gebhart/patrepeval huggingface dataset:
Telomerase in human development and cancer (1997)

A potentially rate-limiting step in cancer progression is the conversion of a normal human cell into one capable of indefinite proliferation. There are at least two different cellular mechanisms that must be overcome before immortalization occurs. The first step generally requires inactivation of the pathways involving two tumor-suppressor genes, p53 and pRB, and the second step almost always involves the reactivation of the ribonucleoprotein enzyme telomerase. Telomerase synthesizes hexameric repeats (TTAGGG) onto telomeric ends, thereby compensating for telomeric losses that in its absence occurs at each cell division. Telomerase is present in human embryonic tissues, is not detected in most adult tissues, but is upregulated or reactivated in almost 90% of all human cancers. In the present article, I review the telomere-telomerase theory of aging and cancer including the roles of telomerase during human development, in differentiation, and in cancer. Research into the regulation of this enzyme may lead to methods to facilitate the accurate diagnosis of cancer and to the development of novel antitelomerase cancer therapeutics.
HER-2 gene amplification can be acquired as breast cancer progresses (2004)

Amplification and overexpression of the HER-2 oncogene in breast cancer is felt to be stable over the course of disease and concordant between primary tumor and metastases. Therefore, patients with HER-2-negative primary tumors rarely will receive anti-Her-2 antibody (trastuzumab, Herceptin) therapy. A very sensitive blood test was used to capture circulating tumor cells (CTCs) and evaluate their HER-2 gene status by fluorescence in situ hybridization. The HER-2 status of the primary tumor and corresponding CTCs in 31 patients showed 97% agreement, with no false positives. In 10 patients with HER-2-positive tumors, the HER-2/chromosome enumerator probe 17 ratio in each tumor was about twice that of the corresponding CTCs (mean 6.64 +/- 2.72 vs. 2.8 +/- 0.6). Hence, the ratio of the CTCs is a reliable surrogate marker for the expected high ratio in the primary tumor. Her-2 protein expression of 10 CTCs was sufficient to make a definitive diagnosis of the HER-2 gene status of the whole population of CTCs in 19 patients with recurrent breast cancer. Nine of 24 breast cancer patients whose primary tumor was HER-2-negative each acquired HER-2 gene amplification in their CTCs during cancer progression, i.e., 37.5% (95% confidence interval of 18.8-59.4%). Four of the 9 patients were treated with Herceptin-containing therapy. One had a complete response and 2 had a partial response.
Production and characterization of human basic fibroblast growth factor from Escherichia coli. (1988)

The cDNA sequence coding for human basic fibroblast growth factor (bFGF) has been cloned downstream of a transcription promoter recognized by the bacteriophage T7 RNA polymerase. Initiation of translation at the fgf gene has been coupled to upstream translation of a fragment of the T7 phi 10 gene. Expression of the fgf gene in this system can lead to an accumulation of approximately 40 mg/liter/A600 unit of bFGF. This material can be purified close to homogeneity from a soluble protein extract on a heparin-Sepharose column. bFGF so obtained has been shown to have bioactivity indistinguishable from human placental fibroblast growth factor in mitogenicity, synthesis of plasminogen activator, and angiogenesis assays.
Levodopa/dopamine replacement strategies in Parkinson's disease-Future directions (2008)

After 40 years, levodopa remains the most effective therapy for the treatment of PD. However, long-term therapy is complicated by motor fluctuations and dyskinesia that can represent a source of significant disability for some patients. Other medical therapies that are currently available for the treatment of PD primarily represent an attempt to prevent or treat motor complications. Surgical therapies improve motor complications in appropriate candidates, but do not provide antiparkinsonian benefits that are superior to levodopa, and are themselves associated with potentially serious side effects. Increasing information suggests that levodopa-induced motor complications relate to pulsatile, nonphysiologic dopamine replacement. A therapeutic strategy that could deliver levodopa/dopamine to the brain in a more continuous and physiologic manner might be expected to provide all of the benefits of standard levodopa with reduced motor complications. Such a levodopa formulation might replace all current dopaminergic antiparkinsonian medications and avoid the need for surgery in most PD patients. However, problems of continuous dopaminergic stimulation must be addressed and avoided, and the issue of nondopaminergic features remains to be addressed.
Observation of Large Changes in the Band Gap Absorption Energy of Small CdSe Nanoparticles Induced by the Adsorption of a Strong Hole Acceptor (2001)

