gebhart/patrepeval huggingface dataset:
Identification of Amino Acid Residues in the α, β, and γ Subunits of the Epithelial Sodium Channel (ENaC) Involved in Amiloride Block and Ion Permeation (1997)

The amiloride-sensitive epithelial Na channel (ENaC) is a heteromultimeric channel made of three alpha beta gamma subunits. The structures involved in the ion permeation pathway have only been partially identified, and the respective contributions of each subunit in the formation of the conduction pore has not yet been established. Using a site-directed mutagenesis approach, we have identified in a short segment preceding the second membrane-spanning domain (the pre-M2 segment) amino acid residues involved in ion permeation and critical for channel block by amiloride. Cys substitutions of Gly residues in beta and gamma subunits at position beta G525 and gamma G537 increased the apparent inhibitory constant (Ki) for amiloride by > 1,000-fold and decreased channel unitary current without affecting ion selectivity. The corresponding mutation S583 to C in the alpha subunit increased amiloride Ki by 20-fold, without changing channel conducting properties. Coexpression of these mutated alpha beta gamma subunits resulted in a non-conducting channel expressed at the cell surface. Finally, these Cys substitutions increased channel affinity for block by external Zn2+ ions, in particular the alpha S583C mutant showing a Ki for Zn2+ of 29 microM. Mutations of residues alpha W582L, or beta G522D also increased amiloride Ki, the later mutation generating a Ca2+ blocking site located 15% within the membrane electric field. These experiments provide strong evidence that alpha beta gamma ENaCs are pore-forming subunits involved in ion permeation through the channel. The pre-M2 segment of alpha beta gamma subunits may form a pore loop structure at the extracellular face of the channel, where amiloride binds within the channel lumen. We propose that amiloride interacts with Na+ ions at an external Na+ binding site preventing ion permeation through the channel pore.
Real-time incremental visualization of dynamic ultrasound volumes using parallel BSP trees (1996)

We present a method for producing real-time volume visualizations of continuously captured, arbitrarily-oriented 2D arrays (slices) of data. Our system constructs a 3D representation on-the-fly from incoming 2D ultrasound slices by modeling and rendering the slices as planar polygons with translucent surface textures. We use binary space partition (BSP) tree data structures to provide non-intersecting, visibility-ordered primitives for accurate opacity accumulation images. New in our system is a method of using parallel, time-shifted BSP trees to efficiently manage the continuously captured ultrasound data and to decrease the variability in image generation time between output frames. This technique is employed in a functioning real-time augmented reality system that a physician has used to examine human patients prior to breast biopsy procedures. We expect the technique can be used for real-time visualization of any 2D data being collected from a tracked sensor moving along an arbitrary path.
Emotions and Speech: Some Acoustical Correlates (1972)

This paper describes some further attempts to identify and measure those parameters in the speech signal that reflect the emotional state of a speaker. High-quality recordings were obtained of professional “method” actors reading the dialogue of a short scenario specifically written to contain various emotional situations. Excerpted portions of the recordings were subjected to both quantitative and qualitative analyses. A comparison was also made of recordings from a real-life situation, in which the emotions of a speaker were clearly defined, with recordings from an actor who simulated the same situation. Anger, fear, and sorrow situations tended to produce characteristic differences in contour of fundamental frequency, average speech spectrum, temporal characteristics, precision of articulation, and waveform regularity of successive glottal pulses. Attributes for a given emotional situation were not always consistent from one speaker to another.
Antisense delivery and protein knockdown within the intact central nervous system (2006)

The ability to down regulate the expression of a specific protein within the intact central nervous system (CNS) is highly desirable from both a research and therapeutic perspective. Antisense has the potential to do this. However, problems of invasive antisense delivery methods and short half life of remain problematic. We overcome this by using Pluronic gel to provide a sustained delivery antisense oligodeoxynucleotides (ODN's) to the intact central nervous system and achieving rapid penetration throughout the spinal cord in 2-3 hours and significant knockdown of our target protein connexin 43 (Cx43) in 4-8 hours (recovering at 48-72 hours). Interestingly CY3-siRNA probes could not be detected penetrating the intact CNS and no knockdown the Cx43 was found. This approach with conventional ODNs could provide a faster and cheaper alternative to knockout mice in the investigation of the functions of specific proteins within the CNS and may also have therapeutic implications for drug discovery and development.
An important role of phosphatidic acid in ABA signaling during germination in Arabidopsis thaliana (2005)

