gebhart/patrepeval huggingface dataset:
Electrospinning and electrically forced jets. II. Applications (2001)

Electrospinning is a process in which solid fibers are produced from a polymeric fluid stream (solution or melt) delivered through a millimeter-scale nozzle. This article uses the stability theory described in the previous article to develop a quantitative method for predicting when electrospinning occurs. First a method for calculating the shape and charge density of a steady jet as it thins from the nozzle is presented and is shown to capture quantitative features of the experiments. Then, this information is combined with the stability analysis to predict scaling laws for the jet behavior and to produce operating diagrams for when electrospinning occurs, both as a function of experimental parameters. Predictions for how the regime of electrospinning changes as a function of the fluid conductivity and viscosity are presented.
Development of a Dual-Index Sequencing Strategy and Curation Pipeline for Analyzing Amplicon Sequence Data on the MiSeq Illumina Sequencing Platform (2013)

Rapid advances in sequencing technology have changed the experimental landscape of microbial ecology. In the last 10 years, the field has moved from sequencing hundreds of 16S rRNA gene fragments per study using clone libraries to the sequencing of millions of fragments per study using next-generation sequencing technologies from 454 and Illumina. As these technologies advance, it is critical to assess the strengths, weaknesses, and overall suitability of these platforms for the interrogation of microbial communities. Here, we present an improved method for sequencing variable regions within the 16S rRNA gene using Illumina's MiSeq platform, which is currently capable of producing paired 250-nucleotide reads. We evaluated three overlapping regions of the 16S rRNA gene that vary in length (i.e., V34, V4, and V45) by resequencing a mock community and natural samples from human feces, mouse feces, and soil. By titrating the concentration of 16S rRNA gene amplicons applied to the flow cell and using a quality score-based approach to correct discrepancies between reads used to construct contigs, we were able to reduce error rates by as much as two orders of magnitude. Finally, we reprocessed samples from a previous study to demonstrate that large numbers of samples could be multiplexed and sequenced in parallel with shotgun metagenomes. These analyses demonstrate that our approach can provide data that are at least as good as that generated by the 454 platform while providing considerably higher sequencing coverage for a fraction of the cost.
Pre-steady-state kinetic analysis of processive DNA replication including complete characterization of an exonuclease-deficient mutant (1991)

The elementary steps of DNA polymerization catalyzed by T7 DNA polymerase have been resolved by transient-state analysis of single nucleotide incorporation, leading to the complete pathway: [formula: see text] where E, D, N, and P represent T7 DNA polymerase, DNA primer/template, deoxynucleoside triphosphate, and inorganic pyrophosphate, respectively. A DNA primer/template consisting of a synthetic 25/36-mer has been used as a substrate for correct nucleotide incorporation of dTTP in all the experiments. The rate constants and equilibrium constants of each step have been established by direct measurement of individual reactions and fit by computer simulation of the data to obtain a single set of rate constants accounting for all the data. Analysis of the single-turnover kinetics provided measurements of equilibrium dissociation constants for 25/36-mer, dTTP, and PPi equal to 18 nM (koff/kon), 18 microM (k-1/k1), and 2 mM (k5/k-5), respectively. The rate-limiting step during single-nucleotide incorporation has been identified as a conformational change, E.Dn.N----E'.Dn.N, which occurs at a rate of 300 s-1 (k2) upon binding of the correct dNTP. Accordingly, tighter binding of the transition states for the reaction resulting from the conformational change facilitates the phosphodiester bond formation. The chemical step itself was excluded as the rate-limiting step because of the small phosphothioate elemental effect. An observed rate constant of 70 s-1 for dTTP (alpha S) incorporation suggest that the chemical step (k3) occurs at a fast rate, greater than or equal to 9000 s-1. Following chemistry, the resulting ternary complex, E'.Dn+1.P, undergoes a second conformational change at a rate of 1200 s-1 (k4), leading to release of PPi and translocation of the DNA to continue subsequent cycles of polymerization. The rate constants of the reverse steps, 100 s-1 (k-2), greater than or equal to 18,000 s-1 (k-3) and 18 s-1 (k-4), were derived as fits to the data based upon simulation of single-turnover kinetics of pyrophosphorolysis including measurements of pyrophosphate exchange and the overall equilibrium constant of 1.0 x 10(4) for elongation of E.25/36-mer and analysis of the kinetics of the pulse-chase experiment. These studies provide the first complete and self-consistent thermodynamic descriptions of DNA polymerase and establish the basis for quantitative assessment of the reactions contributing to its extraordinary fidelity.(ABSTRACT TRUNCATED AT 400 WORDS)
Sequential Activation of a Segmented Ground Pad Reduces Skin Heating During Radiofrequency Tumor Ablation: Optimization via Computational Models (2008)

