gebhart/patrepeval huggingface dataset:
Inhibition of the Ca2+/Calmodulin-dependent Protein Kinase I Cascade by cAMP-dependent Protein Kinase (1999)

Several recent studies have shown that Ca2+/calmodulin-dependent protein kinase I (CaMKI) is phosphorylated and activated by a protein kinase (CaMKK) that is itself subject to regulation by Ca2+/calmodulin. In the present study, we demonstrate that this enzyme cascade is regulated by cAMP-mediated activation of cAMP-dependent protein kinase (PKA). In vitro, CaMKK is phosphorylated by PKA and this is associated with inhibition of enzyme activity. The major site of phosphorylation is threonine 108, although additional sites are phosphorylated with lower efficiency. In vitro, CaMKK is also phosphorylated by CaMKI at the same sites as PKA, suggesting that this regulatory phosphorylation might play a role as a negative-feedback mechanism. In intact PC12 cells, activation of PKA with forskolin resulted in a rapid inhibition of both CaMKK and CaMKI activity. In hippocampal slices CaMKK was phosphorylated under basal conditions, and activation of PKA led to an increase in phosphorylation. Two-dimensional phosphopeptide mapping indicated that activation of PKA led to increased phosphorylation of multiple sites including threonine 108. These results indicate that in vitro and in intact cells the CaMKK/CaMKI cascade is subject to inhibition by PKA-mediated phosphorylation of CaMKK. The phosphorylation and inhibition of CaMKK by PKA is likely to be involved in modulating the balance between cAMP- and Ca2+-dependent signal transduction pathways.
Chronic evaluation of a compact nonseal magnet pump as a nonpulsatile pump for long-term use. (1992)

Use of a nonpulsatile pump is one of the most interesting approaches in the development of artificial hearts. A centrifugal pump without a seal around the rotating part was evaluated in five goats. The size of the pump is 8.4 cm x phi 7.0 cm, including an electric motor. A polypropylene impeller with four fins on the top of a column in which a magnetic ring is embedded spins by coupling with a rotating magnet outside the housing. In the goats, the pump was placed paracorporeally to provide total left heart bypass at a flow rate of 4.6-7.6 L/min, and activated clotting time was controlled at 200-300 sec by continuous heparin infusion. Although the first three goats died within 3 days due to bleeding, embolism, and a jammed impeller, respectively, a pump could be driven for 14 days in the fourth goat, and another pump with a rotational control feedback system ran for 32 days in the fifth goat. Plasma free hemoglobin levels were 13.8 +/- 4.3 mg/dl and 9.5 +/- 2.5 mg/dl, and platelet counts were 53.8 +/- 24.7 x 10(4)/mm3 and 62.0 +/- 22.0 x 10(4)/mm3 after 12 hours and 7 days pumping, respectively. No thrombus was observed in the blood chamber in the last two cases. In conclusion, this pump has possibilities as a nonpulsatile pump for long-term use.
Nucleic Acid Delivery: The Missing Pieces of the Puzzle? (2012)

