gebhart/patrepeval huggingface dataset:
Rational Modification of a Selection Strategy Leads to Deoxyribozymes that Create Native 3‘-5‘ RNA Linkages (2004)

We previously used in vitro selection to identify several classes of deoxyribozymes that mediate RNA ligation by attack of a hydroxyl group at a 5'-triphosphate. In these reactions, the nucleophilic hydroxyl group is located at an internal 2'-position of an RNA substrate, leading to 2',5'-branched RNA. To obtain deoxyribozymes that instead create linear 3'-5'-linked (native) RNA, here we strategically modified the selection approach by embedding the nascent ligation junction within an RNA:DNA duplex region. This approach should favor formation of linear rather than branched RNA because the two RNA termini are spatially constrained by Watson-Crick base pairing during the ligation reaction. Furthermore, because native 3'-5' linkages are more stable in a duplex than isomeric non-native 2'-5' linkages, this strategy is predicted to favor the formation of 3'-5' linkages. All of the new deoxyribozymes indeed create only linear 3'-5' RNA, confirming the effectiveness of the rational design. The new deoxyribozymes ligate RNA with k(obs) values up to 0.5 h(-1) at 37 degrees C and 40 mM Mg2+, pH 9.0, with up to 41% yield at 3 h incubation. They require several specific RNA nucleotides on either side of the ligation junction, which may limit their practical generality. These RNA ligase deoxyribozymes are the first that create native 3'-5' RNA linkages, which to date have been highly elusive via other selection approaches.
Senescent WI-38 cells fail to express EPC-1, a gene induced in young cells upon entry into the G0 state. (1993)

Recently we reported the isolation of cDNAs for a number of genes that are differentially expressed between nonproliferating early (young) and late (senescent) population doubling level (PDL) WI-38 human, fetal lung-derived, fibroblast-like cells. We now demonstrate that one of these isolates, EPC-1 (early PDL cDNA-1), derives from an approximately 1.4-kilobase mRNA species that is expressed at a > or = 100-fold higher level in serum-starved, confluent, young versus similarly treated senescent WI-38 cells. Complete nucleotide sequence analysis of this cDNA confirms its identity with that of a cDNA encoding a secreted, retinal pigmented epithelium differentiation factor as well as similarity of the encoded protein with a number of mammalian serine protease inhibitors. We show that EPC-1 expression is associated with G0 growth arrest in WI-38 cells. The mRNA readily accumulates in density-arrested and/or serum-starved young cells but not in log phase, low density young cells. In contrast, EPC-1 transcript abundance and expression of the encoded, secreted protein are both negligible in senescent WI-38 cells under all culture conditions tested. These findings support the hypothesis that senescent WI-38 cells exhibit a state of growth arrest fundamentally distinct from that of quiescent (G0) young cells.
Probable Person-to-Person Transmission of Avian Influenza A (H5N1) (2005)

Disease in the mother and aunt probably resulted from person-to-person transmission of this lethal avian influenzavirus during unprotected exposure to the critically ill index patient.
Clinical Application of the Tension-Stress Effect for Limb Lengthening (1990)

For 40 years, the author has been developing a system of orthopedics, traumatology, and limb lengthening using a circular transfixion-wire external skeletal fixator, often in combination with biomechanic methods of stimulating the formation of new osseous tissue within a widening osteotomy distraction site. The factors important for neoosteogenesis after osteotomy include: maximum preservation of extraosseous and medullary blood supply; stable external fixation; a delay prior to distraction; a distraction rate of 1 mm per day in frequent small steps; a period of stable neutral fixation after lengthening; and physiologic use of the elongating limb. For a successful fixator application, the apparatus must be applied with consideration given to the number, size, and location of the rings, the placement and tension on the wires, the technique of wire insertion, the effect of soft-tissue transfixion on limb use, and the prevention of bone and joint deformities caused by countertension in soft tissues. Clinical application of the author's techniques permits stature increase in certain forms of dwarfism, correction of deformities and limb-length inequalities, and stump elongation. For many of these applications, motorized distraction can provide continuous limb lengthening while the apparatus is on the patient.
Potassium channel gene therapy can prevent neuron death resulting from necrotic and apoptotic insults (2003)

