gebhart/patrepeval huggingface dataset:
Inhibition of Colony-spreading Activity of Staphylococcus aureus by Secretion of δ-Hemolysin (2012)

Staphylococcus aureus spreads on the surface of soft agar, a phenomenon we termed “colony spreading.” Here, we found that S. aureus culture supernatant inhibited colony spreading. We purified δ-hemolysin (Hld, δ-toxin), a major protein secreted from S. aureus, as a compound that inhibits colony spreading. The culture supernatants of hld-disrupted mutants had 30-fold lower colony-spreading inhibitory activity than those of the parent strain. Furthermore, hld-disrupted mutants had higher colony-spreading ability than the parent strain. These results suggest that S. aureus negatively regulates colony spreading by secreting δ-hemolysin. Staphylococcus aureus spreads on the surface of soft agar, a phenomenon we termed “colony spreading.” Here, we found that S. aureus culture supernatant inhibited colony spreading. We purified δ-hemolysin (Hld, δ-toxin), a major protein secreted from S. aureus, as a compound that inhibits colony spreading. The culture supernatants of hld-disrupted mutants had 30-fold lower colony-spreading inhibitory activity than those of the parent strain. Furthermore, hld-disrupted mutants had higher colony-spreading ability than the parent strain. These results suggest that S. aureus negatively regulates colony spreading by secreting δ-hemolysin.
Assessment and treatment of neuropathic cancer pain following WHO guidelines (1999)

Neuropathic pain syndromes are one of the major problems of cancer pain treatment. The present study surveys 593 cancer patients treated by a pain service following the WHO guidelines for relief of cancer pain. Of these, 380 presented with nociceptive, 32 with neuropathic and 181 with mixed (nociceptive and neuropathic) pain. In patients with nociceptive, mixed and neuropathic pain, the average duration of evaluated pain treatment was 51, 53 and 38 days, respectively. Non-opioid or opioid analgesics were given to 99%, 96% and 79%, antidepressants to 8%, 25% and 19%, anticonvulsants to 2%, 22% and 38% and corticosteroids to 26%, 35% and 22% of patients, respectively. Systemic analgesia was supported by palliative antineoplastic treatment (48%, 56% and 38% of patients), nerve blocks (3%, 6% and 6%), psychotherapy (3%, 7% and 3%), physiotherapy (6%, 12% and 13%) and transcutaneous electric nerve stimulation (1%, 6% and 6%). Analgesic treatment resulted in a significant pain relief in all groups of patients, as the mean pain intensity (NRS) decreased from 66 (nociceptive), 65 (mixed) and 70 (neuropathic) on admission to 26, 30 and 28 after 3 days and 18, 17 and 21 at the end of survey. The total outcome of pain treatment was not predicted by the designation to nociceptive, mixed or neuropathic pain. In conclusion, neuropathic cancer pain is not intractable and can be relieved in the majority of patients by treatment following the WHO guidelines.
Wireless Power Transfer: Metamaterials and Array of Coupled Resonators (2013)

In this paper, we will report some recent progress on wireless power transfer (WPT) based on resonant coupling. Two major technologies will be discussed: the use of metamaterials and array of coupled resonators. With a slab of metamaterial, the near-field coupling between two resonant coils can be enhanced; the power transfer efficiency between coils is boosted by the metamaterial. The principle of enhanced coupling with metamaterial will be discussed; the design of metamaterial slabs for near-field wireless power transfer will be shown; recent experimental results on wireless power transfer efficiency improvement with metamaterial will also be presented. By using an array of resonators, the range of efficient power transfer can be greatly extended. More importantly, this new technology can provide wireless power to both static and mobile devices dynamically. The principle of this technology will be explained; analytical and numerical models will be used to evaluate the performance of a WPT system with an array of resonators; recent experimental developments will also be presented.
Ex Vivo Treatment with a Novel Synthetic Aminoglycoside NB54 in Primary Fibroblasts from Rett Syndrome Patients Suppresses MECP2 Nonsense Mutations (2011)

Our findings suggest that NB54 may induce restoration of the potentially functional MeCP2 in primary RTT fibroblasts and encourage further studies of NB54 and other rationally designed aminoglycoside derivatives as potential therapeutic agents for nonsense MECP2 mutations in RTT.
Local infiltration of high‐ and low‐molecular‐weight RNA from silenced sunflower (Helianthus annuus L.) plants triggers post‐transcriptional gene silencing in non‐silenced plants (2004)