Phosphatidic acid (PA) functions as a lipid signaling molecule in plants. Physiological analysis showed that PA triggers early signal transduction events that lead to responses to abscisic acid (ABA) during seed germination. We measured PA production during seed germination and found increased PA levels during early germination. To investigate the role of PA during seed germination, we focused on the PA catabolic enzyme lipid phosphate phosphatase (LPP). LPP catalyzes the conversion of PA to diacylglycerol (DAG). There are 4 LPP genes in the Arabidopsis genome. Among them, AtLPP2 and AtLPP3 are expressed during seed germination. Two AtLPP2 T-DNA insertional mutants (lpp2-1 and lpp2-2) showed hypersensitivity to ABA and significant PA accumulation during germination. Furthermore, double-mutant analysis showed that ABA-insensitive 4 (ABI4) is epistatic to AtLPP2 but ABA-insensitive 3 (ABI3) is not. These results suggest that PA is involved in ABA signaling and that AtLPP2 functions as a negative regulator upstream of ABI4, which encodes an AP2-type transcription factor, in ABA signaling during germination.
Lipopolysaccharide-treated RAW 264.7 cells produce a mediator that inhibits lipoprotein lipase in 3T3-L1 cells. (1985)

RAW 264.7 cells upon stimulation with lipopolysaccharide secrete a protein mediator(s) that suppresses lipoprotein lipase activity in differentiated 3T3-L1 cells. The mediator(s), which is absent from unstimulated culture supernatants, is nondialyzable and thermolabile. Preliminary characterization suggests that this mediator(s) may be the same as that previously found in medium from lipopolysaccharide-treated thioglycollate-elicited mouse peritoneal macrophage cultures.
Mate Preferences Among Young People: US and China. (2016)

Mate preferences expressed by college students may reflect both the society’s traditional beliefs and the changing nature of cultural values. The current study compared American and Chinese college students’ responses on mate preference choices (N=545). Results show both similarities and differences in mate preferences between these two groups. Out of 18 characteristics, the two groups were similar in eight and differed in ten; and out of 13 rank order ratings, the two groups differed significantly on ten items. Overall, these findings suggest that while there is evidence of convergence in American and Chinese college students’ mate preference values, reflecting the effect of globalization, there are also significant differences in their choices, reflecting social and cultural values of each individual country
Highly Enantioselective Azadiene Diels−Alder Reactions Catalyzed by Chiral N-Heterocyclic Carbenes (2006)

Highly enantioselective, N-heterocyclic carbene (NHC)-catalyzed aza-Diels-Alder reactions are described. A novel chiral triazolium salt based on the cis-1,2-aminoindanol platform serves as an efficient precatalyst for the NHC-catalyzed redox generation of enolate dienophiles that undergo LUMOdiene-controlled Diels-Alder reactions with N-sulfonyl-alpha,beta-unsaturated imines in good yields and with exceptional diastereo- and enantioselectivities (>99% ee). In contrast to uncatalyzed variants, this organocatalytic process proceeds at room temperature without stoichiometric reagents, producing synthetically valuable, enantiomerically pure cis-3,4-disubstituted dihydropyridinone products.
Alloreactive cloned T cell lines. I. Interactions between cloned amplifier and cytolytic T cell lines. (1980)

