gebhart/patrepeval huggingface dataset:
Genetically encoded fluorescent sensors of membrane potential (2008)

Imaging activity of neurons in intact brain tissue was conceived several decades ago and, after many years of development, voltage-sensitive dyes now offer the highest spatial and temporal resolution for imaging neuronal functions in the living brain. Further progress in this field is expected from the emergent development of genetically encoded fluorescent sensors of membrane potential. These fluorescent protein (FP) voltage sensors overcome the drawbacks of organic voltage sensitive dyes such as non-specificity of cell staining and the low accessibility of the dye to some cell types. In a transgenic animal, a genetically encoded sensor could in principle be expressed specifically in any cell type and would have the advantage of staining only the cell population determined by the specificity of the promoter used to drive expression. Here we critically review the current status of these developments.
Increased Nox1 and hydrogen peroxide in prostate cancer (2004)

The results illustrate that human prostate cancer frequently show both increased H(2)O(2) and Nox1, and that in an animal model system increased Nox1/H(2)O(2) correlates with increased tumorigenicity.
First noise and teleseismic recordings on a new ocean bottom seismometer capsule (1984)

Abstract An ocean bottom seismometer capsule designed specifically for the long-term monitoring of teleseisms has been designed and tested. An efficient triggering algorithm consisting of multiple high-pass filters effectively discriminates between locally generated earthquakes and noise, and teleseisms. During a 1-month deep ocean deployment west of the Santa Barbara Channel, a magnitude 5.9 earthquake at a distance of 76° was recorded, in addition to a number of regional events in the 300- to 450-km range. Noise levels were monitored by automatically recording data at intervals. Vertical noise levels were approximately 20 times greater than those recorded at quiet land sites, and horizontal noise levels were about 5 times greater than that. The instrument consists of a microprocessor-controlled data logging system in three parallel pressure tubes, joined by a common baseplate. Wires between the three tubes are contained within the baseplate. There are no external connectors which are exposed to sea water, allowing the deployment time to extend to 1 yr. Data are recorded on two Braemar cassette recorders with a capacity of 15 Mbits each, for a continuous recording time of approximately 43 hr. This is adequate for the expected data acquisition rate, given the robustness of the triggering algorithm. The sensors are Mark Products L4-C 1-Hz seismometers with useful extended low-frequency response to about 30-sec periods for earthquake signals. The three components are leveled with a mechanical gimbal arrangement. The instrument has been successfully deployed 3 times in the Santa Barbara Channel and deep ocean, and should prove extremely useful for extending teleseismic studies into the ocean.
Radiation Therapy for Early-Stage Breast Cancer after Breast-Conserving Surgery (2008)

A 45-year-old woman is found to have invasive breast cancer and undergoes lumpectomy with dissection of the sentinel lymph nodes. After 6 months of adjuvant chemotherapy, radiation therapy is recommended. Radiation therapy has been shown to reduce the risk of local recurrence after breast-conserving surgery. The most serious complications include lung and heart injury and secondary cancers.
A Urokinase-type Plasminogen Activator-inhibiting Cyclic Peptide with an Unusual P2 Residue and an Extended Protease Binding Surface Demonstrates New Modalities for Enzyme Inhibition (2005)

To find new principles for inhibiting serine proteases, we screened phage-displayed random peptide repertoires with urokinase-type plasminogen activator (uPA) as the target. The most frequent of the isolated phage clones contained the disulfide bridge-constrained sequence CSWRGLENHRMC, which we designated upain-1. When expressed recombinantly with a protein fusion partner, upain-1 inhibited the enzymatic activity of uPA competitively with a temperature and pH-dependent K(i), which at 25 degrees C and pH 7.4 was approximately 500 nm. At the same conditions, the equilibrium dissociation constant K(D), monitored by displacement of p-aminobenzamidine from the specificity pocket of uPA, was approximately 400 nm. By an inhibitory screen against other serine proteases, including trypsin, upain-1 was found to be highly selective for uPA. The cyclical structure of upain-1 was indispensable for uPA binding. Alanine-scanning mutagenesis identified Arg(4) of upain-1 as the P(1) residue and indicated an extended binding interaction including the specificity pocket and the 37-, 60-, and 97-loops of uPA and the P(1), P(2), P(3)', P(4)', and the P(5)' residues of upain-1. Substitution with alanine of the P(2) residue, Trp(3), converted upain-1 into a distinct, although poor, uPA substrate. Upain-1 represents a new type of uPA inhibitor that achieves selectivity by targeting uPA-specific surface loops. Most likely, the inhibitory activity depends on its cyclical structure and the unusual P(2) residue preventing the scissile bond from assuming a tetrahedral geometry and thus from undergoing hydrolysis. Peptide-derived inhibitors such as upain-1 may provide novel mechanistic information about enzyme-inhibitor interactions and alternative methodologies for designing effective protease inhibitors.
An Efficient Network-on-Chip Architecture Based on the Fat-Tree (FT) Topology (2006)

