gebhart/patrepeval huggingface dataset:
Differentiation of hemodynamic, humoral and metabolic responses to beta 1- and beta 2-adrenergic stimulation in man using atenolol and propranolol. (1983)

The respective contributions of beta-adrenoceptor subtypes to the hemodynamic, humoral and metabolic consequences of adrenergic stimulation during graded exercise in man were investigated using nonselective beta-adrenoceptor blockade with propranolol and beta 1-adrenoceptor blockade with atenolol. Doses of these agents that produced comparable suppression of beta 1 response as measured by antagonism of cardioacceleration during exercise were selected. Six healthy, nonsmoking males received these drugs in a placebo-controlled, Latin-square, randomized manner using a double-blind protocol. Both drugs produced comparable reductions of systolic blood pressure and elevation of diastolic blood pressure compared with placebo as exercise load increased. Propranolol produced higher peak epinephrine levels than atenolol or placebo (808 +/- 162, 640 +/- 190 and 584 +/- 153 pg/ml, respectively, p = 0.03), but norepinephrine levels did not show significant differences. Plasma renin activity was similarly suppressed both at rest and during all grades of exercise by both drugs. Lactate levels during moderate exercise were significantly lower after propranolol than after either atenolol or placebo (p = 0.03), but were similar at heavy work loads. Plasma glucose values rose on placebo (from 96.5 +/- 2.1 to 97.7 +/- 2.7 mg/dl) and on atenolol (from 99.7 +/- 2.2 to 102.1 +/- 4.8 mg/dl), but fell on propranolol (from 96.4 +/- 1.9 mg/dl to 87.2 +/- 2.5 mg/dl, p less than 0.01). These results indicate that blockade of vascular smooth muscle beta 2 receptors does not substantially alter hemodynamics during intense short-term exercise. Stimulation of renin release and lipolysis are produced through beta 1-adrenoceptor mechanisms, whereas beta 2 adrenoceptors are important in the provision of carbohydrate as an energy substrate for exercising muscle.
Type I IFN protects cancer cells from CD8+ T cell–mediated cytotoxicity after radiation (2019)

Treatment of tumors with ionizing radiation stimulates an antitumor immune response partly dependent on induction of IFNs. These IFNs directly enhance dendritic cell and CD8+ T cell activity. Here we show that resistance to an effective antitumor immune response is also a result of IFN signaling in a different cellular compartment of the tumor, the cancer cells themselves. We abolished type I IFN signaling in cancer cells by genetic elimination of its receptor, IFNAR1. Pronounced immune responses were provoked after ionizing radiation of tumors from 4 mouse cancer cell lines with Ifnar1 knockout. This enhanced response depended on CD8+ T cells and was mediated by enhanced susceptibility to T cell-mediated killing. Induction of Serpinb9 proved to be the mechanism underlying control of susceptibility to T cell killing after radiation. Ifnar1-deficient tumors had an augmented response to anti-PD-L1 immunotherapy with or without radiation. We conclude that type I IFN can protect cancer cells from T cell-mediated cytotoxicity through regulation of Serpinb9. This result helps explain why radiation of tumors can stimulate antitumor immunity yet also result in resistance. It further suggests potential targets for intervention to improve therapy and to predict responses.
DDD—a free graphical front-end for UNIX debuggers (1996)

The Data Display Debugger (DDD) is a novel graphical user interface to GDB and DBX, the popular UNIX debuggers. Besides "usual" features such as viewing source texts and breakpoints, DDD provides a graphical data display , where data structures are displayed as graphs. A simple mouse click dereferences pointers or reveals structure contents. Complex data structures can be explored incrementally and interactively, using automatic layout if preferred. Each time the program stops, the data display reflects the current variable values. DDD has been designed to compete with well-known commercial debuggers; however, it is free software, protected by the GNU general public license. In this paper, we give a quick presentation of DDD and describe its architecture and basic functionality from a technical point of view.
Iron-regulated hemolysin production and utilization of heme and hemoglobin by Vibrio cholerae (1988)