Several T cell clones have been derived by limiting dilution of secondary mixed leukocyte culture cells stimulated by H-2- and M locus (Mls)-disparate spleen cells. When examined for the expression of cytolytic activity and the ability to proliferate, these cell clones can be classified into two major categories. One type of cell is noncytolytic; when cultured with irradiated spleen cells, such clones proliferate in response to Mls determinants. Some, but not all, of these clones express Lyt-1 alloantigens. The other type of cell is cytolytic; these clones do not proliferate when cultured with irradiated allogeneic spleen cells unless supernatant fluid (SF) is added. These cytolytic clones express Lyt-2 alloantigens. Some cytolytic clones are specific for H-2Kd and others for H-2Dd alloantigens. Still other cytolytic cell clones exhibit cross-reactive lysis of different H-2-bearing tumor and Con A blast target cells. Noncytolytic T cell clones, when stimulated by Mls antigens, were examined for their ability to promote proliferation of cytolytic T cell clones. All of the noncytolytic cell clones tested were able to promote proliferation of cytolytic cell clones with the concomitant expression of cytolytic activity directed toward the original stimulating alloantigen (H-2d). Amplification of cytolytic activity was dependent upon stimulation of the noncytolytic amplifier T cell clones by Mls antigens. Specific alloantigen (signal 1), however, was not required for proliferation of the cytolytic cell clones; the amplifying signal (signal 2), delivered by the amplifier cell clones, was sufficient alone to promote proliferation of the cytolytic cell clones. Whereas proliferation of the amplifier cells was radiosensitive, the generation of the soluble amplifying signal was radioresistant. Amplification of cytolytic activity was observed when either amplifier cells were physically separated from responding cytolytic cells in Marbrook cultures or when cytolytic cells were cultured with SF collected from amplifier cell cultures. The amplifying factors were neither antigen specific nor strain specific and could be produced by Lyt-1- cells. The availability of cloned T cell lines that retain specific biologic function offers unique opportunities to characterize cell surface proteins and cell-cell interactions.
Warkitting: The Drive-by Subversion of Wireless Home Routers (2006)

ABSTRACT In this article we introduce the notion of warkitting as the drive-by subversion of wireless home routers through unauthorized access by mobile WiFi clients. We describe how such attacks can be performed, evaluate the vulnerability of currently deployed wireless routers based on experimental data, and examine the impact of these attacks on Internet fraud. Our analysis shows that it is possible in practice to carry out warkitting attacks with low-cost equipment widely available today and that the volume of credential theft possible through warkitting exceeds current estimates of credential theft due to phishing. We discuss how to detect a warkitting attack in progress and show how to analyze warkitted routers for evidence linking it to the attackers.
Cytosolic Delivery of Membrane-Impermeable Molecules in Dendritic Cells Using pH-Responsive Core−Shell Nanoparticles (2007)

Polycations that absorb protons in response to the acidification of endosomes can theoretically disrupt these vesicles via the "proton sponge" effect. To exploit this mechanism, we created nanoparticles with a segregated core-shell structure for efficient, noncytotoxic intracellular drug delivery. Cross-linked polymer nanoparticles were synthesized with a pH-responsive core and hydrophilic charged shell designed to disrupt endosomes and mediate drug/cell binding, respectively. By sequestering the relatively hydrophobic pH-responsive core component within a more hydrophilic pH-insensitive shell, nontoxic delivery of small molecules and proteins to the cytosol was achieved in dendritic cells, a key cell type of interest in the context of vaccines and immunotherapy.
Cimetidine for Prevention and Treatment of Gastroduodenal Mucosal Lesions in Patients in an Intensive Care Unit (1985)

The efficacy of cimetidine in the prevention and treatment of stress-induced gastroduodenal lesions was evaluated in a randomized, double-blind, placebo-controlled study in which serial endoscopy was used to examine patients without clinical evidence of bleeding who were admitted to a medical intensive care unit. Endoscopy showed that 14 of 21 patients treated with cimetidine, compared with 5 of 18 patients treated with placebo, had normal or improved gastroduodenal mucosa (p less than 0.05). Endoscopic signs of bleeding cleared or did not develop in 20 patients treated with cimetidine and in 11 patients treated with placebo (p less than 0.01). Significantly fewer blood transfusions were given to patients with endoscopic signs of bleeding in the cimetidine-treated group (0.5 +/- 0.3 [SE] units) than in placebo-treated patients (4.5 +/- 1.5 units; p less than 0.05). The mortality rate was not statistically different between treatment groups. By preventing established gastroduodenal stress lesions from progressing in severity, cimetidine diminished both bleeding and the need for transfusions.
Robust Tracking for Real-Time Dense RGB-D Mapping with Kintinuous (2012)

Abstract—This paper describes extensions to the Kintinu-ous [1] algorithm for spatially extended KinectFusion, incor-porating the following additions: (i) the integration of multiple 6DOF camera odometry estimation methods for robust track-ing; (ii) a novel GPU-based implementation of an existing dense RGB-D visual odometry algorithm; (iii) advanced fused real-time surface coloring. These extensions are validated with ex-tensive experimental results, both quantitative and qualitative, demonstrating the ability to build dense fully colored models of spatially extended environments for robotics and virtual reality applications while remaining robust against scenes with challenging sets of geometric and visual features. I.
Comparative inhibition of chloramphenicol acetyltransferase gene expression by antisense oligonucleotide analogues having alkyl phosphotriester, methylphosphonate and phosphorothioate linkages (1987)