Radiofrequency (RF) ablation has become an accepted treatment modality for unresectable tumors. The need for larger ablation zones has resulted in increased RF generator power. Skin burns due to ground pad heating are increasingly limiting further increases in generator power, and thus, ablation zone size. We investigated a method for reducing ground pad heating in which a commercial ground pad is segmented into multiple ground electrodes, with sequential activation of ground electrode subsets. We created finite-element method computer models of a commercial ground pad (14 x 23 cm) and compared normal operation of a standard pad to sequential activation of a segmented pad (two to five separate ground electrode segments). A constant current of 1 A was applied for 12 min in all simulations. Time periods during sequential activation simulations were adjusted to keep the leading edge temperatures at each ground electrode equal. The maximum temperature using standard activation of the commercial pad was 41.7 degrees C. For sequential activation of a segmented pad, the maximum temperature ranged from 39.3 degrees C (five segments) to 40.9 degrees C (two segments). Sequential activation of a segmented ground pad resulted in lower tissue temperatures. This method may reduce the incidence of ground pad burns and enable the use of higher power generators during RF tumor ablation.
Formation of dinuclear macrocyclic and mononuclear acyclic complexes of a new trinucleating hexaaza triphenolic Schiff base macrocycle: structure and NLO properties (2000)

Reaction of a new chiral and optically active trinucleating 3 + 3 condensed hexaaza triphenolic Schiff base macrocycle H3L1I with transition metal ions (Zn, Cu, Ni, Co, Fe and Mn) in 1∶3 molar ratio in methanol under reflux conditions resulted in complexes. Analytical data reveal the formation of 2 + 2 condensed dinuclear macrocyclic Schiff base complexes, instead of the expected trinuclear macrocyclic complexes. X-Ray crystallographic studies on three of these complexes established their dinuclearity. On the other hand, reaction of I with metal ions (Zn, Cu, Fe and Mn) in 1∶3 molar ratio in methanol at room temperature for 2 h resulted in one-side condensed mononuclear acyclic complexes. This is confirmed by the crystal structure of the manganese complex. Second-order non-linear properties are discussed.
Sympathetic Mechanisms in Blood Vessels: Nerve and Muscle Relationships (1973)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Primary structure of the Saccharomyces cerevisiae gene for methionyl-tRNA synthetase. (1983)

The sequence of a 5-kilobase DNA insert containing the structural gene for yeast cytoplasmic methionyl-tRNA synthetase has been determined and a unique open reading frame of 2,253 nucleotides encoding a polypeptide chain of 751 amino acids (Mr, 85,500) has been characterized. The data obtained on the purified enzyme (subunit size, amino acid composition, and COOH-terminal sequence) are consistent with the gene structure. The protein sequence deduced from the nucleotide sequence reveals no obvious internal repeats. This protein sequence shows a high degree of homology with that of Escherichia coli methionyl-tRNA synthetase within a region that forms the putative methionyl adenylate binding site. This strongly suggests that both proteins derive from a common ancestor.
Large Area Orientation of Block Copolymer Microdomains in Thin Films via Directional Crystallization of a Solvent (2001)

A fast method for inducing alignment of microdomains in noncrystalline block copolymers is presented. The method is based on the use of crystalline organic materials, which are solvents for the block copolymers above their melting temperatures, and, when cooled and directionally crystallized, act as a substrate on which thin films of the block copolymers are formed. Both lamellar and cylindrical type microdomains in a symmetric polystyrene-block-poly(methyl methacrylate) diblock copolymer and in an asymmetric polystyrene-block-polyisoprene respectively are globally aligned using either benzoic acid (BA) or anthracene (AN) as the crystallizable solvent. The fast directional solidification during the phase separation leads to alignment of the intermaterial dividing surface (IMDS) of both types of microdomains parallel to the fast growth direction of BA and AN crystals (b axis direction in both cases). Depending on film thicknesses, the block copolymers show various microdomain orientations such as vertical lamellae and parallel and perpendicular cylinders to the substrate. With respect to the processing methods currently used to induce orientation in block copolymers, our method allows attainment of ordered patterns over regions larger than 50 μm2 within a few seconds without annealing.
Coherent optical image amplification by an injection-locked dye amplifier at 632.8 nm (1979)

