gebhart/patrepeval huggingface dataset:
Subpicosecond sampling using a noncontact electro-optic probe (1989)

This paper discusses a theoretical as well as experimental study of the performance of electro-optic sampling using a noncontact electro-optic probe, i.e., external electro-optic sampling. Sensitivity, temporal resolution, and the capacitive loading effect of this system are calculated by analysis of a static electric field coupled to an electro-optic crystal placed in close proximity to transmission lines such as microstrip lines and coplanar strips. Full-wave analysis is also applied to investigate effect of the electro-optic crystal on the transient property of high-speed electrical signals. Based on these analytical considerations, we have developed an external electro-optic sampling system using precise probe-positioning technology, which improves the measurement reproducibility. A temporal resolution of 0.5 ps and a spatial resolution of 1 μm are confirmed with this system.
X-ray Crystal Structures of the Escherichia coli RNA Polymerase in Complex with Benzoxazinorifamycins (2013)

Rifampin, a semisynthetic rifamycin, is the cornerstone of current tuberculosis treatment. Among many semisynthetic rifamycins, benzoxazinorifamycins have great potential for TB treatment due to their superior affinity for wild-type and rifampin-resistant Mycobacterium tuberculosis RNA polymerases and their reduced hepatic Cyp450 induction activity. In this study, we have determined the crystal structures of the Escherichia coli RNA polymerase complexes with two benzoxazinorifamycins. The ansa-naphthalene moieties of the benzoxazinorifamycins bind in a deep pocket of the β subunit, blocking the path of the RNA transcript. The C3'-tail of benzoxazinorifamycin fits a cavity between the β subunit and σ factor. We propose that in addition to blocking RNA exit, the benzoxazinorifamycin C3'-tail changes the σ region 3.2 loop position, which influences the template DNA at the active site, thereby reducing the efficiency of transcription initiation. This study supports expansion of structure-activity relationships of benzoxazinorifamycins inhibition of RNA polymerase toward uncovering superior analogues with development potential.
Protein L from Peptostreptococcus magnus binds to the kappa light chain variable domain. (1992)

Protein L is an immunoglobulin light chain-binding protein expressed by some strains of the anaerobic bacterial species Peptostreptococcus magnus. The major variable region subgroups of human kappa and lambda light chains were tested for protein L binding; V kappa I, V kappa III, and V kappa IV bound protein L, whereas no binding occurred with proteins of the V kappa II subgroup or with any lambda light chain subgroups. Studies of the protein L binding capacity of naturally occurring VL fragments, and VL- and CL-related trypsin- and pepsin-derived peptides prepared from a kappa I light chain, localized the site of interaction to the VL domain. The affinity constant for the binding to an isolated V kappa I fragment was comparable to that for the native protein (Ka 0.9 x 10(9) M-1 and Ka 1.5 x 10(9) M-1, respectively). No binding occurred with CL-related fragments. Extensive reduction and alkylation of the V kappa fragment or the native kappa chain resulted in complete loss of protein L binding. Although it is possible, from comparative amino acid sequence data, to identify certain VL-framework region residues that account for the selective binding of protein L by kappa I, kappa III, and kappa IV proteins, our studies indicate that this interaction is essentially dependent upon the tertiary structural integrity of the kappa chain VL domain.
NF-κB Activation by Camptothecin (2000)

