gebhart/patrepeval huggingface dataset:
Contribution of a Thickened Cell Wall and Its Glutamine Nonamidated Component to the Vancomycin Resistance Expressed by Staphylococcus aureus Mu50 (2000)

Staphylococcus aureus Mu50, which has reduced susceptibility to vancomycin, has a remarkably thickened cell wall with an increased proportion of glutamine nonamidated muropeptides. In addition, Mu50 had enhanced glutamine synthetase and L-glutamine D-fructose-6-phosphate aminotransferase activities, which are involved in the cell-wall peptidoglycan synthesis pathway. Furthermore, significantly increased levels of incorporation of (14)C-labeled D-glucose into the cell wall was observed in Mu50. Unlike a femC mutant S. aureus strain, increased levels of production of nonamidated muropeptides in Mu50 was not caused by lower levels of glutamine synthetase activity but was considered to be due to the glutamine depletion caused by increased glucose utilization by the cell to biosynthesize increased amounts of peptidoglycan. After the cells were allowed to synthesize cell wall in the absence or presence of glucose and glutamine, cells with different cell-wall thicknesses and with cell walls with different levels of cross-linking were prepared, and susceptibility testing of these cells demonstrated a strong correlation between the cell-wall thickness and the degree of vancomycin resistance. Affinity trapping of vancomycin molecules by the cell wall and clogging of the outer layers of peptidoglycan by bound vancomycin molecules were considered to be the mechanism of vancomycin resistance of Mu50. The reduced cross-linking and the increased affinity of binding to vancomycin of the Mu50 cell wall presumably caused by the increased proportion of nonamidated muropeptides may also contribute to the resistance to some extent.
Application of Pretrained Deep Neural Networks to Large Vocabulary Conversational Speech Recognition (2012)

The use of Deep Belief Networks (DBN) to pretrain Neural Networks has recently led to a resurgence in the use of Artificial Neural Network- Hidden Markov Model (ANN/HMM) hybrid systems for Automatic Speech Recognition (ASR). In this paper we report results of a DBN-pretrained context-dependent ANN/HMM system trained on two datasets that are much larger than any reported previously with DBN-pretrained ANN/HMM
A Novel Positive Allosteric Modulator of the α7 Neuronal Nicotinic Acetylcholine Receptor:In VitroandIn VivoCharacterization (2005)

Several lines of evidence suggest a link between the alpha7 neuronal nicotinic acetylcholine receptor (nAChR) and brain disorders including schizophrenia, Alzheimer's disease, and traumatic brain injury. The present work describes a novel molecule, 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596), which acts as a powerful positive allosteric modulator of the alpha7 nAChR. Discovered in a high-throughput screen, PNU-120596 increased agonist-evoked calcium flux mediated by an engineered variant of the human alpha7 nAChR. Electrophysiology studies confirmed that PNU-120596 increased peak agonist-evoked currents mediated by wild-type receptors and also demonstrated a pronounced prolongation of the evoked response in the continued presence of agonist. In contrast, PNU-120596 produced no detectable change in currents mediated by alpha4beta2, alpha3beta4, and alpha9alpha10 nAChRs. PNU-120596 increased the channel mean open time of alpha7 nAChRs but had no effect on ion selectivity and relatively little, if any, effect on unitary conductance. When applied to acute hippocampal slices, PNU-120596 increased the frequency of ACh-evoked GABAergic postsynaptic currents measured in pyramidal neurons; this effect was suppressed by TTX, suggesting that PNU-120596 modulated the function of alpha7 nAChRs located on the somatodendritic membrane of hippocampal interneurons. Accordingly, PNU-120596 greatly enhanced the ACh-evoked inward currents in these interneurons. Systemic administration of PNU-120596 to rats improved the auditory gating deficit caused by amphetamine, a model proposed to reflect a circuit level disturbance associated with schizophrenia. Together, these results suggest that PNU-120596 represents a new class of molecule that enhances alpha7 nAChR function and thus has the potential to treat psychiatric and neurological disorders.
New Insights into the Role of Nuclear Factor-κB, a Ubiquitous Transcription Factor in the Initiation of Diseases (1999)