The delivery of genes or RNA interference (RNAi) agents can increase or decrease the expression of virtually any protein in a cell, and this process opens the path for cures to most diseases that afflict humans. However, the high molecular weight, anionic nature, and instability of nucleic acids in the presence of enzymes pose major obstacles to their delivery and frustrates their use as human therapies. This Account describes current ideas about the mechanisms in nonviral nucleic acid delivery and how lipidic and polymeric carriers can overcome some of the critical barriers to delivery. Over the last 20 years, researchers have developed a multitude of polymeric and lipidic vectors, but only a small fraction of these have progressed into clinical trials. None of these vectors has received FDA approval, which indicates that the current vectors do not yet have suitable properties for effective in vivo nucleic acid delivery. Nucleic acid delivery is a multistep process and inefficiencies at any stage result in a dramatic decrease in gene delivery or gene silencing. However, the majority of studies investigating synthetic vectors focus solely on optimization of endosomal escape. A small number of studies address how to improve uptake via targeted delivery, and an even smaller fraction examine the intracellular fate of the delivery systems and nucleic acid cargo. The internalization of genes into the cell nucleus remains an inefficient and mysterious process. In the case of DNA delivery, strategies are needed to increase and accelerate the migration of DNA through the cytoplasm and transport it through the nuclear membrane. siRNA delivery involves fewer barriers. siRNA is more readily released from the carrier and more resistant to enzymatic degradation, and its target is in the cytoplasm; hence, siRNA delivery systems are becoming a clinical reality. With regard to siRNA therapy, the exact cytoplasmic location of RNA-induced silencing complex (RISC) formation and activity is unknown, which makes specific targeting of the RISC for more efficient delivery difficult. Furthermore, we would like to identify the factors that favor the binding of siRNA to Ago-2. If we could understand how the half-life of siRNA and Ago-2/siRNA complex in the cytoplasm can be modulated without interfering with RISC functions that are essential for normal cell activity, we could increase siRNA delivery efficiency. In this Account, we review the current synthetic vectors and propose alternative strategies in a few cases. We also suggest how certain cellular mechanisms might be exploited to improve gene transfection and silencing. Finally, we discuss whether some carriers that deliver the siRNA to cells could also repackage the siRNA into exosomes. The exosomes would then transport the siRNA into a subsequent population of cells that manifest the siRNA effect. This piggy-back mechanism may be responsible for reported deep tissue siRNA effects using certain carriers.
The Proton Sponge: a Trick to Enter Cells the Viruses Did Not Exploit (1997)

Several non-permanent polycations possessing substantial buffering capacity below physiological pH, such as lipopolyamines and polyethylenimines, are efficient transfection agents per se, i.e. without the addition of lysosomotropic bases, or cell targeting, or membrane disruption agents. These vectors have been shown to deliver genes as well as oligonucleotides both in vitro and in vivo. Our hypothesis is that their efficiency relies on extensive endosome swelling and rupture that provides an escape mechanism for the polycation/DNA particles.
Real-time parallel hashing on the GPU (2009)

We demonstrate an efficient data-parallel algorithm for building large hash tables of millions of elements in real-time. We consider two parallel algorithms for the construction: a classical sparse perfect hashing approach, and cuckoo hashing, which packs elements densely by allowing an element to be stored in one of multiple possible locations. Our construction is a hybrid approach that uses both algorithms. We measure the construction time, access time, and memory usage of our implementations and demonstrate real-time performance on large datasets: for 5 million key-value pairs, we construct a hash table in 35.7 ms using 1.42 times as much memory as the input data itself, and we can access all the elements in that hash table in 15.3 ms. For comparison, sorting the same data requires 36.6 ms, but accessing all the elements via binary search requires 79.5 ms. Furthermore, we show how our hashing methods can be applied to two graphics applications: 3D surface intersection for moving data and geometric hashing for image matching.
Reconstructed human skin produced in vitro and grafted on athymic mice1,2 (2002)

This new rHS model gives supple and easy to handle skins while demonstrating an adequate wound healing on mice. These results are promising for the development of this skin substitute for permanent coverage of burn wounds.
Precision readout circuits for capacitive microaccelerometers (2006)

This paper presents a review of capacitive readout front-end circuits for high-precision accelerometers. The primary design parameters and the trade-offs affecting the resolution are presented. The discussions apply to all capacitive microsensor interfaces. Also, a high-sensitivity capacitive accelerometer interface circuit for hybrid-integration with a surface/bulk micromachined micro-g accelerometer is described. The first generation of the circuit resolves 75 aF of capacitance on /spl sim/120 pF parasitic capacitance with a 200 kHz sampling rate, and the second generation resolves 20 aF with 1 MHz sampling rate. The overall sensor-circuit module has a noise floor of 1.6 /spl mu/g//spl radic/Hz at ambient atmosphere.
n-Channel Organic Transistor Materials Based on Naphthalene Frameworks (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTn-Channel Organic Transistor Materials Based on Naphthalene FrameworksJoyce G. Laquindanum, Howard E. Katz, Ananth Dodabalapur, and Andrew J. LovingerView Author Information Bell Laboratories, Lucent Technologies 600 Mountain Ave., Murray Hill, New Jersey 07974 Cite this: J. Am. Chem. Soc. 1996, 118, 45, 11331–11332Publication Date (Web):November 13, 1996Publication History Received17 July 1996Published online13 November 1996Published inissue 13 November 1996https://pubs.acs.org/doi/10.1021/ja962461jhttps://doi.org/10.1021/ja962461jrapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views2792Altmetric-Citations186LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Aromatic compounds,Deposition,Hydrocarbons,Mobility,Semiconductors Get e-Alerts
Oxidative Inactivation of Mitochondrial Aconitase Results in Iron and H2O2-Mediated Neurotoxicity in Rat Primary Mesencephalic Cultures (2009)