Activation of the transcription factor NF-kappaB by extracellular signals involves its release from the inhibitor protein IkappaBalpha in the cytoplasm and subsequent nuclear translocation. NF-kappaB can also be activated by the anticancer agent camptothecin (CPT), which inhibits DNA topoisomerase (Topo) I activity and causes DNA double-strand breaks during DNA replication to induce S phase-dependent cytotoxicity. Here we show that CPT activates NF-kappaB by a mechanism that is dependent on initial nuclear DNA damage followed by cytoplasmic signaling events. NF-kappaB activation by CPT is dramatically diminished in cytoplasts and in CEM/C2 cells expressing a mutant Topo I protein that fails to bind CPT. This response is intensified in S phase cell populations and is prevented by the DNA polymerase inhibitor aphidicolin. In addition, CPT activation of NF-kappaB involves degradation of cytoplasmic IkappaBalpha by the ubiquitin-proteasome pathway in a manner that depends on the IkappaB kinase complex. Finally, inhibition of NF-kappaB activation augments CPT-induced apoptosis. These findings elucidate the progression of signaling events that initiates in the nucleus with CPT-Topo I interaction and continues in the cytoplasm resulting in degradation of IkappaBalpha and nuclear translocation of NF-kappaB to attenuate the apoptotic response.
Suppression of glioblastoma angiogenicity and tumorigenicity by inhibition of endogenous expression of vascular endothelial growth factor. (1996)

The development of new capillary networks from the normal microvasculature of the host appears to be required for growth of solid tumors. Tumor cells influence this process by producing both inhibitors and positive effectors of angiogenesis. Among the latter, the vascular endothelial growth factor (VEGF) has assumed prime candidacy as a major positive physiological effector. Here, we have directly tested this hypothesis in the brain tumor, glioblastoma multiforme, one of the most highly vascularized human cancers. We introduced an antisense VEGF expression construct into glioblastoma cells and found that (i) VEGF mRNA and protein levels were markedly reduced, (ii) the modified cells did not secrete sufficient factors so as to be chemoattractive for primary human microvascular endothelial cells, (iii) the modified cells were not able to sustain tumor growth in immunodeficient animals, and (iv) the density of in vivo blood vessel formation was reduced in direct relation to the reduction of VEGF secretion and tumor formation. Moreover, revertant cells that recovered the ability to secrete VEGF regained each of these tumorigenic properties. These results suggest that VEGF plays a major angiogenic role in glioblastoma.
Characterization of the membrane attack complex inhibitory protein CD59 antigen on human amniotic cells and in amniotic fluid. (1992)

A functional complement system and the potential for its activation are present in human amniotic fluid. We have recently demonstrated that CD59 antigen is present and functionally active on human amniotic epithelial cells (HAEC). We have now further examined the role of this protein on HAEC and have also demonstrated its presence in amniotic fluid (AF). CD59 Ag on HAEC is similar in size to the erythrocyte protein and is anchored via glycosyl phosphatidylinositol. The AF protein retained the capacity to incorporate into target cells and protect against lysis by complement. These data suggest that HAEC secrete into AF a form of CD59 Ag which retains inhibitory activity and which may be important in protection of the foetus from maternal complement in utero.
Age Dependence and Isotype Specificity of Influenza Virus Hemagglutinin Stalk-Reactive Antibodies in Humans (2016)

The present study provides evidence that titers of broadly neutralizing hemagglutinin stalk-reactive antibodies increase with age, possibly due to repeated exposure to divergent influenza viruses. These relatively high levels of antistalk titers may be responsible for lower circulation rates of influenza viruses in older individuals. Our findings suggest that the level of antistalk antibodies is a good surrogate marker for protection against influenza virus infection. In addition, the levels of antistalk antibodies might determine the breadth of protection against different drifted strains.
Molecular Basis for Interactions of G Protein βγ Subunits with Effectors (1998)

Both the alpha and betagamma subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins) communicate signals from receptors to effectors. Gbetagamma subunits can regulate a diverse array of effectors, including ion channels and enzymes. Galpha subunits bound to guanine diphosphate (Galpha-GDP) inhibit signal transduction through Gbetagamma subunits, suggesting a common interface on Gbetagamma subunits for Galpha binding and effector interaction. The molecular basis for interaction of Gbetagamma with effectors was characterized by mutational analysis of Gbeta residues that make contact with Galpha-GDP. Analysis of the ability of these mutants to regulate the activity of calcium and potassium channels, adenylyl cyclase 2, phospholipase C-beta2, and beta-adrenergic receptor kinase revealed the Gbeta residues required for activation of each effector and provides evidence for partially overlapping domains on Gbeta for regulation of these effectors. This organization of interaction regions on Gbeta for different effectors and Galpha explains why subunit dissociation is crucial for signal transmission through Gbetagamma subunits.
Hepatitis C virus NS3 protein polynucleotide-stimulated nucleoside triphosphatase and comparison with the related pestivirus and flavivirus enzymes (1993)

