gebhart/patrepeval huggingface dataset:
Evidence for the involvement of nitric oxide in A2Breceptor-mediated vasorelaxation of mouse aorta (2006)

We have investigated the role of adenosine and its analogs on vasorelaxation of mouse aorta in intact endothelium with rank order of potency as follows: 5'-N-ethylcarboxamidoadenosine (NECA) > 2-chloroadenosine > adenosine >> CGS-21680, which is consistent with the profile of A(2B)-adenosine receptor (A(2B)AR). In endothelium-intact tissues, acetylcholine produced relaxation ranging from 65 to 80% in phenylephrine (PE, 10(-7) M)-precontracted mouse aorta, whereas no relaxation was observed in endothelium-denuded tissues. The A(2B)AR antagonist alloxazine (10(-5) M) shifted concentration-response curve for NECA (EC(50) = 0.005 x 10(-5) M) to the right with an EC(50) of 2.8 x 10(-5) M, demonstrating that this relaxation is partially dependent on functional endothelium mediated predominantly via A(2B)AR in this tissue. This conclusion was further supported by the following findings: 1) in the endothelium-intact mouse aorta, the EC(50) values for NECA and adenosine were found to be 0.05 and 1.99 x 10(-4) M, respectively; however, in denuded endothelium, these values were 0.098 and 3.55 x 10(-4) M, respectively; 2) NECA-induced relaxation was significantly blocked by N(G)-nitro-l-arginine methyl ester (l-NAME; 10(-4) M) in endothelium-intact tissues, which was reversed by pretreatment with l-arginine (10(-4) M), whereas no significant inhibition was found in endothelium-denuded tissues; 3) total nitrites and nitrates (NOx) in intact endothelium with l-NAME (10(-4) M) alone and in combination with l-arginine were 59% (P < 0.05) and 96%, respectively, in comparison with control (PE + NECA); and 4) endothelial nitric oxide synthase gene expression was found to be 67% (P < 0.05) less in endothelium-denuded as opposed to endothelium-intact mouse aorta. Thus these data demonstrate that adenosine-mediated vasorelaxation is partially dependent on A(2B)AR in mouse aorta.
Decelerated Synthesized Speech as a Means of Shaping Speed of Auditory Processing of Children with Delayed Language (1982)

This study investigated whether the rate at which children with delayed language process auditory stimuli can be increased through a process of shaping with synthesized speech stimuli. Results indicate that stimuli with slowed down critical formant cues were easier for these 24 children with delayed language to discriminate and that training with stimuli of extended duration did generalize to stimuli of normal durations. Implications of these findings and usefulness of this methodology are discussed.
Acid Fermentation in Water‐Organic Solvent Two‐Liquid Phase Systems (1987)

Abstract In search of an optimal system for extractive fermentation of an organic acid, fermentations of lactic, citric, and acetic acids were studied in a broth saturated with an organic solvent and in a broth‐organic solvent two‐liquid phase system. Among the 13 solvents tested, only long‐chain hydrocarbons, perfluorodecalin, and methyl oleate were found to be nontoxic to the cells of L. delbrueckii in two‐liquid phase systems. However, a distinction was made between toxicity due to dissolved solvent molecules and that due to a separate solvent phase. Thus, cells of L. delbrueckii, which were not inhibited in n‐dodecanol‐saturated broth, but inhibited in a two‐phase system, were successfully protected by immobilization in carrageenan beads. The same solvent however, partially inhibited the growth of A. niger and A. aceti when present at saturated levels in the broth. The effect of tridodecylamine on lactic acid fermentation in a two‐liquid phase system was investigated in view of enhancing the acid extraction. Since extraction of an acid is favored by low pH, an extractive fermentation of an acid is practical for microorganisms that can grow at pH &lt; pK a , such as A. aceti and A. niger. The amine was found to be toxic to L. delbrueckii above a concentration of 222 mM, and at a level of 50%v, it was deleterious to all cell microorganisms tested, either free or gel entrapped.
Iterative decoding of serially concatenated codes with interleavers and comparison with turbo codes (2002)