When butylamine in relatively high concentrations (0.1−0.25 M) is added to a colloidal solution of CdSe nanoparticles (NPs) that are approximately 1.6 nm in diameter, the band gap absorption changes from a broad, relatively weak absorption centered at 445 nm to a narrow, relatively strong absorption centered at 414 nm. The effect of concentration on the observed spectrum shows an isobestic point, suggesting an equilibrium between two species. The possible mechanisms for such a transformation are discussed.
Hybrid multilevel power conversion system: a competitive solution for high-power applications (2000)

Trends in power semiconductor technology indicate a tradeoff in the selection of power devices in terms of switching frequency and voltage-sustaining capability. New power converter topologies permit modular realization of multilevel inverters using a hybrid approach involving integrated gate commutated thyristors (IGCTs) and insulated gate bipolar transistors (IGBTs) operating in synergism. This paper investigates a hybrid multilevel power conversion system typically suitable for high-performance high-power applications. This system, designed for a 4.16 kV/spl ges/100 hp load is comprised of a hybrid seven-level inverter, a diode bridge rectifier, and an IGBT rectifier per phase. The IGBT rectifier is used on the utility side as a real power flow regulator to the low-voltage converter and as a harmonic compensator for the high-voltage converter. The hybrid seven-level inverter on the load side consists of a high-voltage slow-switching IGCT inverter and a low-voltage fast-switching IGBT inverter. By employing different devices under different operating conditions, it is shown that one can optimize the power conversion capability of the entire system. A detailed analysis of a novel hybrid modulation technique for the inverter, which incorporates stepped synthesis in conjunction with variable pulsewidth of the consecutive steps is included. In addition, performance of a multilevel current-regulated delta modulator as applied to the single-phase full-bridge IGBT rectifier is discussed. Detailed computer simulations accompanied with experimental verification are presented in the paper.
Isolation of the murine S100 protein MRP14 (14 kDa migration-inhibitory-factor-related protein) from activated spleen cells: characterization of post-translational modifications and zinc binding (1996)

MRP14 (macrophage migration-inhibitory factor-related protein of molecular mass 14 kDa) is an S100 calcium binding protein constitutively expressed in human neutrophils which may be associated with cellular activation/inflammation. Murine MRP14 expression was up-regulated following concanavalin A activation of spleen cells, and the protein was isolated from conditioned medium in high yield (approx. 500 ng/ml). MRP14 had a mass of 12972 +/- 2 Da by electrospray ionization MS, whereas the theoretical mass derived from the cDNA sequence, after removal of the initiator Met, was 12918 Da, suggesting that the protein was post-translationally modified. We identified four post-translational modifications of MRP14: removal of the N-terminal Met, N-terminal acetylation, disulphide bond formation between Cys79 and Cys90, and 1-methylation of His106; the calculated mass was then 12971.8 Da. Methylation of His106 was further characterized after incubation of spleen cells with L-[methyl-3H]Met during concanavalin A stimulation. Sequential analysis of a peptide (obtained by digestion with Lys C) containing methylated His indicated that > 80% of the label in the cycle corresponded to His106, suggesting that the methyl residue was transferred from S-adenosyl-L-methionine. Comparison of the C18 reverse-phase HPLC retention times of phenylthiocarbamoyl derivatives of a hydrolysed digest peptide of MRP14 with those of standards confirmed methyl substitution on the 1-position of the imidazole ring. MRP14 bound more 85Zn2+ than the same amounts of the 10 kDa chemotactic protein (CP10) or S100 beta. Ca2+ decreased Zn2+ binding in S100 beta but it did not influence binding to MRP14, suggesting that the Zn2+ binding site was distinct from and independent of the two Ca2+ binding domains.
A cyclic dinucleotide containing 2-aminopurine is a general fluorescent sensor for c-di-GMP and 3′,3′-cGAMP (2014)

