gebhart/patrepeval huggingface dataset:
Potentiation of DNA-Damage-Induced Cytotoxicity by G2Checkpoint Abrogators (2003)

Cell cycle checkpoints are activated in response to DNA-damage to ensure that accurate copies of the cellular genome are passed on to the next generation and to avoid replication and segregation of damaged DNA. These cellular control systems can be overcome by combining conventional DNA-damaging agents with compounds that target the cell cycle regulatory pathways, to enhance cytotoxicity. Tumor cells often comprise a corrupted G(1) cell cycle checkpoint while the G(2) cell cycle checkpoint is still intact. This review describes the concept of G(2) checkpoint abrogation with recognized (methylxanthines, UCN-01) and novel G(2) checkpoint abrogators to potentiate the cytotoxicity of DNA-damaging drugs and ionizing radiation. It illustrates the potential of G(2) checkpoint abrogators to preferentially sensitize p53-mutated, treatment resistant tumor cells for genotoxic treatment. Identification of the targets of caffeine and UCN-01 to be key-players of the G(2) checkpoint (ATM/ATR and Chk1, respectively) promoted the search for novel inhibitors of this checkpoint. Even though a direct causal link between G(2) checkpoint abrogation and chemo-/radiosensitization is difficult to prove the multitude of these novel compounds validate that inhibition of critical elements of the G(2) checkpoint (ATM/ATR-Chk1/Chk2-CDC25C-cascade) potentiates the cytotoxicity of DNA-damaging agents.
3-D localization of gamma ray sources with coded apertures for medical applications (2015)

Several small gamma cameras for radioguided surgery using CdTe or CdZnTe have parallel or pinhole collimators. Coded aperture imaging is a well-known method for gamma ray source directional identification, applied in astrophysics mainly. The increase in efficiency due to the substitution of the collimators by the coded masks renders the method attractive for gamma probes used in radioguided surgery. We have constructed and operationally verified a setup consisting of two CdTe gamma cameras with Modified Uniform Redundant Array (MURA) coded aperture masks of rank 7 and 19 and a video camera. The 3-D position of point-like radioactive sources is estimated via triangulation using decoded images acquired by the gamma cameras. We have also developed code for both fast and detailed simulations and we have verified the agreement between experimental results and simulations. In this paper we present a simulation study for the spatial localization of two point sources using coded aperture masks with rank 7 and 19.
Pharmaceutical Stress Testing : Predicting Drug Degradation (2005)

"This reference discusses the predictive power and limitations of current stress testing strategies and emphasizes the critical role of stress testing in the determination of the stability characteristics of pharmaceuticals-offering an extensive compilation of drug degradation studies from real-world examples in the literature. Richly illustrated and extensively referenced, this source details the execution and interpretation of small molecule stress testing studies, provides a comprehensive overview of the major aspects of the prediction of drug degradation, presents up-to-date approaches to pharmaceutical stress testing, and much more"--Provided by publisher
Rotors and Spiral Waves in Atrial Fibrillation (2003)

Despite many years of research, the mechanisms of atrial fibrillation (AF) are still poorly understood, and we currently are unable to adequately treat most patients with AF. Recently, the demonstration in both human and animal studies that the pulmonary veins (PVs) and the posterior left atrial (LA) wall play a substantial role in triggering and in driving the fibrillatory activity has opened new avenues for research into the mechanisms of initiation and maintenance AF at many levels of integration. This article focuses on recent studies at the whole-heart level that support the hypothesis that maintenance of AF, whether paroxysmal or persistent, may depend on the periodic activity of a small number of rotors in the posterior LA wall-PV region. These rotors activate the atria at exceedingly high frequencies and result in fibrillatory conduction. Recent clinical studies involving either segmental PV isolation or circumferential PV ablation support this view. Such encouraging results suggest that collaboration between basic and clinical electrophysiologists will lead to a more precise understanding of the manner in which rotors stabilize in the PV-LA junction, which should open new doors for the development of innovative approaches for the prevention, diagnosis, and treatment of AF.
Kinetics of Human Motion (2002)

