gebhart/patrepeval huggingface dataset:
Measuring Curvature and Velocity Vector Fields for Waves of Cardiac Excitation in 2-D Media (2004)

Excitable media theory predicts the effect of electrical wavefront morphology on the dynamics of propagation in cardiac tissue. It specifies that a convex wavefront propagates slower and a concave wavefront propagates faster than a planar wavefront. Because of this, wavefront curvature is thought to be an important functional mechanism of cardiac arrhythmias. However, the curvature of wavefronts during an arrhythmia are generally unknown. We introduce a robust, automated method to measure the curvature vector field of discretely characterized, arbitrarily shaped, two-dimensional (2-D) wavefronts. The method relies on generating a smooth, continuous parameterization of the shape of a wave using cubic smoothing splines fitted to an isopotential at a specified level, which we choose to be -30 mV. Twice differentiating the parametric form provides local curvature vectors along the wavefront and waveback. Local conduction velocities are computed as the wave speed along lines normal to the parametric form. In this way, the curvature and velocity vector field for wavefronts and wavebacks can be measured. We applied the method to data sampled from a 2-D numerical model and several examples are provided to illustrate its usefulness for studying the dynamics of cardiac propagation in 2-D media.
CELLULAR UPTAKE AND INTRACELLULAR QUANTIFICATION OF FLUORESCENT LABELED T20ME-SATE PROOLIGONUCLEOTIDES (2001)

Fluorescein labeled Me-SATE T20 models were synthesized. The high uptake of these prooligos in HeLa cells was confirmed by fluorescence microscopy, flow cytometry and by spectrofluorometry.
Lossless compression of video sequences (1996)

We investigate lossless compression schemes for video sequences. A simple adaptive prediction scheme is presented that exploits temporal correlations or spectral correlations in addition to spatial correlations. It is seen that even with motion compensation, schemes that utilize only temporal correlations do not perform significantly better than schemes that utilize only spectral correlations. Hence, we look at hybrid schemes that make use of both spectral and temporal correlations. The hybrid schemes give significant improvement in performance over other techniques. Besides prediction schemes, we also look at some simple error modeling techniques that take into account prediction errors made in spectrally and/or temporally adjacent pixels in order to efficiently encode the prediction residual. Implementation results on standard test sequences indicate that significant improvements can be obtained by the proposed techniques.
A Novel Classification of Lung Cancer into Molecular Subtypes (2012)

The remarkably heterogeneous nature of lung cancer has become more apparent over the last decade. In general, advanced lung cancer is an aggressive malignancy with a poor prognosis. The discovery of multiple molecular mechanisms underlying the development, progression, and prognosis of lung cancer, however, has created new opportunities for targeted therapy and improved outcome. In this paper, we define "molecular subtypes" of lung cancer based on specific actionable genetic aberrations. Each subtype is associated with molecular tests that define the subtype and drugs that may potentially treat it. We hope this paper will be a useful guide to clinicians and researchers alike by assisting in therapy decision making and acting as a platform for further study. In this new era of cancer treatment, the 'one-size-fits-all' paradigm is being forcibly pushed aside-allowing for more effective, personalized oncologic care to emerge.
Register allocation for embedded systems to simultaneously reduce energy and temperature on registers (2013)

Energy and thermal issues are two important concerns for embedded system design. Diminished energy dissipation leads to a longer battery life, while reduced temperature hotspots decelerate the physical failure mechanisms. The instruction fetch logic associated with register access has a significant contribution towards the total energy consumption. Meanwhile, the register file has also been previously shown to exhibit the highest temperature compared to the rest of the components in an embedded processor. Therefore, the optimization of energy and the resolution of the thermal issue for register accesses are of great significance. In this article, register allocation techniques are studied to simultaneously reduce energy consumption and heat buildup on register accesses for embedded systems. Contrary to prevailing intuition, we observe that optimizing energy and optimizing temperature on register accesses conflict with each other. We introduce a rotator hardware in the instruction decoder to facilitate a balanced solution for the two conflicting objectives. Algorithms for register allocation and refinement are proposed based on the access patterns and the effects of the rotator. Experimental results show that the proposed algorithms obtain notable improvements of energy and peak temperature for embedded applications.
Therapeutic efficacy of J-111,225, a novel trans-3,5-disubstituted pyrrolidinylthio-1β-methylcarbapenem, against experimental murine systemic infections (2000)