El Tor and non-O1 strains of Vibrio cholerae were analyzed to determine whether synthesis of secreted hemolysin was influenced by the concentration of iron in the medium. Synthesis of hemolysin was found to be iron regulated in both El Tor and non-O1 isolates. Increased levels of hemolytic activity were detected in supernatants of iron-starved cells. Spontaneous hemolysin-deficient mutants of one non-O1 strain were found to occur at high frequency. These variants also failed to synthesize vibriobactin, the iron transport compound utilized by V. cholerae. Another non-O1 strain was found to synthesize both hemolysin and vibriobactin constitutively. When the cloned Escherichia coli fur gene, encoded on the plasmid pABN203, was introduced into this constitutive strain, normal iron regulation of both hemolysin and vibriobactin was reestablished. The ability of V. cholerae to utilize mammalian iron compounds was determined, and it was found that both hemin and hemoglobin could serve as sole sources of iron.
Transgenic plants : methods and protocols (2005)

Transgenic plants serve as essential tools for research in plant biology and are the basis of modern agricultural biotechnology. In Transgenic Plants: Methods and Protocols, leading scientists describe readily reproducible techniques they have perfected for the genetic transformation and regeneration of plants. The authors cover the most commonly used transformation systems, including Agrobacterium tumefaciens, Agrobacterium rhizogenes, particle bombardment, electroporation, floral-dip, and chloroplast transformation, as well as the regeneration of whole transgenic plants by organogenesis and somatic embryogenesis from different explant cells/tissues and from such diverse plant species as tomato, cassava, conifers, and citrus. Also described are the use of selectable and reporter markers, positive selection (for maize transformation), and the controlled excision and removal of marker genes from both nuclei and plastids once transgenic shoots have been efficiently generated. Additional techniques employ quantitative real-time PCR, reverse transcription PCR, fluorescence in situ hybridization, and thermal asymmetric interlaced PCR. Risk assessment methods offer the opportunity to study Agrobacterium persistence in plant tissues and to investigate the possibility of transgene dispersal. The protocols follow the successful Methods in Molecular Biology™ series format, each one offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and easy to use, Transgenic Plants: Methods and Protocols offers both novice and experienced researchers a cutting-edge laboratory manual covering all aspects of plant genetic transformation and transgenic crops
A New Family of Sequential Elements With Built-in Soft Error Tolerance for Dual-VDD Systems (2008)

In this paper, we propose some soft-error-tolerant latches and flip-flops that can be used in dual-VDD systems. By utilizing local redundancy and inner feedback techniques, the latches and flip-flops can recover from soft errors caused by cosmic rays and particle strikes. The proposed flip-flop can be used as a level shifter without the problems of static leakage and redundant switching activity. Implemented in a standard 0.18- mum technology, the proposed latches and flip-flops show superior performance compared to conventional ones in terms of delay and power while keeping the soft-error-tolerant characteristic. Experimental results show that compared to the traditional built-in soft-error-tolerant D latch, the D-QN delay of the new D latch is 29.1% less than that of the traditional built-in soft-error-tolerant D latch while consuming 16.5% less power as well. The D-Q delay and power of the new flip-flop are about 47.7% and 54% less than those of the traditional high speed level-converting flip-flop, respectively. In addition, the proposed flip-flop is more robust to soft errors. The critical charge which represents the minimum charge at the D input required to cause an error of the flip-flop can be increased by more than 46.4%. The time window during which the flip-flop will be erroneous caused by single-event upsets at the D input is reduced by more than 22.2%.
Imaging neural circuit dynamics with a voltage-sensitive fluorescent protein (2012)

