gebhart/patrepeval huggingface dataset:
THE INTERACTION BETWEEN HYDROGEN PEROXIDE AND BIOFILMS (2015)

The interaction between biofilms consisting of catalase-positive bacteria Pseudomonas aeruginosa, Pseudomonas fluorescence and Klebsiella pneumoniae and hydrogen peroxide was investigated in a fiat plate reactor. The experimental results using a hydrogen peroxide micro electrode showed that the penetrations of hydrogen peroxide into biofilms was greatly retarded. This was comparable to the results reported using other oxidizing antimicrobial agents. An increase in dissolved oxygen concentration inside the biofilm measured by a dissolved oxygen microelectrode was found immediately after hydrogen peroxide treatment. Crude extracts from biofilms and planktonic cells using the same three experimental species all showed catalase activity, as determined by monitoring the breakdown of hydrogen peroxide. Thus the enzyme catalase is very likely to be active in the biofilm response to hydrogen peroxide treatment. A catalase inhibitor, 3-amino-1,2,4-triazole showed its inhibitory effect (IC50=50mM) when incubated with cell extracts. When this inhibitor was applied to either planktonic cells in the batch culture or to the biofilms in the reactor, inhibitory activity was observed only with planktonic cells (IC50=200mM). There was no significant inhibitory effect on response of the biofilms to hydrogen peroxide.
Structure of the MscL Homolog from Mycobacterium tuberculosis : A Gated Mechanosensitive Ion Channel (1998)

Mechanosensitive ion channels play a critical role in transducing physical stresses at the cell membrane into an electrochemical response. The MscL family of large-conductance mechanosensitive channels is widely distributed among prokaryotes and may participate in the regulation of osmotic pressure changes within the cell. In an effort to better understand the structural basis for the function of these channels, the structure of the MscL homolog from Mycobacterium tuberculosis was determined by x-ray crystallography to 3.5 angstroms resolution. This channel is organized as a homopentamer, with each subunit containing two transmembrane alpha helices and a third cytoplasmic alpha helix. From the extracellular side, a water-filled opening approximately 18 angstroms in diameter leads into a pore lined with hydrophilic residues which narrows at the cytoplasmic side to an occluded hydrophobic apex that may act as the channel gate. This structure may serve as a model for other mechanosensitive channels, as well as the broader class of pentameric ligand-gated ion channels exemplified by the nicotinic acetylcholine receptor.
Expression of Na,K-ATPase-β1 subunit increases uptake and sensitizes carcinoma cells to oxaliplatin (2009)

The ovarian carcinoma subline A2780/C10B (C10B) is an oxaliplatin resistant clone derived from the human ovarian carcinoma cell line A2780. The C10B cells are characterized by mesenchymal phenotype, decreased platinum uptake and increased glutathione levels (Hector et al. in Cancer Lett 245:195–204, 2007; Varma et al. in Oncol Rep 14:925–932, 2005). Na,K-ATPase-β subunit (Na,K-β1) functions as a cell–cell adhesion molecule in epithelial cells and is reduced in a variety of carcinoma cells that show mesenchymal phenotype. The purpose of this study is to evaluate the relationship between Na,K-β expression and sensitivity to oxaliplatin. Cell lines used include A2780, C10B, C10B transfected with Na,K-β1 (C10B-Na,K-β) and a canine kidney carcinoma cell line MSV-MDCK also transfected with Na,K-β1 (MSV-MDCK-β subunit). Cytotoxicity studies were performed by sulforhodamine-blue assay. The Na,K-α1 and Na,K-β1 subunit localization and expression were by immunofluorescence microscopy and Western blot analysis. Platinum accumulation measurements were by atomic absorption spectrophotometry. C10B cells express highly reduced levels of Na,K-β1 subunit. Exogenous expression of Na,K-β1 increased platinum accumulation and sensitized C10B cells to oxaliplatin. The pharmacological inhibitor of Na,K-ATPase ouabain did not alter the oxaliplatin accumulation indicating that Na,K-β1 sensitizes cells in a Na,K-ATPase enzyme activity independent manner. These findings were also confirmed in MSV-MDCK-β subunit cells. This study for the first time reveals that reduced expression of the Na,K-β1 protein is associated with oxaliplatin resistance in cancer cells and demonstrates a novel role for this protein in sensitizing the cells to oxaliplatin. This study suggests a potentially important role for Na,K-β1 in both prognosis and therapy of oxaliplatin resistant malignancies.
Nonviral Skin Gene Therapy (2000)

