gebhart/patrepeval huggingface dataset:
Activation of an MDM2-specific Caspase by p53 in the Absence of Apoptosis (1999)

Cells undergoing p53-mediated apoptosis activate caspase 3-like activities, resulting in the cleavage of the MDM2 oncoprotein and other apoptotic substrates such as poly(ADP-ribose) polymerase. To investigate the mechanism of p53-mediated apoptosis and to determine whether cleavage of MDM2 has a potential role in regulating p53, we examined caspase activation and cleavage of MDM2 in a cell line undergoing p53-mediated growth arrest and delayed apoptosis. We found that in H1299 cells expressing a temperature-sensitive human p53, a distinct caspase activity specific for the MDM2 cleavage site DVPD is induced by p53 prior to the onset of apoptosis and loss of viability. This is accompanied by the cleavage of MDM2 but not the apoptotic substrate poly(ADP-ribose) polymerase. The cleaved MDM2 loses the ability to promote p53 degradation and may potentially function in a dominant-negative fashion to stabilize p53. These results suggest that p53 activation may induce a positive feedback effect by cleavage of MDM2 through a unique caspase.
Severe genital herpes infections in HIV-infected individuals with impaired herpes simplex virus-specific CD8+cytotoxic T lymphocyte responses (1997)

The specific mechanisms underlying the varied susceptibility of HIV-infected (HIV+) individuals to opportunistic infections (OI) are still incompletely understood. One hypothesis is that quantitative differences in specific T cell responses to a colonizing organism determine the development of an AIDS-defining OI. We evaluated this hypothesis for herpes simplex virus (HSV) infection, a common OI in HIV+ patients. Using limiting dilution analyses, the frequency of HSV-specific CD8+ cytotoxic T lymphocyte precursors (pCTL) and proliferative precursors were quantitated in peripheral blood mononuclear cells from 20 patients coinfected with HIV and HSV-2. The frequency of HSV-specific CD8+ pCTL in HSV+HIV+ individuals was significantly lower than in HSV+HIV- individuals (1 in 77,000 vs. 1 in 6,000, P = .0005) and was not different than in HSV-HIV- individuals (1 in 100,000, P = .24). HIV+ patients who suffered more severe genital herpes recurrences had significantly lower HSV-specific CD8+ pCTL frequencies than those patients with mild recurrences (1 in 170,000 vs. 1 in 26,000, P = .03). In contrast, no significant difference was seen in proliferative precursor frequencies between those patients with mild vs. severe genital herpes (1 in 3,800 vs. 1 in 6,600, P > .5). Quantitative differences in pCTL frequency to HSV appear to be the most important host factor influencing the frequency and severity of HSV reactivation in HIV+ patients. Studies to reconstitute such immunity, especially in people with acyclovir-resistant HSV, appear warranted.
Changes in gene expression and protein phosphorylation in murine cells, transformed or abortively infected with wild type and mutant simian virus 40. (1983)

The mechanism of SV40-induced cellular transformation was investigated by two-dimensional gel analysis of 35S- and 32P-labeled proteins of various cells. These included rat and mouse cells, either transformed or abortively infected by SV40 wild type, small t deletion mutants, and a large T temperature-sensitive mutant. Synthesis, turnover, or (de)phosphorylation of multiple protein spots was found to be reproducibly and quantitatively influenced by the transformed and/or infected status. Several of these alterations were attributable to the biological activity of either large T or small t antigen. Most changes in 35S-labeled proteins corresponded to a decreased intensity of the gel spots in transformed cells, while hyperphosphorylated proteins were more common than hypophosphorylated ones. About half of the polypeptide alterations in 35S-and 32P-labeled SV40-transformed rat cells, including a set of 35S-labeled small t-dependent changes were shared by Rous sarcoma virus-transformed cells. In contrast, small t-dependent (de)phosphorylation was rarely detected. Phosphoamino acid analysis of selected phosphoprotein spots of rat cells and alkaline hydrolysis of whole two-dimensional gels did not reveal any evidence for increased tyrosine-specific phosphorylation after SV40-induced transformation. Abortively infected mouse cells showed many protein alterations, also observed in stably transformed cells. However, the latter cells contained additional changes, also affecting several phosphoproteins and possibly related to the establishment of transformation. These findings are discussed in relation to the biological functions, known or presumed, for SV40 large T and small t antigens during transformation.
Biocatalytic Carbon Paste Sensors Based on a Mediator Pasting Liquid (2004)