Sequence motifs within the nonstructural protein NS3 of members of the Flaviviridae family suggest that this protein possesses nucleoside triphosphatase (NTPase) and RNA helicase activity. The RNA-stimulated NTPase activity of this protein from prototypic members of the Pestivirus and Flavivirus genera has recently been established and enzymologically characterized. Here, we experimentally demonstrate that the NS3 protein from a member of the third genus of Flaviviridae, human hepatitis C virus (HCV), also possesses a polynucleotide-stimulated NTPase activity. Characterization of the purified HCV NTPase activity showed that it exhibited reaction condition optima with respect to pH, MgCl2, and salt identical to those of the representative pestivirus and flavivirus enzymes. However, each NTPase also possessed several unique properties when compared with one another. Notably, the profile of polynucleotide stimulation of the NTPase activity was distinct for the three enzymes. The HCV NTPase was the only one whose activity was significantly enhanced by a deoxyribopolynucleotide. Additional distinguishing features among the three enzymes relating to the kinetic properties of their NTPase activities are discussed. These studies provide a foundation for investigation of the putative RNA helicase activity of these proteins and for further study of the role of the NS3 proteins of members of the Flaviviridae in the replication cycle of these viruses.
Norovirus and Sapovirus Infections in Thailand (2004)

Stool specimens collected between November 2002 and April 2003 from hospitalized infants with acute gastroenteritis from four distinct geographical regions in Thailand were examined for norovirus (NoV) and sapovirus (SaV) by reverse transcription-PCR and sequence analysis. Of the 80 specimens examined, we identified 11 NoV and 9 SaV single infections, and 3 NoV/SaV mixed infections. The majority of NoV strains (64%) belonged to genogroup II/ genotype 4 (GII/4; Lordsdale cluster). Other NoV strains co-circulating belonged to GII/1, GII/3, GII/6, and one new genotype cluster (GII/New). The majority of SaV strains (83%) were from the Manchester cluster. One isolated SaV strain represented a recently discovered novel genogroup within the SaV genus (SG-V), and another isolated SaV strain represented a novel SaV genogroup II cluster.
Cloning and nucleotide sequence analysis of the Lactobacillus delbrueckii ssp. lactis DSM7290 cysteine aminopeptidase gene pepC (1994)

A genomic library of Lactobacillus delbrueckii ssp. lactis DSM7290 in the low copy number vector pLG339, was screened for the presence of peptidase genes. Using the chromogenic substrate gly-ala-β-naphthylamide, which is not a substrate for any of the recently cloned peptidases of DSM7290, and the multiple peptidase deficient Escherichia coli strain CM89, allowed the isolation of clones, which contained the equivalent hydrolytic activity. To identify genes encoding the conserved catalytic active site of cysteine proteases, partial nucleotide sequencing with a degenerate oligonucleotide was performed on recombinant plasmids isolated from such clones. This allowed to identify two out of nine clones to carry the Lactobacillus pepC gene. A total of 2026 nucleotides were determined, and sequence analysis revealed a gene with strong homology to the recently cloned Lb. helveticus (73.2%) and Lactococcus lactis (51.03%) pepC genes, and the derived protein showed homology with the active site of a large number of cysteine proteases. The predicted open reading frame consists of 449 codons, coding for a protein of 50 909 Da. The enzyme is functional and extremely overexpressed in E. coli.
Multiple and time-scheduled in situ DNA delivery mediated by β-cyclodextrin embedded in a polyelectrolyte multilayer (2006)