A serially concatenated code with interleaver consists of the cascade of an outer encoder, an interleaver permuting the outer codewords bits, and an inner encoder whose input words are the permuted outer codewords. We propose a new, low-complexity iterative decoding algorithm for serially concatenated codes and apply it to perform simulation comparisons with parallel concatenated convolutional codes known as "turbo codes".
Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor (2015)

The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier.
Transgenic mice produced by retroviral transduction of male germ-line stem cells (2001)

Male germ-line stem cells are the only cell type in postnatal mammals that have the capability to self-renew and to contribute genes to the next generation. Genetic modification of these cells would provide an opportunity to study the biology of their complex self-renewal and differentiation processes, as well as enable the generation of transgenic animals in a wide range of species. Although retroviral vectors have been used as an efficient method to introduce genes into a variety of cell types, postnatal male germ-line stem cells have seemed refractory to direct infection by these viruses. In addition, expression of genes transduced into several types of stem cells, such as embryonic or hematopoietic, is often attenuated or silenced. We demonstrate here that in vitro retroviral-mediated gene delivery into spermatogonial stem cells of both adult and immature mice results in stable integration and expression of a transgene in 2–20% of stem cells. After transplantation of the transduced stem cells into the testes of infertile recipient mice, approximately 4.5% of progeny from these males are transgenic, and the transgene is transmitted to and expressed in subsequent generations. Therefore, there is no intrinsic barrier to retroviral transduction in this stem cell, and transgene expression is not extinguished after transmission to progeny.
Bridging Ral GTPase to Rho Pathways (1995)

Ra1A and Ra1B are GTPases of unknown function and are activated by proteins, Ra1GDS, that interact with the active form of another GTPase, Ras. To elucidate Ral function, we have searched for proteins interacting with an activated form of Ra1A using the two-hybrid method and a Jurkat cell library. We have identified a partial cDNA encoding a protein, RLIP1, which binds to activated Ra1A and this binding requires an intact effector domain of Ra1A. Biochemical data with purified Ra1A confirm the genetic results. This protein also bears a region of homology with GTPase-activating protein (GAP) domains that are involved in the regulation of GTPases of the Rho family and, indeed, RLIP1 displays a GAP activity acting upon Rac1 and CDC42, but not RhoA. This GAP region is not required for RLIP1 binding to Ra1. The whole cDNA was cloned, and it encodes a 76-kDa polypeptide, RLIP76, which also binds RalA. The Rho pathway is involved in membrane and cytoskeleton modifications after mitogenic stimulation and acts in parallel to and synergistically with the Ras pathway. We propose that these pathways are linked through a cascade composed of Ras --> Ra1GDS --> Ra1 --> RLIP76 --> CDC42/Rac1/Rho, allowing modulation of the Rho pathway by the Ras pathway.
Discovery of Multifold Modified Sialosides as Human CD22/Siglec-2 Ligands with Nanomolar Activity on B-Cells (2014)

Sialic acids are abundant in higher domains of life and lectins recognizing sialosaccharides are heavily involved in the regulation of the human immune system. Modified sialosides are useful tools to explore the functions of those lectins, especially members of the Siglec (sialic acid binding immunoglobulin like lectin) family. Here we report design, synthesis, and affinity evaluation of novel sialoside classes with combined modification at positions 2, 4, and 9 or 2, 3, 4, and 9 of the sialic acid scaffold as human CD22 (human Siglec-2) ligands. They display up to 7.5 × 10(5)-fold increased affinity over αMe Neu5Ac (the minimal Siglec ligand). CD22 is a negative regulating coreceptor of the B-cell receptor (BCR). In vitro experiments with a human B-lymphocyte cell line showed functional blocking of CD22 upon B-cell receptor (BCR) stimulation in the presence of nanomolar concentrations of the novel ligands. The observed increased Ca(2+) response corresponds to enhanced cell activation, providing an opportunity to therapeutically modulate B-lymphocyte responses, e.g., in immune deficiencies and infections.
A Common 8q24 Variant and the Risk of Colon Cancer: A Population-Based Case-Control Study (2008)