The preparation and advantages of a new generation of carbon paste enzyme electrodes where the redox mediator acts also as the pasting liquid are described. The mediator pasting liquid concept is illustrated for amperometric biosensing of glucose in connection with either the tert-pentylferrocene or n-butylferrocene mediator/binder along with the glucose oxidase enzyme. The attractive performance and advantages of the new device is indicated from comparison to a conventional carbon paste biosensor using a mineral oil binder and the dimethylferrocene electron acceptor. The simplified preparation of the biosensor is coupled with a greatly improved sensitivity and an extended linear range. The mediator pasting liquid imparts high thermal stability onto the embedded enzyme and leads to good resistance to oxygen effects. Owing to the huge mediator reservoir, stability problems associated with the leaching of the mediator are greatly reduced. The fundamental aspects of the electrode behavior have been examined first in the absence of the enzyme. Variables affecting the performance of the new carbon paste biosensor have been investigated and optimized. Such use of the electron acceptor as a binder as well as the mediator offers considerable promise for the biosensing of numerous analytes of clinical and environmental significance.
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy (2010)

Adenosine monophosphate-activated protein kinase (AMPK) is a conserved sensor of intracellular energy activated in response to low nutrient availability and environmental stress. In a screen for conserved substrates of AMPK, we identified ULK1 and ULK2, mammalian orthologs of the yeast protein kinase Atg1, which is required for autophagy. Genetic analysis of AMPK or ULK1 in mammalian liver and Caenorhabditis elegans revealed a requirement for these kinases in autophagy. In mammals, loss of AMPK or ULK1 resulted in aberrant accumulation of the autophagy adaptor p62 and defective mitophagy. Reconstitution of ULK1-deficient cells with a mutant ULK1 that cannot be phosphorylated by AMPK revealed that such phosphorylation is required for mitochondrial homeostasis and cell survival during starvation. These findings uncover a conserved biochemical mechanism coupling nutrient status with autophagy and cell survival.
Strategies for Multiple Sequence Alignment (2002)

We present an overview of multiple sequence alignments to outline the practical consequences for the choices among different techniques and parameters. We begin with a discussion of the scoring methods for quantifying the quality of a multiple sequence alignment, followed by a discussion of the algorithms implemented within a variety of multiple sequence alignment programs. We also discuss additional alignment details such as gap penalty and distance metrics. The paper concludes with a discussion on how to improve alignment quality and the limitations of the techniques described in this paper
Adenomas and follicular carcinomas of the thyroid display two major patterns of chromosomal changes (2005)

It was recently shown by flow and static cytometry that a large sub-group of follicular adenomas of the thyroid--fetal/embryonal adenomas--display an aneuploid phenotype. It was also shown that thyroid lesions with a DNA content within the triploid range were either fetal adenomas or follicular carcinomas with a fetal adenoma growth pattern. Follicular tumours with growth patterns other than the so-called fetal adenoma-like pattern were usually diploid or near-diploid. In an attempt to clarify the pattern of chromosomal imbalances in follicular tumours, comparative genomic hybridization (CGH) analysis was performed in a series of 18 follicular neoplasms (ten fetal/embryonal and four common follicular adenomas and four minimally invasive follicular carcinomas). For each tumour, the DNA content was determined by flow cytometry and, in some cases, also by static cytometry. Finally, the copy number of selected chromosomes was determined by interphase fluorescence in situ hybridization (FISH) using centromere probes. With the exception of the single diploid fetal adenoma, all fetal adenomas displayed several DNA copy number changes, with frequent gains of several chromosomes, which were found to be either tetrasomic or trisomic by FISH. This genetic pattern was also present in the single case of follicular carcinoma with aneuploidy and fetal adenoma-like growth pattern. Follicular adenomas other than fetal adenomas, and the remaining follicular carcinomas, showed more losses than gains of chromosomes. These results suggest that follicular tumourigenesis may follow at least two pathways: one characterized by prominent aneuploidy and numerous gains, in which the tumours display a fetal adenoma-like growth pattern; and another accompanied by less obvious aneuploidy or even quasi-diploidy and dominant chromosome losses, in which the tumours display a common follicular architecture.
Inhaled dry powder apomorphine (VR040) for ‘off ’ periods in Parkinson's disease: an in-clinic double-blind dose ranging study (2013)