In a murine model of systemic infection with methicillin-resistant Staphylococcus aureus (MRSA), J-111,225 showed an ED(50) value of 5. 83 mg/kg, which was comparable to vancomycin (ED(50) 4.84 mg/kg), whereas imipenem failed to cure infected mice (ED(50) >100 mg/kg). Against a mixed infection caused by MRSA and Pseudomonas aeruginosa, monotherapy with J-111,225 showed an ED(50) value of 7.23 mg/kg, whereas combined treatment with vancomycin plus imipenem (1:1) had an ED(50) of 20.86 mg/kg. J-111,225 showed good therapeutic efficacy against methicillin-susceptible S. aureus, penicillin-resistant Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae and P. aeruginosa. The unusually broad spectrum suggests that monotherapy with this novel carbapenem may be suitable for polymicrobial infections associated with MRSA.
A Small-Molecule E2F Inhibitor Blocks Growth in a Melanoma Culture Model (2008)

HLM006474 was identified using a computer-based virtual screen and the known crystal structure of the DNA-bound E2F4/DP2 heterodimer. Treatment of multiple cell lines with HLM006474 resulted in the loss of intracellular E2F4 DNA-binding activity as measured by electrophoretic mobility shift assay within hours. Overnight exposure to HLM006474 resulted in down-regulation of total E2F4 protein as well as known E2F targets. The effects of HLM006474 treatment on different cell lines varied but included a reduction in cell proliferation and an increase in apoptosis. HLM006474 induced apoptosis in a manner distinct from cisplatin and doxorubicin. E2F4-null mouse embryonic fibroblasts were less sensitive than wild-type counterparts to the apoptosis-inducing activity of the compound, revealing its biological specificity. A375 cells were extremely sensitive to the apoptosis-inducing activity of the compound in two-dimensional culture, and HLM006474 was a potent inhibitor of melanocytes proliferation and subsequent invasion in a three-dimensional tissue culture model system. Together, these results suggest that interference with E2F activity using small molecules may have clinical application in cancer therapy.
The Role and Nature of Anti-Tamper Techniques in U.S. Defense Acquisition (1999)

Military technology can be compromised following foreign sales to an ally, accidental loss, or capture during a conflict by an enemy. Because U.S. military hardware and software have a high technical content that provides a qualitative edge, protection of this technological superiority is a high priority. Program managers can mitigate such risks with a relatively new set of technologies inclusively known as "anti-tamper." Program managers need to know the state of the art in anti-tamper technology and of the emerging DoD and U.S. Air Force policy on its use. This article covers anti-tamper policies; explains how, where, and when to insert these technologies; and describes some anti-tamper technologies now in use.
Oil Core−Polymer Shell Microcapsules Prepared by Internal Phase Separation from Emulsion Droplets. I. Characterization and Release Rates for Microcapsules with Polystyrene Shells (2004)

Microcapsules with an oil core surrounded by a polymeric shell have been prepared by the controlled phase separation of polymer dissolved within the oil droplets of an oil-in-water emulsion. The dispersed oil phase consists of the shell polymer (polystyrene), a good solvent for the polymer (dichloromethane), and a poor solvent for the polymer (typically hexadecane). Removal of the good solvent results in phase separation of the polymer within the oil droplets. If the three interfacial tensions between the core oil, the shell-forming polymer, and the continuous phase are of the required relative magnitudes, a polymer shell forms surrounding the poor solvent. A UV-responsive organic molecule was added to the oil phase, prior to emulsification, to investigate the release of a model active ingredient from the microcapsules. This molecule should be soluble in the organic core but also have some water solubility to provide a driving force for release into the continuous aqueous phase. As the release rate of the active ingredient is a function of the thickness of the polymeric shell, for controlled release applications, it is necessary to control this parameter. For the preparative method described here, the thickness of the shell formed is directly related to the mass of polymer dissolved in the oil phase. The rate of volatile solvent removal influences the porosity of the polymer shell. Rapid evaporation leads to cracks in the shell and a relatively fast release rate of the active ingredient. If a more gentle evaporation method is employed, the porosity of the polymer shell is decreased, resulting in a reduction in release rate. Cross-linking the polymer shell after capsule formation was also found to decrease both the release rate and the yield of the active ingredient. The nature of the oil core also affected the release yield.
Harpin and hydrogen peroxide induce the expression of a homologue of gp91-phox in Arabidopsis thaliana suspension cultures (1998)