Population signals from neuronal ensembles in cortex during behavior are commonly measured with EEG, local field potential (LFP), and voltage-sensitive dyes. A genetically encoded voltage indicator would be useful for detection of such signals in specific cell types. Here we describe how this goal can be achieved with Butterfly, a voltage-sensitive fluorescent protein (VSFP) with a subthreshold detection range and enhancements designed for voltage imaging from single neurons to brain in vivo. VSFP-Butterfly showed reliable membrane targeting, maximum response gain around standard neuronal resting membrane potential, fast kinetics for single-cell synaptic responses, and a high signal-to-noise ratio. Butterfly reports excitatory postsynaptic potentials (EPSPs) in cortical neurons, whisker-evoked responses in barrel cortex, 25-Hz gamma oscillations in hippocampal slices, and 2- to 12-Hz slow waves during brain state modulation in vivo. Our findings demonstrate that cell class-specific voltage imaging is practical with VSFP-Butterfly, and expand the genetic toolbox for the detection of neuronal population dynamics.
Effective Exon Skipping and Restoration of Dystrophin Expression by Peptide Nucleic Acid Antisense Oligonucleotides in mdx Mice (2007)

Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy, arising from mutations in the dystrophin gene that preclude the synthesis of functional protein. Antisense oligonucleotides (AOs) have been shown to induce specific exon skipping and thereby restore the reading frame and expression of functional dystrophin. In this report, we examine the effects of peptide nucleic acid (PNA) oligonucleotides and PNAs conjugated with peptides including TAT, muscle-specific peptide (MSP), adeno-associated virus 6 (AAV6) functional domain (AAV6), and AAV8 functional domain (AAV8), on exon skipping in vitro and in vivo. Efficient skipping of targeted exon 23 was achieved in cultured mdx myoblasts with PNA and PNA-peptide conjugates. Furthermore, single intramuscular injections of PNA and all PNA-peptide conjugates resulted in significant numbers of dystrophin-positive fibers in the injected tibialis anterior (TA) muscles of mdx mice, with no apparent local toxicity. Similar effects of exon skipping and dystrophin expression were obtained in mice of all ages. PNA and PNA-AAV6, PNA-AAV8 conjugates induced dystrophin expression in a dose-dependent manner. Our results demonstrate that PNAs have a higher efficiency of exon skipping than 2'O methyl phosphorothioate AOs do, and have a potential use in AO chemistry for antisense therapy of DMD.
Introducing meta-services for biomedical information extraction (2008)

We introduce the first meta-service for information extraction in molecular biology, the BioCreative MetaServer (BCMS; http://bcms.bioinfo.cnio.es/). This prototype platform is a joint effort of 13 research groups and provides automatically generated annotations for PubMed/Medline abstracts. Annotation types cover gene names, gene IDs, species, and protein-protein interactions. The annotations are distributed by the meta-server in both human and machine readable formats (HTML/XML). This service is intended to be used by biomedical researchers and database annotators, and in biomedical language processing. The platform allows direct comparison, unified access, and result aggregation of the annotations.
Physical Compatibility and Chemical Stability of a Concentrated Solution of Atropine Sulfate (2 mg/mL) for Use as an Antidote in Nerve Agent Casualties. (2015)

Atropine is one of the preferred antidotes for nerve gas exposure. Effective therapy requires large doses. Stockpiling of atropine in forms currently available commercially can be costly and can require a large storage area. Other problems in using the commercial product are the time required to break the large number of ampules needed for treatement, and the large volume of medication that must be administered. A preparation of concentrated atropine for injection from atropine powder is the ideal solution, but the stability of this preparation is unknown. A formulation for concentrated atropine sulfate solution (2 mg/mL) was developed using pharmaceutical-grade powder. The solution was prepared in isotonic saline solution and packaged in polypropylene syringes, which were sealed with syringe caps. Assessment of physical stability under several storage conditions was based on clarity, color, and pH monitoring. Chemical stability of the preparation was determined by using a stability-indicating high-performance liquid chromatographic method. All solutions remained clear and colorless, and the pH changed only slightly over the study period. The potency of the atropine sulfate solution remained above the United States Pharmacopeia limit of 93% for the duration of the study. The solutions were physically compatible and chemically stable when stored for 28 days at 35 deg C and exposed to light, 364 days at 23 deg C and exposed to light, or 364 days at 5 deg C and protected from light. Concentrated solutions of atropine sulfate can be compounded quickly and easily by using commercially available pharmaceutical-grade powder as the active ingredient. The extended shelf-life allows the preparation to be readily available in the field as required.
In-line E-beam wafer metrology and defect inspection: the end of an era for image-based critical dimensional metrology? New life for defect inspection (2013)