Three recent studies identified common variants on 8q24 that confer modestly increased susceptibility to colorectal cancer. Here, we replicate the association in a population-based case-control study of colon cancer, including 561 cases and 721 unrelated controls. The rs6983267 marker was significantly associated with colon cancer risk. Compared with those homozygous for the T allele, the heterozygous and homozygous carriers for the G allele had an age-adjusted odds ratio of 1.39 (95% confidence interval, 1.03-1.88) and 1.68 (95% confidence interval, 1.21-2.33), respectively. An additive model showed strong evidence for a gene-dose response relationship (P(trend) = 0.0022). The association remained statistically significant when restricted to Caucasians only (527 cases and 679 controls; P(trend) = 0.0056). Further adjustment for other known risk factors did not alter the results. Stratified analysis revealed no evidence for effect modification by family history of colorectal cancer, age, or gender. These data replicate the association identified from recent studies, providing additional evidence supporting the rs6983267 genetic polymorphism as a marker predisposing to colon cancer.
Enhancement of clonogenicity of human multiple myeloma by dendritic cells (2006)

Infiltration by dendritic cells (DCs) is a common feature of most human tumors. Prior studies evaluating the interaction of DCs with tumors have focused largely on their immunologic properties (for review see Banchereau, J., and R.M. Steinman. 1998. Nature. 392:245-252). In this study, we show that the clonogenicity of several human tumor cell lines and primary tumor cells from myeloma patients is enhanced by their interactions with DCs. Myeloma cells cultured in the presence of DCs have an altered phenotype with an increased proportion of cells lacking terminal plasma cell differentiation marker CD138. DC-tumor interaction also leads to the up-regulation of B cell lymphoma 6 expression in myeloma cells. Effects of DCs on myeloma cells are inhibited by blockade of the receptor activator of NF-kB (RANK)-RANK ligand and B cell-activating factor-APRIL (a proliferation-inducing ligand)-mediated interactions. Together, these data suggest that tumor-DC interactions may directly impact the biology of human tumors, particularly multiple myeloma, and may be a target for therapeutic intervention.
Protein Dissimilation by Human Salivary-sediment Bacteria (1989)

Proteins of known composition and structural characteristics were incubated (1.0 mg/mL) with re-suspended salivary sediment (2.5% v/v) in a lactate-salt medium with an initial pH of 5.2 for two hr at 37 degrees C. Hydrolysis of the proteins was monitored by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Hydrogen ion, amines, and ammonia were measured by use of a combined pH electrode, high-performance liquid chromatography, and glutamate dehydrogenase, respectively. Of the proteins studied, the caseins alpha s1, beta, and kappa and the histones H1 and H3 were extensively hydrolyzed by the salivary-sediment bacteria. The hydrolysis of these proteins was attributed to their relative lack of tertiary (folded) structure. The only amine detected was the polyamine putrescine arising from the catabolism of arginine following the hydrolysis of the arginine-rich histone H3. None of the other proteins extensively hydrolyzed by salivary sediment, although containing arginyl and lysyl residues, served as substrates for putrescine or cadaverine production. Pre-hydrolysis of the arginine-rich histone H3 and poly-L-arginine with trypsin resulted in a marked increase in putrescine produced, suggesting that the salivary-sediment proteolytic activity was not "trypsin-like". Incubation of salivary-sediment bacteria with the caseins and the histone H3 resulted in an increase in ammonium ion concentration and an associated decrease in hydrogen ion concentration. The increase in ammonium ion concentration not attributed to arginine hydrolysis was correlated with the content of glutaminyl plus asparaginyl residues of the proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
Decreased Protein Expression and Intermittent Recoveries in BiP Levels Result from Cellular Stress during Heterologous Protein Expression in Saccharomyces cerevisiae (2002)