Several classes of oligonucleotide antisense compounds of sequence complementary to the start of the mRNA coding sequence for chloramphenicol acetyl transferase (CAT), including methylphosphonate, alkyltriester, and phosphorothioate analogues of DNA, have been compared to "normal" phosphodiester oligonucleotides for their ability to inhibit expression of plasmid-directed CAT gene activity in CV-1 cells. CAT gene expression was inhibited when transfection with plasmid DNA containing the gene for CAT coupled to simian virus 40 regulatory sequences (pSV2CAT) or the human immunodeficiency virus enhancer (pHIVCAT) was carried out in the presence of 30 microM concentrations of analogue. For the oligo-methylphosphonate analogue, inhibition was dependent on both oligomer concentration and chain length. Analogues with phosphodiester linkages that alternated with either methylphosphonate, ethyl phosphotriester, or isopropyl phosphotriester linkages were less effective inhibitors, in that order. The phosphorothioate analogue was about two-times more potent than the oligo-methylphosphonate, which was in turn approximately twice as potent as the normal oligonucleotide.
Synthesis of 6-Substituted 9-Benzyl-8-hydroxypurines with Potential Interferon-Inducing Activity (2003)

Various 6-substituted 9-benzyl-8-hydroxypurines were synthesized in order to investigate the structure-activity relationship at the 6-position of 9-benzyl-8-hydroxyadenine (1), which is a lead compound for the screening of interferon (IFN)-inducing activity. 6-Unsubstituted, mercapto-, methylthio- and hydroxy-9-benzyl-8-hydroxypurines (2-5) were prepared from 5-amino-1-benzyl-4-cyano-2-hydroxyimidazole (9). Synthesis of a 6-methoxy analog (6) was conducted from 5-amino-4-benzylamino-6-chloropyrimidine (13). 6-Alkylamino and acylaminopurines (7 and 8) were also prepared by alkylation and acylation of 1, respectively. Since these compounds (2-8) indicated no activity, it was found that a free amino group of 1 is required for the expression of IFN-inducing activity.
Types of human intrafusal muscle fibers (1979)

The histochemical and fine structural profiles of human intrafusal muscle fibers were studied. Spindles were located in freshly frozen specimens taken from biopsied normal external intercostal muscles, and periodic 10- and 50-mum-thick cross sections were processed alternately for enzyme histochemical and electron microscopic examination. Nuclear bag fibers were of two types, bag1 and bag2, histochemically, and they displayed two distinct types of ultrastructure. Nuclear chain fibers were histochemically and ultrastructurally homogeneous. Regional differences in enzymatic staining and ultrastructure occurred along individual intrafusal fibers. Human bag1 and bag2 fibers appear to be analogous to the two types of nuclear bag fiber identified in animal spindles and are considered to have different roles in spindle function. The presence of three types of intrafusal fibers should be taken into account when studying spindle abnormalities in human neuromuscular disorders.
임상연구 : 생리혈에 존재하는 탈락된 자궁내막조직의 체외배양 시 나타나는 변화와 특성에 관한 연구 (2000)