Metrology measurement and defect inspection steps in routes are more pervasive than many people realize and the number continues to grow. Digging deeper, it turns out that E-beam metrology and defect inspection tools typically occupy the most overall steps and therefore are extremely critical tools for semiconductor development and manufacturing. The Critical Dimension Scanning Electron Microscope (CDSEM) is an E-beam tool responsible for image-based structural metrology measurements while the E-beam review (EBR) and E-beam inspection (EBI) tools are responsible for defect inspection. The CDSEM faces significant future challenges in a world where device architectures are changing (as with the FinFET device), increasing the need for more structural measurement parameters such as sidewall angle, height and undercut, than the CDSEM can deliver. These applications are now migrating to scattering-based tools, also referred to as model- or computational-based structural metrology techniques. We explore the history of the CDSEM, the key fundamental limits (primarily resolution) of the CDSEM preventing it from capturing these applications and assess if an image-based structural metrology tool is still needed given the niche that scattering tools are filling. The answer is yes. Next we discuss whether the CDSEM will eventually meet those needs or if other alternative solutions are needed. Lastly, we discuss an industry survey on which image-based technique holds the most promise to solve these challenges. Regarding defect inspection, resolution is also a concern for the applications that need to detect extremely small defects which current optical-based Brightfield tools cannot address. While resolution is a primary concern in structural metrology, current EBI and EBR tools possess the resolution needed for defect inspection and have extendibility through at least the next advanced technology node. We also explore the niche E-beam is filling in defect inspection, evaluate the idea that a better synergistic solution exists today between the CDSEM and the EBI tools and propose a future E-beam landscape where E-beam tool variety in future fabs is significantly reduced to enhance productivity.
Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist (2003)

Stromal cell-derived factor 1 (SDF1/CXCL12) and its cognate receptor, CXCR4, play key regulatory roles in CD34+ cell trafficking. We investigated whether AMD3100, a selective CXCR4 antagonist, could mobilize hematopoietic progenitor cells from marrow to peripheral blood in healthy human volunteers. Initially, 10 persons each received a single dose of AMD3100 (80 microsubcutaneously), which induced rapid, generalized leukocytosis associated with an increase in peripheral blood CD34+ cells, representing pluripotent hematopoietic progenitors by in vitro colony-forming unit assays, from 3.8 +/- 0.5/microL to 20.7 +/- 3.5/microL at 6 hours. Subsequent dose-response studies showed a maximum increase in circulating CD34+ cells from 2.6 +/- 0.3/microL to 40.4 +/- 3.4/microL at 9 hours after 240 micro/kg AMD3100. Serial administration of AMD3100 (80 microg/kg/d for 3 days) resulted in consistent, reversible increases in peripheral blood CD34+ cells. AMD3100 was well tolerated and caused only mild, transient toxicity. These findings suggest potential clinical application of AMD3100 for CD34+ cell mobilization and collection for hematopoietic stem cell transplantation.
Mass spectrometry and the age of the proteome (1998)

Mass spectrometry has become an important technique to correlate proteins to their genes. This has been achieved, in part, by improvements in ionization and mass analysis techniques concurrently with large-scale DNA sequencing of whole genomes. Genome sequence information has provided a convenient and powerful resource for protein identification using data produced by matrix-assisted laser desorption/ionization time-of-flight (MALDI/TOF) and tandem mass spectrometers. Both of these approaches have been applied to the identification of electrophoretically separated protein mixtures. New methods for the direct identification of proteins in mixtures using a combination of enzymatic proteolysis, liquid chromatographic separation, tandem mass spectrometry and computer algorithms which match peptide tandem mass spectra to sequences in the database are also emerging. This tutorial review describes the principles of ionization and mass analysis for peptide and protein analysis and then focuses on current methods employing MALDI and electrospray ionization for protein identification and sequencing. Database searching approaches to identify proteins using data produced by MALDI/TOF and tandem mass spectrometry are also discussed.
Indenter tip radius and load frame compliance calibration using nanoindentation loading curves (1999)