A novel approach for an efficient network-on-chip using a modified Fat Tree is presented. Contention is eliminated and latency is reduced through an improved topology and router architecture. The adopted topology increases performance without a substantial increase in the routing cost. This is achieved by using an improved buffer-less, paremeterizable router architecture. The proposed router architecture is simple to implement yet can achieve the required packet collision avoidance. Simulation results that show the level of performance achieved by both the topology and the router architecture are presented. A throughput of more than 90% is achieved way above the 40-50% usually seen in other networks on chips.
Inhibition of nuclear protein import by nonhydrolyzable analogues of GTP and identification of the small GTPase Ran/TC4 as an essential transport factor [published erratum appears in J Cell Biol 1994 Jan;124(1-2):217] (1993)

We have investigated a possible involvement of GTPases in nuclear protein import using an in vitro transport system involving digitonin-permeabilized cells supplemented with exogenous cytosol. Transport in this system was measured with a novel ELISA-based assay that allows rapid quantitative analysis. GTP gamma S and other nonhydrolyzable analogues of GTP were found to rapidly inhibit the rate of in vitro nuclear import. Transport inhibition by GTP gamma S was dependent on the concentrations of permeabilized cells and cytosol, and was strongly enhanced by a cytosolic factor(s). The predominant cytosolic component responsible for this inhibition was found in a 20-30-kD fraction in molecular sieving chromatography. Furthermore, a component(s) of this 20-30-kD fraction was itself required for efficient nuclear import. Biochemical complementation with bacterially expressed protein demonstrated that this essential GTP gamma S-sensitive transport factor was Ran/TC4, a previously described GTPase of the Ras superfamily found in both nucleus and cytoplasm. Ran/TC4 and its guanine nucleotide release protein RCC1 have previously been implicated in DNA replication, cell cycle checkpoint control, and RNA synthesis, processing and export. Our results suggest that Ran/TC4 serves to integrate nuclear protein import with these other nuclear activities.
Ion channel agonists: expectations for therapy (1991)

Journal Article Ion channel agonists: expectations for therapy Get access E. Carmeliet E. Carmeliet Laboratory of Physiology, University of LeuvenCampus Gasthuisberg, Herestraat, 49, 3000 Leuven, Belgium Correspondence: Dr E. Carmeliet, Laboratory of Physiology, University of Leuven, Campus Gasthuisberg, Herestraat, 49, 3000 Leuven, Belgium Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal, Volume 12, Issue suppl_F, December 1991, Pages 30–37, https://doi.org/10.1093/eurheartj/12.suppl_F.30 Published: 01 December 1991
Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study (2009)

Remote IPC reduces ischemic chest discomfort during PCI, attenuates procedure-related cTnI release, and appears to reduce subsequent cardiovascular events.
Effect of long‐term l‐dopa administration on striatal extracellular dopamine release (1991)

When L-dopa was administered acutely to rats, the increase in the extracellular level of dopamine in the corpus striatum was attenuated by 43% in animals that had received L-dopa daily for 60 days as compared with animals receiving placebo. These findings indicate that chronic treatment with L-dopa impairs striatal dopamine formation or release.
Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts (1985)

We report results of a pilot study designed to evaluate the effects of in vitro depletion of T lymphocytes from donor marrow in patients receiving HLA-identical marrow grafts for treatment of hematologic malignancies. Twenty patients aged 31 to 50 years were prepared for transplantation with cyclophosphamide (120 mg/kg) and fractionated total body irradiation (12.0 or 15.75 Gy). All received cyclosporine after grafting. The donor marrows were treated with a mixture of eight murine monoclonal antibodies and rabbit serum complement in a manner that achieved a 2- to 3-log depletion of T cells in most patients. Initial engraftment occurred promptly in 19 of the patients, and only three had clinically significant acute graft-versus-host disease. Depletion of donor T cells, however, was associated with an increased incidence of graft failure, which occurred as late as 244 days after transplantation. Graft failure was transient in one patient but apparently was irreversible in seven others. Three of the seven patients had cytogenetic but not morphological evidence of leukemic relapse at the time of graft failure. All seven patients with irreversible graft failure have died, six after receiving second bone marrow transplants. Seven of the eight cases of graft failure occurred among the 11 patients prepared for transplantation with 12.0 Gy of total-body irradiation, and only one occurred among the nine patients with advanced malignancies who received 15.75 Gy of total-body irradiation. This association with irradiation dose suggests that host factors were partly responsible for the graft failures. Because graft failure seldom occurs in irradiated recipients of unmodified HLA-identical allogeneic marrow transplants, it appears that T cells in the donor marrow may serve a beneficial function in helping to maintain sustained engraftment possibly by eliminating host cells that can cause graft failure. Optimal application of in vitro manipulation of donor marrow as a method for preventing graft-versus-host disease will require more effective immunosuppression of the recipient in order to assure sustained engraftment and function of donor stem cells.
Comparative hybrid arrest by tandem antisense oligodeoxyribonucleotides or oligodeoxyribonucleoside methylpbosphonates in a cell-free system (1988)

Antisense oligonucleotides containing either anionic diester or neutral methylphosphonate internucleoside linkages were prepared by automated synthesis, and were compared for their ability to arrest translation of human dihydrofolate reductase (DHFR) mRNA in a nuclease treated rabbit reticulocyte lysate. In the case of oligodeoxyribonucleotides, tandem targeting of three 14-mers resulted in synergistic and complete selective inhibition of DHFR synthesis at a total oligomer concentration of 25 microM. Hybrid arrest by three or six tandem oligodeoxyribonucleoside methylphosphonates was dramatically less effective. This difference does not result from preferential recognition of hybrids involving oligodeoxyribonucleotides by endogenous RNaseH activity. A ribonuclease protection assay demonstrated that antisense oligodeoxyribonucleoside methylphosphonates bind selectively to target RNA sequences, but with 275 fold lower affinity than the corresponding oligodeoxyribonucleotides. This low binding affinity results in poor arrest of translation, and may be related to the stereochemistry of the methylphosphonate linkage.
과학수업 분석도구를 활용한 수업분석 프로그램이예비유아교사의 과학교수효능감에 미치는 영향 (2014)

본 연구는 과학수업 분석도구를 활용한 수업분석 프로그램이 예비유아교사의 과학교수효능감에 긍정적 영향을 끼치는지, 그 긍정적 영향의 구체적인 내용은 무엇인지를 심층적으로 알아보고자 하는데 목적이 있다. 이를 위해 본 연구자가 직접 개발한 과학수업 계획(안)과 실행으로 구성된 분석도구를 활용하여 수업분석 프로그램을 한 학기동안 적용하였으며 과학교수효능감 자료와 수업분석에 대한 심층면담과 저널쓰기 자료를 수집하여 분석하였다. 연구결과 과학수업 분석도구를 활용한 수업분석 프로그램은 예비유아교사의 과학교수효능감에 긍정적인 영향을 끼쳤으며 그 구체적인 내용으로 계획안 작성에 대한 인식 변화, 계획안 구성요소에 대한 재인식, 교육과정과 계획안의 관련성 이해, 수업일관성 경험, 수업에 대한 자신감이 계획(안) 분석과정에서 나타났으며, 교사의 수업전문성에 대한 인식, 과학교수방법에 대한 이해, 유아의 발달적 특성에 대한 관심, 과학수업 자료 및 매체의 중요성 인식, 과학수업에 대한 이해와 자신감이 수업실행 분석과정에서 나타났다. 예비유아교사의 과학교수효능감 증진을 위하여 과학수업 분석도구를 활용한 보다 체계적이고 구체적인 수업분석 경험이 효과적인 교사교육내용 및 방법이 될 수 있음을 시사하였다.
Chemical‐Mechanical Polishing in Semidirect Contact Mode (1995)

In a typical chemical‐mechanical polishing (CMP) process for interlevel dielectric planarization, the oxide removal rate is strongly dependent on the parameters such as applied load, relative speed, and pad surface properties. However, the experimental results presented in this work show that by maintaining a thin fluid film between the pad and the wafer and thereby reducing the role of the asperities in the pad, the oxide removal rate can be made independent of these polishing parameters. In this semidirect contact mode, the CMP process, carried out on 2 in. wafers, resulted in a uniform polish rate across the wafer, high run‐to‐run reproducibility, high selectivity between materials of differing chemical properties, and eliminated the need for pad surface conditioning and in situ end‐point determination equipment.
Peptides Derived from the C2 Domain of Protein Kinase Cϵ (ϵPKC) Modulate ϵPKC Activity and Identify Potential Protein-Protein Interaction Surfaces (2006)

Peptides derived from protein kinase C (PKC) modulate its activity by interfering with critical protein-protein interactions within PKC and between PKC and PKC-binding proteins (Souroujon, M. C., and Mochly-Rosen, D. (1998) Nat. Biotechnol. 16, 919-924). We previously demonstrated that the C2 domain of PKC plays a critical role in these interactions. By focusing on epsilonPKC and using a rational approach, we then identified one C2-derived peptide that acts as an isozyme-selective activator and another that acts as a selective inhibitor of epsilonPKC. These peptides were used to identify the role of epsilonPKC in protection from cardiac and brain ischemic damage, in prevention of complications from diabetes, in reducing pain, and in protecting transplanted hearts. The efficacy of these two peptides led us to search for additional C2-derived peptides with PKC-modulating activities. Here we report on the activity of a series of 5-9-residue peptides that are derived from regions that span the length of the C2 domain of epsilonPKC. These peptides were tested for their effect on PKC activity in cells in vivo and in an ex vivo model of acute ischemic heart disease. Most of the peptides acted as activators of PKC, and a few peptides acted as inhibitors. PKC-dependent myristoylated alanine-rich C kinase substrate phosphorylation in epsilonPKC knock-out cells revealed that only a subset of the peptides were selective for epsilonPKC over other PKC isozymes. These epsilonPKC-selective peptides were also protective of the myocardium from ischemic injury, an epsilonPKC-dependent function (Liu, G. S., Cohen, M. V., Mochly-Rosen, D., and Downey, J. M. (1999) J. Mol. Cell. Cardiol. 31, 1937-1948), and caused selective translocation of epsilonPKC over other isozymes when injected systemically into mice. Examination of the structure of the C2 domain from epsilonPKC revealed that peptides with similar activities clustered into discrete regions within the domain. We propose that these regions represent surfaces of protein-protein interactions within epsilonPKC and/or between epsilonPKC and other partner proteins; some of these interactions are unique to epsilonPKC, and others are common to other PKC isozymes.
Hydrogen‐Transfer‐Mediated α‐Functionalization of 1,8‐Naphthyridines by a Strategy Overcoming the Over‐Hydrogenation Barrier (2017)

A general catalytic hydrogen transfer-mediated α-functionalization of 1,8-naphthyridines is reported for the first time that benefits from a hydrogen transfer-mediated activation mode for non-activated pyridyl cores. The pyridyl α-site selectively couples with the C8-site of various tetrahydroquinolines (THQs) to afford novel α-functionalized tetrahydro 1,8-naphthyridines, a class of synthetically useful building blocks and potential candidates for the discovery of therapeutic and bio-active products. The utilization of THQs as inactive hydrogen donors (HDs) appears to be a key strategy to overcome the over-hydrogenation barrier and address the chemoselectivity issue. The developed chemistry features operational simplicity, readily available catalyst and good functional group tolerance, and offers a significant basis for further development of new protocols to directly transform or functionalize inert N-heterocycles.
Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection (2005)

Worldwide HIV-1 vaccine efforts are guided by the principle that HIV-specific T cell responses may provide protection from infection or delay overt disease. However, no clear correlates of T cell-mediated immune protection have been identified. Here, we examine in a HLA-B27(+) HIV seronegative vaccinee persistent HIV-specific vaccine-induced anti-Gag CD4(+) and CD8(+) T cell responses. Although these responses exhibited those characteristics (multifunctionality, appropriate memory phenotype, and targeting of epitopes associated with long-term nonprogression) predicted to correlate with protection from infection, the subject became HIV infected. After HIV infection, the vaccine-induced CD8(+) T cells expanded, but both CD4(+) and CD8(+) T cell responses acquired the functional and phenotypic patterns characteristic of chronic HIV infection. The virus quickly escaped the vaccine-induced T cell response, and the subject progressed more rapidly than expected for someone expressing the HLA-B27 allele. These data suggest that control of HIV by vaccine-elicited HIV-specific T cell responses may be difficult, even when the T cell response has those characteristics predicted to provide optimal protection.
Conserved hepatitis C virus sequences are highly immunogenic for CD4+ T cells: Implications for vaccine development (1999)

The HLA class II-restricted T-cell response to hepatitis C virus (HCV) antigens is believed to influence the final outcome of hepatitis C, because it is vigorous in patients who recover from acute hepatitis C, but it is weak in those who develop a chronic infection. For this reason, exogenous stimulation of T-cell responses in chronic HCV infection may represent a strategy to cure patients with chronic hepatitis C by approximating the vigor of their T-cell reactivity to that of patients who succeed in recovering from hepatitis. It may also be a preventive approach to avoid spread of the virus by facilitating the development of a vigorous protective response at the very early stages of infection. T-cell-based vaccines composed of immunodominant, promiscuous, and conserved T-cell epitopes may represent a powerful tool to achieve optimal stimulation of the T-cell reactivity. To identify HLA class II-restricted T-cell epitopes useful for this purpose, 22 subjects with acute HCV infection were studied and followed for an average time of 29 months. Eight of them recovered from hepatitis, and 14 developed a chronic infection. Overlapping 20-mer peptides covering the entire core and NS4 antigens and a panel of peptides representing highly conserved regions of core, NS3, NS4, and NS5 were used. By direct peripheral blood T-cell stimulation and by fine-specificity analysis of HCV-specific T-cell lines and clones, highly immunogenic T-cell epitopes were identified within core, NS3, and NS4. All these epitopes are immunodominant and highly conserved among the known HCV isolates. Moreover, they are promiscuous, because they can be presented to T cells by different HLA class II molecules. Immunodominance, sequence conservation, and promiscuity make these epitopes ideal components of preventive or therapeutic T-cell-based vaccines against HCV.
High-speed phonon imaging using frequency-multiplexed kinetic inductance detectors (2010)

We present a measurement of phonon propagation in a silicon wafer utilizing an array of frequency-multiplexed superconducting resonators coupled to a single transmission line. The electronic readout permits fully synchronous array sampling with a per-resonator bandwidth of 1.2 MHz, allowing submicrosecond array imaging. This technological achievement is potentially vital in a variety of low-temperature applications, including single-photon counting, quantum-computing, and dark-matter searches.
Mutants of Bovine Pancreatic Trypsin Inhibitor Lacking Cysteines 14 and 38 Can Fold Properly (1987)

It is a generally accepted principle of biology that a protein's primary sequence is the main determinant of its tertiary structure. However, the mechanism by which a protein proceeds from an unfolded, disordered state to a folded, relatively well-ordered, native conformation is obscure. Studies have been initiated to examine the "genetics" of protein folding, with mutants of bovine pancreatic trypsin inhibitor (BPTI) being used to explore the nature of the specific intramolecular interactions that direct this process. Previous work with BPTI chemically modified at cysteines 14 and 38 indicated that transient disulfide bond formation by these residues contributed to efficient folding at 25 degrees C. In the present work, mutants of BPTI in which these cysteines were replaced by alanines or threonines were made and the mutant proteins were produced by a heterologous Escherichia coli expression system. At 25 degrees C in vitro, the refolding behavior of these mutants was characterized by a pronounced lag. However, when expressed at 37 degrees C in E. coli, or when refolded at 37 degrees or 52 degrees C in vitro, the mutant proteins folded readily into the native conformation, albeit at a rate somewhat slower than that exhibited by wild-type BPTI. These results indicate that, at physiological temperatures, BPTI lacking cysteines 14 and 38 can refold quantitatively.
Ray tracing with cones (1984)

A new approach to ray tracing is introduced. The definition of a “ray” is extended into a cone by including information on the spread angle and the virtual origin. The advantages of this approach, which tries to model light propagation with more fidelity, include a better method of anti-aliasing, a way of calculating fuzzy shadows and dull reflections, a method of calculating the correct level of detail in a procedural model and texture map, and finally, a procedure for faster intersection calculation.