Using grafting procedures, we have characterized post-transcriptional gene silencing (PTGS) in transgenic sunflower expressing beta-glucuronidase (GUS) activity. Silencing was observed as early as 2 weeks after grafting of non-silenced scions on to silenced rootstock. Transmission of the systemic signal occurs solely from stock to scion, is independent of the physiological age of the rootstock and is not heritable. Furthermore, we report, for the first time in plants, an easy and low-cost method of activating RNA silencing by infiltration of purified RNA from silenced plants. Local application of total RNA derived from silenced sunflower plants to leaves of non-silenced plants induces PTGS in newly developed leaves above the point of infiltration, as shown by reduced GUS activity and mRNA levels. Silenced plants contain 21-23-nucleotide RNAs hybridizing to transgene target sequences, in contrast with leaves of non-silenced plants. However, de novo production of GUS-specific short RNA in non-silenced plants can be activated by leaf infiltration of low-molecular-weight RNAs isolated from leaves of silenced plants. Significant levels were detected as early as 2 weeks after infiltration, peaked at 3 weeks and declined 5 weeks after infiltration. Our results provide evidence that RNA infiltration in sunflower induces transient silencing and is not transmitted to offspring. This approach could be of major use in dissecting the mechanisms involved in PTGS.
PDP-10 virtual machines (1973)

The architecture of the DEC PDP-10 prohibits using standard methods to construct a virtual PDP-10 on it. However, by simulating all executive-mode instructions and in rare cases user-mode instructions, a “hybrid” virtual machine may be constructed. Building on such a simulator and an operating system with hierarchical process relationships, the author has easily constructed a prototype virtual machine.
Very Slow Turnover of β-Cells in Aged Adult Mice (2005)

Although many signaling pathways have been shown to promote beta-cell growth, surprisingly little is known about the normal life cycle of preexisting beta-cells or the signaling pathways required for beta-cell survival. Adult beta-cells have been speculated to have a finite life span, with ongoing adult beta-cell replication throughout life to replace lost cells. However, little solid evidence supports this idea. To more accurately measure adult beta-cell turnover, we performed continuous long-term labeling of proliferating cells with the DNA precursor analog 5-bromo-2-deoxyuridine (BrdU) in 1-year-old mice. We show that beta-cells of aged adult mice have extremely low rates of replication, with minimal evidence of turnover. Although some pancreatic components acquired BrdU label in a linear fashion, only 1 in approximately 1,400 adult beta-cells were found to undergo replication per day. We conclude that adult beta-cells are very long lived.
Independent and Combined Effects of Exercise and Vitamin D on Muscle Morphology, Function and Falls in the Elderly (2010)

Regular exercise, particularly progressive resistance training (PRT), is recognized as one of the most effective strategies to prevent age-related muscle loss (sarcopenia), but its effects on muscle function are mixed. However, emerging data indicates that high velocity PRT (fast concentric muscle contractions) is more effective for improving functional outcomes than traditional PRT. In terms of falls prevention, high-challenging balance training programs appear to be most effective. There is also compelling evidence that supplemental vitamin D is an effective therapeutic option for falls prevention. The findings from a recent meta-analysis revealed that supplemental vitamin D at a dose of at least 700-1,000 IU/d or an achieved serum 25(OH)D level of at least 60 nmol/L was associated with reduced falls risk among older individuals. Based on these findings, it is possible that the combination of exercise and vitamin D could have a synergistic effect on muscle morphology and function, particularly since both interventions have been shown to have beneficial effects on type II "fast twitch" muscle fibers and systemic inflammation, which have both been linked to losses in muscle mass and function. Unfortunately however, the findings from the limited number of factorial 2 × 2 design RCTs indicate that additional vitamin D does not enhance the effects of exercise on measures of muscle morphology, function or falls risk. However, none of these trials were adequately powered to detect a "synergistic" effect between the two treatment strategies, but it is likely that if an exercise-by-vitamin D interaction does exist, it may be limited to situations when vitamin D deficiency/insufficiency is corrected. Further targeted research in "high risk" groups is still needed to address this question, and evaluate whether there is a threshold level of serum 25(OH)D to maximize the effects of exercise on muscle and falls risk.
Contributions of a disulfide bond to the structure, stability, and dimerization of human IgG1 antibody CH3 domain (2007)