Nonviral skin gene therapy is an effective method to directly deliver and transiently express genes in the skin. Several different nonviral delivery methods have been successfully used and are analyzed here for their efficiency and efficacy in achieving specific therapeutic applications. For one important and frequently used application of nonviral skin gene therapy, genetic immunization, the types of resulting immune responses (Th1 versus Th2) will depend on which delivery method is used. In addition, we discuss the contributions of DNA as an immunostimulatory adjuvant in genetic immunization and how activation of skin dendritic cells and induction of IL-12 expression are mechanistically important in this process. Nonviral skin gene therapy has also been successfully used to enhance tumor regression in animal models, frequently by inducing a specific immune response against the tumor. In the future, nonviral skin gene therapy may be successfully used for the treatment of additional skin diseases if genes can be selectively delivered and expressed in specific skin cells, and if increased level and duration of gene expression can be achieved.
Only Early Intervention with Gamma-Aminobutyric Acid Cell Therapy Is Able to Reverse Neuropathic Pain After Partial Nerve Injury (2001)

Pharmacological treatment for neuropathic pain, although often effective for brief periods, can result in intractable persistent pain with certain patients. Cell therapy for neuropathic pain is a newly developing technology useful for an examination of enhanced normal sensory function after nerve injury with the placement of cells near the spinal cord, and grafts of immortalized cells bioengineered to chronically supply the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) have been used to reverse the chronic pain behaviors. However, it is not known whether there is a therapeutic window for the use of intervention with cell therapy after partial nerve injury. To investigate whether neuropathic pain is sensitive to the timing of placement of cell grafts, neuronal cells bioengineered to synthesize GABA were transplanted in the lumbar subarachnoid space one to four weeks after unilateral chronic constriction injury (CCI) of the sciatic nerve and sensory behaviors were evaluated before and after CCI and transplants. Both thermal hyperalgesia and tactile allodynia were reversed when transplants were placed either one or two weeks after partial nerve injury, compared to maintenance of these behaviors with the injury alone. However, if GABA cells were placed any later than 2 weeks after nerve injury, such intervention was ineffective to reverse the thermal and tactile hypersensitivities induced by the injury. This suggests that altered spinal GABA levels may contribute to the early development of chronic neuropathic pain and that early intervention with cellular therapy to restore GABA may prevent the development of that pain.
Selective inhibition of dopamine-beta-hydroxylase in the peripheral tissues by 5-dimethyldithiocarbamylpicolinic acid; its effect on stress-induced ulcer, ethanol-induced sleep and blood pressure. (1974)

Administration of 5-dimethyldithiocarbamylpicolinic acid (YP-279), an inhibitor of dopamine- β-hydroxylase, caused selective reduction of peripheral norepinephrine (NE) biosynthesis and reduced the blood pressure of spontaneously hypertensive rats, as well as normotensive rats, but had no effect on brain NE biosynthesis. YP-279, which does not appear to cross the blood-brain barrier, did not affect either stress-induced gastric ulcer or ethanol-induced sleeping time, both of which are thought to he mediated through the central nervous system. Evidence that YP-279 is a selective inhibitor of the peripheral dopamine-β-hydroxylase is 1) that the conversion of 3H-dopamine into 3H-NE in rat brains was not inhibited by intraperitoneal injection of this compound, but the conversion of 3H-dopamine into 3H-NE in rat hearts was effectively inhibited and 2) that this inhibitor could not be detected in the brain after its intraperitoneal administration, but could be detected in other tissues. In contrast, 5-butylpicolinic acid and its derivatives (analog of YP-279), which also inhibit dopamine-β-hydroxylase, that do pass the bloodbrain barrier exhibited all of the positive effects indicated above as well as abilities to prevent stress-induced gastric ulcers and to prolong ethanol-induced sleep. 5-Butylpicolinic acid and its derivatives, except for YP-279, were found in brain and peripheral tissues. They also inhibited the conversion of 3H-dopamine into 3H-NE in the brain as well as in other tissues.
Hygienic behavior in the honey bee (Apis mellifera L.) and the modulatory role of octopamine (2003)