External contact forces statics of multilink serial chains - transformational analysis statics of multilink chains - stability of equilibrium inertial properties of the human body joint torques and forces - the inverse problem of dynamics mechanical work and energy in human movement. Appendices: inertial properties of cadavers inertial properties measured in living subjects geometric modeling of human body segments.
Binaltorphimine-related bivalent ligands and their .kappa. opioid receptor antagonist selectivity (1988)

In an effort to develop selective antagonists for kappa opioid receptors, bivalent ligands that contain opioid antagonist pharmacophores derived from naltrexone or other morphinans were synthesized and tested on the guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. The minimum requirements for kappa selectivity are at least one free phenolic OH group and one N-cyclopropyl or N-ally substituent. Several compounds (3, 8, 10) with kappa selectivity as good as or better than norbinaltorphimine (nor-BNI, 2) were discovered. The structure-activity relationship revealed that the pyrrole ring functions strictly as a spacer and does not contribute to kappa selectivity. The pharmacologic data suggest that only one antagonist pharmacophore may be required for kappa selectivity and that the other morphinan portion of the molecule confers selectivity by interacting with a unique subsite proximal to the antagonist pharmacophore recognition locus.
Dendritic Cells Harbor Infectious Porcine CircovirusType 2 in the Absence of Apparent Cell Modulation or Replication of theVirus (2003)

Dendritic cells (DCs) play crucial roles in innate and adaptive immune responses, rendering them critical targets for virus infections. Porcine circovirus type 2 (PCV2) is associated with the development of postweaning multisystemic wasting syndrome (PMWS) in piglets. We demonstrate here that 80 to 90% of monocyte-derived and bone marrow-derived DCs interact with PCV2 similar to the early stages of an infection. There was no evidence for virus replication, but the virus did persist in DCs without loss of infectivity nor the induction of cell death. This could reflect an abortive infection, but there was no evidence of virus uncoating-the infectivity remained intact for at least 5 days. Alternatively, the results may reflect DC endocytosis of antigenic material. However, there was no modulation of DC surface major histocompatibility complex class I and class II, CD80/86, CD25, CD16, or CD14. Furthermore, infected DC did not transmit virus to syngeneic T lymphocytes, even when the latter were activated. Such coculture did not induce PCV2 replication or death of the lymphocytes or DCs. These results demonstrate that PCV2 can persist in DCs in the absence of virus replication or degradation. Such a silent virus infection presents a novel mechanism of not only immune evasion but also escaping the DC degradation pathway. Because of their migratory capacity, infection of DCs thus provides a potent vehicle for transport of the virus throughout the host without the need for replication. In addition, the lymphopenia seen in PMWS is not a direct effect of the virus on lymphocytes but would require additional events, as proposed by others.
A novel 4.6F/sup 2/ NOR cell technology with lightly doped source (LDS) junction for high density flash memories (2002)

We have reported a 4.6F/sup 2/ NOR cell with a gate length of 0.3 /spl mu/m. The lightly doped source (LDS) junction is adopted to extend the effective channel length. The word line and source line pitch are significantly decreased with the self-aligned contact processing and W-pad source interconnection. Moreover, the LDS NOR cell shows the improved retention capability and the reduced oxide trapping.
Inhibition of Cell Migration, Spreading, and Focal Adhesions by Tumor Suppressor PTEN (1998)

The tumor suppressor PTEN is a phosphatase with sequence similarity to the cytoskeletal protein tensin. Here the cellular roles of PTEN were investigated. Overexpression of PTEN inhibited cell migration, whereas antisense PTEN enhanced migration. Integrin-mediated cell spreading and the formation of focal adhesions were down-regulated by wild-type PTEN but not by PTEN with an inactive phosphatase domain. PTEN interacted with the focal adhesion kinase FAK and reduced its tyrosine phosphorylation. Overexpression of FAK partially antagonized the effects of PTEN. Thus, PTEN phosphatase may function as a tumor suppressor by negatively regulating cell interactions with the extracellular matrix.
Characterization of a novel heparan sulfate proteoglycan found in the extracellular matrix of liver sinusoids and basement membranes. (1991)