Necrotic insults such as seizure are excitotoxic. Logically, membrane hyperpolarization by increasing outwardly conducting potassium channel currents should attenuate hyperexcitation and enhance neuron survival. Therefore, we overexpressed a small-conductance calcium-activated (SK2) or voltage-gated (Kv1.1) channel via viral vectors in cultured hippocampal neurons. We found that SK2 or Kv1.1 protected not only against kainate or glutamate excitotoxicity but also increased survival after sodium cyanide or staurosporine. In vivo overexpression of either channel in dentate gyrus reduced kainate-induced CA3 lesions. In hippocampal slices, the kainate-induced increase in granule cell excitability was reduced by overexpression of either channel, suggesting that these channels exert their protective effects during hyperexcitation. It is also important to understand any functional disturbances created by transgene overexpression alone. In the absence of insult, overexpression of Kv1.1, but not SK2, reduced baseline excitability in dentate gyrus granule cells. Furthermore, while no behavioral disturbances during spatial acquisition in the Morris water maze were observed with overexpression of either channel, animals overexpressing SK2, but not Kv1.1, exhibited a memory deficit post-training. This difference raises the possibility that the means by which these channel subtypes protect may differ. With further development, potassium channel vectors may be an effective pre-emptive strategy against necrotic insults.
Simulating asynchronous architectures on transputer networks (2002)

Recently, there has been a resurgence of interest in asynchronous design techniques due to the potential of asynchronous logic for higher performance, power efficiency and immunity from clock related timing problems. Occam, a CSP based parallel language provides for the rapid development of asynchronous architectural simulation models which may then be executed on a transputer network to achieve high performance. The paper discusses issues related to the design and execution of such models.
Split dnaE Genes Encoding Multiple Novel Inteins in Trichodesmium erythraeum (2003)

Three inteins were found when analyzing a pair of split dnaE genes encoding the catalytic subunit of DNA polymerase III in the oceanic N2-fixing cyanobacterium Trichodesmium erythraeum. The three inteins (DnaE-1, DnaE-2, and DnaE-3) were clustered in a 70-amino acid (aa) region of the predicted DnaE protein. The DnaE-1 intein is 1258 aa long and three times as large as a typical intein, due to the presence of large tandem repeats in which a 57-aa sequence is repeated 17 times. The DnaE-2 intein has a more typical size of 428 aa with putative protein splicing and endonuclease domains. The DnaE-3 intein is a split intein consisting of a 102-aa N-terminal part and a 36-aa C-terminal part encoded on the first and second split dnaE genes, respectively. Synthesis of a mature DnaE protein is predicted to involve expression of two split dnaE genes followed by two protein cis-splicing reactions and one protein trans-splicing reaction. Tandem repeats in the DnaE-1 intein inhibited the protein splicing activity of this intein when tested in Escherichia coli cells and may potentially regulate DnaE synthesis in vivo.
Cholinesterase inhibitors for Alzheimer's disease (2006)

The three cholinesterase inhibitors are efficacious for mild to moderate Alzheimer's disease. It is not possible to identify those who will respond to treatment prior to treatment. There is no evidence that treatment with a ChEI is not cost effective. Despite the slight variations in the mode of action of the three cholinesterase inhibitors there is no evidence of any differences between them with respect to efficacy. There appears to be less adverse effects associated with donepezil compared with rivastigmine. It may be that galantamine and rivastigmine match donepezil in tolerability if a careful and gradual titration routine over more than three months is used. Titration with donepezil is more straightforward and the lower dose may be worth consideration.
Fluorescence Resonance Energy Transfer Analysis of RNase L-Catalyzed Oligonucleotide Cleavage (2000)