Inhaled apomorphine shows significant promise as a replacement for intermittent subcutaneous injections; further studies are appropriate to optimize efficacy and tolerability.
Preparation of Ag/SiO2 Nanosize Composites by a Reverse Micelle and Sol−Gel Technique (1999)

Spherical nanosize Ag/SiO2 composite particles have been synthesized within reverse micelles via metal alkoxide hydrolysis and condensation. The size of the particles and the thickness of the coating can be controlled by manipulating the relative rates of the hydrolysis and condensation reactions of tetraethoxysilane (TEOS) within the microemulsion. Composite particles in the size range 20−35 nm are produced. As the molar ratio of water to surfactant is increased above 10, the size distribution broadens. Absorption spectra have been used to dynamically monitor the reaction and growth. The effects of other synthesis parameters, such as the molar ratio of water to TEOS and the amount of base catalyst, are discussed. Possible mechanisms for the formation of the nanocomposite particles are also discussed.
IFN- β -Dependent Inhibition of Tumor Growth by the Vascular Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid (DMXAA) (2008)

By attacking established tumor vasculature, vascular disrupting agents (VDAs) represent an alternative approach to the treatment of cancer. One such VDA, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), is scheduled for phase III trials for prostate and lung cancer in combination with conventional chemotherapies. In this work, we identify interferon-beta (IFN-beta) as a central mediator in the host's response to DMXAA. In mice bearing Lewis lung adenocarcinomas, a single intraperitoneal dose of DMXAA was shown to effect a highly significant reduction in tumor growth rate in wild-type mice that was not seen in IFN-beta-null mice. Moreover, intratumoral cytokine expression was shown to be dependent on host-derived IFN-beta, as DMXAA-treated IFN-beta-null mice demonstrated a lack of induction of not only IFN-beta but also the antiangiogenic cytokine, IP-10, in excised tumor tissue. These results support the conclusion that DMXAA derives its potent anticancer properties in part through elicitation of IFN-beta expression by host-derived elements.
Stereotypic Movement Disorder (1997)

Article AbstractLetter to the Editor Sir: Castellanos et al. (March 1996 issue) recently reported that DSM-IV stereotypic movement disorder can be diagnosed in intellectually normal adult patients. This paper is another in a series of fascinating studies conducted by Rapoport and colleagues on the differential response of unwanted repetitive behaviors such as hair pulling and nail biting to clomipramine and desipramine. The idea that such behaviors fall on an obsessive-compulsive disorder (OCD) spectrum of conditions may provide a valuable heuristic in both clinical and research settings.
Lessons and limitations of South African research : stopping cop killing (2002)

One issue that has been of particular concern in South Africa over the last few years has been the high 
number of violent incidents in which members of the SAPS have been killed. Research has been done to 
determine the risk profile of police, the circumstances of killings both on and off duty, and the motives of 
police killers. But there are unanswered questions and further research could contribute to a better 
understanding of the dangers facing police.
Pilot evaluation of 1-amino-2-[18F] fluorocyclopentane-1-carboxylic acid (anti-2-[18F] FACPC) PET-CT in recurrent prostate carcinoma (2010)

