gebhart/patrepeval huggingface dataset:
Mechanism of MenE Inhibition by Acyl-Adenylate Analogues and Discovery of Novel Antibacterial Agents (2015)

MenE is an o-succinylbenzoyl-CoA (OSB-CoA) synthetase in the bacterial menaquinone biosynthesis pathway and is a promising target for the development of novel antibacterial agents. The enzyme catalyzes CoA ligation via an acyl-adenylate intermediate, and we have previously reported tight-binding inhibitors of MenE based on stable acyl-sulfonyladenosine analogues of this intermediate, including OSB-AMS (1), which has an IC50 value of ≤25 nM for Escherichia coli MenE. Herein, we show that OSB-AMS reduces menaquinone levels in Staphylococcus aureus, consistent with its proposed mechanism of action, despite the observation that the antibacterial activity of OSB-AMS is ∼1000-fold lower than the IC50 for enzyme inhibition. To inform the synthesis of MenE inhibitors with improved antibacterial activity, we have undertaken a structure-activity relationship (SAR) study stimulated by the knowledge that OSB-AMS can adopt two isomeric forms in which the OSB side chain exists either as an open-chain keto acid or a cyclic lactol. These studies revealed that negatively charged analogues of the keto acid form bind, while neutral analogues do not, consistent with the hypothesis that the negatively charged keto acid form of OSB-AMS is the active isomer. X-ray crystallography and site-directed mutagenesis confirm the importance of a conserved arginine for binding the OSB carboxylate. Although most lactol isomers tested were inactive, a novel difluoroindanediol inhibitor (11) with improved antibacterial activity was discovered, providing a pathway toward the development of optimized MenE inhibitors in the future.
Effect of chemical reagents on the fine structure of cellulose. Part III. Action of caustic soda on cotton and ramie (1966)

Abstract The changes in x‐ray orientation brought about by the treatment of cotton and ramie with caustic soda of different concentrations have been studied. With ramie the effect of the treatment is to decrease the x‐ray orientation, while with cotton the reverse is true. The cause of this difference is traced to a difference in the morphology of the two fibers rather than a difference in their fine structure.
Myeloperoxidase Concentrations in the Stool as a New Parameter of Inflammatory Bowel Disease. (1998)

Neutrophils play a predominant role in inflammatory and immune reactions in inflammatory bowel disease. It is well established that the level of myeloperoxidase, a constituent of neutrophil azurophil granules, reflects the number of neutrophil. We examined the usefulness of determining stool levels of myeloperoxidase in patients with inflammatory bowel disease. Myeloperoxidase levels in stool extracts were measured using a radio-immunoassay in 33 patients with ulcerative colitis, 32 with Crohn's disease, 9 inflammatory disease controls and 15 normal controls. Stool levels of myeloperoxidase in active inflammatory bowel disease patients increased significantly, and correlated with laboratory parameters and endoscopic grade of inflammation. A paired analysis showed a decrease in myeloperoxidase levels after the resolution of disease exacerbation. These results suggest that stool myeloperoxidase is a simple, noninvasive, and relevant marker of disease activity.
Characterization of the Functional Roles of Amino Acid Residues in Acceptor-binding Subsite +1 in the Active Site of the Glucansucrase GTF180 from Lactobacillus reuteri 180 (2015)

α-Glucans produced by glucansucrase enzymes hold strong potential for industrial applications. The exact determinants of the linkage specificity of glucansucrase enzymes have remained largely unknown, even with the recent elucidation of glucansucrase crystal structures. Guided by the crystal structure of glucansucrase GTF180-ΔN from Lactobacillus reuteri 180 in complex with the acceptor substrate maltose, we identified several residues (Asp-1028 and Asn-1029 from domain A, as well as Leu-938, Ala-978, and Leu-981 from domain B) near subsite +1 that may be critical for linkage specificity determination, and we investigated these by random site-directed mutagenesis. First, mutants of Ala-978 (to Leu, Pro, Phe, or Tyr) and Asp-1028 (to Tyr or Trp) with larger side chains showed reduced degrees of branching, likely due to the steric hindrance by these bulky residues. Second, Leu-938 mutants (except L938F) and Asp-1028 mutants showed altered linkage specificity, mostly with increased (α1 → 6) linkage synthesis. Third, mutation of Leu-981 and Asn-1029 significantly affected the transglycosylation reaction, indicating their essential roles in acceptor substrate binding. In conclusion, glucansucrase product specificity is determined by an interplay of domain A and B residues surrounding the acceptor substrate binding groove. Residues surrounding the +1 subsite thus are critical for activity and specificity of the GTF180 enzyme and play different roles in the enzyme functions. This study provides novel insights into the structure-function relationships of glucansucrase enzymes and clearly shows the potential of enzyme engineering to produce tailor-made α-glucans.
Plutonium partitioning in the Purex process with hydrazine-stabilized hydroxylamine nitrate (1975)