A method is described for monitoring the cleavage of an oligoribonucleotide substrate by the 2-5A-dependent RNase L based on fluorescence resonance energy transfer (FRET). The oligoribonucleotide, rC11U2C7, was labeled covalently at its 5'-terminus with fluorescein and at its 3'-terminus with rhodamine to provide a substrate for RNase L. On cleavage, the fluorescence at 538 nm (with 485 nm excitation) increased by a factor of 2.8, allowing real-time quantitation of the reaction progress. The method was performed easily in a 96-well plate format and allowed quantitative high throughput analyses of RNase L activity with different activators.
Three Human Homologs of a Murine Gene Encoding an Inhibitor of Stem Cell Proliferation (1990)

The G0S19 genes are members of the "small inducible" family of genes, which have similar exon-intron organizations and encode secreted proteins with similar dispositions of cysteine and proline residues. G0S19-1 mRNA is increased shortly after the addition of lectin or cycloheximide to cultured human blood mononuclear cells. The cDNA sequence is homologous to that of a murine gene encoding an inhibitory cytokine (MIP1 alpha/SCI), which decreases hemopoietic stem cell proliferation. The homology extends to the 3' noncoding region, which contains two conserved elements: (i) GGGACTCTTC, a potential transcription factor NF chi B-binding site, and (ii) TTTTGTAATTTATTTT, which is found in some related genes (e.g., that encoding the immediate early protein ornithine decarboxylase). A similar but complementary sequence is present in human immunodeficiency virus. Two of the three human genes that hybridize to G0S19-1 cDNA were sequenced. G0S19-1 has 5' AP1-like recognition elements as found in some other phorbol ester-responsive genes (e.g., c-fos). G0S19-2 has a 5' Alu sequence, but is likely to be expressed because of the conservation of sections of the gene believed to be important for function. The 5' flanks of both genes contain the nucleotide motifs CK-2 and SRE, indicating cytokine-like genes with the potential to respond to growth factors. G0S19-1 is the main G0S19 gene expressed in adult T lymphocytes and may encode a homeostatic negative regulator of the size of cell populations (or subpopulations) which are derived ultimately from marrow stem cells. As such, it is a potential antioncogene.
Gaze-orchestrated dynamic windows (1981)

Consider a large-format display before the user, bearing a multiplicity of “windows,” like little movies, the majority dynamic and in color. There are upwards of 20 windows, say, more than a person can ordinarily absorb at once. Some of the windows come and go, reflecting their nature as direct TV linkages into real-time, real-world events. Others are non-real-time, some dynamic, others static but capable of jumping into motion. Such an ensemble of information inputs reflects the managerial world of the top-level executive of the not too distant electronic future: a world of brevity, fragmentation, variety, above all one of an overwhelming onslaught of events. The multiplicity and simultaneity of such a display situation ordinarily would make coping with it untenable. The intent of the reported research is to introduce order and control, through the creation of a dynamic, gaze-interactive interface. Making the behavior and reactivity of the “windows” contingent upon measured eyemovements - the point-of-regard of the observer - aims both to help the observer to cope with the onslaught of events on the one hand, yet enable on the other hand continuing close contact with that everchanging ensemble. A simulation of such a world is described and demonstrated in the composite medium of computer, videodisc, and video special effects. Eye-tracking technology, integrated with speech and manual inputs, controls the display's visual dynamics, and orchestrates its sound accompaniments. All elements are combined to form a testbed for the conception generally, and to explore the associated human factors and stagecraft.
Emerging concepts in liquid biopsies (2017)

Characterizing and monitoring tumor genomes with blood samples could achieve significant improvements in precision medicine. As tumors shed parts of themselves into the circulation, analyses of circulating tumor cells, circulating tumor DNA, and tumor-derived exosomes, often referred to as "liquid biopsies", may enable tumor genome characterization by minimally invasive means. Indeed, multiple studies have described how molecular information about parent tumors can be extracted from these components. Here, we briefly summarize current technologies and then elaborate on emerging novel concepts that may further propel the field. We address normal and detectable mutation levels in the context of our current knowledge regarding the gradual accumulation of mutations during aging and in light of technological limitations. Finally, we discuss whether liquid biopsies are ready to be used in routine clinical practice.
Nasal Polyposis: From Pathogenesis to Treatment, An Update (2011)

