocidins and play a role in the regulation of the immune response and degradation of extracellular matrix proteins respectively. As another AMP-like protein of the neutrophil granule content, bactericidal/permeability increasing protein (BPI) is both able to permeabilise bacterial membranes and to function as an opsonin. The whey acidic protein (WAP) domain containing class of AMPs, including secretory leukocyte protease inhibitor (SLPI), elafin and trappin-2, is equally important in inhibition of neutrophil serine proteases and killing of microbes. Certain CC or CXC chemokines are known to possess antimicrobial properties and therefore are called kinocidins. Several kinocidins, including thrombocidin-1 and -2, are contained in the α-granules of platelets. A cytoplasmic AMP described as ubiquicidin turned out to be identical with the strongly basic ribosomal protein S30. Proteolytic cleavage of the histone protein H2A in the stomach gives rise to an AMP initially described as buforin I. Adrenomedullin is a hormone-like AMP exhibiting vasodilatory and hypotensive effects. Lysozyme is mainly known for its cell wall degrading activity, but is also capable of non-enzymatic killing of bacteria. An iron-binding protein present in milk and other secretions named lactoferrin was shown to possess antimicrobial and antiviral activity and has been implicated in protection against cancer. Clinical studies on the treatment of infectious diseases have been performed with artificial peptides derived from human lactoferrin, histatins and BPI in addition to porcine protegrins, frog magains and bovine indolicidin. Omiganan, representing an indolicidin derivative, has been demonstrated to be effective in the treatment of acne and catheter-related local infections and is currently considered to be the most promising AMP-based drug candidate.
A 1993 Update on Biohazards Affecting Clinical Engineers and BMETs (1994)

In late 1993, a survey was sent to the subscribers of the Journal of Clinical Engineering to determine: (1) if employers were responding to the biohazards protection needs of BMETs and CEs; (2) if personal protective equipment was being utilized; (3) if occupational exposure perceptions and concerns had changed since a previous survey four years ago; and (4) if educational efforts targeting BMETs and CEs were still needed. The 267 respondents were divided into four groups according to certification status and job title. Results showed that employers were doing an excellent job of providing personal protective equipment, but 50% of the BMETs and CEs chose not to use it. Even though though the occupational exposure illness and disability rate increased to 21% from the 1989 survey rate of 18%, BMETs and CEs still feel confident in their abilities to recognize potential biohazard problems based on visual clues, which can be an error in judgement that can lead to serious adverse effects including illness, disability, or death.