Recombinant human monoclonal antibodies have become important protein-based therapeutics for the treatment of various diseases. The antibody structure is complex, consisting of beta-sheet rich domains stabilized by multiple disulfide bridges. The dimerization of the C(H)3 domain in the constant region of the heavy chain plays a pivotal role in the assembly of an antibody. This domain contains a single buried, highly conserved disulfide bond. This disulfide bond was not required for dimerization, since a recombinant human C(H)3 domain, even in the reduced state, existed as a dimer. Spectroscopic analyses showed that the secondary and tertiary structures of reduced and oxidized C(H)3 dimer were similar, but differences were observed. The reduced C(H)3 dimer was less stable than the oxidized form to denaturation by guanidinium chloride (GdmCl), pH, or heat. Equilibrium sedimentation revealed that the reduced dimer dissociated at lower GdmCl concentration than the oxidized form. This implies that the disulfide bond shifts the monomer-dimer equilibrium. Interestingly, the dimer-monomer dissociation transition occurred at lower GdmCl concentration than the unfolding transition. Thus, disulfide bond formation in the human C(H)3 domain is important for stability and dimerization. Here we show the importance of the role played by the disulfide bond and how it affects the stability and monomer-dimer equilibrium of the human C(H)3 domain. Hence, these results may have implications for the stability of the intact antibody.
The Discovery of I-BET726 (GSK1324726A), a Potent Tetrahydroquinoline ApoA1 Up-Regulator and Selective BET Bromodomain Inhibitor (2014)

Through their function as epigenetic readers of the histone code, the BET family of bromodomain-containing proteins regulate expression of multiple genes of therapeutic relevance, including those involved in tumor cell growth and inflammation. BET bromodomain inhibitors have profound antiproliferative and anti-inflammatory effects which translate into efficacy in oncology and inflammation models, and the first compounds have now progressed into clinical trials. The exciting biology of the BETs has led to great interest in the discovery of novel inhibitor classes. Here we describe the identification of a novel tetrahydroquinoline series through up-regulation of apolipoprotein A1 and the optimization into potent compounds active in murine models of septic shock and neuroblastoma. At the molecular level, these effects are produced by inhibition of BET bromodomains. X-ray crystallography reveals the interactions explaining the structure-activity relationships of binding. The resulting lead molecule, I-BET726, represents a new, potent, and selective class of tetrahydroquinoline-based BET inhibitors.
Chemical Profiling of Selected Plants of Zingiberaceae Used in Ethnomedicine of Koraput, India (2020)

The present study aims to quantify the phytochemicals present in ten selected species such as Zingiber roseum (Roxb.) Roscoe, Curcuma aromatica Salisb., Curcuma amada Roxb., Zingiber officinale Roscoe, Curcuma angustifolia Roxb, Alpinia calcarata (Haw.) Roscoe, Hedychium coronarium J.Koenig, Kaempferia galanga L., Curcuma longa L., Curcuma caesia Roxb of Zingiberaceae, which are commonly used in ethnomedicine by the tribal people of Koraput, India. The phenol, flavonoid, alkaloid, saponin, tannin, and ascorbic acid are major pharmaceutical parameters that are responsible for ethnomedicinal values were present in varying proportions. The plant species also contain significant amount of antioxidants that can be exploited as a potential source for herbal remedy for various diseases. Thus, public awareness and community-based programmes need to be encouraged at all levels for ex situ and in situ conservation of such species and will further use in exploration of new drugs for pharmaceutical industries.
A fundamental role for cell cycle regulation in the chemosensitivity of cancer cells? (1992)

The majority of clinically effective anticancer drugs inhibit some aspect of the machinery responsible for DNA replication and chromosome segregation. Drug action also arrests cells at defined points in the cell cycle called checkpoints. These checkpoints ensure that subsequent cell cycle events are inhibited until the inflicted damage is repaired. The fidelity of checkpoint control and susceptibility of cells to apoptosis while repair is underway may be important factors in the success of chemotherapy. We discuss these concepts and focus particularly on possible applications to improved antitumor therapy with DNA damaging agents.
Intracellular calcium dependence of gene expression in single T lymphocytes. (1994)