1B mixer-settler was reduced by using a split-scrub - a low acid scrub in stage one and a higher acid scrub in stage three - to remove acid from the solvent exiting the 1A centrifugal contactor. 8 references, 14 figures, 1 table.
Lipid Modification Strategies in the Production of Nutritionally Functional Fats and Oils (1998)

Rapid improvements in the understanding of the nutritional requirements of both infants and adults has led to new developments in the modification of fats and oils. Specific targets include the improvement in growth and development of infants, treatment of disease in adults, and disease prevention. Efforts have been focussed on the production of structured lipids using medium-chain acids and long-chain polyunsaturated fatty acids (PUFAs), as well as the concentration of long-chain PUFAs from new and existing sources. Short- and medium-chain fatty acids are metabolized differently than long-chain fatty acids and have been used as a source of rapid energy for preterm infants and patients with fat malabsorption-related diseases. Long-chain PUFAs, specifically docosahexaenoic acid and arachidonic acid, are important both in the growth and development of infants, while n-3 PUFAs have been associated with reduced risk of cardiovascular disease in adults. Based on the requirements for individual fat components by different segments of the population, including infants, adults, and patients, ideal fats can be formulated to meet their needs. By using specific novel fat sources and lipid modification techniques, the concentrations of medium-chain, long-chain saturated, and long-chain polyunsaturated fatty acids as well as cholesterol can be varied to meet the individual needs of each of these groups. While genetic modification of oilseeds and other novel sources of specific lipid components are still being developed, chemical and lipase-catalyzed interesterification reactions have moved to the forefront of lipid modification technology. Fractionation of fats and oils to provide fractions with different nutritional properties has potential, but little work has been performed on the nutritional applications of this method. The choice of suitable lipid modification technologies will depend on the target lipid structure, production costs, and consumer demand. A combination of some or all of the present lipid modification techniques may be required for this purpose.
Use of objective speech quality measures in selecting effective spectral estimation techniques for speech enhancement (2003)

Objective quality measures are used to determine optimal enhancement performance versus variation parameter settings for the enhancement algorithms. Issues addressed include: (1) the amount of magnitude averaging needed for highest speech quality using spectral subtracting; (2) choice of spectral estimation technique for colored noise characterization; and (3) terminating criterion for best speech quality for short-time Wiener filtering and constrained iterative enhancement algorithms. Additive white Gaussian noise and slowly varying colored aircraft cockpit noise are considered in the evaluation. Results show that constrained iterative enhancement resulted in the highest quality improvement for a white Gaussian distortion in seven iterations. Over a large number of colored noise conditions the best objective qualities resulted when Bartlett and maximum-entropy spectra were used in the enhancement algorithms. For aircraft cockpit noise, further improvement was observed when noise characterization was updated more frequently.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
H-1 Virus Viremia in the Human. (1965)

SummaryA viremia and subsequently HA-I and neutralizing antibodies were found in each of 2 human subjects injected with H-1 virus, indicating that the human is susceptible to, and can support, the proliferation of this agent. Studies of blood samples from one of the 2 individuals indicated that the viremia had a cyclic pattern.
A four-level-metal fully planarized interconnect technology for dense high performance logic and SRAM applications (2002)

The authors describe a four-level-metal (4LM) interconnect technology used to wire high-density, high-performance logic and SRAM chip designs. Process features includes oxide planarization under all metal levels, tungsten studs for contacts and interlevel vias, layered titanium and aluminium-0.5% copper metal lines patterned by reactive ion etch (RIE), and fusible metal links for redundancy applications. Functional 300K circuit ASIC logic test sites (4LM) and 256K SRAMs (3LM) have been fabricated in both 125-mm and 200-mm wafer sizes. Process details are described along with the results of standard electrical tests and reliability stresses.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Saliency Density Maximization for Efficient Visual Objects Discovery (2011)