Nuclear factor-kappaB (NF-kappaB) is a ubiquitous transcription factor that governs the expression of genes encoding cytokines, chemokines, growth factors, cell adhesion molecules, and some acute phase proteins in health and in various disease states. NF-kappaB is activated by several agents, including cytokines, oxidant free radicals, inhaled particles, ultraviolet irradiation, and bacterial or viral products. Inappropriate activation of NF-kappaB has been linked to inflammatory events associated with autoimmune arthritis, asthma, septic shock, lung fibrosis, glomerulonephritis, atherosclerosis, and AIDS. In contrast, complete and persistent inhibition of NF-kappaB has been linked directly to apoptosis, inappropriate immune cell development, and delayed cell growth. Therefore, development of modulatory strategies targeting this transcription factor may provide a novel therapeutic tool for the treatment or prevention of various diseases.
Aryl Hydrocarbon Receptor-Mediated Signal Transduction (1997)

The aryl hydrocarbon (or dioxin) receptor (AhR) is a ligand-activated basic helix-loop-helix (bHLH) protein that heterodimerizes with the bHLH protein ARNT (aryl hydrocarbon nuclear translocator) forming a complex that binds to xenobiotic regulatory elements in target gene enhancers. Genetic, biochemical, and molecular biology studies have revealed that the AhR mediates the toxic and biological effects of environmentally persistent dioxins and related compounds. Cloning of the receptor and its DNA-binding partner, ARNT, has facilitated detailed efforts to understand the mechanisms of AhR-mediated signal transduction. These studies have determined that this unique receptor consists of several functional domains and belongs to a subfamily of bHLH proteins that share a conserved motif termed the PAS domain. In addition, recent genetic studies have revealed that expression of the AhR is a requirement for proper embryonal development, which appears to be a common function shared by many other bHLH proteins. This review is a summary of recent molecular studies of AhR-mediated gene regulation.
Mutations in the CYP11B1 gene causing congenital adrenal hyperplasia and hypertension cluster in exons 6, 7, and 8. (1993)

Steroid 11 beta-hydroxylase deficiency (failure to convert 11-deoxycortisol to cortisol) is the second most common cause of congenital adrenal hyperplasia and results in a hypertensive form of the disease. The 11 beta-hydroxylase enzyme is encoded by the CYP11B1 gene on chromosome 8q22. Two mutations in CYP11B1 have previously been reported in patients with 11 beta-hydroxylase deficiency--Arg-448-->His and a 2-bp insertion in codon 394. We now report eight previously uncharacterized mutations causing this disorder. Seven are point mutations (three nonsense and four missense) and one is a single base pair deletion causing a frameshift. We have used an in vitro transfection assay to show that all five known missense mutations causing 11 beta-hydroxylase deficiency abolish enzymatic activity. In principle, deletions of CYP11B1 could be generated by unequal crossing-over between CYP11B1 and the adjacent CYP11B2 gene, but no such deletions were found among the deficiency alleles in this study. Seven of the 10 known mutations are clustered in exons 6-8, a nonrandom distribution within the gene. This may reflect the location of functionally important amino acid residues within the enzyme or an increased tendency to develop mutations within this region of the gene.
Recombinant Adeno-Associated Virus Vectors Efficiently and Persistently Transduce Chondrocytes in Normal and Osteoarthritic Human Articular Cartilage (2003)

Successful gene transfer into articular cartilage is a prerequisite for gene therapy of articular joint disorders. In the present study we tested the hypothesis that recombinant adeno-associated virus (rAAV) vectors are capable of effecting gene transfer in isolated articular chondrocytes in vitro, articular cartilage tissue in vitro, and sites of articular damage in vivo. Using an rAAV vector carrying the Escherichia coli beta-galactosidase gene (lacZ) under the control of the cytomegalovirus (CMV) immediate-early promoter/enhancer (rAAV-lacZ), transduction efficiency exceeded 70% for isolated normal human adult articular chondrocytes, and osteoarthritic human articular chondrocytes. These were comparable to the transduction efficiency obtained with neonatal bovine articular chondrocytes. Transduction of explant cultures of articular cartilage resulted in reporter gene expression within the tissue of all three cartilage types to a depth exceeding 450 microm, which remained present until 150 days. When rAAV-lacZ vectors were applied to femoral chondral defects and osteochondral defects in vivo in a rat knee model, reporter gene expression was achieved for at least 10 days after transduction. These data suggest that AAV-based vectors can efficiently transduce and stably express foreign genes in articular chondrocytes, including chondrocytes of normal and osteoarthritic human articular cartilage. The data further suggest that the same rAAV vectors are capable of transducing chondrocytes in situ within their native matrix to a depth sufficient to be of potential clinical significance. Finally, the data demonstrate that these rAAV vectors are capable of effectively delivering recombinant genes to chondral and osteochondral defects in vivo.
Disruption of a coronary stent during atherectomy for restenosis (1991)