Using reverse transcription-polymerase chain reaction and degenerate primers based on conserved sequences, a partial cDNA from Arabidopsis thaliana has been cloned that encodes part of a homologue of gp91-phox of NADPH oxidase. It is expressed in Arabidopsis shoots, roots and flowers and its expression in suspension cultures is up-regulated by elicitation with harpin or exposure to hydrogen peroxide.
ZC3H12A (MCPIP1): Molecular characteristics and clinical implications (2010)

Understanding ZC3H12A gives a comprehensive panorama that promises to improve our understanding of processes in which this gene is involved including autoimmune, infectious and cardiovascular diseases.
Inflammatory Components of Adipose Tissue as Target for Treatment of Metabolic Syndrome (2009)

Obesity is an independent risk factor in the etiology of various metabolic diseases such as insulin resistance, type 2 diabetes and cardiovascular diseases. In this chapter, we discuss obesity-induced inflammation as a potential link with obesity-related metabolic syndrome, and discuss how obesity-related inflammatory components such as immune cells, and cytokines/chemokines and adipocy-tokines, provoke obesity-related pathologies. In particular, we focus on the hypothesis that anti-inflammatory food factors/phytochemicals may be useful for inhibiting the initiation and development of obesity-induced inflammation and metabolic syndrome.
Dextromethorphan and sigma ligands: Common sites but diverse effects (1989)

There is increasing evidence that sigma ligands and dextromethorphan (DM) bind to at least one common high-affinity site. DM and other antitussives do not produce psychotomimetic effects. This suggested that sigma ligands may produce their characteristic effects through another site, and prompted us to review critically the literature on the side effects of sigma opiates. Contrary to what is generally accepted, the dysphoric and psychotomimetic side effects of sigma opiates are mediated by the levo-and not by the dextrorotatory isomers. Moreover, these effects are unequivocally naloxone-reversible. Therefore, the current version of the "sigma receptor", with high affinity for the dextrorotatory sigma opiates, cannot explain the psychotomimetic effects of the levorotatory enantiomers. Thus, neither the "sigma ligands" nor its newly defined "receptor" are involved in the psychotomimetic effects of sigma opiates. Further experimentation with more selective drugs and with a combination of different methods will be necessary to identify the different binding sites, and to establish their physiological role and therapeutic potential.
Noiseless Preflashing of the WFPC2 CCDs (2001)

ABSTRACT We present results from analysis of WFPC2 images obtained prior to and following preflashing the CCDs (WFPC2 CAL program ID: 8450). A crowded field in the globular cluster Omega Cen (HD116790) was observed, and the WFPC2 calibration lamp was used as the preflash source for the CCDs. A modest enhancement of ~3% in the detected counts was measured for point sources far from the horizontal shift register (at Y=800) for the preflash exposure. For the preflashed exposure, the second image after a preflash showed a decrease in the detected counts. The CCDs essentially returned to a previous sensitivity level.
Bioluminescent click beetles revisited (1989)

In studying beetle bioluminescence in the early 1960s, Dr. McElroy and his colleagues found that the Jamaican click beetle, Pyrophorus plagiophthalamus, was capable of emitting different colours of light. They further found that the luciferin substrate used by this beetle was the same as that in the firefly, demonstrating that the different colours of bioluminescence were due to differences in the structure of the luciferases. We have recently cloned cDNAs from this beetle species which code for at least four different luciferases. The luciferases are distinguishable by their different colours of bioluminescence when expressed in Escherichia coli. The sequence differences between these different luciferases are few, so the amino acids responsible for the different colours of emission must also be few. Through the construction of hybrid luciferases, by rearranging fragments of the original cDNA clones, we have identified some of these amino acid determinants of colour.
Patterning and morphogenesis of the vertebrate inner ear (2007)