1266 Objectives Aminocyclopentane carboxylic acid (ACPC) is an unnatural alicyclic amino acid which was originally developed as a therapeutic agent for malignant tumors via competitive inhibition of valine synthesis by tumor cells. Anti-2-[18F]FACPC is an ACPC analogue with high uptake in the DU-145 prostate cancer cell line in-vitro. Methods 5 patients with elevated PSA (1.1-20.5 ng/mL) after curative therapy for prostate carcinoma, underwent 60 minute dynamic imaging of the pelvis on a GE Discovery PET-CT after IV injection of 193-340 MBq of anti-2-[18F]FACPC. Uptake was compared against recently performed PET scans in the same patients with the leucine analogue, anti-[18F]FACBC, at similar time points and validated via pathology, clinical and imaging follow-up. Results At 5 min, mean(SD) SUVmax of known lesions is 4.1(1.3) for FACPC and 4.3(1.1) for FACBC. Yet, blood pool is significantly higher for FACPC with SUVmean 2.7(0.5) compared to FACBC 1.3(0.3). Lesion/blood pool SUV ratio for FACPC is 1.4(0.5) vs. 3.4(0.8) for FACBC. At 20 min, mean(SD) SUVmax of known lesions is 2.8(1.0) for FACPC and 3.9(0.8) for FACBC. Yet, bladder demonstrates intense activity for FACPC with SUVmean of 41.8(31) compared with FACBC 1.5(0.7). Lesion/bladder SUV ratio for FACPC is 0.8(1.6) vs. 3.2(1.2) for FACBC. Bone lesions in one patient were only identified with FACBC. Conclusions While prostate bed lesions are visible on early imaging with anti-2-[18F]FACPC, there is relatively high blood pool obscuring evaluation of nodal disease. As blood pool fades, nodal uptake decreases and high bladder activity then obscures pelvic structures. Compared with anti-[18F]FACBC in these 5 patients, imaging characteristics for anti-2-[18F]FACPC are unfavorable for pelvic prostate carcinoma detection. Research Support Research sponsored by the Georgia Cancer Coalition
Enhancing Isoprene Production by Genetic Modification of the 1-Deoxy- d -Xylulose-5-Phosphate Pathway in Bacillus subtilis (2011)

To enhance the production of isoprene, a volatile 5-carbon hydrocarbon, in the Gram-positive spore-forming rod-shaped bacterium Bacillus subtilis, 1-deoxy-d-xylulose-5-phosphate synthase (Dxs) and 1-deoxy-d-xylulose-5-phosphate reductoisomerase (Dxr) were overexpressed in B. subtilis DSM 10. For the strain that overexpresses Dxs, the yield of isoprene was increased 40% over that by the wild-type strain. In the Dxr overexpression strain, the level of isoprene production was unchanged. Overexpression of Dxr together with Dxs showed an isoprene production level similar to that of the Dxs overproduction strain. The effects of external factors, such as stress factors including heat (48°C), salt (0.3 M NaCl), ethanol (1%), and oxidative (0.005% H(2)O(2)) stress, on isoprene production were further examined. Heat, salt, and H(2)O(2) induced isoprene production; ethanol inhibited isoprene production. In addition, induction and repression effects are independent of SigB, which is the general stress-responsive alternative sigma factor of Gram-positive bacteria.
Intra-tympanic injections in the treatment of tinnitus (1992)

Prolonged reduction or abolition of tinnitus has been reported in about two-thirds of patients treated with a single or weekly-repeated injection through the tympanic membrane of either dexamethasone or lignocaine. In a small-scale trial of these treatments, dexamethasone gave 6 patients little benefit but few side-effects. Lignocaine gave 5 patients no lasting benefit but violent vertigo for several hours. A. Axelsson (personal communication) had similar experience with 6 patients treated with intra-tympanic lignocaine. It is concluded that this form of treatment does not seem sufficiently effective to offset its low acceptability.
Interactions among Strategies Associated with Bacterial Infection: Pathogenicity, Epidemicity, and Antibiotic Resistance (2002)