Directional coronary atherectomy is being used in the treatment of atherosclerotic lesions in coronary vessels and vein grafts. This report describes the use of atherectomy for the treatment of restenosis of a coronary stent. The procedure was complicated by disruption of the stent which was snared by the atherectomy cutter.
Measuring the effects of internet path faults on reactive routing (2003)

Empirical evidence suggests that reactive routing systems improve resilience to Internet path failures. They detect and route around faulty paths based on measurements of path performance. This paper seeks to understand why and under what circumstances these techniques are effective.To do so, this paper correlates end-to-end active probing experiments, loss-triggered traceroutes of Internet paths, and BGP routing messages. These correlations shed light on three questions about Internet path failures: (1) Where do failures appear? (2) How long do they last? (3) How do they correlate with BGP routing instability?Data collected over 13 months from an Internet testbed of 31 topologically diverse hosts suggests that most path failures last less than fifteen minutes. Failures that appear in the network core correlate better with BGP instability than failures that appear close to end hosts. On average, most failures precede BGP messages by about four minutes, but there is often increased BGP traffic both before and after failures. Our findings suggest that reactive routing is most effective between hosts that have multiple connections to the Internet. The data set also suggests that passive observations of BGP routing messages could be used to predict about 20% of impending failures, allowing re-routing systems to react more quickly to failures.
Spectral phase transfer for indirect phase control of sub-20-fs deep UV pulses (2005)

We demonstrate the transfer of a shaped spectral phase in a pulse with a sub-20-fs pulse Fourier limit of a Ti:sapphire laser to that in a deep UV pulse at 256 nm in a sum- frequency-mixing process. The generated UV pulse maintains a sufficiently broad spectrum to form a sub-20-fs pulse due to broadband sum-frequency mixing with the group-delay-dispersion-matched scheme. The spectral phases of the deep UV pulse are measured with spectral phase interferometry for direct electric field reconstruction and compared with the phase applied to the Ti:sapphire laser pulse.
CDX2-driven leukemogenesis involves KLF4 repression and deregulated PPARγ signaling (2012)

Aberrant expression of the homeodomain transcription factor CDX2 occurs in most cases of acute myeloid leukemia (AML) and promotes leukemogenesis, making CDX2, in principle, an attractive therapeutic target. Conversely, CDX2 acts as a tumor suppressor in colonic epithelium. The effectors mediating the leukemogenic activity of CDX2 and the mechanism underlying its context-dependent properties are poorly characterized, and strategies for interfering with CDX2 function in AML remain elusive. We report data implicating repression of the transcription factor KLF4 as important for the oncogenic activity of CDX2, and demonstrate that CDX2 differentially regulates KLF4 in AML versus colon cancer cells through a mechanism that involves tissue-specific patterns of promoter binding and epigenetic modifications. Furthermore, we identified deregulation of the PPARγ signaling pathway as a feature of CDX2-associated AML and observed that PPARγ agonists derepressed KLF4 and were preferentially toxic to CDX2+ leukemic cells. These data delineate transcriptional programs associated with CDX2 expression in hematopoietic cells, provide insight into the antagonistic duality of CDX2 function in AML versus colon cancer, and suggest reactivation of KLF4 expression, through modulation of PPARγ signaling, as a therapeutic modality in a large proportion of AML patients.
Re-Stenosis after Successful Coronary Angioplasty (1988)