The positional cues for formation of individual inner ear components are dependent on pre-established axial information conferred by inductive signals from tissues surrounding the developing inner ear. This review summarizes some of the known molecular pathways involved in establishing the three axes of the inner ear, anterior-posterior (AP), dorsal-ventral (DV) and medial-lateral (ML). Signals required to establish the AP axis of the inner ear are not known, but they do not appear to be derived from the hindbrain. In contrast, the hindbrain is essential for establishing the DV axis of the inner ear by providing inductive signals such as Wnts and Sonic hedgehog. Signaling from the hindbrain is also required for the formation of the ML axis, whereas formation of the lateral wall of the otocyst may be a result of first establishing both the AP and DV axes. In addition, this review addresses how genes induced within the otic epithelium as a result of axial specification continue to mediate inner ear morphogenesis.
Stimulation of the Subthalamic Nucleus Changes the Firing Pattern of Pallidal Neurons (2003)

To clarify the mechanism underlying improvement of parkinsonian signs by high-frequency electrical stimulation (HFS) of the subthalamic nucleus (STN), we investigated the effects of STN HFS on neuronal activity of the internal and external segment of the globus pallidus (GPi and GPe, respectively) in two rhesus monkeys rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. A scaled-down version of the chronic stimulating electrode used in humans, consisting of four metal contacts 0.50 mm in length each separated by 0.50 mm, was implanted through a cephalic chamber targeting the STN. Histological reconstruction revealed that the cathode was located in the STN in both monkeys. Extracellular recordings from a total of 110 pallidal neurons during STN stimulation were performed. Poststimulus time histograms of single neurons triggered by 2 Hz STN stimulation pulses at 2.4-3.0 V revealed short-latency excitations at 2.5-4.5 and 5.5-7.0 msec after stimulation onset and inhibitions at 1.0-2.5, 4.5-5.5, and 7.0-9.0 msec for both GPe and GPi neurons. These short-latency responses were present with 136 Hz stimulation, at voltages effective for alleviation of parkinsonian signs, resulting in a significant increase in mean discharge rate and a stimulus-synchronized regular firing pattern. These results indicate that activation of the STN efferent fibers and resultant changes in the temporal firing pattern of neurons in GPe and GPi underlie the beneficial effect of HFS in the STN in Parkinson's disease and further support the role of temporal firing patterns in the basal ganglia in the development of Parkinson's disease and other movement disorders.
Relationship of Animal Protein-Rich Diet to Kidney Stone Formation and Calcium Metabolism* (1988)

We wished to determine whether different types of dietary protein might have different effects on calcium metabolism and on the propensity for renal stone formation. Fifteen young normal subjects were studied during three 12-day dietary periods during which their diet contained vegetable protein, vegetable and egg protein, or animal protein. While these three diets were constant with respect to Na, K, Ca, P, Mg, and quantity of protein, they had progressively higher sulfur contents. As the fixed acid content of the diets increased, urinary calcium excretion increased from 103 +/- 15 ( +/- SEM) mg/day (2.6 +/- 0.4 mmol/day) on the vegetarian diet to 150 +/- 13 mg/day (3.7 +/- 0.3 mmol/day) on the animal protein diet (P less than 0.02). Despite the increased urinary calcium excretion, there was a modest reduction of urinary cAMP excretion and serum PTH and 1,25-dihydroxyvitamin D levels consistent with acid-induced bone dissolution. There was no change in fractional intestinal 47Ca absorption. The inability to compensate for the animal protein-induced calciuric response may be a risk factor for the development of osteoporosis. The animal protein-rich diet was associated with the highest excretion of undissociated uric acid due to the reduction in urinary pH. Moreover, citrate excretion was reduced because of the acid load. However, oxalate excretion was lower than during the vegetarian diet [26 +/- 1 mg/day (290 +/- 10 mumol/day) vs. 39 +/- 2 mg/day (430 +/- 20 mumol/day); P less than 0.02]. Urinary crystallization studies revealed that the animal protein diet, when its electrolyte composition and quantity of protein were kept the same as for the vegetarian diet, conferred an increased risk for uric acid stones, but, because of opposing factors, not for calcium oxalate or calcium phosphate stones.
Ferroelectric Hafnium Oxide Based Materials and Devices: Assessment of Current Status and Future Prospects (2015)