A novel heparan sulfate proteoglycan (HSPG) present in the extracellular matrix of rat liver has been partially characterized. Proteoglycans were purified from a high salt extract of total microsomes from rat liver and found to consist predominantly (approximately 90%) of HSPG. A polyclonal antiserum raised against this fraction specifically recognized HSPG by immunoprecipitation and immunoblotting. The intact, fully glycosylated HSPG migrated as a broad smear (150-300 kD) by SDS-PAGE, but after deglycosylation with trifluoromethanesulfonic acid only a single approximately 40-kD band was seen. By immunocytochemistry this HSPG was localized in the perisinusoidal space of Disse associated with irregular clumps of basement membrane-like extracellular matrix material, some of which was closely associated with the hepatocyte sinusoidal cell surface. It was also localized in biosynthetic compartments (rough ER and Golgi cisternae) of hepatocytes, suggesting that this HSPG is synthesized and deposited in the space of Disse by the hepatocyte. The anti-liver HSPG IgG also stained basement membranes of hepatic blood vessels and bile ducts as well as those of kidney and several other organs (heart, pancreas, and intestine). An antibody that recognizes the basement membrane HSPG found in the rat glomerular basement membrane did not precipitate the 150-300-kD rat liver HSPG. We conclude that the liver sinusoidal space of Disse contains a novel population of HSPG that differs in its overall size, its distribution and in the size of its core protein from other HSPG (i.e., membrane-intercalated HSPG) previously described in rat liver. It also differs in its core protein size from HSPG purified from other extracellular matrix sources. This population of HSPG appears to be a member of the basement membrane HSPG family.
NM23-H1 and NM23-H2 messenger RNA abundance in human hepatocellular carcinoma. (1995)

nm23 was originally identified as an antimetastatic gene, the expression of which was inversely correlated with tumor metastatic potential in rodent model systems. Subsequently, two related human nm23 genes, nm23-H1 and nm23-H2, were identified. The relationship between expression of nm23-H1 and nm23-H2 in hepatocellular carcinoma specimens from 30 patients and metastatic potential was investigated with the use of a quantitative reverse transcription-PCR procedure. The abundance of nm23-H1 and nm23-H2 mRNA was compared with serum alpha-fetoprotein concentration, tumor size (maximum diameter), and histopathological parameters such as portal vein tumor thrombus, intrahepatic metastasis, capsular formation, capsular infiltration, differentiation of tumor cells, and TNM stage. The abundance of nm23-H1 mRNA showed a significant inverse correlation with intrahepatic metastasis and TNM stage. Furthermore, we confirmed that reduced expression of nm23-H1 mRNA was in accordance with a reduced amount of NM23-H1 protein using Western blot analysis. No correlation was apparent between nm23-H2 mRNA abundance and intrahepatic metastasis. These data support the conclusion that nm23-H1 may play a more important role than nm23-H2 in intrahepatic metastasis in hepatocellular carcinoma. Furthermore, nm23-H1 mRNA abundance may be a predictor of intrahepatic metastasis, the most important factor correlated with the metastatic potential of hepatocellular carcinoma.
Defined, Feeder‐Independent Medium for Human Embryonic Stem Cell Culture (2007)

The developmental potential of human ES cells makes them an important tool in developmental, pharmacological, and clinical research. For human ES cell technology to be fully exploited, however, culture efficiency must be improved, large-scale culture enabled, and safety ensured. Traditional human ES cell culture systems have relied on serum products and mouse feeder layers, which limit the scale, present biological variability, and expose the cells to potential contaminants. Defined, feeder-independent culture systems improve the safety and efficiency of ES cell technology, enabling translational research. The protocols herein are designed with the standard research laboratory in mind. They contain recipes for the formulation of mTeSR (a defined medium for human ES cell culture) and detailed protocols for the culture, transfer, and passage of cells grown in these feeder-independent conditions. They provide a basis for routine feeder-independent culture, and a starting point for additional optimization of culture conditions.
Use of an oral stable isotope label to confirm variation in red blood cell mean age that influences HbA1c interpretation (2014)