Coherent amplification of images illuminated by the 632.8-nm radiation of He-Ne has been successfully demonstrated using a two-stage injection-locked pulsed dye amplifier technique. A gain of three times has been measured using Cresyl Violet 620 and Rhodamine B in ethanol, while maintaining signal bandwidth, relative phase, and direction, over a one-quarter μs pulse duration. A space bandwidth product of 500 000 was obtained by incorporation of the image amplifier into an optical image processing system.
Host-Bacterial Mutualism in the Human Intestine (2005)

The distal human intestine represents an anaerobic bioreactor programmed with an enormous population of bacteria, dominated by relatively few divisions that are highly diverse at the strain/subspecies level. This microbiota and its collective genomes (microbiome) provide us with genetic and metabolic attributes we have not been required to evolve on our own, including the ability to harvest otherwise inaccessible nutrients. New studies are revealing how the gut microbiota has coevolved with us and how it manipulates and complements our biology in ways that are mutually beneficial. We are also starting to understand how certain keystone members of the microbiota operate to maintain the stability and functional adaptability of this microbial organ.
MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13 (2011)

Many human aneuploidy syndromes have unique phenotypic consequences, but in most instances it is unclear whether these phenotypes are attributable to alterations in the dosage of specific genes. In human trisomy 13, there is delayed switching and persistence of fetal hemoglobin (HbF) and elevation of embryonic hemoglobin in newborns. Using partial trisomy cases, we mapped this trait to chromosomal band 13q14; by examining the genes in this region, two microRNAs, miR-15a and -16-1, appear as top candidates for the elevated HbF levels. Indeed, increased expression of these microRNAs in primary human erythroid progenitor cells results in elevated fetal and embryonic hemoglobin gene expression. Moreover, we show that a direct target of these microRNAs, MYB, plays an important role in silencing the fetal and embryonic hemoglobin genes. Thus we demonstrate how the developmental regulation of a clinically important human trait can be better understood through the genetic and functional study of aneuploidy syndromes and suggest that miR-15a, -16-1, and MYB may be important therapeutic targets to increase HbF levels in patients with sickle cell disease and β-thalassemia.
An acoustic echo canceller using subband sampling and decorrelation methods (1993)

An acoustic echo canceller based on signal decorrelation and subband techniques is developed. A decorrelation algorithm is combined with a variable loop gain method. Echo cancellation characteristics superior to those of the conventional normalized least-mean-square (NLMS) adaptation algorithm are obtained through computer simulation. The implementation of an acoustic subband echo canceller with high speech quality is demonstrated. Experiments confirm echo cancellation in excess of 40 dB over the 7 kHz frequency band using hardware with a total of 4000 tap finite impulse response (FIR) filters. The decorrelation algorithm increases convergence speeds for colored signals by about three times, and for speech signals by more than two times over those of the NLMS algorithm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Modern antiepileptic drug development has failed to deliver: Ways out of the current dilemma (2011)

Despite the development of various new antiepileptic drugs (AEDs) since the early 1990s, the available evidence indicates that the efficacy and tolerability of drug treatment of epilepsy has not substantially improved. What are the reasons for this apparent failure of modern AED development to discover drugs with higher efficacy? One reason is certainly the fact that, with few exceptions, all AEDs have been discovered by the same conventional animal models, particularly the maximal electroshock seizure test (MES) in rodents, which served as a critical gatekeeper. These tests have led to useful new AEDs, but obviously did not help developing AEDs with higher efficacy in as yet AED-resistant patients. This concern is not new but, surprisingly, has largely been unappreciated for several decades. A second-admittedly speculative-reason is that progress in pharmacologic treatment of drug-resistant epilepsy will not be made unless and until we develop drugs that specifically target the underlying disease. Although better preclinical approaches will not be able to circumvent regulatory requirements, more efficacious drugs may allow us to abandon clinically questionable trials with intentionally less efficacious controls and noninferiority designs, and require evidence for comparative effectiveness. The failure of AED development has led to increasing disappointment among clinicians, basic scientists, and industry and may halt any further improvement in the treatment of epilepsy unless we find ways out of this dilemma. Therefore, we need new concepts and fresh thinking about how to radically change and improve AED discovery and development. In this respect, the authors of this critical review will discuss several new ideas that may hopefully lead to more efficacious drug treatment of epilepsy in the future.
Emerging Technologies in UAV Aerodynamics (2013)