Nasal polyps (NP) are common benign degeneration of nasal sinus mucosa with a prevalence around 4% in the adult population. The causes are still uncertain but there is a strong association with allergy, infection, asthma and aspirin sensitivity. Histologically, the presence of a large quantity of extracellular fluid, mast cell degranulation and eosinophilia has been demonstrated. Typically the patients show nasal obstruction, anosmia and rhinorrhoea. Nasal endoscopic examination and CT imaging allow evaluation of the disease extension. A combined medical and surgical treatment is recommended for symptoms control in preventing symptomatic NP recurrence. We will review the current knowledge in the pathogenesis and treatment of this complex disease entity.
Charateristics of Voltage Dependent Calcium Uptake and Norepinephrine Release in Hypothalamus of DOCA-salt Hypertensive Rats (1993)

Purpose of the present study was to clarify the role of noradrenergic neural activities in hypothalamus for either triggering or maintaining hypertension in deoxycorticosterone (DOCA)-salt hypertensive rats. Two groups of animals were prepared: 1) normotensive Wistar rats and 2) DOCA-salt induced hypertensive rats. Voltage dependent (45)^Ca^(++) uptake, endogenous norepinephrine release, and the catecholamine content in the hypothalamus of DOCA-salt hypertensive and normotensive Wistar rats were compared. Animals at 4, 6 and 16 week-old of two groups were sacrificed by decapitation and hypothalamus was dissected out. Voltage dependent calcium uptake and norepinephrine release were determined from hypothalamic synaptosomes either in low potassium or high potassium stimulatory condition by using (45)^Ca^(++) isotope and HPLC-ECD technique. Degrees of voltage dependent (45)^Ca^(++) uptake and norepinephrine release in hypothalamic synaptosomes of 16-week-old DOCA-salt hypertensive rats were significantly greater than those of age matched normotensive control rats. The norepinephrine and dopamine contents of hypothalamus were about the same in two groups of animals. These results suggest that the alteration of evoked norepinephrine release related to calcium uptake in hypothalamus may play a role in the maintenance of hypertension in DOCA-salt hypertensive rats.
ADAM9 Promotes Lung Cancer Metastases to Brain by a Plasminogen Activator-Based Pathway (2014)

The transmembrane cell adhesion protein ADAM9 has been implicated in cancer cell migration and lung cancer metastasis to the brain, but the underpinning mechanisms are unclear and clinical support has been lacking. Here, we demonstrate that ADAM9 enhances the ability of tissue plasminogen activator (tPA) to cleave and stimulate the function of the promigratory protein CDCP1 to promote lung metastasis. Blocking this mechanism of cancer cell migration prolonged survival in tumor-bearing mice and cooperated with dexamethasone and dasatinib (a dual Src/Abl kinase inhibitor) treatment to enhance cytotoxic treatment. In clinical specimens, high levels of ADAM9 and CDCP1 correlated with poor prognosis and high risk of mortality in patients with lung cancer. Moreover, ADAM9 levels in brain metastases derived from lung tumors were relatively higher than the levels observed in primary lung tumors. Our results show how ADAM9 regulates lung cancer metastasis to the brain by facilitating the tPA-mediated cleavage of CDCP1, with potential implications to target this network as a strategy to prevent or treat brain metastatic disease.
Second-generation antisense oligonucleotides: structure—activity relationships and the design of improved signal-transduction inhibitors (1996)