Cells are inherently robust to environmental perturbations and have evolved to recover readily from short-term exposure to heat, pH changes, and nutrient deprivation during times of stress. The stress of unfolded protein accumulation has been implicated previously in low protein yields during heterologous protein expression. Here we describe the dynamics of the response to this stress, termed the unfolded protein response (UPR), during the expression of the single chain antibody 4-4-20 (scFv) in Saccharomyces cerevisiae. Expression of scFv decreased the growth rate of yeast cells whether the scFv was expressed from single-copy plasmids or integrated into the chromosome. However, the growth rates recovered at longer expression times, and surprisingly, the recovery occurred more quickly in the high-copy integration strains. The presence of a functional UPR pathway was necessary for a recovery of normal growth rates. During the growth inhibition, the UPR pathway appeared to be activated, resulting in decreased intracellular scFv levels and intermittent recovery of the chaperone BiP within the endoplasmic reticulum. Intracellular scFv was observed primarily in the endoplasmic reticulum, consistent with activation of the UPR pathway. Although the intracellular scFv levels dropped over the course of the expression, this was not a result of scFv secretion. A functional UPR pathway was necessary for the drop in intracellular scFv, suggesting that the decrease was a direct response of UPR activation. Taken together, these results suggest that control of heterologous gene expression to avoid UPR activation will result in higher production levels.
Algorithmic sequential decision-making in the frequency domain for life threatening ventricular arrhythmias and imitative artefacts: a diagnostic system (1989)

A preliminary study to approach the problem of reliably detecting life threatening ventricular arrhythmias in real time is described. An algorithm (DIAGNOSIS) has been developed in order to classify ECG signal records on the basis of the computation of four simple parameters calculated from a representation in the frequency domain. This algorithm uses a set of rules constituting an operative classification scheme based on the comparison of the parameters with a set of pre-established thresholds. This allows us to differentiate four general categories: ventricular fibrillation-flutter, ventricular rhythms, imitative artefacts and predominant sinus rhythm.
Constructed Wetlands for Rehabilitation and Reuse of Surface Waters in Tropical and Subtropical Areas – First Results from Small-scale Plots Using Vertical Flow Beds (1999)

The application of constructed wetlands is seen to be a valuable way to treat polluted surface waters for rehabilitation of the water body (shallow lakes) and for reuse as irrigation and drinking water. In a first step a construction and operation design was worked out for small-scale plots which have been operated in Europe and at a site in China. The small-scale plots are designed as subsurface flow systems with a downflow and upflow compartment in series. The different layers consist of sand and gravel with a minimum hydraulic conductivity of about 10−4 m/s. Several small-scale plots, planted with different species, have been tested in parallel. During almost one year of operation the monitoring of the systems aimed at: checking the effectiveness of different plant species, variation of loading rates and intervals and variation of recirculation to the system. The results for some relevant parameters (BOD5, NH4-N, N, P) show a high overall efficiency – strongly depending on operation conditions such as feed rate, alternate feeding and resting time. As a result the construction design has been modified for the construction of pilot systems in China. The whole project was carried out within the INCO-DC programme of EC with partners from Germany and China.
The Decorin Sequence SYIRIADTNIT Binds Collagen Type I (2007)

Decorin belongs to the small leucine-rich repeat proteoglycan family, interacts with fibrillar collagens, and regulates the assembly, structure, and biomechanical properties of connective tissues. The decorin-collagen type I-binding region is located in leucine-rich repeats 5-6. Site-directed mutagenesis of this 54-residue-long collagen-binding sequence identifies Arg-207 and Asp-210 in leucine-rich repeat 6 as crucial for the binding to collagen. The synthetic peptide SYIRIADTNIT, which includes Arg-207 and Asp-210, inhibits the binding of full-length recombinant decorin to collagen in vitro. These collagen-binding amino acids are exposed on the exterior of the beta-sheet-loop structure of the leucine-rich repeat. This resembles the location of interacting residues in other leucine-rich repeat proteins.
Fabrication of Monodisperse Gel Shells and Functional Microgels in Microfluidic Devices (2007)