These results suggest a role of ROS-sensitive m-aconitase as a source of Fe2+ and H2O2 and as a contributing factor to neurotoxicity.
Polymorphic Packing Arrangements in a Class of Engineered Organic Crystals (1997)

Polymorphism occurs in the family of engineered cocrystals that form from N,N ‘-bis(p-X-phenyl)melamines (X = H, F, Cl, Br, I, CH3, and CF3) and barbital. X-ray powder diffraction indicates that only one crystalline phase formed for X = Cl, F, and CH3, that primarily one phase occurred for X = H and I, but that a small contribution from an alternative phase or phases was possibly also present, and that at least two different polymorphs exist for both X = Br and CF3. Agreement of positions of peaks in experimental XPD traces and reflections calculated from single-crystal data is good, while agreement in intensities is good in some cases but only fair in others. Reasons for this disagreement are likely to include the physical design of the diffractometer and preferred orientation of crystallites in the sample. Two of the polymorphic forms of X = Br are converted to a third on annealing at 140 °C. Steric effects seem the most probable origin of the polymorphism: the bromine-substituted diphenylmelamine crystallizes in several polymorphs, and the bromine substituent is intermediate in size for the family of substituents examined. This cocrystal forms one polymorph that is formed by cocrystals having larger substituents (I and CH3) and one that packs similarly to a cocrystal having a smaller substituent (Cl).
Peptide Synthesis and Applications (2005)

This article is published as a chapter in a book but is also cited as an article in a journal series
Detection of Avian malaria infections in wild and captive penguins (1995)

Sera from wild African black-footed penguins (Spheniscus demersus L., 1758), Adelie penguins (Pygoscelis adeliae Houbron, 1841), Gentoo penguins (Pygoscelis papua Forster, 1781), king penguins (Apten- odytes patagonicus Miller, 1778), and little blue penguins (Eudyptula minor Forster, 1781) and from captive yellow-eyed penguins (Megadyptes antipodes Houbron, 1841) and Magellanic penguins (Spheniscus magellanicus Forster, 1781) were tested by enzyme-linked immunosorbent assays for the presence of avian malaria antibodies (Ab). Plasmodiurn falciparum sporozoite (R32tet32) and gametocyte (P.F.R27) antigens were used. Specificity of anti-5. demersus, anti-duck, anti-chicken, and anti-turkey IgG labeled with alkaline phosphatase was deter- mined for homologous and heterologous sera of 8 avian species (including 6 penguin species). The penguin conjugate was the most specific for the various penguin species immunoglobulins. It was possible to detect penguin immunoglobulins at a dilution of 10~4•. The relative binding of anti-S. demersus IgG was equal to relative binding of commercial conjugates. Kinetic profiles and overall magnitudes of malarial Ab detected by the 2 antigens were not significantly different. Antarctic P. adeliae were negative for malarial Ab, all New Zealand M. antipodes were positive, and the positivity prevalence of the remaining penguins ranged from 33 to 92%. Antibody titers and the prevalence of infection of wild S. demersus were significantly lower than those reported for captive North American S. demersus.
LONG-TERM RESULTS OF A CONTROLLED PROSPECTIVE STUDY WITH TRANSFUSION OF DONOR-SPECIFIC BONE MARROW IN 57 CADAVERIC RENAL ALLOGRAFT RECIPIENTS (1991)

