gebhart/patrepeval huggingface dataset:
Rearrangements involving chromosome band 11Q23 in acute leukaemia. (1993)

Rearrangements involving chromosome band 11q23 are very common in acute leukaemia, both lymphoblastic and myeloid (monoblastic), and are less common in lymphoma. Although several different genes have been cloned from translocation breakpoints, the great majority of translocations involve the MLL (myeloid-lymphoid leukaemia) gene. The MLL gene has several different names, ALL1, Htrx, HRX; the central part of the gene codes for multiple zinc fingers which show strong homology to the Drosophila trithorax gene. MLL is involved in four common translocations as well as in 25 uncommon or rare translocations, insertions and deletions. The translocation breakpoints occur within an 8.3 kb region which can be detected with a 0.74 kb cDNA probe. Twenty-five percent of patients have a deletion 3' of the breakpoint which includes the zinc finger region. Patients who previously received drugs that inhibit topoisomerase II often develop acute leukaemia with translocations involving 11q23. These translocations break MLL in the same 8.3 kb region. In the three breakpoints cloned to date, the translocation has led to a fusion gene on the derivative 11 chromosome with a chimaeric transcript, consisting of 5' MLL and the 3' segment of the other gene. Although transcripts were also cloned from the other derivative chromosome, all the evidence indicates that the critical fusion gene is on the derivative 11 chromosome. The molecular dissection of these rearrangements will provide insights into the biology of MLL and into the interaction of MLL with topoisomerase II inhibitors. In addition, this research has provided DNA probes that will be important for diagnosis and for monitoring patients during the course of their disease.
Engineering highly efficient backsplicing and translation of synthetic circRNAs (2021)

Circular RNAs (circRNAs) are highly stable RNA molecules that are attractive templates for expression of therapeutic proteins and non-coding RNAs. In eukaryotes, circRNAs are primarily generated by the spliceosome through backsplicing. Here, we interrogate different molecular elements including intron type and length, <i>Alu</i> repeats, internal ribosome entry sites (IRESs), and exon length essential for circRNA formation and exploit this information to engineer robust backsplicing and circRNA expression. Specifically, we leverage the finding that the downstream intron can tolerate large inserts without affecting splicing to achieve tandem expression of backspliced circRNAs and tRNA intronic circRNAs from the same template. Further, truncation of selected intronic regions markedly increased circRNA formation in different cell types <i>in vitro</i> as well as AAV-mediated circRNA expression in cardiac and skeletal muscle tissue <i>in vivo</i>. We also observed that different IRES elements and exon length influenced circRNA expression and translation, revealing an exonic contribution to splicing, as evidenced by different RNA species produced. Taken together, these data provide new insight into improving the design and expression of synthetic circRNAs. When combined with AAV capsid and promoter technologies, the backsplicing introns and IRES elements constituting this modular platform significantly expand the gene expression toolkit.
In vitroBACE-1 Inhibitory Phenolic Components from the Seeds ofPsoralea corylifolia (2008)

A new isoflavone, neocorylin ( 1) was isolated from the seeds extract of Psoralea corylifolia L. (Fabaceae), together with eight known constituents ( 2 - 9), i. e., bakuchiol ( 2), psoralen ( 3), bavachromene ( 4), isobavachromene ( 5), bavachalcone ( 6), isobavachalcone ( 7), 7,8-dihydro-8-(4-hydrophenyl)-2,2-dimethyl-2 H,6 H-[1,2- B:5,4- B']dipyran-6-one ( 8), and bavachinin ( 9). The structure of the new isoflavone 1 was elucidated as 7-hydroxy-3-[2-methyl-2-(4-methylpenten-3-yl)-2 H-chromen-6-yl]-4 H-chromen-4-one by spectroscopic analyses. Neocorylin ( 1) as well as related compounds 2, 4 - 6, 8 and 9 exhibited a significant inhibitory effect on baculovirus-expressed BACE-1 in vitro.
Swimming against the streamz (2012)