The basic premise of gene therapy is that genes can be used to produce in situ therapeutic proteins. The controlled delivery of DNA complexes from biomaterials offers the potential to enhance gene transfer by maintaining an elevated concentration of DNA within the cellular microenvironment. Immobilization of the DNA to the substrate to which cells adhere maintains the DNA in the cell microenvironment for subsequent cellular internalization. Here, layer-by-layer (LBL) films made from poly(L-glutamic acid) (PLGA) and poly(L-lysine) (PLL) containing DNA were built in the presence of charged cyclodextrins. The biological activities of these polyelectrolyte films were tested by means of induced production of a specific protein in the nucleus or in the cytoplasm by cells in contact with the films. This type of coating offers the possibility for either simultaneous or sequential interfacial delivery of different DNA molecules aimed at cell transfection. These results open the route to numerous potential applications in patch vaccination, for example.
Near-zero-energy end states in topologically trivial spin-orbit coupled superconducting nanowires with a smooth confinement (2012)

A one-dimensional spin-orbit coupled nanowire with proximity-induced pairing from a nearby $s$-wave superconductor may be in a topological nontrivial state, in which it has a zero-energy Majorana bound state at each end. We find that the topological trivial phase may have fermionic end states with an exponentially small energy, if the confinement potential at the wire's ends is smooth. The possible existence of such near-zero-energy levels implies that the mere observation of a zero-bias peak in the tunneling conductance is not an exclusive signature of a topological superconducting phase, even in the ideal clean single channel limit.
Modulation of Gamma-Aminobutyric AcidA Receptor Function by Thiopental in the Rat Spinal Dorsal Horn Neurons (2006)

To assess the actions of thiopental at the spinal dorsal horn level, we examined the effects of thiopental using the whole cell patch-clamp technique on mechanically dissociated rat spinal dorsal horn neurons. Thiopental, at large concentrations, elicited a current (I(Thio)) through activation of chloride conductance, and its threshold concentration was approximately 50 microM. I(Thio) was sensitive to bicuculline, a gamma-aminobutyric acid (GABA)A receptor antagonist, but not to strychnine, a glycine receptor antagonist. At a clinically relevant concentration (30 muM), thiopental markedly enhanced the peak amplitude of a subsaturating GABA-induced current (I(GABA)) but not that of a saturating GABA-induced current. Furthermore, thiopental prolonged the time constants of both desensitization and deactivation of I(GABA). At a large concentration (300 muM), it inhibited the peak amplitude of I(GABA), which may be the result of open-channel blockade. In addition, at 30 microM, thiopental increased the duration and decreased the frequency of GABAergic miniature inhibitory postsynaptic currents. These results indicate that thiopental enhances GABAergic inhibitory transmission and suggest that GABA(A) receptors in the spinal cord are a potential target through which thiopental causes immobility and depresses the response to noxious stimuli.
Reduced accumulation of specific microRNAs in colorectal neoplasia. (2003)

Short non-coding RNAs are known to regulate cellular processes including development, heterochromatin formation, and genomic stability in eukaryotes. Given the impact of these processes on cellular identity, a study was undertaken to investigate possible changes in microRNA (miRNA) levels during tumorigenesis. A total of 28 different miRNA sequences was identified in a colonic adenocarcinoma and normal mucosa, including 3 novel sequences and a further 7 that had previously been cloned only from mice. Human homologues of murine miRNA sequences, miR-143 and miR-145, consistently display reduced steady-state levels of the mature miRNA at the adenomatous and cancer stages of colorectal neoplasia.
Challenges of management and therapy in patients with a functionally single ventricle after Fontan operation. (2011)