Experimental studies have shown that antilymphocyte globulin combined with transfusion of donor-specific bone marrow cells can induce partial tolerance to allograft tissue. We have adapted these protocols to clinical use and present the results of 57 cadaveric renal allograft recipients who received Minnesota ALG followed by the transfusion of cryopreserved donor-specific bone marrow. A group of 54 patients received the contralateral kidney and similar immunosuppression without the marrow transfusion and serve as controls. Both groups received quadruple immunosuppression with MALG, cyclosporin, azathioprine, and prednisone. In the bone marrow group, after a 10-14 day induction course of ALG, cryopreserved marrow was transfused on the seventh day after the last dose of ALG. The median follow-up in both groups is 16 months, (range 2.5-33 months). Six grafts have been lost in the bone marrow group, (three rejections, 2 deaths [Cr 2.0, 2.3], 1 recurrent disease). In the control group 16 grafts have been lost (13 rejections, 3 deaths [Cr 1.7, 2.5, 3.0]). Five patients in the control group have biopsy-proved chronic rejection compared to one in the bone marrow group. 17 patients in the bone marrow group have been tapered off the prednisone, and three of these patients have had mild late rejection episodes without graft loss. The two groups were compared for differences in the number of rejection episodes, estimated renal plasma flow, glomerular filtration rate, and urine protein. No differences were found. The allograft survival of the bone marrow group was significantly greater (P less than .01) than the control group. The graft survival rates for the bone marrow group at 12 and 18 months were 90% (confidence limits [CL] 85-94) and 85% (CL 78-90), respectively. In the the control group the 12 and 18 month allograft survival rates were 71% (CL 63-78) and 67% (CL 58-74), respectively. The survival in the control group was similar to our overall transplant experience with quadruple therapy. Mixed lymphocyte culture analysis shows a trend to diminished donor-specific responsiveness in the bone marrow group. The use of cryopreserved donor-specific bone marrow is associated with improved allograft survival in cadaveric kidney allograft recipients. However, a more effective induction protocol is needed to reduce the overall number of rejection episodes.
Molecular signatures of vaccine adjuvants (2015)

Mass vaccination has saved millions of human lives and improved the quality of life in both developing and developed countries. The emergence of new pathogens and inadequate protection conferred by some of the existing vaccines such as vaccines for tuberculosis, influenza and pertussis especially in certain age groups have resulted in a move from empirically developed vaccines toward more pathogen tailored and rationally engineered vaccines. A deeper understanding of the interaction of innate and adaptive immunity at molecular level enables the development of vaccines that selectively target certain type of immune responses without excessive reactogenicity. Adjuvants constitute an imperative element of modern vaccines. Although a variety of candidate adjuvants have been evaluated in the past few decades, only a limited number of vaccine adjuvants are currently available for human use. A better understanding of the mode of action of adjuvants is pivotal to harness the potential of existing and new adjuvants in shaping a desired immune response. Recent advancement in systems biology powered by the emerging cutting edge omics technology has led to the identification of molecular signatures rapidly induced after vaccination in the blood that correlate and predict a later protective immune response or vaccine safety. This can pave ways to prospectively determine the potency and safety of vaccines and adjuvants. This review is intended to highlight the importance of big data analysis in advancing our understanding of the mechanisms of actions of adjuvants to inform rational development of future human vaccines.
Structure of adenosine deaminase mRNAs from normal and adenosine deaminase-deficient human cell lines. (1984)

The structure of human adenosine deaminase mRNA from normal and mutant lymphoblasts was examined by sequence analysis of a cDNA for normal mRNA and electrophoretic analyses of DNA fragments generated by S1 endonuclease cleavage of mRNA-cDNA hybrids. The 1,533-base sequence of the cloned cDNA represents the complete mRNA sequence with the possible exception of some of the 5' untranslated region. S1 nuclease analyses of hybrids between cloned cDNA and normal adenosine deaminase mRNA confirmed that a 76-base sequence in a previously examined adenosine deaminase cDNA is an intron. S1 nuclease analyses of mRNAs from seven mutant cell lines demonstrated that four of the mutants, those in the GM-2471, GM-2756, GM-4258, and GM-2606 cells, contain small defects, such as single-base changes, that are not detectable by the S1 nuclease technique. Three of the mRNAs, those in GM-3043, GM-2294, and GM-2825A cells, do contain defects detectable with S1 nuclease. These defects differ from each other and have been mapped to specific regions of the mRNA. Some or all of these defective mRNAs are postulated to result from anomalous RNA processing.
A patch‐clamp study of bovine chromaffin cells and of their sensitivity to acetylcholine. (1982)