Activity streams have become prevalent on the web and are starting to emerge in enterprises. In this work, we present Streamz, a novel application that uses a faceted search approach to provide employees with advanced capabilities of search, navigation, attention management, and other types of analytics on top of an enterprise activity stream. We provide a detailed description of the Streamz tool as well as usage analysis based on user interface logs and interviews of active users.
Characterization of human gamma 4 switch region polymorphisms suggests a meiotic recombinational hot spot within the Ig locus: influence of S region length on IgG4 production. (1998)

Human gamma4 gene RFLPs, revealed after BamHI digestion, show IGHG4 alleles of 9.0 (9.2), 9.4, and 9.6 kb at various frequencies in different ethnic populations. Studies in immunodeficient individuals have previously suggested that the 9.4 BamHI allele is associated with a higher serum level of IgG4 than the 9.0 (9.2) BamHI allele, but it is not clear whether this is associated with the S region itself or other control elements. In addition, a duplication of the 9.4-kb gamma4 allele has recently been observed in a high proportion of normal donors. We therefore undertook a study of the structural basis for the difference in Ab levels in the various gamma4 alleles. We demonstrate that the Sgamma4 alleles differ in length due to deletions and insertions of a varying number of 79-bp Sgamma4 repeat units. Two novel RFLPs, 8.8 and 9.1 kb, were also observed. The alleles are likely to be generated by unequal crossing over, and the breakpoints cluster in Sgamma4 repeat units that contain chi-like motifs, implicating chi-like sequences in the meiotic recombination. Our data support the idea that the 9.4-kb BamHI allele is more productive than the 9.0 (9.2)-kb allele in normal healthy donors, possibly due to the extended switch regions, whereas duplication of the gamma4 gene has no effect on switching and IgG4 serum levels.
Structural transitions involved in a novel amyloid‐like β‐sheet assemblage of tripeptide derivatives (2003)

Self-assembly of two tripeptide derivatives containing three nonpolar isoleucine moieties and polar oxyethylene groups are studied in methanol. Peptide A [CH3(OCH2CH2)3OCH2CO(Ile)3OCH3] and peptide B [CH3(OCH2CH2)3OCH2CO(Ile)3NH (CH2CH2O)3CH3] take a mixture of unordered and helical conformation at low concentration (8.5 x 10(-4) M). However, at high concentration (2 x 10(-3) M), both the peptide showed significant increase in the helical conformation. An interesting conformational transition of peptides A and B at various methanol contents was observed in the solvated films of these compounds by spectroscopic methods like the far-uv circular dichroism and Fourier transform infrared (FT-IR) techniques. Peptide B, which contains more polar oxyethylene groups than A, showed a highly cooperative conformational transition when the methanol content was decreased. This transition was characterized by a large increase of beta-sheet, retaining a alpha-helical contribution. Peptide A showed a conformational transition resulting in a beta-sheet in the aggregated state. From the CD spectra, the ratio in the ellipticity indicates that peptide B forms twisted antiparallel beta-sheet conformation, whereas peptide A takes a parallel beta-sheet conformation. The results obtained in this work indicates the role of polar derivatization on the conformational preference of peptides having similar sequence.
Effects of the Spermicidal Agent Nonoxynol-9 on Vaginal Microbial Flora (1992)

The use of nonoxynol-9--containing vaginal contraceptive preparations increases vaginal (and urethral) colonization by Escherichia coli. Nonoxynol-9 is toxic to various microorganisms, including Lactobacillus acidophilus, but has little or no direct effect on E. coli. L. acidophilus, which is present in the vaginas of most normal women, generates H2O2 which, when combined with peroxidase and a halide, was toxic to E. coli. This toxicity was inhibited by nonoxynol-9 due to the selective destruction of the lactobacilli. In contrast, at higher concentrations, nonoxynol-9 was toxic to E. coli when combined with peroxidase and a halide. This toxicity was shared with certain other nonionic detergents and was due to the formation of peroxides in the preparations on prolonged exposure to oxygen. E. coli colonization may, in part, reflect the balance between these opposing effects of nonoxynol-9 on the vaginal antimicrobial system. Further, damage to normal tissues by peroxides in nonoxynol-9 preparations needs to be considered.
Large-Scale Power Combining and Mixed-Signal Linearizing Architectures for Watt-Class mmWave CMOS Power Amplifiers (2015)