OVER the past decade, percutaneous transluminal coronary angioplasty has gained wide acceptance as the procedure of choice in many patients with atherosclerotic coronary artery disease. As experience with the procedure has grown, its rate of success has risen to approximately 90 percent and the incidence of acute complications has fallen; as a result, emergency coronary-artery bypass surgery is required in less than 4 percent of patients.1 2 3 Despite these improvements, re-Stenosis in the days, weeks, or months after successful angioplasty of a narrowed coronary artery occurs in 25 to 35 percent of patients,3 4 5 6 7 or 45 to 55 percent of those with . . .
Liposome-supported peritoneal dialysis for detoxification of drugs and endogenous metabolites (2014)

Peritoneal dialysis confers therapeutic advantages in patients with renal insufficiency and has proven beneficial in other indications, such as removal of excess metabolites or overdosed drugs. However, it is used in only about 10% of the dialyzed population worldwide, partly owing to the lower clearance rate compared with hemodialysis. We have developed a dialysis medium based on liposomes with a transmembrane pH gradient (basic or acidic aqueous core) that could improve the efficacy of peritoneal dialysis, specifically for the removal of excess metabolites or overdosed drugs. These scavenging vesicles are able to extract ionizable drugs and toxic metabolites into the peritoneal space and can be easily withdrawn from the body at the end of dialysis. This approach was used to successfully remove ammonia from rats with a greater extraction efficiency than traditional peritoneal dialysis, and may therefore prove useful in the treatment of severe hyperammonemia. Liposomal dialysis was also used to concentrate exogenous compounds in the rat peritoneal cavity, allowing for sequestration of several drugs that are frequently involved in overdose in people. In particular, liposomal dialysis counteracted the hypotensive action of the cardiovascular drug verapamil more efficiently than did control dialysis in a rat model of drug overdose. These findings highlight the versatility and advantage of this liposome-based approach for emergency dialysis.
Organization of the T-cell receptor alpha-chain gene and rearrangement in human T-cell leukaemias. (1986)

The structure and rearrangement of the human T-cell receptor alpha-chain gene have been analysed. The constant region segment is comprised of four exons, with the 3' non-coding region present as a separate exon. Two J alpha segments have been identified by sequence analysis about 4 X 10(3) and 15 X 10(3) base-pairs upstream from the constant region segment. Analysis of alpha-chain rearrangements in a panel of T-cells reveals the presence of at least four more J alpha segments within 19 X 10(3) base-pairs of C alpha and suggests the existence of additional J alpha segments further upstream. This dispersed organization of the J alpha region contrasts with the clustered organization observed in other lymphoid rearranging genes. The use of J alpha probes in diagnostic purposes for T-cell leukaemia is not, therefore, convenient and will require a number of different probes to ensure complete analysis of the locus.
Neutralizing anti-insulin-like growth factor receptor 1 antibodies inhibit receptor function and induce receptor degradation in tumor cells. (2002)

Insulin-like growth factor receptor 1 (IGFR1) plays a crucial role in oncogenic transformation [C. Sell et al., Mol. Cell. Biol., 14: 3604-3612,1994]. Compared with the normal human mammary epithelial cell line MCF12A, MCF7 human mammary carcinoma cells overexpress IGFR1 on the cell surface. To measure the effects of IGFR1 inhibition on tumor cells, we tested two mouse neutralizing antibodies against human IGFR1 in cell-based assays. Both MAB391 and anti-IR3 antibodies inhibit IGFR1 autophosphorylation upon IGF-I ligand stimulation with IC50s of 0.58 and 0.80 nM, respectively. When cells were treated with neutralizing anti-IGFR1 antibodies for > or = 4 h, the total receptor level was dramatically decreased. IGF-I-stimulated activation of AKT was also inhibited by anti-IGFR1 antibodies. Furthermore, MAB391 and anti-IR3 inhibited the growth of MCF7 cells in soft agar. In addition to MCF7 cells, MAB391 also inhibited IGFR1 autophosphorylation and induced IGFR1 down-modulation in HT29 colorectal and Du145 prostate cancer cells. Therefore, neutralizing antibodies against IGFR1 represent a valid approach to inhibit growth of tumor cells.
Landmarks and City Hall: How Historic Preservation Contributes to Municipal Government (1996)