S.N30-N35
Transport, Phosphorylation, and Toxicity of a Tricyclic Nucleoside in Cultured Novikoff Rat Hepatoma Cells and Other Cell Lines and Release of Its Monophosphate by the Cells 2 (1976)

1,4,5,6,8-Pentaazaacenaphthylene-3-amino-1,5-dihydro-5-methyl-(5-14C)-1-beta-D-ribofuranysly (NSC-154020), a tricyclic 7-deazapurine nucleoside (TCN), was rapidly incorporated into the acid-soluble pool by cultured Novikoff rat hepatoma cells, mouse L-cells, HeLa cells, and HEp-2 cells, but little incorporation into nucleic acids occurred. More than 90% of the intracellular radioactivity was associated with the monophosphate (MP) of the substrate concentration followed normal Michaelis-Menten kinetics. Comparison of the kinetic constants for the uptake of adenosine and the TCN and of the inhibition of their uptake by each other suggests that both were transported by the same system (Michaelis constant approximately 6-10 muM) and with about the same efficiency. The TCN was also phosphorylated in a cellfree extract containing adenosine kinase activity at about the same rate as was adenosine, but not further phosphorylation of the analogue MP occurred. No significant deamination or degradation of the adenosine analogue to its base and ribose-1-phosphate was observed. TCN inhibited the replication of all four types of cells propagated in suspension culture; however, Novikoff cells were several times more sensitive than were the other three cell types, despite the finding that the TCN-MP, probably the main toxic principle, accumulated to about the same concentration in cells of all four lines. Complete inhibition of replication of Novikoff cells were several times more sensitive than were the other three cell types, despite the finding that the TCN-MP, probably the main toxic principle, accumulated to about the same concentration in cells of all four lines. Complete inhibition of replication of Novikoff cells and cell death occurred at concentration as low as 15 muM TCN. At these concentrations, TCN, within 2 hours of its addition, completely inhibited the incorporation of [14C]formate int0 nucleotides and nucleic acids of Novikoff cells. An inhibition of the denovo synthesis of purine and pyrimidines, however, was not the only toxic effect of the TCN since high concentrations of uridine, adenine, guanine, and hypoxanthine, either alone or combined, failed to prevent the inhibition of cell replication by TCN. Also, between 1 and 3 hours of treatment, 70-80% of the Novikoff cells fragmented into four to eight vesicles per cell. These fragments were impermeable to trypan blue, still exhibited some metabolic activity such as the phosphorylation of AMP and TCN, but failed to replicate when the drug was removed. No similar fragmentation was observed with the other cell lines. Novikoff and L-cells rapidly released TCN-MP into the culture fluid. After 4 hours of incubation, 70-100% of the total radioactivity in the medium was associated with the MP. Only a little TCN-MP was released from HeLa and HEp-2 cells. A TCN-resistant mutant of Novikoff cells failed to phosphorylate the analogue and was deficient in adenosine kinase.
The Activity of HDAC8 Depends on Local and Distal Sequences of Its Peptide Substrates (2008)

This paper introduces a flexible assay for characterizing the activities of the histone deacetylase enzymes. The approach combines mass spectrometry with self-assembled monolayers that present acetylated peptides and enables a label-free and one-step assay of this biochemical activity. The assay was used to characterize the activity of HDAC8 toward peptides taken from the N-terminal tail of the H4 histone and reveals that a distal region of the peptide substrate interacts with the deacetylase at an exosite and contributes to the activity of the substrate. Specifically, a peptide corresponding to residues 8-19 of H4 and having lysine 12 acetylated is an active substrate, but removal of the KRHR (residues 16-19) sequence abolishes activity. Mutation of glycine 11 to arginine in the peptide lacking the KRHR sequence restores activity, demonstrating that both local and distal sequences act synergistically to regulate the activity of the HDAC. Assays with peptides bearing multiply acetylated residues, but in which each acetyl group is isotopically labeled, permit studies of the processive deacetylation of peptides. Peptide substrates having an extended sequence that includes K20 were used to demonstrate that methylation of this residue directly affects HDAC8 activity at K12. This work provides a mechanistic basis for the regulation of HDAC activities by distal sequences and may contribute to studies aimed at evaluating the role of the histone code in regulating gene expression.