In T lymphocytes, intracellular Ca2+ concentration ([Ca2+]i) rises within seconds of T-cell antigen-receptor stimulation and initiates the synthesis and secretion of interleukin 2, a cytokine essential for T-cell proliferation and the immune response. Using video-imaging techniques, we tracked [Ca2+]i signals in individual T cells and measured subsequent expression of a beta-galactosidase reporter gene (lacZ) controlled by the NF-AT element of the interleukin 2 enhancer. [Ca2+]i spikes elicited by monoclonal antibody binding to the CD3 epsilon subunit of the T-cell receptor were positively correlated with gene expression, but varied widely between individual cells and were therefore difficult to relate quantitatively to lacZ expression. The [Ca2+]i dependence of NF-AT-regulated gene expression was determined by elevating [Ca2+]i with either thapsigargin or ionomycin and then "clamping" [Ca2+]i to various, stable levels by altering either extracellular [Ca2+] or extracellular [K+]. Raising [Ca2+]i from resting levels of 70 nM to between 200 nM and 1.6 microM increased the fraction of cells expressing lacZ, with Kd approximately 1 microM. Activation of protein kinase C enhanced the [Ca2+]i sensitivity of gene expression (Kd = 210 nM), whereas stimulation of protein kinase A inhibited [Ca2+]i-dependent gene expression. The experiments described here provide single-cell measurements linking a second messenger to gene expression in individual cells.
strabismus, a novel gene that regulates tissue polarity and cell fate decisions in Drosophila (1998)

Polarity in the Drosophila eye is manifested as a dorsoventral reflection of two chiral forms of the individual unit eyes, or ommatidia. These forms fall on opposite sides of a dorsoventral midline of mirror symmetry known as the equator. Polarity is established in the eye imaginal disc as cells adopt their fates and as the ommatidial precursors undergo coordinated rotation within the epithelium; the mechanisms that coordinate these early patterning events remain poorly understood. We have identified a novel gene, strabismus (stbm), which is required to establish polarity in the eye, legs and bristles of Drosophila. Many stbm ommatidia are reversed anteroposteriorly and/or dorsoventrally. In stbm eye discs, ommatidial rotation is delayed and some ommatidial precursors initiate rotation in the wrong direction. Mosaic analysis indicates that stbm is ommatidium autonomous and required in most, if not all, photoreceptors within an ommatidium to establish normal polarity. stbm also appears to play an instructive role during the establishment of the fates of photoreceptors R3 and R4. stbm encodes a novel protein with a potential PDZ domain-binding motif and two possible transmembrane domains. Sequence analysis of both vertebrate and invertebrate homologs indicates that stbm has been highly conserved throughout evolution.
N-Halosuccinimide/BF3−H2O, Efficient Electrophilic Halogenating Systems for Aromatics (2004)

N-Halosuccinimides (NXS, 1) are efficiently activated in trifluoromethanesulfonic acid and BF(3)-H(2)O, allowing the halogenations of deactivated aromatics. Because BF(3)-H(2)O is more economic, easy to prepare, nonoxidizing, and offers sufficiently high acidity (-H(0) approximately 12, only slightly lower than that of trifluoromethanesulfonic acid), an efficient new electrophilic reagent combination of NXS/BF(3)-H(2)O has been developed. DFT calculations at the B3LYP/6-311++G//B3LYP/6-31G level suggest that protonated N-halosuccinimides undergo further protosolvation at higher acidities to reactive superelectrophilic species capable either in the transfer of X(+) from the protonated forms of NXS to the aromatic substrate or in forming a highly reactive and solvated X(+) which would readily react with the aromatic substrates. Structural aspects of the BF(3)-H(2)O complex have also been investigated.
A comparison of three radiologic scoring systems for the long-term assessment of rheumatoid arthritis: Findings of an ongoing prospective inception cohort study of 132 women followed up for a median of twelve years (2000)

The Kellgren scoring system is the most efficient method for monitoring the radiologic progression of RA. The Kellgren and the SHS are equally sensitive to change early in the disease, whereas the Kellgren score becomes more sensitive to change late in the disease in patients with erosions.
Measurements of conduction times with catheter electrodes during pacing from different ventricular sites. (1975)