Marques P. (2013). Emerging technologies in UAV aerodynamics. International Journal of Unmanned Systems Engineering. 1(S1): 3-4. Novel unmanned aerial vehicle (UAV) technologies address innovative airframe concepts for reasons of fuel efficiency, aircraft noise signature attenuation and reduced maintenance costs. New aerodynamic technologies prioritise flow control and flapless designs, in place of traditional hinged control surfaces, for enhanced manoeuvrability, reduced wing structural weight, and improved stealth. This technical note presents contemporary advances in Blended Wing Body (BWB) airframe design and flow control mechanisms for flapless flight control. Based upon the Coanda effect, engine thrust vectoring provides pitch control and Circulation Control (CC) replaces conventional ailerons for roll control. The integration of flapless aerodynamic technology in blended wing-body aircraft is envisaged to play a crucial role in future experimental flight research programmes for the development of next generation UAV concepts. © Marques Aviation Ltd – Press. 1. BLENDED WING BODY DESIGN The Blended Wing Body concept offers promising advantages in structural, aerodynamic and operational efficiency over the conventional fuselage-and-wing designs (Fig. 1). The unmanned Boeing X-48 Blended Wing Body experimental aircraft represents the futuristic philosophy supported by Boeing
Turning a disadvantage into an advantage: synthesizing high-quality organometallic halide perovskite nanosheet arrays for humidity sensors (2017)

A humidity sensor made of uniform perovskite nanosheet arrays displayed good performance, and hence represents a new application for perovskite materials.
Identification of 33 candidate oncogenes by screening for base-specific mutations (2014)

This work reveals a variety of new recurrent candidate oncogene mutations to be further scrutinised as potential therapeutic targets.
CD95L Cell Surface Cleavage Triggers a Prometastatic Signaling Pathway in Triple-Negative Breast Cancer (2013)

Triple-negative breast cancers (TNBC) lacking estrogen and progesterone receptors and HER2 amplification have a relatively high risk of metastatic dissemination, but the mechanistic basis for this risk is not understood. Here, we report that serum levels of CD95 ligand (CD95L) are higher in patients with TNBC than in other patients with breast cancer. Metalloprotease-mediated cleavage of CD95L expressed by endothelial cells surrounding tumors generates a gradient that promotes cell motility due to the formation of an unconventional CD95-containing receptosome called the motility-inducing signaling complex. The formation of this complex was instrumental for Nox3-driven reactive oxygen species generation. Mechanistic investigations revealed a Yes-Orai1-EGFR-PI3K pathway that triggered migration of TNBC cells exposed to CD95L. Our findings establish a prometastatic function for metalloprotease-cleaved CD95L in TNBCs, revisiting its role in carcinogenesis.
Role of the α2B-Adrenergic Receptor in the Development of Salt-Induced Hypertension (1999)