Forty years ago, Fontan and Baudet performed the first life-saving operation on a patient with a functionally single ventricle. This multi-stage procedure established the connection between systemic venous circulation and pulmonary arteries. As a consequence, the pulmonary circulation is supplied in a passive way, whereas the single ventricle pumps the blood into the systemic circulation only. Over the years, the technique of creating the abovementioned vascular connections has undergone several modifications. Due to the fundamental non-physiological hemodynamic relations between arterial pulmonary and systemic venous pressures, numerous complications can be observed in these patients including: supraventricular arrhythmias, thromboemboli, hepatic dysfunction, protein-losing enteropathy, heart failure, worsening cyanosis, systemic venous collateralization, and pulmonary arteriovenous malformations, as well as connective tissue lesions in bronchi. Although based on an ingenious concept, the operation remains of a palliative character. Occasionally, heart transplantation is the ultimate resolution. Pharmacological therapy, and surgical conversion, often appear to be ineffective. However, this procedure has enabled many patients to reach adulthood and enjoy their lives to the full. This fact poses a great challenge for cardiologists wishing to become more knowledgeable and experienced as regards such patients, if we are not to waste such fabulous surgical achievements.
Test off Philippines boosts horizontal drilling technology (1989)

This article reports on a testing program conducted on the Galoc la horizontal well located offshore Manila. It involved a single multi-rate test to assess the well's flow potential. The problems encountered were low flow rates, high solids and water production, and major loss of drilling fluid to the formation between tests. Results of the testing are discussed and recommendations based on this experience are presented.
Algorithms for hyper-parameter optimization (2011)

Several recent advances to the state of the art in image classification benchmarks have come from better configurations of existing techniques rather than novel ap-proaches to feature learning. Traditionally, hyper-parameter optimization has been the job of humans because they can be very efficient in regimes where only a few trials are possible. Presently, computer clusters and GPU processors make it pos-sible to run more trials and we show that algorithmic approaches can find better results. We present hyper-parameter optimization results on tasks of training neu-ral networks and deep belief networks (DBNs). We optimize hyper-parameters using random search and two new greedy sequential methods based on the ex-pected improvement criterion. Random search has been shown to be sufficiently efficient for learning neural networks for several datasets, but we show it is unreli-able for training DBNs. The sequential algorithms are applied to the most difficult DBN learning problems from [1] and find significantly better results than the best previously reported. This work contributes novel techniques for making response surface models P (y|x) in which many elements of hyper-parameter assignment (x) are known to be irrelevant given particular values of other elements. 1
Inflammation in Glaucoma: From the back to the front of the eye, and beyond (2020)

The pathophysiology of glaucoma is complex, multifactorial and not completely understood. Elevated intraocular pressure (IOP) and/or impaired retinal blood flow may cause initial optic nerve damage. In addition, age-related oxidative stress in the retina concurrently with chronic mechanical and vascular stress is crucial for the initiation of retinal neurodegeneration. Oxidative stress is closely related to cell senescence, mitochondrial dysfunction, excitotoxicity, and neuroinflammation, which are involved in glaucoma progression. Accumulating evidence from animal glaucoma models and from human ocular samples suggests a dysfunction of the para-inflammation in the retinal ganglion cell layer and the optic nerve head. Moreover, quite similar mechanisms in the anterior chamber could explain the trabecular meshwork dysfunction and the elevated IOP in primary open-angle glaucoma. On the other hand, ocular surface disease due to topical interventions is the most prominent and visible consequence of inflammation in glaucoma, with a negative impact on filtering surgery failure, topical treatment efficacy, and possibly on inflammation in the anterior segment. Consequently, glaucoma appears as an outstanding eye disease where inflammatory changes may be present to various extents and consequences along the eye structure, from the ocular surface to the posterior segment, and the visual pathway. Here we reviewed the inflammatory processes in all ocular structures in glaucoma from the back to the front of the eye and beyond. Our approach was to explain how para-inflammation is necessary to maintain homoeostasis, and to describe abnormal inflammatory findings observed in glaucomatous patients or in animal glaucoma models, supporting the hypothesis of a dysregulation of the inflammatory balance toward a pro-inflammatory phenotype. Possible anti-inflammatory therapeutic approaches in glaucoma are also discussed.