Millimeter wave (mmWave) CMOS power amplifiers (PAs) have traditionally been limited in output power due to the low breakdown voltage of scaled CMOS technologies and poor quality of on-chip passives. Moreover, high data-rates and efficient spectrum utilization demand highly linear PAs with high efficiency under back-off. A novel linearizing architecture which simultaneously employs large-scale power combining, linearization through dynamic load modulation, and improved efficiency under back-off by supply-switching and load modulation is introduced. A quarter-wave combiner that exploits lumped spiral inductor equivalents of quarter-wave transmission lines with higher characteristic impedance enables one-step, low-loss, eight-way combining with a measured efficiency of 75% at 45 GHz. Eight-way combining of stacked SOI CMOS PAs results in a PA array with watt-class ( 27 dBm) saturated output power (3 × higher than prior art) and ultra-wideband operation (33-46 GHz) in 45 nm SOI CMOS. Another 45 nm SOI CMOS prototype, a three-bit digital to mmWave PA array, utilizing the proposed linearizing architecture achieves 23.3 dBm of saturated output power at 42.5 GHz, PAE -6dB /PAE peak = 67.7% as well as excellent linearity (DNL 0.5 LSB} and INL 1 LSB using end-point fit).
Involvement of bone morphogenetic protein-4 and bone morphogenetic protein-7 in the differentiation of the adrenergic phenotype in developing sympathetic neurons (1996)

The neurotransmitter phenotype of sympathetic neurons is specified by interactions with the surrounding embryonic tissues. Adrenergic differentiation is elicited early during development in the vicinity of notochord and dorsal aorta and the importance of axial midline tissues for adrenergic differentiation has been well documented. We now provide evidence that bone morphogenetic proteins, BMP-4 and BMP-7 are signals produced by the dorsal aorta that direct sympathetic neuron differentiation. BMP-4 and BMP-7 are expressed in the dorsal aorta at critical times during sympathetic neuron differentiation and have the ability to enhance the formation of adrenergic sympathetic neurons both in cultures of neural crest cells and when ectopically expressed in the developing embryo.
Glycophorin A Protects K562 Cells from Natural Killer Cell Attack (1995)

Glycophorin A is a protein with an abundant glycosylation (60% carbohydrate by weight), and studies have suggested that resistance of target cells to natural killing may be correlated with the level of glycophorin A expression. To assess the role of glycophorin A and of its carbohydrates in sensitivity to lysis by natural killer (NK) cells, the glycoprotein was inserted into the membrane of K562 target cells using electropulsation. Peripheral blood lymphocytes were used as effector cells. When glycophorin A was inserted into the membrane, the level of resistance to NK cell attack increased with the number of glycophorin A molecules electroinserted. The resistance to lysis was not due to a defect in target cell-effector cell binding. Electroassociation of glycophorin A did not cause a decrease in the expression of either "positive signals" for NK cells (such as CD71, CD15, and CD32 antigens) or cellular adhesion molecules (CD18, CD29, CD54, and CD58). Furthermore, electroinsertion of glycophorin A did not trigger any "negative signals," such as class I HLA antigen expression. Finally, it was shown that the sialic acid and O-linked oligosaccharides of glycophorin A did not play any role in its effect against NK cells. Conversely, the unique N-linked oligosaccharide was shown to be essential for resistance to occur.
On the Differential Geometry of 3D Flow Patterns: Generalized Helicoids and Diffusion MRI Analysis (2007)

Configurations of dense locally parallel 3D curves occur in medical imaging, computer vision and graphics. Examples include white matter fibre tracts, textures, fur and hair. We develop a differential geometric characterization of such structures by considering the local behaviour of the associated 3D frame field, leading to the associated tangential, normal and bi-normal curvature functions. Using results from the theory of generalized minimal surfaces we adopt a generalized helicoid model as an osculating object and develop the connection between its parameters and these curvature functions. These developments allow for the construction of parametrized 3D vector fields (sampled osculating objects) to locally approximate these patterns. We apply these results to the analysis of diffusion MRI data via a type of 3D streamline flow. Experimental results on data from a human brain demonstrate the advantages of incorporating the full differential geometry.
Scanning fluorescent microscopy analysis is applicable for absolute and relative cell frequency determinations (2004)