Cyclic dinucleotides have emerged as second messengers that regulate diverse processes in bacteria, as well as regulating the production of type I interferons in metazoans. Fluorescent sensors for these important second messengers are highly sought-after for high-throughput inhibitor discovery, yet most sensors reported to date are not amenable for high-throughput screening purposes. Herein, we demonstrate that a new analog, 3',3'-cG(d2AP)MP, which is a 2-aminopurine (2AP)-containing cyclic dinucleotide, self-associates in the presence of Mn(2+) with an association constant of 120,000 M(-1). 3'3'-cG(d2AP)MP can also form a heterodimer with cGAMP, activator of immune regulator, STING, or the bacterial biofilm regulator, c-di-GMP in the presence of Mn(II). Upon dimer formation, the fluorescence of 3',3'-cG(d2AP)MP is quenched and this provides a convenient method to monitor the enzymatic processing of both DGC and PDE enzymes, opening up several opportunities for the discovery of inhibitors of nucleotide signaling.
Analysis of digitized waveforms using Shannon entropy (1993)

A novel symbol-oriented, information-theoretic approach to signal analysis is described based on application of Shannon entropy. It is shown that this can be a preferred alternate to conventional digital signal energy analysis by making an experimental comparison of scanned ultrasonic images formed from Shannon entropy, signal energy, and log signal energy measurements. In these images, which were made by c scanning a Plexiglas bar with drill-hole ‘‘defects,’’ the Shannon entropy exhibits approximately two to three times the sensitivity of the two energy measures. However, the Shannon entropy analysis of waveforms suffers from a severe fundamental defect. It depends on the properties of the analog-to-digital converter (ADC) used to acquire the waveform as well as the properties of the waveform itself. As digitizer dynamic range is increased the Shannon entropy ultimately saturates at a level governed by the properties of the digitizer alone. This effect arises from the necessary limited bandwidth of a real ADC; if ADC bandwidth were not limited, the Shannon entropy would grow without bound with increasing dynamic range. To overcome this difficulty, a variant of the Shannon entropy is defined that depends only on the properties of the waveform. It is then shown that this variant is sensitive to the same scattering features as is the Shannon entropy for data acquired from the Plexiglas specimen discussed initially. Furthermore, the variant offers the same sensitivity improvements obtained from the Shannon entropy analysis. Finally, computation of this variant for waveforms having noise is described. Derivation of the variant is given in Appendix A of this work. Several of its more interesting features are also discussed there. Derivation of the procedure required to compute the variant is given in Appendix B.
Five putative subclasses of swine IgG identified from the cDNA sequences of a single animal. (1994)

We report the sequences of more than 40 partial and complete swine C gamma cDNAs obtained by PCR cloning of first strand cDNA, and from a cDNA expression library, all from a single animal. These seem to represent five IgG subclasses, that can be grouped into two clusters; one contains IgG1 and IgG3 and the other, IgG2a, IgG2b and IgG4. IgG2a and IgG2b differ by only three amino acids, but single strand conformational polymorphism analyses of PCR-amplified IgG2-specific segments in animals of different breeds, argues for their putative subclass status. Major subclass differences are found in the hinge and C gamma 3, but differences in upper hinge length, associated with segmental flexibility in the IgGs of other species, are absent. All subclasses have identical middle hinge segments that can accommodate three interheavy chain disulfide bridges. The putative swine IgG subclasses have their greatest similarity with those of the human except for the near absence of hinge region variation. Swine subclasses such as ruminant IgG2a, have a lower hinge deletion which in human IgG1, contains one of the motifs believed necessary for interaction with Fc gamma Rs. IgG1 was the most frequently encountered subclass cDNA (25 of 43) and the single swine-mouse hybridoma tested had a sequence identical to IgG1. Partial sequence analyses of genomic clones identified one clone identical with the IgG1/IgG3 subclass cluster, two identical to the IgG2b/IgG4 subclass group, and two identical to each other but different from any of the expressed sequences reported here. Genomic blots suggest that up to eight C gamma genes are present in the genome.
A Novel Pathogenic PSEN1 Mutation in a Family with Alzheimer's Disease: Phenotypical and Neuropathological Features (2011)