The finite-element method has been used to simulate the indentation process of a variety of isotropic elastic-plastic materials indented by a rigid conical indenter with a perfectly sharp tip and round tips of various radii. Analyses of the obtained loading curves showed that the load frame compliance Cf of the nanoindentation instrument and the tip roundness r of the indenter can be determined from the loading curve. In a real indentation experiment, the obtained raw load-depth data during the loading stage can be described by the second-order polynomial dependence of depth on the square root of load, from which the Cf and r values are determined. An experimental procedure has thus been proposed for Cf and r calibration using the loading curves of a hard and isotropic material. Nanoindentation experiments on fused silica demonstrate the reliability of the proposed technique for accurate and quick Cf and r calibration.
Photons to the Rescue: Microelectronics Becomes Microphotonics (2000)

The evolution of the information age is being paced by the introduction of new materials and components more than by the design of systems, software, and networks. A rebuilding of the world’s information infrastructure is taking place to give instantaneous availability of data, voice, and video. Electrons transmitted through metal wires have an information carrying capacity that is limited by the resistance and capacitance of the cable and the terminating electronic circuits. Photons transmitted through fiber are capacity-limited only by the dispersion of the medium. Each network node that requires transduction from photonics to electronics limits the performance and affordability of the network. A key frontier is the large scale integration and manufacturing of photonic components to enable the distribution of high bit rate optical streams to the individual information appliance.
Fish oil, but not flaxseed oil, decreases inflammation and prevents pressure overload-induced cardiac dysfunction (2008)

Dietary supplementation with omega-3 PUFA derived from fish, but not from vegetable sources, increased plasma adiponectin, suppressed inflammation, and prevented cardiac remodelling and dysfunction under pressure overload conditions.
Transient-evoked otoacoustic emissions in children after cisplatin chemotherapy☆☆☆★★★♢ (1998)

Little is known about cisplatin ototoxicity in pediatric patients. Measurement of otoacoustic emissions is a rapid, reproducible, objective method of evaluating hearing. We examined whether transient-evoked otoacoustic emissions in pediatric patients exposed to cisplatin in the past correlated with audiographic findings. Twelve patients were entered into the study (mean age at treatment 7.8 years, mean cumulative dose 442.5 mg/mm2, mean 7.1 doses). Hearing at 3000 Hz was preserved in 82.6% of patients. In the higher frequencies significant sensorineural hearing loss was noted: 43.5% at 4 kHz; 81.0% at 6 kHz; and 90.5% at 8 kHz. Transient-evoked otoacoustic emissions were measurable in 11 of 12 patients. Middle ear disease accounted for abnormal otoacoustic emission seen in three patients (1 with effusion, 2 with significant negative middle ear pressure). When the middle ear was normal, a statistically significant correlation was seen between the transient-evoked otoacoustic emissions reproducibility and pure-tone threshold (correlation coefficient = –0.69, p = 0.008). Increased hearing loss was also associated with young age at first dose of cisplatin (p = 0.044), high number of chemotherapy cycles (p = 0.042), and high cumulative dose (p = 0.042). (Otolaryngol Head Neck Surg 1998;118:584-8.)
Evolutionary origin of inhibitor cystine knot peptides (2003)

The inhibitor cystine knot (ICK) fold is an evolutionarily conserved structural motif shared by a large group of polypeptides with diverse sequences and bioactivities. Although found in different phyla (animal, plant, and fungus), ICK peptides appear to be most prominent in venoms of cone snail and spider. Recently, two scorpion toxins activating a calcium release channel have been found to adopt an ICK fold. We have isolated and identified both cDNA and genomic clones for this family of ICK peptides from the scorpion Opistophthalmus carinatus. The gene characterized by three well-delineated exons respectively coding for three structural and functional domains in the toxin precursors illustrates the correlation between exon and module as suggested by the "exon theory of genes." Based on the analysis of precursor organization and gene structure combined with the 3-D fold and functional data, our results highlight a common evolutionary origin for ICK peptides from animals. In contrast, ICK peptides from plant and fungus might be independently evolved from another ancestor.