SFM proved to be a reliable alternative method, providing results comparable to LSC and FCM. SBC proved to be more suitable for rare-cell detection than FCM. SFM with digital slides may prove an acceptable adaptation of conventional fluorescent microscopes in order to perform rare-cell detection.
Identification of Potent Ras Signaling Inhibitors by Pathway‐Selective Phenotype‐Based Screening (2004)

Ras-tplatz: Die Anwendung einer effizienten Strategie für Phänotyp-basiertes Screening von Bibliotheken auf eine Serie von Sulindac-Derivaten (siehe Schema) führte zur Entdeckung von Inhibitoren des Ras-Signalwegs. Die Ergebnisse unterstreichen den Vorteil der Verwendung von biologisch vorvalidierten Verbindungsklassen in der chemisch-biologischen Forschung. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2004/z52587_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
High expression levels of collagenase‐1 and stromelysin‐1 correlate with shorter disease‐free survival in human metastatic melanoma (2001)

Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading extracellular matrix. Their role has been emphasized in tumor invasion, metastasis and tumor-induced angiogenesis. We studied the expression of collagenase-1 (MMP-1), stromelysin-1 (MMP-3) and collagenase-3 (MMP-13) in 70 melanoma metastases obtained from 56 patients treated with combined chemoimmunotherapy. The patients were divided into 2 groups using a cut-off point of 0% for MMP-1 expression and 20% for MMP-3 expression. We found that patients with MMP-1 positive metastases (n = 38) had significantly shorter disease-free survival compared to patients with MMP-1 negative metastases (n = 18) (median 11.2 vs. 17.0 months, p = 0.0383). The disease-free survival of patients with high levels of MMP-3 expression in their metastases (> or = 20% positive tumor cells, n = 14) was also significantly shorter compared to patients with lower levels of expression (n = 42) (median 5.1 vs. 14.0 months, p = 0.0294). The expression of MMP-13 did not correlate to survival parameters. We also found that the presence of melanin, a pigment produced by melanocytes, correlated with high expression levels of MMP-1 (p = 0.0002), MMP-3 (p < 0.0001) and MMP-13 (p = 0.0009). The high expression levels of MMP-13 were also associated with the presence of visceral metastases (p = 0.0284). Our findings suggest that MMP-1 and -3 may have a special role in melanoma metastasis formation and thus they could be used to measure the biological activity of the disease.
Project Athena: Supporting distributed computing at MIT (1992)

Project Athena™ was an educational computing initiative at the Massachusetts Institute of Technology, undertaken in partnership with the IBM Corporation and Digital Equipment Corporation from 1983 to 1991. This paper gives an overview of the network-based distributed computing services, developed for a number of UNIX™-capable workstations. These services are extensions to the native operating systems of the workstations, and provide interoperability as well as systems administration facilities in a large heterogeneous workstation environment. Under Project Athena, a mature distributed computing environment was developed. Its organization and support structure may be used as a model when planning a new installation, whether on a university or commercial campus. A section of this paper deals with the support requirements for distributed computing environments, based on the Project Athena experience.
Erythropoietin and Oxidative Stress (2008)

Unmitigated oxidative stress can lead to diminished cellular longevity, accelerated aging, and accumulated toxic effects for an organism. Current investigations further suggest the significant disadvantages that can occur with cellular oxidative stress that can lead to clinical disability in a number of disorders, such as myocardial infarction, dementia, stroke, and diabetes. New therapeutic strategies are therefore sought that can be directed toward ameliorating the toxic effects of oxidative stress. Here we discuss the exciting potential of the growth factor and cytokine erythropoietin for the treatment of diseases such as cardiac ischemia, vascular injury, neurodegeneration, and diabetes through the modulation of cellular oxidative stress. Erythropoietin controls a variety of signal transduction pathways during oxidative stress that can involve Janus-tyrosine kinase 2, protein kinase B, signal transducer and activator of transcription pathways, Wnt proteins, mammalian forkhead transcription factors, caspases, and nuclear factor kappaB. Yet, the biological effects of erythropoietin may not always be beneficial and may be poor tolerated in a number of clinical scenarios, necessitating further basic and clinical investigations that emphasize the elucidation of the signal transduction pathways controlled by erythropoietin to direct both successful and safe clinical care.
Platelet-derived growth factor mimics phorbol diester action on epidermal growth factor receptor phosphorylation at threonine-654. (1985)