1. Bovine chromaffin cells were enzymatically isolated and kept in short term tissue culture. Their electrical properties were studied using recent advances of the patch-clamp technique (Hamill, Marty, Neher, Sakmann & Sigworth, 1981). 2. When a patch pipette was sealed tightly to a chromaffin cell ('cell-attached configuration') current wave forms due to intracellular action potentials could be observed. The frequency of the wave forms was altered by changing the pipette potential. When acetylcholine was present in the pipette solution, acetylcholine-induced single channel currents were evident in the patch recording. Action potential wave forms were then often seen to follow acetycholine-induced single channel currents. 3. In the cell-attached configuration, large single channel current events did not resemble square pulses but showed exponential relaxations with time constants of the order of 50 ms. 4. After rupture of the patch of membrane, the pipette--cell seal remained stable ('whole-cell recording', Hamill et al. 1981). Chromaffin cells were found to have a resting potential of -50 to -80 mV, and an input resistance around 5 G omega. The high cell resistance accounts for the relaxing currents evident in the cell-attached configuration. 5. In the best cases, the effective time constant of the voltage clamp in the whole-cell recording mode was 15 microseconds. Exchange of small ions such as Na+ ions between pipette and cell interior solutions was then complete within 15 s. 6. Acetylcholine-induced currents were obtained at various acetylcholine concentrations. Single acetylcholine-induced channels had a slope conductance of 44 pS between -100 and -55 mV, and a mean duration of 27 ms at -80 mV (at room temperature).
UVA Irradiation-induced Activation of Activator Protein-1 is Correlated with Induced Expression of AP-1 Family Members in the Human Keratinocyte Cell Line HaCaT¶ (2002)

To determine whether the transcription factor activator protein-1 (AP-1) could be modulated by ultraviolet A (UVA) exposure, we examined AP-1 DNA-binding activity and transactivation after exposure to UVA in the human immortalized keratinocyte cell line HaCaT. Maximal AP-1 transactivation was observed with 250 kJ/m2 UVA between 3 and 4 h after irradiation. DNA binding of AP-1 to the target 12-O-tetradecanoylphorbol-13-acetate response element sequence was maximally induced 1-3 h after irradiation. Both de novo transcription and translation contributed to the UVA-induced AP-1 DNA binding. c-Fos was implicated as a primary component of the AP-1 DNA-binding complex. Other components of the complex included Fra-2, c-Jun, JunB and JunD. UVA irradiation induced protein expression of c-Fos, c-Jun, Fra-1 and Fra-2. Phosphorylated forms of these induced proteins were determined at specific time points. A strong correlation existed between UVA-induced AP-1 activity and accumulation of c-Fos, c-Jun and Fra-1 proteins. UVA irradiation also induced c-fos and c-jun mRNA expression and transcriptional activation of the c-fos gene promoter. These results demonstrate that UVA irradiation activates AP-1 and that c-fos induction may play a critical role in the response of these human keratinocytes to UVA irradiation.
Loss performance analysis of an ATM multiplexer loaded with high-speed on-off sources (1991)

The performance of an asynchronous transfer mode (ATM) multiplexer whose input consists of the superposition of a multiplicity of homogeneous on-off sources modeled by a two-state Markovian process is studied. The approach is based on the approximation of the actual input process by means of a suitably chosen two-state Markov modulated Poisson process (MMPP), as a simple and effective choice for the representation of superposition arrival streams. To evaluate the cell loss performance, a new matching procedure that leads to accurate results compared to simulation is developed. The application limits of the proposed method are also discussed. The outstanding physical meaning of this procedure permits a deep insight into the multiplexer performance behavior as the source parameters and the multiplexer buffer size are varied.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>