Filtered bipolar catheter electodes, I mm apart, were used to pace and record from the high right atrium, right ventricular apex, right ventricular outflow tract, right ventricular inflow tract, middle cardiac vein, great cardiac vein, and endocardium of the left ventricular septal surface. Right ventricular apex to middle cardiac vein and the middle cardiac vein to right ventricular apex conduction intervals gave a rough estimate of anteroposterior and posteroanterior "transseptal plus free left ventricular wall" conduction times, respectively. On the other hand, the right ventricular apex to left ventricular septal surface and left ventricular septal surface to right ventricular apex intervals represented pure "transseptal" conduction times, since both sets of electrodes were in contact with the respective septal surface. During stimulation of the intermediately located right ventricular inflow tract propagation to the right ventricular apex and right ventricular outflow tract was longer than between these two sites. Moreover, conduction was almost as delayed to the right ventricular apex and right ventricular outflow tract as it was to the left ventricular septal surface. These findings were attributed to the peculiar electrophysiological behaviour of the right ventricular inflow tract muscle. Pacing from different segments of the great cardiac vein produced QRS morphologies and arrival of excitation patterns consistent with the relation between the anatomical location of this structure and the recording electrodes. However, from this study no inferences could be drawn regarding the conduction velocity or specific conduction pathways used by the stimulus in its journey from stimulating to recording areas.
Identification and Characterization of a Novel Inositol Hexakisphosphate Kinase (2001)

The inositol pyrophosphate disphosphoinositol pentakisphosphate (PP-InsP(3)/InsP(7)) is formed in mammals by two recently cloned inositol hexakiphosphate kinases, InsP(6)K1 and InsP(6)K2 (Saiardi, A., Erdjument-Bromage, H., Snowman, A. M., Tempst, P., and Snyder, S. H. (1999) Curr. Biol. 9, 1323-1326). We now report the identification, cloning, and characterization of a third InsP(7) forming enzyme designated InsP(6)K3. InsP(6)K3 displays 50 and 45% sequence identity to InsP(6)K1 and InsP(6)K2, respectively, with a smaller mass (46 kDa) and a more basic character than the other two enzymes. InsP(6)K3 is most enriched in the brain where its localization resembles InsP(6)K1 and InsP(6)K2. Intracellular disposition discriminates the three enzymes with InsP(6)K2 being exclusively nuclear, InsP(6)K3 predominating in the cytoplasm, and InsP(6)K1 displaying comparable nuclear and cytosolic densities.
A simple edge-sensitive image interpolation filter (2002)

A novel scheme for edge-preserving image interpolation is introduced, which is based on the use of a simple nonlinear filter which accurately reconstructs sharp edges. Simulation results show the superior performances of the proposed approach with respect to other interpolation techniques.
Baseline structure analysis of handwritten mathematics notation (2002)

The structure of mathematics notation is particularly difficult to recognize in handwritten notation because irregular symbol placements are common. We present an efficient and robust method of parsing handwritten and typeset mathematics notation without backtracking. The system is designed to be easily adaptable to various dialects of mathematics notation. The following strategies are used: (1) separate the analysis of layout, syntax, and semantics, (2) recursively apply search functions and image partitioning to recognize dominant and nested baselines, and (3) use tree transformations to express computations in a compact, efficiently executable form.
Genetic and physiological characterization of Escherichia coli mutants deficient in phosphoenolpyruvate carboxykinase activity (1980)

Mutants doubly deficient in phosphoenolpyruvate carboxykinase (pck) and phosphoenolpyruvate synthetase (pps) were unable to grow with succinate as the sole carbon source. A number of pck mutations isolated from pps strains by penicillin selection mapped at 74 min on the Escherichia coli chromosome, between glpD and aroB. Several of the strains containing these mutations had a protein antigenically related to phosphoenolpyruvate carboxykinase, and therefore, the mutations probably represented mutations in the structural gene for this enzyme. Phosphoenolpyruvate carboxykinase was regulated at the level of transcription by catabolite repression. Enzyme levels also increased in stationary-phase cultures by a mechanism independent of cyclic adenosine monophosphate or the product of the relA gene.