Honey bees, Apis mellifera, which perform hygienic behavior, quickly detect, uncap and remove diseased brood from the nest. This behavior, performed by bees 15-20 days old and prior to foraging, is likely mediated by olfactory cues. Because the neuromodulator octopamine (OA) plays a pivotal role in olfactory-based behaviors of honey bees, we examined whether bees bred for hygienic and nonhygienic behavior differed with regard to their OA expression and physiology. We compared the staining intensity of octopamine-immunoreactive (OA-ir) neurons in the deutocerebral region of the brain, medial to the antennal lobes, between hygienic and nonhygienic bees (based on genotype and phenotype). We also tested how the olfactory responses of the two lines, based on electroantennograms (EAGs), were affected by oral administration of OA and of epinastine, a highly specific OA antagonist. Our results revealed that bees expressing hygienic behavior (irrespective of genotype) possessed OA-ir neurons that exhibited more intense labeling than same-aged bees not performing the behavior. In bees bred for nonhygienic behavior, OA significantly increased the EAG response to low concentrations of diseased brood odor. Conversely, in bees bred for hygienic behavior, epinastine significantly reduced the magnitude of the EAG response, a reduction not observed in nonhygienic bees. Our results provide two lines of evidence that OA has the potential to facilitate the detection and response of honey bees to diseased brood. We discuss the contributions of OA for behavioral shaping and its ability to bias the nervous system to express one form of behavior over another.
Complete genome sequencing of Anaplasma marginale reveals that the surface is skewed to two superfamilies of outer membrane proteins (2004)

The rickettsia Anaplasma marginale is the most prevalent tick-borne livestock pathogen worldwide and is a severe constraint to animal health. A. marginale establishes lifelong persistence in infected ruminants and these animals serve as a reservoir for ticks to acquire and transmit the pathogen. Within the mammalian host, A. marginale generates antigenic variants by changing a surface coat composed of numerous proteins. By sequencing and annotating the complete 1,197,687-bp genome of the St. Maries strain of A. marginale, we show that this surface coat is dominated by two families containing immunodominant proteins: the msp2 superfamily and the msp1 superfamily. Of the 949 annotated coding sequences, just 62 are predicted to be outer membrane proteins, and of these, 49 belong to one of these two superfamilies. The genome contains unusual functional pseudogenes that belong to the msp2 superfamily and play an integral role in surface coat antigenic variation, and are thus distinctly different from pseudogenes described as byproducts of reductive evolution in other Rickettsiales.
Tocilizumab and Remdesivir in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19) (2020)

Tocilizumab and remdesivir may be effective for treatment of severe COVID-19 in pregnancy, but additional data are needed to guide risk-benefit considerations.
FLEX: a tolerant and cooperative user interface to databases (1990)

FLEX a user interface to relational databases, can be used satisfactorily by users with different levels of expertise. FLEX is based on a formal query language, but is tolerant of incorrect input. It never rejects queries; instead, it adapts flexibility and transparently to their level of correctness and well-formedness, providing interpretations of corresponding accuracy and specificity. The most prominent design feature of FLEX is the smooth concatenation of several independent mechanisms, each capable of handling input of decreasing level of correctness and well-formedness. Each input is cascaded through this series of mechanisms until an interpretation is found. FLEX is also cooperative. It never delivers empty answers without explanation or assistance. By following up each failed query with a set of more general queries, FLEX determines whether an empty answer is genuine, in which case it suggests related queries that have nonempty answers, or whether it reflects erroneous presuppositions on the part of the user, in which case it then explains them.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Materialism (1999)