Infections have been the major cause of disease throughout the history of human populations. With the introduction of antibiotics, it was thought that this problem should disappear. However, bacteria have been able to evolve to become antibiotic resistant. Nowadays, a proficient pathogen must be virulent, epidemic, and resistant to antibiotics. Analysis of the interplay among these features of bacterial populations is needed to predict the future of infectious diseases. In this regard, we have reviewed the genetic linkage of antibiotic resistance and bacterial virulence in the same genetic determinants as well as the cross talk between antibiotic resistance and virulence regulatory circuits with the aim of understanding the effect of acquisition of resistance on bacterial virulence. We also discuss the possibility that antibiotic resistance and bacterial virulence might prevail as linked phenotypes in the future. The novel situation brought about by the worldwide use of antibiotics is undoubtedly changing bacterial populations. These changes might alter the properties of not only bacterial pathogens, but also the normal host microbiota. The evolutionary consequences of the release of antibiotics into the environment are largely unknown, but most probably restoration of the microbiota from the preantibiotic era is beyond our current abilities.
Second Harmonic Alternating Current Polarography with a Reversible Electrode Process (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSecond Harmonic Alternating Current Polarography with a Reversible Electrode ProcessD. E. Smith and W. H. ReinmuthCite this: Anal. Chem. 1961, 33, 4, 482–485Publication Date (Print):April 1, 1961Publication History Published online1 May 2002Published inissue 1 April 1961https://pubs.acs.org/doi/10.1021/ac60172a002https://doi.org/10.1021/ac60172a002research-articleACS PublicationsRequest reuse permissionsArticle Views79Altmetric-Citations32LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The Krüppel-associated box-A (KRAB-A) domain of zinc finger proteins mediates transcriptional repression. (1994)

We have previously reported the cloning, sequencing, and partial characterization of Kid-1, a zinc finger-encoding cDNA from the rat kidney. The Kid-1 protein and approximately one-third of all other zinc finger proteins contain a highly conserved region of approximately 75 amino acids at their NH2 terminus named Krüppel-associated box (KRAB), which is subdivided into A and B domains. The evolutionary conservation, wide distribution, and genomic organization of the KRAB domains suggest an important role of this region in the transcriptional regulatory function of zinc finger proteins. The functional significance of the KRAB domain was evaluated by studying transcriptional activities of yeast GAL4-rat Kid-1 fusion proteins containing various regions of the non-zinc-finger domain of Kid-1. Transcriptional repressor activity of GAL4-Kid-1 fusion proteins maps to the KRAB-A domain. The KRAB-A domain of another zinc finger protein, ZNF2, also has repressor activity. Site-directed mutagenesis of conserved amino acids in this motif results in decreased repressor activity. Thus, we have established a functional significance for the KRAB-A domain, a consensus sequence common in zinc finger proteins.
Identification of Regulatory Phosphorylation Sites in Mitogen-activated Protein Kinase (MAPK)-activated Protein Kinase-1a/p90 That Are Inducible by MAPK (1998)

Mitogen-activated protein kinase-activated protein kinase-1 (MAPKAP-K1; also known as p90rsk) contains two protein kinase domains in a single polypeptide. The N-terminal kinase domain is necessary for the phosphorylation of peptide substrates, whereas the C-terminal kinase domain is required for full activation of the N-terminal domain. Here we identify six sites in MAPKAP-K1a that become phosphorylated in transfected COS-1 cells. The inactive form of MAPKAP-K1a in unstimulated cells is partially phosphorylated at Ser222 and Ser733. Stimulation with phorbol 12-myristate 13-acetate induces the phosphorylation of Thr360, Ser364, Thr574, and Ser381 and increases the phosphorylation of Ser222 and Ser733. Our data indicate that mitogen-activated protein kinase activates the C-terminal kinase domain by phosphorylating Thr574 and contributes to the activation of the N-terminal kinase domain by phosphorylating Ser364. The activated C-terminal domain phosphorylates Ser381, which, together with phosphorylation of Ser364, activates the N-terminal kinase domain. The phosphorylation of Ser222 and Ser733, which can be catalyzed by the N-terminal domain, does not activate MAPKAP-K1a per se, but Ser222 phosphorylation appears to be required for activation. Ser222, Ser364, and Ser381 are situated in analogous positions to phosphorylation sites in protein kinase B, protein kinase C, and p70S6K, suggesting a common mechanism of activation for these growth factor-stimulated protein kinases.