Comments expressed are based, in part, on experiences while working with the staff of the Kentucky Heritage Council, (the State Historic Preservation Office), and while providing technical services to cities in Kentucky in connection with their historic preservation programs.Compare two comments in Time magazine.In 1968 it reported the announcement of a 2,000,000-square-foot office tower to be built on top of Grand Central Terminal, a designated New York City landmark.This is the proposed building that led to the U.S. Supreme Court decision on historic
Characterization and Optimization of Peptide Arrays for the Study of Epitope−Antibody Interactions Using Surface Plasmon Resonance Imaging (2002)

The characterization of peptide arrays on gold surfaces designed for the study of peptide-antibody interactions using surface plasmon resonance (SPR) imaging is described. A two-step process was used to prepare the peptide arrays: (i) a set of parallel microchannels was used to deliver chemical reagents to covalently attach peptide probes to the surface by a thiol-disulfide exchange reaction; (ii) a second microchannel with a wraparound design was used as a small-volume flow cell (5 microL) to introduce antibody solutions to the peptide surface. As a demonstration, the interactions of the FLAG epitope tag and monoclonal anti-FLAG M2 were monitored by SPR imaging using a peptide array. This peptide-antibody pair was studied because of its importance as a means to purify fusion proteins. The surface coverage of the FLAG peptide was precisely controlled by creating the peptide arrays on mixed monolayers of alkanethiols containing an amine-terminated surface and an inert alkanethiol. The mole fraction of peptide epitopes was also controlled by reacting solutions containing FLAG peptide and the non-interacting peptide HA or cysteine. By studying variants based on the FLAG binding motif, it was possible to distinguish peptides differing by a single amino acid substitution using SPR imaging. In addition, quantitative analysis of the signal was accomplished using the peptide array to simultaneously determine the binding constants of the antibody-peptide interactions for four peptides. The binding constant, K(ads), for the FLAG peptide was measured and found to be 1.5 x 10(8) M(-1) while variants made by the substitution of alanine for residues based on the binding motif had binding constants of 2.8 x 10(7), 5.0 x 10(6), and 2.0 x 10(6) M(-1).
The efficacy of oral ivermectin for the treatment of chronic blepharitis in patients tested positive for Demodex spp. (2011)

Demodex folliculorum and D brevis are common ectopic parasites that inhabit the pilosebaceous units of the human skin. They are associated with dermatological problems such as acne, rosacea and folliculitis.1 In ophthalmology, they are considered an aetiological factor of chronic blepharitis, meibomian gland dysfunction and ocular surface inflammation. Pathogenesis is controversial as Demodex can also be found in many asymptomatic patients. In this study, we aimed to investigate the efficacy and safety of the oral use of ivermectin in the treatment of chronic, recalcitrant blepharitis.

Patients diagnosed as having chronic symptomatic blepharitis resistant to conventional treatment were included (figure 1A). The participants provided written informed consent, and the study was approved by the institutional review board/ethics committee and followed the tenets of the Declaration of Helsinki. All patients underwent a thorough ophthalmic examination, including tear break-up time (BUT), symptoms' questionnaire and ocular surface disease index (OSDI), and were tested for the presence …
Bacterial biofilms and the bioelectric effect (1996)

Bacterial biofilms are acknowledged to be a major factor in problems of ineffective sterilization often encountered in clinics, hospitals, and industrial processes. There have been indications that the addition of a relatively small direct current electric field with the sterilant used to combat the biofilm greatly increases the efficacy of the sterilization process. The results of the experiments reported in this paper support the concept of the "bioelectric effect" as reported by J.W. Costerton, B. Ellis, K. Lam, F. Johnson, and A.E. Khoury (Antimicrob. Agents Chemother, 38:2803-2809, 1994). With a current of 1 mA flowing through the chamber containing the biofilm, an increase in the killing of the bacteria of about 8 log orders was observed at the end of 24 h (compared with the control with the same amount of antibacterial agent but no current). We also confirmed that the current alone does not affect the biofilm and that there appear to be optimum levels of both the current and the sterilant that are needed to obtain the maximum effect.