HbA1c is commonly used to monitor glycemic control. However, there is growing evidence that the relationship between HbA1c and mean blood glucose (MBG) is influenced by variation in red blood cell (RBC) lifespan in hematologically normal individuals. Correction of HbA1c for mean RBC age (MRBC ) requires a noninvasive, accurate, and affordable method to measure RBC survival. In this study, we evaluated whether a stable isotope approach would satisfy these requirements. RBC lifespan and MRBC were determined in a group of nine hematologically normal diabetic and nondiabetic subjects using oral (15) N-glycine to label heme in an age cohort of RBC. The MRBC was 58.7 ± 9.1 (2SD) days and RBC lifespan was 106 ± 21 (2SD) days. This degree of variation (±15-20%) is consistent with previous studies using other techniques. In a subset of seven subjects, MRBC determined with the biotin label technique were available from approximately five years prior, and strongly correlated with the stable isotope values (R(2) = 0.79). This study suggests that the MRBC is stable over time but varies substantially among individuals, and supports the importance of its variation in HbA1c interpretation. The characteristics of the stable isotope method support its suitability for studies to directly evaluate the impact of variation in MRBC on the interpretation of HbA1c.
Theory and Application of Audio-Based Assessment of Cough (2018)

Cough is a common symptom of many respiratory diseases. Many medical literatures underline that a system for the automatic, objective, and reliable detection of cough events is important and very promising to detect pathology severity in chronic cough disease. In order to track the development status of an audio-based cough monitoring system, we briefly described the history of objective cough detection and then illustrated the cough sound generating principle. The probable endpoints of cough clinical studies, including cough frequency, intensity of coughing, and acoustic properties of cough sound, were analyzed in this paper. Finally, we introduce some successful cough monitoring equipment and their recognition algorithm in detail. It can be obtained that, firstly, acoustic variability of cough sounds within and between individuals makes it difficult to assess the intensity of coughing. Furthermore, now great progress in audio-based cough detection is being made. Moreover, accurate portable objective monitoring systems will be available and widely used in home care and clinical trials in the near future.
C-Acylation of Hippurate and Related Esters Utilizing Multiple Anion Intermediates and Ethyl 4-Aminobenzoate (1990)

Abstract Hippurate and related esters were polymetalated with excess lithium diisopropylamide (LDA) at 0°C, and the resulting multiple anion intermediates were condensed with ethyl 4-aminobenzoate to afford C-acylated products.
The 5' proximal helix of 16S rRNA is involved in the binding of streptomycin to the ribosome. (1993)

Single mutations at the end of the 5' proximal helix and in the 915 region (13U-->A or C; 914A-->U or G), and double mutations (13U-->A and 914A-->U; 13U-->C and 914A-->G) were constructed into Escherichia coli 16S ribosomal RNA. The mutations were introduced into an expression plasmid containing the rrnB operon under the transcriptional control of the temperature-inducible lambda PL promoter. None of the mutant 16S rRNAs affected cell growth when expressed. Ribosomes extracted after induction of expression of the mutant 16S rRNAs were assayed for their capacity to bind the error-inducing drug streptomycin and for translational misreading in the presence of streptomycin. All mutations impaired the binding of streptomycin, and consequently its capacity to stimulate misreading. Our results demonstrate the involvement of the 5' proximal helix of 16S rRNA in the binding of streptomycin and confirm the participation of the 915 region. They do not support a previous suggestion [Leclerc, D. and Brakier-Gingras, L. (1991) FEBS Lett., Vol. 279, pp. 171-174] that base pairing between nucleotides 13 and 914 stabilizes the binding of streptomycin.
Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer (2008)

If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.
Improved procedure for oxidations with the chromium trioxide-pyridine complex (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImproved procedure for oxidations with the chromium trioxide-pyridine complexRonald Ratcliffe and Ronald RodehorstCite this: J. Org. Chem. 1970, 35, 11, 4000–4002Publication Date (Print):November 1, 1970Publication History Published online1 May 2002Published inissue 1 November 1970https://pubs.acs.org/doi/10.1021/jo00836a108https://doi.org/10.1021/jo00836a108research-articleACS PublicationsRequest reuse permissionsArticle Views2220Altmetric-Citations484LEARN 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
Purification and Properties of Pantothenate Kinase from Brevibacterium ammoniagenes IFO 12071 (1973)