Mikrogelstrukturen wie kugelförmige Mikrogelhüllen (Bild oben links) und kugelförmige Mikrogelpartikel, die Quantenpunkte, magnetische Nanopartikel und Polymermikropartikel enthalten (übrige Bilder), wurden mit einer Kapillar-Mikrofluidik-Technik hergestellt. Das Volumen der Partikel nimmt bei Temperaturänderungen ab oder zu, was z. B. für Anwendungen im Wirkstofftransport genutzt werden kann. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2007/z604206_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
In vivo pathway of thermal hyperalgesia by intrathecal administration of α,β‐methylene ATP in mouse spinal cord: Involvement of the glutamate‐NMDA receptor system (1999)

1. The aim of the present study is to characterize the role of the P2X receptor in spinal nociceptive processing in vivo. We investigated the mechanisms of the P2X receptor agonist alpha,beta-methylene ATP (alpha,betameATP)-induced modulation of acute nociceptive signalling in mouse spinal cord. 2. Intrathecal administration of alpha,betameATP produced a significant and dose-dependent thermal hyperalgesic response. This response was completely blocked by intrathecal pretreatment with the non-selective P2 receptor antagonist, pyridoxal-phosphate-6-azophenyl-2',4'-disulphonate (PPADS) and the selective P2X1, P2X3 and P2X2-3 receptor antagonist, 2',3'-O-(2,4,6-trinitrophenyl)adenosine 5'-triphosphate (TNP-ATP). Pretreatment with alpha,betameATP 15, 30 and 60 min prior to administration of a second dose of alpha,betameATP diminished the alpha,betameATP-induced thermal hyperalgesia. 3. A potent agonist for the P2X1 receptor, beta,gamma-methylene-L-ATP, did not show the hyperalgesic response, indicating that the P2X1 receptor is not involved in the spinal nociceptive pathway. 4. In fura-2 experiments using mouse dorsal root ganglion (DRG) neurons, alpha,betameATP (100 microM) increased intracellular Ca2+ ([Ca2+]i). This was not produced by a second application of alpha,betameATP. The same DRG neurons also showed a marked [Ca2+]i increase in response to capsaicin (3 microM). 5. Intrathecal pretreatment with the Ca2+-dependent exocytosis inhibitor, botulinum neurotoxin B, abolished the thermal hyperalgesia by alpha,betameATP. Furthermore, thermal hyperalgesia was significantly inhibited by the N-methyl-D-aspartate (NMDA) receptor antagonists, 2-amino-5-phosphonopentanoate (APV), dizocilpine and ifenprodil. 6. These findings suggest that alpha,betameATP-induced thermal hyperalgesia may be mediated by the spinal P2X3 receptor subtype that causes unresponsiveness by repetitive agonist applications, and that alpha,betameATP (perhaps through P2X3 receptors) may evoke spinal glutamate release which, in turn, leads to the generation of thermal hyperalgesia via activation of NMDA receptors.
Improved Consistent Sampling, Weighted Minhash and L1 Sketching (2010)

We propose a new Consistent Weighted Sampling method, where the probability of drawing identical samples for a pair of inputs is equal to their Jaccard similarity. Our method takes deterministic constant time per non-zero weight, improving on the best previous approach which takes expected constant time. The samples can be used as Weighted Minhash for efficient retrieval and compression (sketching) under Jaccard or L1 metric. A method is presented for using simple data statistics to reduce the running time of hash computation by two orders of magnitude. We compare our method with the random projection method and show that it has better characteristics for retrieval under L1. We present a novel method of mapping hashes to short bit-strings, apply it to Weighted Minhash, and achieve more accurate distance estimates from sketches than existing methods, as long as the inputs are sufficiently distinct. We show how to choose the optimal number of bits per hash for sketching, and demonstrate experimental results which agree with the theoretical analysis.