Conference Article| August 01 1996 Second-generation antisense oligonucleotides: structure—activity relationships and the design of improved signal-transduction inhibitors K.-H. Altmann; K.-H. Altmann *Ciba-Geigy Ltd., Central Research Laboratories, R-1060.2.34, CH-4002 Basel, Switzerland Search for other works by this author on: This Site PubMed Google Scholar D. Fabbro; D. Fabbro †Ciba-Geigy Ltd., Pharmaceutical Division, Department of Oncology, CH-4002 Basel, Switzerland Search for other works by this author on: This Site PubMed Google Scholar N. M. Dean; N. M. Dean ‡ISIS Pharmaceuticals, Department of Molecular Pharmacology, 2280 Faraday Avenue, Carlsbad, CA 92008, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar T. Geiger; T. Geiger †Ciba-Geigy Ltd., Pharmaceutical Division, Department of Oncology, CH-4002 Basel, Switzerland Search for other works by this author on: This Site PubMed Google Scholar B. P. Monia; B. P. Monia ‡ISIS Pharmaceuticals, Department of Molecular Pharmacology, 2280 Faraday Avenue, Carlsbad, CA 92008, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar M. Müllert; M. Müllert †Ciba-Geigy Ltd., Pharmaceutical Division, Department of Oncology, CH-4002 Basel, Switzerland Search for other works by this author on: This Site PubMed Google Scholar P. Nicklin P. Nicklin §Ciba Geigy Ltd., Pharmaceutical Division, Department of Toxicology, Horsham, West Sussex RH12 4AB, U.K. Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Received: March 20 1996 Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1996 Biochemical Society1996 Biochem Soc Trans (1996) 24 (3): 630–637. https://doi.org/10.1042/bst0240630 Article history Received: March 20 1996 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation K.-H. Altmann, D. Fabbro, N. M. Dean, T. Geiger, B. P. Monia, M. Müllert, P. Nicklin; Second-generation antisense oligonucleotides: structure—activity relationships and the design of improved signal-transduction inhibitors. Biochem Soc Trans 1 August 1996; 24 (3): 630–637. doi: https://doi.org/10.1042/bst0240630 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: PS-ODN, phosphorothioate oligodeoxynucleotide, PKC, protein kinase C This content is only available as a PDF. © 1996 Biochemical Society1996 Article PDF first page preview Close Modal You do not currently have access to this content.
Electrical characterization of ISFETs (2007)

Methodology of electrical characterization of ISFETs has been described. It is based on a three-stage approach. First, electrical measurements of ISFET-like MOSFETs and extraction of basic parameters of the MOSFET compact model are performed. Next, mapping of the ISFET channel conductances and a number of other characteristic parameters is carried out using a semi-automatic testing setup. Finally, ISFET sensitivity to solution pH is evaluated. The methodology is applied to characterize ISFETs fabricated in the Institute of Electron Technology (IET).
Colonic delivery of 4‐aminosalicylic acid using amylose–ethylcellulose‐coated hydroxypropylmethylcellulose capsules (2002)

The specific coating protected the drug until the capsule reached the colon, where 4-aminosalicylic acid was slowly released and absorbed. Thus, such a formulation has the potential for use in the treatment of inflammatory bowel disease.
Remote Sensing Of The Earth: A Synoptic View (1989)

Remote sensing of the Earth may be traced back to the first prehistoric explorer who climbed a nearby hill to study the lay of the land. But it was not until 150 years ago that Louis Jacques Mande Daguerre and Joseph Nicéphore Niepce invented the daguerreotype, which provided the foundation for modern photography and, through it, a means to record a remotely sensed image. Twenty years later, in 1859, Gaspard Félix Tournachon Clateu (later known in the literature as Félix Nadar) took the first known aerial image from a balloon. That set the stage for the use of balloon-based cameras by Union troops to photograph Confederate defenses around Richmond, Virginia, during the Civil War. Kites were also used as platforms for early photography. A particularly notable example is a very-large-format image (1.4×2.4 m) taken by G. R. Lawrence after the 1906 San Francisco earthquake and fire. A cluster of 17 kites flown from a ship in the bay carried the camera aloft. The first known photos from an aircraft were taken in 1909 in Italy by a passenger in a plane piloted by Wilbur Wright. Aerial photography was used for reconnaissance during World War I and was further developed for that purpose during World War II, resulting in the creation of special cameras and films, including color and color infrared film for detecting camouflage.