Detection of salient objects in an image remains a challenging problem despite extensive studies in visual saliency, as the generated saliency map is usually noisy and incomplete. In this paper, we propose a new method to discover the salient object without prior knowledge on its shape and size. By searching the sub-image, i.e., a bounding box of maximum saliency density, the new formulation can automatically crop the salient objects of various sizes in spite of the cluttered background, and is capable to handle different types of saliency maps. A global optimal solution is obtained by the proposed density-based branch-and-bound search. The proposed method can apply to both images and videos. Experimental results on a public dataset of 5000 images show that our unsupervised detection approach is comparable to the state-of-the-art learning-based methods. Promising results are also observed in the salient object detection for videos with a good potential in video retargeting.
Calcineurin Is Downstream of the Inositol 1,4,5-Trisphosphate Receptor in the Apoptotic and Cell Growth Pathways (2000)

The inositol 1,4,5-trisphosphate receptor (IP(3)R) is a calcium (Ca(2+)) release channel found on the endoplasmic reticulum of virtually all types of cells. Human T lymphocytes (Jurkat) that are made deficient in IP(3)R do not generate Ca(2+) signals in response to T cell receptor stimulation, fail to translocate the nuclear factor for activated T cells to the nucleus, and are remarkably resistant to induction of apoptosis with CD95 (Fas), dexamethasone, gamma irradiation, and T cell receptor stimulation using anti-CD3 antibody. Expression of constitutively active calcineurin A in IP(3)R-deficient T cells restored nuclear factor for activated T cells translocation to the nucleus and dephosphorylation of Bad and rendered the cells sensitive to apoptotic inducers. Induction of apoptosis required both active calcineurin A (DeltaCnA) and activation-dependent colocalization of CnA with its substrate. Thus, the Ca(2+)-dependent phosphatase calcineurin (CnA) is downstream of the IP(3)R in both the cell growth and apoptotic signaling pathways.
Design and analysis of LacI-repressed promoters and DNA-looping in a cyanobacterium (2014)

The artificial constitutive promoters herein characterized can be utilized for expression in cyanobacteria, as demonstrated for LacI. The inefficient repression of Ptrc and Ptrc1O-proximal in Synechocystis, as compared to E. coli, may be due to insufficient LacI expression, or differences in RNAP subunits. DNA-looping works as a transcriptional regulation mechanism similarly as in E. coli. DNA-looping contributes strongly to Ptrc2O-library repression in Synechocystis, even though they contain the weakly-repressed primary lacO of Ptrc1O-proximal and relatively low levels of LacI/cell. Hence, Synechocystis RNAP may be more sensitive to DNA-looping than E. coli RNAP, and/or the chromatin torsion resistance could be lower. Two strong and highly repressed Ptrc2O promoters could be used without induction, or together with an unstable LacI.
The role of plasminogen activator in adhesion prevention. (1991)

The reduction in peritoneal plasminogen activator activity (believed to be the pathogenic mechanism of adhesion formation) and its replacement with recombinant tissue plasminogen activator (rt-PA) have been investigated in the prevention of initial (primary) and recurrent adhesion production. Other, potentially harmful, effects of intra-abdominal rt-PA application have also been examined. This included effects on wound and colonic healing and hemostasis. The prevention of adhesion formation was studied in primary and recurrent adhesion formation using a rabbit model. Primary adhesions formed in one of 14 occasions (7 per cent) with rt-PA compared with 12 of 15 occasions (80 per cent) with placebo (chi-square equals 15.542, p less than 0.001). Recurrent adhesions formed on two of 27 occasions (7 per cent) with rt-PA compared with 22 of 28 occasions with placebo (79 per cent) and 12 of 12 occasions with control rabbits (100 per cent, chi-square equals 40.588, p less than 0.0001). The application of rt-PA to abdominal wounds in the rabbit failed to show any reduction in wound strength at four, seven and ten days. Colonic anastomotic healing was unaltered by rt-PA at three, five and seven days. There was no difference seen in hemorrhagic events between control, placebo or rt-PA rabbits at any stage. The use of rt-PA is an exciting development in the field of adhesion prevention; it is an effective inhibitor of adhesion formation and intra-abdominal administration appears safe in a rabbit model.
Netarsudil ophthalmic solution 0.02% for the treatment of patientswith open-angle glaucoma or ocular hypertension (2018)