We report a novel presenilin1 (PSEN1) gene mutation (I143 V) in a four-generation family with Alzheimer's disease. Clinical, molecular, and neuropathological examinations were performed on index patient; thirteen affected subjects were also identified. The index patient presented at 55 with personality changes, apathy, reduction of verbal fluency, and temporal and spatial disorientation. At 68, she showed visual hallucinations; blurred language, and rigidity. She became bedridden and died at 75. A novel mutation at codon 143 was found in PSEN1 gene, changing isoleucine to valine. The brain showed severe atrophy of the frontal and temporal lobes. Parenchymal amyloid-β (Aβ) deposits were abundant, diffuse to grey structures and contained Aβ42, but very few Aβ40. Amyloid angiopathy was absent. Neurofibrillary changes were severe. Our study confirms that PSEN1 mutations can be associated with unusual phenotypes. The peculiarity of the age at onset (not very early), the long course, and the frontal involvement, together with the rather complete absence of Aβ40 and of amyloid angiopathy, widen the spectrum of PSEN1-linked phenotypes.
Increased urine catecholamines and cortisol in women with irritable bowel syndrome. (1996)

Increases in indicators of sympathetic nervous system activation in women seeking health care for IBS may reflect greater symptom distress or may contribute to increased symptom distress.
Medicinal Chemistry of Neuronal Voltage-Gated Sodium Channel Blockers (2001)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTMedicinal Chemistry of Neuronal Voltage-Gated Sodium Channel BlockersThorsten Anger, David J. Madge, Mushtaq Mulla, and Dieter RiddallView Author Information The Wolfson Institute for Biomedical Research, Cruciform Building, Gower Street, London WC1E 6AE, United Kingdom Cite this: J. Med. Chem. 2001, 44, 2, 115–137Publication Date (Web):January 11, 2001Publication History Received5 April 2000Published online11 January 2001Published inissue 1 January 2001https://pubs.acs.org/doi/10.1021/jm000155hhttps://doi.org/10.1021/jm000155hreview-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views2850Altmetric-Citations117LEARN 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 SUBJECTS:Assays,Genetics,Ions,Screening assays,Sodium Get e-Alerts
The role of mixotrophy in plankton bloom dynamics, and the consequences for productivity (2005)

Abstract Mixotrophy (=heterotrophy and photosynthesis by a single individual) is a common phenomenon in aquatic ecosystems, in particular under light- or nutrient-limitation. However, it is not usually considered in mathematical models of biological populations. This paper shows how different types of mixotrophy might be usefully incorporated into a general predator–prey model, and explores the consequences for plankton bloom dynamics and productivity. It is demonstrated, analytically and numerically, that even small levels of type III mixotrophy (a small fraction of the zooplankton also being involved in primary production) have significant effects on a system's equilibrium structure, stability, and short-term dynamics. Type III mixotrophy has a stabilizing effect on the system by reducing its excitability, i.e. its propensity to exhibit blooms. Compared with the non-mixotrophic benchmark, for a phytoplankton bloom to be triggered in a system with type III mixotrophy, a much larger perturbation is necessary. Type II mixotrophy (a small fraction of algae engage in phagotrophy) and type I mixotrophy (equal phagotrophy and phototrophy) are briefly discussed. The potential consequences for productivity are also studied. Our results indicate that the phytoplankton–zooplankton system becomes more productive in the presence of type III mixotrophy.
Up‐regulation of bone morphogenetic protein receptor IB by growth factors enhances BMP‐2‐induced human bone cell functions (2006)