Pantothenate kinase (ATP: pantothenate 4′-phosphotransferase, EC 2.7.1.33) was purified about 200-fold from the cell extract of Brevibacterium ammoniagenes IFO 12071 by ammonium sulfate fractionation, DEAE-cellulose chromatography, and Sephadex G-150 gel filtration. The purified enzyme gave a single band on polyacrylamide gel electrophoresis. The molecular weight was calculated approximately 45,000. The enzyme catalyzed the formation of pantothenic acid 4′-phosphate and ADP from pantothenate and ATP in the presence of Mg2+ ATP could be substituted for, partly, by ITP, GTP, and UTP. The enzyme phosphorylated not only pantothenate, but also pantothenoylcysteine, pantetheine, and pantothenyl alcohol. Apparent Km values were 6.7×10−5 m for pantothenate, 3.5×10−5 m for ATP, and 10−3 m for Mg2+. The reaction was inhibited by the intermediates of CoA biosynthesis, of which CoA itself was a most effective inhibitor. Other properties of the enzyme were also investigated.
The TGF-β, PI3K/Akt and PTEN pathways: established and proposed biochemical integration in prostate cancer (2008)

A key to the development of improved pharmacological treatment strategies for cancer is an understanding of the integration of biochemical pathways involved in both tumorigenesis and cancer suppression. Furthermore, genetic markers that may predict the outcome of targeted pharmacological intervention in an individual are central to patient-focused treatment regimens rather than the traditional 'one size fits all' approach. Prostate cancer is a highly heterogeneous disease in which a patient-tailored care program is a holy grail. This review will describe the evidence that demonstrates the integration of three established pathways: the tumour-suppressive TGF-beta (transforming growth factor-beta) pathway, the tumorigenic PI3K/Akt (phosphoinositide 3-kinase/protein kinase B) pathway and the tumour-suppressive PTEN (phosphatase and tensin homologue deleted on chromosome 10) pathway. It will discuss gene polymorphisms and somatic mutations in relevant genes and highlight novel pharmaceutical agents that target key points in these integrated pathways.
Genome Sequence of Thermotolerant Bacillus methanolicus: Features and Regulation Related to Methylotrophy and Production of l -Lysine and l -Glutamate from Methanol (2012)

Bacillus methanolicus can utilize methanol as its sole carbon and energy source, and the scientific interest in this thermotolerant bacterium has focused largely on exploring its potential as a biocatalyst for the conversion of methanol into L-lysine and L-glutamate. We present here the genome sequences of the important B. methanolicus model strain MGA3 (ATCC 53907) and the alternative wild-type strain PB1 (NCIMB13113). The physiological diversity of these two strains was demonstrated by a comparative fed-batch methanol cultivation displaying highly different methanol consumption and respiration profiles, as well as major differences in their L-glutamate production levels (406 mmol liter(-1) and 11 mmol liter(-1), respectively). Both genomes are small (ca 3.4 Mbp) compared to those of other related bacilli, and MGA3 has two plasmids (pBM19 and pBM69), while PB1 has only one (pBM20). In particular, we focus here on genes representing biochemical pathways for methanol oxidation and concomitant formaldehyde assimilation and dissimilation, the important phosphoenol pyruvate/pyruvate anaplerotic node, the tricarboxylic acid cycle including the glyoxylate pathway, and the biosynthetic pathways for L-lysine and L-glutamate. Several unique findings were made, including the discovery of three different methanol dehydrogenase genes in each of the two B. methanolicus strains, and the genomic analyses were accompanied by gene expression studies. Our results provide new insight into a number of peculiar physiological and metabolic traits of B. methanolicus and open up possibilities for system-level metabolic engineering of this bacterium for the production of amino acids and other useful compounds from methanol.