Once-daily (p.m.) netarsudil ophthalmic solution 0.02% (Rhopressa) is approved in the United States for lowering elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Netarsudil, a Rho kinase (ROCK) inhibitor that lowers IOP primarily by increasing trabecular outflow, produces statistically and clinically significant reductions in mean IOP from baseline, with comparable effects on nocturnal and diurnal IOP. In three phase III trials of patients with elevated IOP, the ocular hypotensive efficacy of once-daily netarsudil 0.02% met the criteria for noninferiority to twice-daily timolol 0.5% at all time points over 3 months in patients with baseline IOP less than 25 mmHg. The most frequent adverse event (AE) was generally mild conjunctival hyperemia, the severity of which did not increase with continued dosing. Netarsudil was associated with minimal treatment-related serious or systemic AEs, likely due to the lack of systemic exposure. This report summarizes the available preclinical and clinical data on netarsudil.
Dopaminergic Modulation of Excitatory Postsynaptic Currents in Rat Neostriatal Neurons (1997)

Gamma-aminobutyric acid (GABA)-containing medium spiny neurons constitute approximately 90% of the neuronal population in the neostriatum (caudate and putamen) and play an important role in motor programming. Cortical glutamatergic afferents provide the main excitatory drive for these neurons, whereas nigral dopaminergic neurons play a crucial role in regulating their activity. To further investigate the mechanisms underlying the dopaminergic modulation of medium spiny neuronal activity, we tested the effect of dopamine receptor agonists on excitatory synaptic transmission recorded from these neurons. Excitatory postsynaptic currents (EPSCs) were evoked by local stimulation and recorded from medium spiny neurons in postnatal rat striatal thin brain slices. Recordings were made using the whole cell patch-clamp technique under voltage clamp and conditions that selected for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate- and kainate-type glutamate receptor-mediated components of the EPSC. Incubation of slices in 10 microM dopamine resulted in a 33 +/- 11% (mean +/- SE) decrease in the amplitude of evoked EPSCs, an effect that developed during seconds. The relative variability in amplitude of dopamine's effects on medium spiny neuron EPSCs may reflect activation of different receptor subtypes with opposing effects. In contrast to the results with dopamine, incubation of slices in SKF 38393, a D1-type dopamine receptor selective agonist, resulted in dose-dependent potentiation of the medium spiny neuron EPSC that developed during several minutes. At a concentration of 5 microM, SKF 38393 resulted in a 29 +/- 4.5% increase in EPSC amplitude, an effect that was blocked by preincubation with the D1-selective antagonist, SCH 23390 (10 microM). On the other hand, 5 microM SKF 38393 had no apparent effect on medium spiny neuron currents activated by exogenous application of glutamate or kainate. However, because of the inherent limitations of rapid agonist perfusion in the brain slice preparation (caused by slow agonist diffusion and rapid glutamate receptor desensitization) and because of anatomic evidence that colocalizes D1 and glutamate receptors to medium spiny neuron dendrites, our results leave open the possibility that the effect of D1 receptor activation on the EPSC is mediated via modulation of postsynaptic glutamate receptor responsiveness. The significant potentiation by D1 receptor agonists of EPSC amplitude at the cortico-striatal medium spiny synapse that we observed, in part, may underlie the role of D1 receptors in facilitating medium spiny neuronal firing, with implications for understanding regulation of movement.
Mixed-Donor, α-Hydroxy Acid-Containing Chelates for Binding and Light-Triggered Release of Iron (2010)