Bone morphogenetic proteins (BMP) stimulate osteoblast differentiation by signal transduction via three BMP receptors (BMPR-IA, -IB, and -II). Several growth factors, including transforming growth factor-beta1 (TGF-beta1), fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-AB (PDGF-AB), have also been shown to play an important part in osteogenesis. The mechanism underlying these activities is unclear, but these growth factors could modulate the BMP/BMPR pathway by up-regulating BMPR expression, thereby enhancing the osteogenic responses of bone cells to the BMP. In this study we have therefore examined the effects of TGF-beta1, FGF-2, and PDGF-AB on BMPR expression and BMP-2-mediated osteoblast functions in primary human bone cells. The results showed that although the ligand BMP-2 and growth factors had little effect on BMPR-IA and -II transcript expression, they significantly up-regulated BMPR-IB mRNA specifically. However, only the growth factors, but not the ligand BMP-2, increased the surface expression of the BMPR-IB antigen, which was found to be due to a differential effect of BMP-2 and the growth factors on the Smurf1/Smad6-induced breakdown process. Pre-incubation of the cells with the growth factors significantly augmented BMP-2-induced Smad1/5/8 phosphorylation, and Dlx5 expression ALP activity, compared with that of cells treated with BMP-2 alone. When cells were transfected with siRNA targeting BMPR-IB, the growth factors neither up-regulated BMPR-IB transcript expression nor enhanced BMP-2-induced Smad1/5/8 phosphorylation, Dlx5 expression and ALP activity. The results indicate that increased BMPR-IB by TGF-beta1, FGF-2, and PDGF-AB significantly enhances BMP-2-induced osteogenic functions in vitro, suggesting that they might positively modulate bone formation by up-regulating BMPR-IB in vivo.
Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis (2008)

Lung edema formation in this model was the result of marked increases in both pulmonary microvascular permeability and pressure. Pulmonary vascular hyperpermeability peaked 12 hrs postinjury and was related to vascular endothelial growth factor overexpression. Early myocardial failure was a potential contributor to the constant increase in pulmonary capillary pressure. The sepsis-induced increase in peripheral microvascular permeability was associated with significant accumulation of fluid and protein in the third space.
Inhibition of Breast Cancer Cell Growth and Invasiveness by Dual Silencing of HER-2 and VEGF (2010)

Overexpression of HER-2 accounts for approximately 25% of all breast cancer cases, while 87.7% of HER-2 positive breast cancers are associated with upregulated VEGF. The objective of this study is to explore the combination therapy of blocking HER-2 and VEGF expressions simultaneously using siRNA. This is the first report to examine the effect of dual silencing of HER-2 and VEGF genes on tumor growth and invasiveness. We have designed nine HER-2 siRNAs and ten VEGF siRNAs, and identified potent siRNA which can silence the target gene up to 75-83.5%. The most potent HER-2 and VEGF siRNAs were used to conduct functional studies in HER-2 positive breast cancer cells. Tumor invasiveness properties including cell morphology change, in vitro migration, cell spreading, and adhesion to ECM were evaluated. In addition, cell proliferation and apoptosis were examined after the siRNA treatment. Our data demonstrated for the first time that HER-2 siRNA could inhibit cell migration and invasion abilities. Combination of HER-2 and VEGF siRNAs exhibited synergistic silencing effect on VEGF. Both HER-2 siRNA and VEGF siRNA showed significant inhibition on cell migration and proliferation. HER-2 siRNA also demonstrated dramatic suppression on cell spreading and adhesion to ECM, as well as induction of apoptosis. Dual silencing of HER-2 and VEGF exhibited significant cell morphology change, and substantial suppression on migration, spreading, cell adhesion, and proliferation. Our observations suggested that HER-2 positive breast cancer may be more effectively treated by dual inhibition of HER-2 and VEGF gene expressions using siRNA.