Abstract Schopenhauer argues that the world of objects must be material, and that the only use for the concept of substance is that of matter. He argues that materialism is correlative with idealism. Even the brain functions of the subject are material processes. However, materialism is one‐sided because it does not account for the point of view of the consciousness of the subject of knowledge, from which idealism indispensably starts.
The Polyproline Site in Hinge 2 Influences the Functional Capacity of Truncated Dystrophins (2010)

Mutations in dystrophin can lead to Duchenne muscular dystrophy or the more mild form of the disease, Becker muscular dystrophy. The hinge 3 region in the rod domain of dystrophin is particularly prone to deletion mutations. In-frame deletions of hinge 3 are predicted to lead to BMD, however the severity of disease can vary considerably. Here we performed extensive structure-function analyses of truncated dystrophins with modified hinges and spectrin-like repeats in mdx mice. We found that the polyproline site in hinge 2 profoundly influences the functional capacity of a microdystrophin(DeltaR4-R23/DeltaCT) with a large deletion in the hinge 3 region. Inclusion of polyproline in microdystrophin(DeltaR4-R23/DeltaCT) led to small myofibers (12% smaller than wild-type), Achilles myotendinous disruption, ringed fibers, and aberrant neuromuscular junctions in the mdx gastrocnemius muscles. Replacing hinge 2 of microdystrophin(DeltaR4-R23/DeltaCT) with hinge 3 significantly improved the functional capacity to prevent muscle degeneration, increase muscle fiber area, and maintain the junctions. We conclude that the rigid alpha-helical structure of the polyproline site significantly impairs the functional capacity of truncated dystrophins to maintain appropriate connections between the cytoskeleton and extracellular matrix.
Libraries for genomic SELEX (1997)

An increasing number of proteins are being identified that regulate gene expression by binding specific nucleic acidsin vivo. A method termed genomic SELEX facilitates the rapid identification of networks of protein-nucleic acid interactions by identifying within the genomic sequences of an organism the highest affinity sites for any protein of the organism. As with its progenitor, SELEX of random-sequence nucleic acids, genomic SELEX involves iterative binding, partitioning, and amplification of nucleic acids. The two methods differ in that the variable region of the nucleic acid library for genomic SELEX is derived from the genome of an organism. We have used a quick and simple method to construct Escherichia coli, Saccharomyces cerevisiae, and human genomic DNA PCR libraries that can be transcribed with T7 RNA polymerase. We present evidence that the libraries contain overlapping inserts starting at most of the positions within the genome, making these libraries suitable for genomic SELEX.
Genotype-Phenotype Studies in Bipolar Disorder Showing Association Between the DAOA/G30 Locus and Persecutory Delusions: A First Step Toward a Molecular Genetic Classification of Psychiatric Phenotypes (2005)

These data suggest that bipolar affective disorder with persecutory delusions constitutes a distinct subgroup of bipolar affective disorder that overlaps with schizophrenia.
A mitochondrial protein associated with cytoplasmic male sterility in the T cytoplasm of maize (1987)

Mitochondrial DNA in the T male-sterile cytoplasm (cms-T) of maize contains an open reading frame (ORF 13) associated with the T type of sterility. Antibodies raised to a chemically synthesized oligopeptide corresponding to ORF 13 were used to establish the expression of a 13-kDa protein from this reading frame. The 13-kDa polypeptide is synthesized uniquely in cms-T maize and purifies with the membrane fraction of T mitochondria. We assign the symbol urf13-T to designate this mitochondrial gene. Presence of the nuclear restorer gene Rf1 in cms-T plants results in a decrease in abundance of 13-kDa protein and alteration in the transcripts of urf13-T.
Biochemical Characterization of Soybean Ovary Growth from Anthesis to Abscission of Aborting Ovaries (1986)