A series of five new alpha-hydroxy acid-containing chelates inspired by photoactive marine siderophores, along with their Fe(III) complexes, have been synthesized and characterized. These chelates, designated X-Sal-AHA, each contributes a bidentate salicylidene moiety (X-Sal, X = 5-NO(2), 3,5-diCl, H, 3,5-di-tert-butyl, or 3-OCH(3) on the phenolate ring) and a bidentate alpha-hydroxy acid moiety (AHA). The X-ray crystal structure of Na[Fe(3)(3,5-diCl-Sal-AHA)(3)(mu(3)-OCH(3))] shows an Fe(III) trimer with the triply deprotonated, trianionic ligands each spanning two Fe(III)'s that are bridged by the hydroxyl group of the ligand. Additionally, a mu(3)-methoxy anion caps the Fe(III)(3) face. Electrospray ionization mass spectra demonstrate that this structure is representative of the Fe(III) complexes of all five derivatives in methanol solution, with the exception of the X = 3,5-di-t-Bu derivative having a mu(3)-OH bridge rather than a methoxy bridge. Stability constants determined from reduction potentials range from 10(34) for the 5-NO(2) derivative to >10(40) for the 3,5-di-tBu derivative. All five complexes are photoactive when irradiated by sunlight, with the relative rate of photolysis as monitored by Fe(II) transfer correlating with the Hammett sigma(+) parameter for the phenolate ring substituents.
Intracellular steps of bacterial cell wall peptidoglycan biosynthesis: enzymology, antibiotics, and antibiotic resistance (1992)

T. D. H. Bugg and C. T. Walsh, Nat. Prod. Rep., 1992, 9, 199 DOI: 10.1039/NP9920900199
Cutting Edge: TRANK, a Novel Cytokine That Activates NF-κB and c-Jun N-Terminal Kinase (1998)

We searched the expressed sequence tag database using sequence homology and identified a novel cytokine, which we have named TRANK (thioredoxin peroxidase-related activator of NF-kappa B and c-Jun N-terminal kinase). The predicted amino acid sequence of TRANK was highly homologous to that of the thiol-specific antioxidant proteins. Unlike these proteins, however, TRANK had a putative secretory signal polypeptide and was found to be secreted by cells. TRANK was expressed in most tissues and cell lines, and the gene that encodes it was mapped to chromosome Xp21-22.1. TRANK activated NF-kappa B and induced the degradation of the inhibitory subunit of NF-kappa B. In addition, TRANK up-regulated the expression of NF-kappa B-dependent gene products, ICAM-1, and inducible nitric oxide synthase. TRANK also activated c-Jun N-terminal kinase and induced the proliferation of normal human foreskin fibroblasts. Its homology with antioxidant proteins, wide distribution in tissues, and ability to activate NF-kappa B and c-Jun N-terminal kinase suggest that TRANK plays an important role in inflammation.
A charge damage study using an electron beam low k treatment (2004)

Organosilicate glass (OSG) deposited by plasma enhanced chemical vapour deposition (PECVD) is a likely candidate for 65nm node low k interconnect dielectric. Electron beam (e-beam) treatment efficiently stiffens porous PECVD OSG and may enable extension of PECVD OSG beyond the 65 nm node. Charge damage during e-beam exposure should be considered before implementing e-beam treatments for low k dielectrics. The effects of e-beam cathode potential on CMOS transistor threshold voltage and gate dielectric leakage current are investigated using 130nm node CMOS transistors. The impact of e-beam treatments was negligible on devices with 1.7nm gate dielectrics, but can adversely impact the 6.7nm dielectric devices.
Optical key distribution system using atmospheric turbulence as the randomness generating function: classical optical protocol for information assurance (2013)

We describe an experimental laboratory system that generates and distributes random binary sequence bit streams between two optical terminals (labeled Alice and Bob). The random binary sequence is generated through probing the optical channel of a turbulent atmosphere between the two terminals with coincident laser beams. The two laser beams experience differential phase delays while propagating through the atmospheric optical channel. The differential phase delays are detected and sampled at each terminal to yield raw random bit streams. The random bit streams are processed to remove bit errors and, through privacy amplification, to yield a bit stream known only to Alice and Bob. The same chaotic physical mechanism that provides randomness also provides confidentiality. The laboratory system yielded secret key bit rates of a few bits/second . For external optical channels over longer channel lengths with atmospheric turbulence levels, secret bit rates of 10 s of bits/second are predicted.
Isolation of DNA from agarose gels using DEAE-paper. Application to restriction site mapping of adenovirus type 16 DNA (1980)

A new method for isolating DNA from agarose gels is described. The method involves the simultaneous transfer of all DNA-fragments from an agarose slab gel onto DEAE-cellulose paper and the elution of the individual fragments from the paper with 1 M NaCl. DNA isolated from agarose gels in this way is susceptible to cleavage with several restriction endonucleases, and can be labeled in vitro with E coli DNA-polymerase I, T4 DNA-polymerase and T4 polynucleotide kinase. We have used the method to construct restriction endonuclease maps of adenovirus type 16 DNA.