Salt sensitivity is a common trait in patients with essential hypertension and seems to have both an inherited and an acquired component (eg, is influenced by aging and renal insufficiency). Experimental evidence suggests that salt loading induces hypertension via a neurogenic mechanism mediated by the alpha2-adrenergic receptors (alpha2-AR). To explore the alpha2-AR subtype involved in this mechanism, we studied 2 groups of mice genetically engineered to be deficient in one of the 3 alpha2-AR subtype genes (either alpha2B-AR +/- or alpha2C-AR -/- knockout mice) compared with their wild-type counterparts. The mice (n=10 to 14 in each group) were submitted to subtotal nephrectomy and given 1% saline as drinking water for up to 35 days. Blood pressure (BP) was monitored by tail-cuff readings and confirmed at the end point by direct intra-arterial BP recording. The alpha2B-AR-deficient mice had an attenuated BP response in this protocol (baseline 101.8+/-2.7 versus end point 109.9+/-2.8 mm Hg), whereas the BP of their wild-type counterparts went from a baseline 101.9+/-2.3 to an end point 141.4+/-7.1 mm Hg. The other 2 groups had BP increases of 44. 6+/-5.17 and 46.7+/-7.01 mm Hg, with no difference between the mice deficient in the alpha2C-AR gene subtype versus their wild-type counterparts. Body weight, renal remnant weight, and residual renal function were no different among groups. These data suggest that a full complement of alpha2B-AR genes is necessary to raise BP in response to dietary salt loading, whereas complete absence of the alpha2C-AR subtype does not preclude salt-induced BP elevation. It is unclear whether the mechanism(s) involved in this process are of central origin (inability to increase sympathetic outflow), vascular origin (inability to vasoconstrict), or renal origin (inability to retain excess salt and fluid).
Potent quinoxaline-spaced phosphono .alpha.-amino acids of the AP-6 type as competitive NMDA antagonists: synthesis and biological evaluation (1993)

A series of alpha-amino-3-(phosphonoalkyl)-2-quinoxalinepropanoic acids was synthesized and evaluated for NMDA receptor affinity using a [3H] CPP binding assay. Functional antagonism of the NMDA receptor complex was evaluated in vitro using a stimulated [3H]TCP binding assay and in vivo by employing an NMDA-induced seizure model. Some analogues also were evaluated in the [3H]-glycine binding assay. Several compounds of the AP-6 type show potent and selective NMDA antagonistic activity both in vitro and in vivo. In particular alpha-amino-7-chloro-3-(phosphonomethyl)-2-quinoxalinepropanoic acid (1) displayed an ED50 of 1.1 mg/kg ip in the NMDA lethality model. Noteworthy is alpha-amino-6,7-dichloro-3-(phosphonomethyl)-2-quinoxalinepropanoic++ + acid (3) with a unique dual activity, displaying in the NMDA receptor binding assay an IC50 of 3.4 nM and in the glycine binding assay an IC50 of 0.61 microM.
Heat shock protein 90 (HSP90) inhibition in squamous cell carcinoma of the head and neck (SCCHN): An in vitro analysis with a focus on p16 status. (2013)

2552 Background: Despite advances in therapy, the overall 5 year survival for SCCHN is close to 50%. Cisplatin and radiation therapy remain the current standard for treating locally advanced SCCHN. Novel treatment approaches are urgently needed, especially in HPV negative disease. We examined the expression of HSP90 in HPV positive and negative SCCHN and investigated if the HSP90 inhibitor ganetespib can sensitize mutant p53 SCCHN to cisplatin and radiation therapy in vitro. Methods: Phase 1 trials of ganetespib at 150 mg/m 2 have shown the maximum clinically achievable concentration (CAC) in patients to be ~166 nM. We treated p53 deficient or mutant p53 SCCHN cells (SCC25 and Detroit 568, CAL27and FADU, respectively) with ganetespib at 10-50 nM alone and in combination with cisplatin or radiation therapy and assessed survival. We measured HSP90, HSP70 and p53 protein expression levels in SCCHN cell lines by immunoblotting and analyzed HSP90 protein levels in p16 positive and p16 negative SCCHN tumor samples by immunohistochemistry. Results: Ganetespib at CAC was significantly more cytotoxic in mutant p53 compared to p53 deficient SCCHN cells (p &lt; 0.05). When combined with CAC doses of cisplatin or radiation therapy, ganetespib displayed strong sensitizing activity (p &lt; 0.05 and p &lt; 0.01 respectively). Ganetespib treatment upregulated HSP70 and HSP90 expression while decreasing p53 expression in the mutant cell lines. HSP90 expression was significantly higher in p16 negative than p16 positive SCCHN tumor samples (79.5% vs. 51%, ANOVA p = 0.016). Conclusions: Our results demonstrate a potential efficacy of ganetespib as a single agent and in combination with cisplatin and radiation therapy in SCCHN. HSP90 expression is upregulated in p16 negative SCCHN. Further exploration of the role of HSP90 in SCCHN, and utility of HSP90 inhibitors, is warranted.