Addition of platelet-derived growth factor (PDGF) to quiescent WI-38 human fetal lung fibroblasts mimics the effect of tumor-promoting phorbol diesters to inhibit the high-affinity binding of 125I-labeled epidermal growth factor (125I-EGF). PDGF, like phorbol diesters, was found to increase the phosphorylation state of EGF receptors immunoprecipitated from intact fibroblasts that were labeled to equilibrium with [32P]phosphate. Phosphoamino acid analysis of the EGF receptors indicated that both PDGF and phorbol diesters increased the level of [32P]phosphoserine and [32P]phosphothreonine. Phosphopeptide mapping of the EGF receptor demonstrated that PDGF increased the phosphorylation of several sites and induced the phosphorylation of a site that was not observed to be phosphorylated on EGF receptors isolated from control cells. This latter phosphorylation site on the EGF receptor was identified as threonine-654, previously shown to be phosphorylated in response to phorbol diesters in intact cells or by purified protein kinase C in vitro. Further, it was observed that PDGF mimicked the action of phorbol diesters to inhibit the EGF-dependent tyrosine phosphorylation of the EGF receptor in [32P]phosphate-labeled fibroblasts. These results are consistent with the hypothesis that increases in diacylglycerol and Ca2+ levels caused by addition of PDGF to fibroblasts activate protein kinase C and that this kinase, at least in part, mediates the effect of PDGF on the phosphorylation of the EGF receptor. The data further suggest that protein kinase C may play an important role in the regulation of cellular metabolism and proliferation by PDGF.
Evidence for Proteasome Involvement in Polyglutamine Disease: Localization to Nuclear Inclusions in SCA3/MJD and Suppression of Polyglutamine Aggregation in vitro (1999)

Spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), is one of at least eight inherited neurodegenerative diseases caused by expansion of a polyglutamine tract in the disease protein. Here we present two lines of evidence implicating the ubiquitin-proteasome pathway in SCA3/MJD pathogenesis. First, studies of both human disease tissue and in vitro models showed redistribution of the 26S proteasome complex into polyglutamine aggregates. In neurons from SCA3/MJD brain, the proteasome localized to intranuclear inclusions containing the mutant protein, ataxin-3. In transfected cells, the proteasome redistributed into inclusions formed by three expanded polyglutamine proteins: a pathologic ataxin-3 fragment, full-length mutant ataxin-3 and an unrelated GFP-polyglutamine fusion protein. Inclusion formation by the full-length mutant ataxin-3 required nuclear localization of the protein and occurred within specific subnuclear structures recently implicated in the regulation of cell death, promyelocytic leukemia antigen oncogenic domains. In a second set of experiments, inhibitors of the proteasome caused a repeat length-dependent increase in aggregate formation, implying that the proteasome plays a direct role in suppressing polyglutamine aggregation in disease. These results support a central role for protein misfolding in the pathogenesis of SCA3/MJD and suggest that modulating proteasome activity is a potential approach to altering the progression of this and other polyglutamine diseases.
Manual of environmental microbiology. (2007)

Section I: Introduction to Environmental Microbiology Section II: General Methodology Section III: Water Microbiology in Public Health Section IV: Aquatic Environments Section V: Soil, Rhizosphere and Phyllosphere Section VI: Subsurface and Landfills Section VII: Aerobiology Section VIII: Biotransformation and Biodegradation
A BULKY LIGAND AND ITS ORGANOMETALLIC COMPOUND: SYNTHESIS OF HEPTAMETHYLINDENE AND A FERROCENE-TYPE COMPLEX, Fe(η5-C9Me7)2 (1981)

Abstract A bulky new indene, 1-H-1,2,3,4,5,6,7-heptamethylindene, has been synthesized and its application to organometallic chemistry is suggested.