Soybean (Glycine max [L.] Merr.) ovary growth was measured from anthesis to 6 days after anthesis (DAA) to establish a timetable of biochemical events that might be useful in identifying processes that initiate abscission. Two procedures were developed to provide samples with either high or low percent pod set for ;IX93-100,' a semideterminate line having long racemes. Characteristics measured were fresh and dry weight, soluble and insoluble protein, soluble carbohydrate, starch, RNA, and DNA. Setting ovaries grew more rapidly than abscising ovaries. Since there was a daily increase in ovary weight in both groups, all measured characteristics showed daily increases when expressed on perovary basis. Statistically significant differences between groups were detected between 2 and 5 DAA for most characteristics. When chemical composition was expressed on concentration basis, starch level was significantly higher in setting ovaries at 5 and 6 DAA. Regression analysis showed that these deviations between setting and abscising samples started between anthesis and 1 DAA. We conclude that processes leading to eventual shedding of fertilized ovaries (called flower abortion in soybeans) commence soon after anthesis of the shed flower, and that setting and abscising ovaries do not differ in protein, soluble carbohydrate, starch, or nucleic acid content when abscission processes begin.
Progressive multifocal leukoencephalopathy associated with immunosuppressive therapy in rheumatic diseases: Evolving role of biologic therapies (2012)

PML has been reported in patients with ARD treated with various immunosuppressive agents. The limitations of this study preclude definitive attribution of causality. While the paucity of confirmed cases recently exposed to anti-TNF therapy suggests a causal relationship is unlikely, a specific signal is emerging with regard to rituximab and PML. Although this is a rare adverse event associated with RTX therapy, the devastating nature of PML mandates continued vigilance, particularly in patients with current or prior exposure to an alkylating agent.
Challenges and Opportunities in Targeting the Menin–MLL Interaction (2014)

Menin is an essential co-factor of oncogenic MLL fusion proteins and the menin-MLL interaction is critical for development of acute leukemia in vivo. Targeting the menin-MLL interaction with small molecules represents an attractive strategy to develop new anticancer agents. Recent developments, including determination of menin crystal structure and development of potent small molecule and peptidomimetic inhibitors, demonstrate the feasibility of targeting the menin-MLL interaction. On the other hand, biochemical and structural studies revealed that MLL binds to menin in a complex bivalent mode engaging two MLL motifs, and therefore inhibition of this protein-protein interaction represents a challenge. This review summarizes the most recent achievements in targeting the menin-MLL interaction as well as discusses potential benefits of blocking menin in cancer.
Monalysin, a Novel ß-Pore-Forming Toxin from the Drosophila Pathogen Pseudomonas entomophila, Contributes to Host Intestinal Damage and Lethality (2011)

Pseudomonas entomophila is an entomopathogenic bacterium that infects and kills Drosophila. P. entomophila pathogenicity is linked to its ability to cause irreversible damages to the Drosophila gut, preventing epithelium renewal and repair. Here we report the identification of a novel pore-forming toxin (PFT), Monalysin, which contributes to the virulence of P. entomophila against Drosophila. Our data show that Monalysin requires N-terminal cleavage to become fully active, forms oligomers in vitro, and induces pore-formation in artificial lipid membranes. The prediction of the secondary structure of the membrane-spanning domain indicates that Monalysin is a PFT of the ß-type. The expression of Monalysin is regulated by both the GacS/GacA two-component system and the Pvf regulator, two signaling systems that control P. entomophila pathogenicity. In addition, AprA, a metallo-protease secreted by P. entomophila, can induce the rapid cleavage of pro-Monalysin into its active form. Reduced cell death is observed upon infection with a mutant deficient in Monalysin production showing that Monalysin plays a role in P. entomophila ability to induce intestinal cell damages, which is consistent with its activity as a PFT. Our study together with the well-established action of Bacillus thuringiensis Cry toxins suggests that production of PFTs is a common strategy of entomopathogens to disrupt insect gut homeostasis.
Equation-based congestion control for unicast applications (2000)

This paper proposes a mechanism for equation-based congestion control for unicast traffic. Most best-effort traffic in the current Internet is well-served by the dominant transport protocol, TCP. However, traffic such as best-effort unicast streaming multimedia could find use for a TCP-friendly congestion control mechanism that refrains from reducing the sending rate in half in response to a single packet drop. With our mechanism, the sender explicitly adjusts its sending rate as a function of the measured rate of loss events, where a loss event consists of one or more packets dropped within a single round-trip time. We use both simulations and experiments over the Internet to explore performance.