목적: 자궁내막증의 체외 모형에 적합한 생리혈 내의 탈락된 자궁내막조직을 체외배양하면서 나타나는 변화와 특성에 관하여 살펴보고자 하였다. 연구 방법: 정상적인 생리주기를 갖는 10명의 여성으로부터 Wallace catheter를 이용하여 생리혈을 채취하였다. 원심분리 방법으로 생리혈을 세척한 후, 수획한 탈락된 자궁내막조직은 10% fetal bovine serum이 첨가된 Ham's F-10배양액에서 7일 동안 배양하였다. 배양한 자궁내막조직 세포의 특성을 확인하기 위해 cytokeratin과 vimentin에 대한 항체를 이용하여 면역조직학적 염색을 실시하였다. 결과: 생리혈의 평균 양은 0.7ml이였으며, 세척 후 혈액세포와 탈락된 자궁내막조직이 포함된 침전부위의 평균 양은 0.3ml 이였다. 체외배양 한 자궁내막조직의 15% 정도가 배양접시 표면에 부착된 후 증식하였다. 일차적으로 상피세포와 섬유아세포가 배양접시의 표면에 부착하여 증식하였으며, 기질세포들은 상피세포 위에서 증식하였다. 면역조직학적 염색에서 상피세포, 기질세포, 섬유아세포 등이 확인되었으며, 공촛점주사 현미경을 이용한 체외배양된 탈락된 자궁내막조직의 3차원적인 구조 관찰에서 외부에는 상피세포가, 내부에는 기질세포가 존재함을 확인하였다. 결론: 생리혈 내의 탈락된 자궁내막조직의 체외배양 시 상피세포와 기질세포가 밀접한 연관성을 유지하면서 증식하는 것을 관찰하였으며, 이러한 체외배양 체계는 자궁내막증의 병인에 대한 연구에 유용하게 적용될 수 있는 체외 모형으로 사료된다.
Chemical Biology of Lysine Demethylases (2011)

Abnormal levels of DNA methylation and/or histone modifications are observed in patients with a wide variety of chronic diseases. Methylation of lysines within histone tails is a key modification that contributes to increased gene expression or repression depending on the specific residue and degree of methylation, which is in turn controlled by the interplay of lysine methyl transferases and demethylases. Drugs that target these and other enzymes controlling chromatin modifications can modulate the expression of clusters of genes, potentially offering higher therapeutic efficacy than classical agents acting on downstream biochemical pathways that are susceptible to degeneracy. Lysine demethylases, first discovered in 2004, are the subject of increasing interest as therapeutic targets. This review provides an overview of recent findings implicating lysine demethylases in a range of therapeutic areas including oncology, immunoinflammation, metabolic disorders, neuroscience, virology and regenerative medicine, together with a summary of recent advances in structural biology and small molecule inhibitor discovery, supporting the tractability of the protein family for the development of selective druglike inhibitors.
Activation of RAW264.7 Macrophages by Bacterial DNA and Lipopolysaccharide Increases Cell Surface DNA Binding and Internalization (2004)

Bacterial DNA containing unmethylated CpG motifs is a pathogen-associated molecular pattern (PAMP) that interacts with host immune cells via a toll-like receptor (TLR) to induce immune responses. DNA binding and internalization into cells is independent of TLR expression, receptor-mediated, and required for cell activation. The objective of this study was to determine whether exposure of immune cells to bacterial DNA affects DNA binding and internalization. Treatment of RAW264.7 cells with CpG oligodeoxynucleotide (ODN) for both 18 and 42 h resulted in a significant increase in DNA binding, whereas non-CpG ODN had no effect on DNA binding. Enhanced DNA binding was non-sequence-specific, inhibited by unlabeled DNA, showed saturation, was consistent with increased cell surface DNA receptors, and resulted in enhanced internalization of DNA. Treatment with Escherichia coli DNA or lipopolysaccharide (LPS) also resulted in a significant increase in DNA binding, but treatment with interleukin-1alpha, tumor necrosis factor-alpha, or phorbol 12-myristate 13-acetate had no effect on DNA binding. Soluble factors produced in response to treatment with CpG ODN or LPS did not affect DNA binding. These studies demonstrate that one consequence of activating the host innate immune response by bacterial infection is enhanced binding and internalization of DNA. During this period of increased DNA internalization, RAW264.7 cells were hypo-responsive to continued stimulation by CpG ODN, as assessed by tumor necrosis factor-alpha activity. We speculate the biological significance of increasing DNA binding and internalization following interaction with bacterial PAMPs may provide a mechanism to limit an ongoing immune inflammatory response by enhancing clearance of bacterial DNA from the extracellular environment.
Transition metal-mediated cycloaddition reactions of alkynes in organic synthesis (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTransition metal-mediated cycloaddition reactions of alkynes in organic synthesisNeil E. SchoreCite this: Chem. Rev. 1988, 88, 7, 1081–1119Publication Date (Print):November 1, 1988Publication History Published online1 May 2002Published inissue 1 November 1988https://pubs.acs.org/doi/10.1021/cr00089a006https://doi.org/10.1021/cr00089a006research-articleACS PublicationsRequest reuse permissionsArticle Views4779Altmetric-Citations888LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts