gebhart/patrepeval huggingface dataset:
[The pharmacologic activity of p-substituted DL-2-phenylglycine octyl esters]. (1990)

DL-2-phenylglycine octyl ester has antiphlogistic, analgesic and spasmolytic activities as shown in different animal models. The antiphlogistic effectiveness is changed only a little by the p-substitution at the phenyl ring, whereas the analgesic action is markedly influenced. Most of the substituted compounds are significantly more active than the unsubstituted ester. DL-2-(benzyloxyphenyl)glycine octyl ester is the most active compound, it has furthermore the highest therapeutic quotient. Using the i.p. application its efficacy exceeds that of acetylsalicylic acid, phenylbutazone and indometacin, respectively. The spasmolytic activity is differently changed by the substituents. The most active ester, DL-2-(p-methoxyphenyl)glycine octyl ester, is about two times more active than papaverine. In histamine induced spasm the effectiveness is low compared with the specific antagonist mepyramine. The results obtained show that the activities of the p-substituted DL-2-phenylglycine octyl esters are different with regard to the three investigated pharmacological properties.
The Human Cytomegalovirus IE1 Protein Antagonizes PML Nuclear Body-Mediated Intrinsic Immunity via the Inhibition of PML <i>De Novo</i> SUMOylation (2016)

The human cytomegalovirus IE1 protein acts as an important antagonist of a cellular restriction mechanism that is mediated by subnuclear structures termed PML nuclear bodies. This function of IE1 is required for efficient viral replication and thus constitutes a potential target for antiviral strategies. In this paper, we further elucidate the molecular mechanism for how IE1 antagonizes PML NBs. We show that tight binding of IE1 to PML interferes with the de novo SUMOylation of a distinct lysine residue that is also the target of stress-mediated hyperSUMOylation of PML. This is of importance since it represents a novel mechanism used by a viral antagonist of intrinsic immunity. Furthermore, it highlights the possibility of developing small molecules that specifically abrogate this PML-antagonistic activity of IE1 and thus inhibit viral replication.
A real-time control, management and information transport architecture for broadband networks (2003)

A unified framework of an architecture for broadband networks is outlined. The network architecture is based on three fundamental principles: the separation principle, the layering principle and the principle of asynchronous resource management. Based on these three principles the network objects are organized into an integrated reference model (IRM). The IRM consists of the traffic control, the management and information transport architecture. These architectures run on different time scales. Their main requirement is to guarantee quality of service as negotiated at call set up. The traffic control model employed consists of a statistical and a dynamic database and a set of distributed algorithms that interact by writing and reading onto these databases. They are part of a network database capable of supporting monitoring, control, configuration and fault management tasks. The design of the network database is exemplified by modeling one of the fundamental building blocks of the future gigabit architecture.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Apollo Expeditions to the Moon (1975)

The Apollo program is described from the planning stages through Apollo 17. The organization of the program is discussed along with the development of the spacecraft and related technology. The objectives and accomplishments of each mission are emphasized along with personal accounts of the major figures involved. Other topics discussed include: ground support systems and astronaut selection.
A fascial frustum valve for aortic valve replacement (1971)

The promising qualities of autologous fascia lata in heart valve replacement have resulted in a search for improved methods of fascial heart valve manufacture. This paper describes a simply made and inserted and reliably competent unsupported fascial valve for aortic valve replacement.
Effect of protein-synthesis inhibitors on testosterone production in rat testis interstitial tissue and Leydig-cell preparations (1975)

Luteinizing-hormone-stimulated testosterone biosynthesis was inhibited by cycloheximide during incubation of rat testis intersitial tissue in vitro and also by puromycin and cycloheximide during incubation of Leydig-cell preparations, but not by chloramphenicol. These results suggest that a protein regualtor(s) formed by cytoplasmic protein synthesis is involved in steroidogenesis in the rat testis. The specific effect of cycloheximide and puromycin on protein synthesis rather than on other non-specific processes is suggested by the inhibition of protein synthesis and steroidogenesis with different doses of the inhibitors and the lack of effect of cycloheximide on luteinizing-hormone-induced adenosine 3':5'-cyclic monophosphate production. Stimulation of testosterone production by luteinizing hormone during superfusion of interstitial tissue was detectable within 10-20 min and reached a maximum of 120 min, and thereafter slowly decreased. Cycloheximide added at maximum steroid production caused a rapid decrease in testosterone synthesis which followed first-order kinetics (half-life 13 min), thus indicating that the protein regulator(s) has a short half-life. No effect of cycloheximide, puromycin or chloramphenicol on testosterone production in the absence of added luteinizing hormone was found, suggesting that the basal production of testosterone is independent of protein synthesis.
Myomegalin Is a Novel Protein of the Golgi/Centrosome That Interacts with a Cyclic Nucleotide Phosphodiesterase (2001)

Subcellular targeting of the components of the cAMP-dependent pathway is thought to be essential for intracellular signaling. Here we have identified a novel protein, named myomegalin, that interacts with the cyclic nucleotide phosphodiesterase PDE4D, thereby targeting it to particulate structures. Myomegalin is a large 2,324-amino acid protein mostly composed of alpha-helical and coiled-coil structures, with domains shared with microtubule-associated proteins, and a leucine zipper identical to that found in the Drosophila centrosomin. Transcripts of 7.5-8 kilobases were present in most tissues, whereas a short mRNA of 2.4 kilobases was detected only in rat testis. A third splicing variant was expressed predominantly in rat heart. Antibodies against the deduced sequence recognized particulate myomegalin proteins of 62 kDa in testis and 230-250 kDa in heart and skeletal muscle. Immunocytochemistry and transfection studies demonstrate colocalization of PDE4D and myomegalin in the Golgi/centrosomal area of cultured cells, and in sarcomeric structures of skeletal muscle. Myomegalin expressed in COS-7 cells coimmunoprecipitated with PDE4D3 and sequestered it to particulate structures. These findings indicate that myomegalin is a novel protein that functions as an anchor to localize components of the cAMP-dependent pathway to the Golgi/centrosomal region of the cell.
Theranostic Oxygen Delivery Using Ultrasound and Microbubbles (2012)

Means to overcome tumor hypoxia have been the subject of clinical investigations since the 1960's; however these studies have yet to find a treatment which is widely accepted. It has been known for nearly a century that hypoxic cells are more resistant to radiotherapy than aerobic cells, and tumor hypoxia is a major factor leading to the resistance of tumors to radiation treatment as well as several cytotoxic agents. In this manuscript, the application of ultrasound combined with oxygen-carrier microbubbles is demonstrated as a method to locally increase dissolved oxygen. Microbubbles can also be imaged by ultrasound, thus providing the opportunity for image-guided oxygen delivery. Simulations of gas diffusion and microbubble gas exchange show that small amounts (down to 5 vol%) of a low-solubility osmotic gas can substantially increase microbubble persistence and therefore production rates and stability of oxygen-carrier microbubbles. Simulations also indicate that the lipid shell can be engineered with long-chain lipids to increase oxygen payload during in vivo transit. Experimental results demonstrate that the application of ultrasound to destroy the microbubbles significantly enhances the local oxygen release. We propose this technology as an application for ultrasound image-guided release of oxygen directly to hypoxic tissue, such as tumor sites to enhance radiotherapy.
Vaginal microbiota and viral sexually transmitted diseases. (2013)

Healthy vaginal microbiota is an important biological barrier to pathogenic microorganisms. When this predominantly Lactobacillus community is disrupted, decreased in abundance and replaced by different anaerobes, bacterial vaginosis (BV) may occur. BV is associated with prevalence and incidence of several sexually transmitted infections. This review provides background on BV, discusses the epidemiologic data to support a role of altered vaginal microbiota for acquisition of sexually transmitted diseases and analyzes mechanisms by which lactobacilli could counteract sexually transmitted viral infections.
Planning of Deepwater Drilling Operations with Aerated Fluids (1999)

Abstract Although underbalanced drilling (UBD) has been used for many years, with more than 11,000 wells drilled underbalanced in Canada and the USA, this technique has been almost exclusively applied to onshore fields. Despite a few experiences offshore, questions related to safety, logistics, and equipment placement have kept offshore UBD restricted to fixed platforms or jack-up rigs. Nevertheless, the industry trend towards offshore deepwater production has made it imperative to make this technology technically and economically viable for use in floater units as well. This paper describes current efforts being made by a group of companies involved in a Joint Industry Project (JIP) focused on planning and drilling a deepwater offshore well from a semi-submersible platform using nitrified fluid. Although the well will not be drilled underbalanced for this first well, it will be the first well to be drilled from a floating vessel using a gasified fluid. The main issues addressed in the project include: field data analysis, drilling hydraulics and cuttings transport experiments and modeling, software development and validation, formation damage experiments and modeling, wellbore stability failure mechanisms, operational procedures, safety issues, equipment development and/or conversion and benefits quantification for the process. Several of the key issues are discussed in this paper.
Longitudinal gradient coil optimization in the presence of transient eddy currents (2007)

The switching of magnetic field gradient coils in magnetic resonance imaging (MRI) inevitably induces transient eddy currents in conducting system components, such as the cryostat vessel. These secondary currents degrade the spatial and temporal performance of the gradient coils, and compensation methods are commonly employed to correct for these distortions. This theoretical study shows that by incorporating the eddy currents into the coil optimization process, it is possible to modify a gradient coil design so that the fields created by the coil and the eddy currents combine together to generate a spatially homogeneous gradient that follows the input pulse. Shielded and unshielded longitudinal gradient coils are used to exemplify this novel approach. To assist in the evaluation of transient eddy currents induced within a realistic cryostat vessel, a low-frequency finite-difference time-domain (FDTD) method using the total-field scattered-field (TFSF) scheme was performed. The simulations demonstrate the effectiveness of the proposed method for optimizing longitudinal gradient fields while taking into account the spatial and temporal behavior of the eddy currents.
A Channel Model for Multiple Input Multiple Output in-home Power Line Networks (2011)

Multiple-Input Multiple-Output (MIMO) techniques have recently become an important research field for enhancing the performance of in-home Power Line Communication (PLC) systems by exploiting the additional Protective Earth wire. The development of such systems requires an accurate description of the propagation channel. This paper presents a statistical model for the MIMO PLC channel, based on an extensive set of MIMO channel measurements performed in five houses. In this model, the Phase-Neutral link is described as a multipath channel with frequency variable attenuation, following a formalism first proposed by Zimmermann and extended statistically by Tonello. The full channel matrix is obtained by suitably modifying the path phase. The resulting channel matches our experimental measurements, and reproduces the correlation observed in the measured MIMO channel matrix.
Au<sup>I</sup> Catalysis on a Coordination Polymer: A Solid Porous Ligand with Free Phosphine Sites (2013)

The best things in life are free: LSK-1 is a porous polymer with free phosphine sites homogeneously distributed within the structure. Post- functionalization gave a AuI-impregnated solid (16 % w/w) that was used as a recyclable heterogeneous catalyst.
Spike-Driven Synaptic Dynamics Generating Working Memory States (2003)

The collective behavior of a network, modeling a cortical module of spiking neurons connected by plastic synapses is studied. A detailed spike-driven synaptic dynamics is simulated in a large network of spiking neurons, implementing the full double dynamics of neurons and synapses. The repeated presentation of a set of external stimuli is shown to structure the network to the point of sustaining working memory (selective delay activity). When the synaptic dynamics is analyzed as a function of pre- and postsynaptic spike rates in functionally defined populations, it reveals a novel variation of the Hebbian plasticity paradigm: in any functional set of synapses between pairs of neurons (e.g., stimulated-stimulated, stimulated-delay, stimulated-spontaneous), there is a finite probability of potentiation as well as of depression. This leads to a saturation of potentiation or depression at the level of the ratio of the two probabilities. When one of the two probabilities is very high relative to the other, the familiar Hebbian mechanism is recovered. But where correlated working memory is formed, it prevents overlearning. Constraints relevant to the stability of the acquired synaptic structure and the regimes of global activity allowing for structuring are expressed in terms of the parameters describing the single-synapse dynamics. The synaptic dynamics is discussed in the light of experiments observing precise spike timing effects and related issues of biological plausibility.
Ion Beam Etching of InP. II. Reactive Etching with Halogen-Based Source Gases (1983)

The reactive-ion beam etching (R-IBE) characteristics of InP with Cl 2 , CCl 2 F 2 and CHF 3 have been studied. Some R-IBE characteristics of GaAs have also been studied. The etching rate for each gas has been determined as a function of ion energy, current density and angle of indidence. The highest etching rate, around 2000 Å/min, is obtained in Cl 2 -IBE, while the two other source gases yield an etching rate lower than that of Ar-IBE. In the case of CCl 2 F 2 -IBE, the addition of Ar is found to enhance the etching considerably. These IBE techniques are used to fabricate a grating structure with a period around 2500 A.
Microstimulation of the primate neostriatum. II. Somatotopic organization of striatal microexcitable zones and their relation to neuronal response properties (1985)

Sensorimotor response properties of neostriatal neurons were characterized in conjunction with assessments of the motor effects of intrastriatal microstimulation in unanesthetized rhesus monkeys. Neuronal activity and microexcitability were assessed at 250- to 500-micron intervals and, in some cases, at 25- to 100-micron intervals. The results are based on the functional characterization of 878 putamen and 224 caudate neurons and analysis of the effects of microstimulation at each of these recording sites. Recording/stimulation sites were located between stereotaxic planes A6 and A22 in 81 microelectrode tracks from three monkeys. A total of 443 (50.4%) putamen neurons showed discrete responses to the sensorimotor examination. Of neurons with sensorimotor responses, 232 (52.4%) showed increased rates of discharge in relation to both active and passive movements of specific body parts. An additional 193 (43.6%) cells increased their rates of discharge only during the monkey's active movements of specific body parts. The remaining 18 (4.0%) cells appeared to respond exclusively to passive somatosensory stimulation. The sensorimotor response areas of putamen neurons ranged in size from an entire limb to a single joint. Putamen neurons were somatotopically organized throughout the rostrocaudal extent of the nucleus. Neurons with sensorimotor response areas involving the leg were located in the dorsolateral putamen, those with orofacial representations were located ventromedially, and those with arm representations were located in an intermediate position. Microstimulation evoked discrete movements of individual body parts at 21.6% of the 878 putamen sites. Over 95% (181/190) of the effective sites were located within the central half of the rostrocaudal extent of the putamen, between stereotaxic planes A10 and A17. The pattern of somatotopic organization revealed by microstimulation was the same as that derived from sensorimotor response properties of putamen neurons. Moreover, a close correspondence was observed between the movements evoked from a given SMZ and the functional properties of local neurons. In contrast to the results obtained in the putamen, none of the 224 stimulation sites in the caudate nucleus was microexcitable, and only 17 (7.6%) of the caudate neurons had definable sensorimotor response properties. This is consistent with the view that the primate putamen, by virtue of its anatomic connections with the sensorimotor and premotor cortical fields, is more directly involved in motor functions, whereas the caudate nucleus, by virtue of its connections with cortical "association" areas, is involved in more complex behavioral functions.
Cell Cycle-Dependent Expression of Phosphorylated Histone H2AX: Reduced Expression in Unirradiated but not X-Irradiated G<sub>1</sub>-Phase Cells (2003)

Exposure of cells to ionizing radiation causes phosphorylation of histone H2AX at sites flanking DNA double-strand breaks. Detection of phosphorylated H2AX (gammaH2AX) by antibody binding has been used as a method to identify double-strand breaks. Although generally performed by observing microscopic foci within cells, flow cytometry offers the advantage of measuring changes in gammaH2AX intensity in relation to cell cycle position. The importance of cell cycle position on the levels of endogenous and radiation-induced gammaH2AX was examined in cell lines that varied in DNA content, cell cycle distribution, and kinase activity. Bivariate analysis of gammaH2AX expression relative to DNA content and synchronization by centrifugal elutriation were used to measure cell cycle-specific expression of gammaH2AX. With the exception of xrs5 cells, gammaH2AX level was approximately 3 times lower in unirradiated G(1)-phase cells than S- and G(2)-phase cells, and the slope of the G(1)-phase dose-response curve was 2.8 times larger than the slope for S-phase cells. Cell cycle differences were confirmed using immunoblotting, indicating that reduced antibody accessibility in intact cells was not responsible for the reduced antibody binding in G(1)-phase cells. Early apoptotic cells could be easily identified on flow histograms as a population with 5-10-fold higher levels of gammaH2AX, although high expression was not maintained in apoptotic cells by 24 h. We conclude that expression of gammaH2AX is associated with DNA replication in unirradiated cells and that this reduces the sensitivity for detecting radiation-induced double-strand breaks in S- and G(2)-phase cells.
Experimental and clinical studies of the extracellular direct current (DC) potential (2016)

Direct current (DC) potentials are slow electrical potentials measured in the extracellular space which reflect biophysicochemical phenomena in neurons and astrocytes such as spreading depolarization (SD) or ictal epileptic events (IEE). It is nevertheless assumed that DC potentials can also arise at the blood-brain barrier (BBB). For example, the latter may apply to CO2-dependent DC shifts, which I further investigated in rats in study 1. To start with, I found that one of the major supporting arguments for this hypothesis is invalid, namely the DC change following intracarotideal dehydrocholate (DHC) application, because intracarotideal DHC causes not only BBB opening but also middle cerebral artery thrombosis with focal cerebral ischemia. Intracarotideal DHC is thus not a suitable model to study isolated BBB opening. Nevertheless, I then applied a number of neuronal/astrocytic channel blockers topically to the brain. They should have altered the CO2-dependent DC shift if it were of neuronal/astrocytic origin, but they failed to do so. Moreover, the typical CO2-dependent DC shift was lacking in brain slices, which lack an intact BBB, whereas DC shifts of SDs or IEEs are preserved. This further supported the origin of the CO2-dependent DC shift at the BBB. Using pH- and K+-selective microelectrodes in vivo, we then found further evidence that the CO2-dependent DC shift is specifically generated by the proton gradient across the BBB. Thus, it seems to be a marker for the closed paracellular pathway, which maintains the ion gradients across the BBB under physiological conditions. Using this tool, we then provided functional evidence for previous results with electron microscopy for the first time that the BBB opens in a hierarchical manner under pathological conditions. First, the transcellular pathway allows macromolecules such as albumin to pass. Only later, the paracellular pathway opens for small molecules such as protons or potassium. In the second study, we investigated the detection of SDs using DC/alternating current (AC)-scalp-electroencephalography (EEG) simultaneously with invasive DC/AC-electrocorticography (ECoG) in patients with aneurysmal subarachnoid hemorrhage (aSAH). DC/AC-ECoG is the gold standard to measure SDs. However, we also found correlates of both DC and AC changes of SDs in the scalp-EEG. This may offer a non-invasive approach to detect SDs in patients in the future, but the tool requires further refinement. In the third study, we investigated hemodynamic responses to SDs and IEEs in an aSAH patient using DC /AC-ECoG and laser-Doppler flowmetry. We found that hypoemic responses occurred not only during SDs but also during IEEs. Interestingly, these hypoemic responses showed a spatial association with increased BBB permeability, indicating a possible relationship between BBB dysfunction and abnormal hemodynamic responses to SDs and IEEs.