gebhart/patrepeval huggingface dataset:
DNA binding and antigene activity of a daunomycin-conjugated triplex-forming oligonucleotide targeting the P2 promoter of the human c-myc gene (2004)

Triplex-forming oligonucleotides (TFO) that bind DNA in a sequence-specific manner might be used as selective repressors of gene expression and gene-targeted therapeutics. However, many factors, including instability of triple helical complexes in cells, limit the efficacy of this approach. In the present study, we tested whether covalent linkage of a TFO to daunomycin, which is a potent DNA-intercalating agent and anticancer drug, could increase stability of the triple helix and activity of the oligonucleotide in cells. The 11mer daunomycin-conjugated GT (dauno-GT11) TFO targeted a sequence upstream of the P2 promoter, a site known to be critical for transcription of the c-myc gene. Band-shift assays showed that the dauno-GT11 formed triplex DNA with enhanced stability compared to the unmodified TFO. Band shift and footprinting experiments demonstrated that binding of dauno-GT11 was highly sequence-specific with exclusive binding to the 11 bp target site in the c-myc promoter. The daunomycin-conjugated TFO inhibited transcription in vitro and reduced c-myc promoter activity in prostate and breast cancer cells. The daunomycin-conjugated TFO was taken up by cells with a distinctive intracellular distribution compared to free daunomycin. However, cationic lipid-mediated delivery was required for enhanced cellular uptake, nuclear localization and biological activity of the TFO in cells. Dauno-GT11 reduced transcription of the endogenous c-myc gene in cells, but did not affect expression of non-target genes, such as ets-1 and ets-2, which contained very similar target sequences in their promoters. Daunomycin-conjugated control oligonucleotides unable to form triplex DNA with the target sequence did not have any effect in these assays, indicating that daunomycin was not directly responsible for the activity of daunomycin-conjugated TFO. Thus, attachment of daunomycin resulted in increased triplex stability and biological activity of the 11mer GT-rich TFO without compromising its specificity. These results encourage further testing of this approach to develop novel antigene therapeutics.
X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs (2001)

The three-dimensional structures of avian H5 and swine H9 influenza hemagglutinins (HAs) from viruses closely related to those that caused outbreaks of human disease in Hong Kong in 1997 and 1999 were determined bound to avian and human cell receptor analogs. Emerging influenza pandemics have been accompanied by the evolution of receptor-binding specificity from the preference of avian viruses for sialic acid receptors in alpha2,3 linkage to the preference of human viruses for alpha2,6 linkages. The four new structures show that HA binding sites specific for human receptors appear to be wider than those preferring avian receptors and how avian and human receptors are distinguished by atomic contacts at the glycosidic linkage. alpha2,3-Linked sialosides bind the avian HA in a trans conformation to form an alpha2,3 linkage-specific motif, made by the glycosidic oxygen and 4-OH of the penultimate galactose, that is complementary to the hydrogen-bonding capacity of Gln-226, an avian-specific residue. alpha2,6-Linked sialosides bind in a cis conformation, exposing the glycosidic oxygen to solution and nonpolar atoms of the receptor to Leu-226, a human-specific residue. The new structures are compared with previously reported crystal structures of HA/sialoside complexes of the H3 subtype that caused the 1968 Hong Kong Influenza virus pandemic and analyzed in relation to HA sequences of all 15 subtypes and to receptor affinity data to make clearer how receptor-binding sites of HAs from avian viruses evolve as the virus adapts to humans.
Anti-Syn Isomerization of Carbazole-3-carbaldehyde Hydrazone Derivative. Isolation and Characteristics of Syn Isomer (1992)

Abstract 9-Isopropylcarbazole-3-carbaldehyde diphenylhydrazone (anti-form) isomerized to syn-form upon UV light irradiation both in solution and in solid polymer film. The syn-form was successfully isolated in crystalline state by extracting with hexane and recrystallization.
Carbonic anhydrase : from biochemistry and genetics to physiology and clinical medicine : proceedings of the International Workshop on Carbonic Anhydrase, held in Spoleto, Italy in March 1990 (1991)

This work encompasses the proceedings of an international workshop on carbon anhydrase, which was held in Italy in March, 1990, highlighting its relevance in biochemistry and genetics and its implications for physiology and clinical medicine.
Gene delivery: A single nuclear localization signal peptide is sufficient to carry DNA to the cell nucleus (1999)

Translocation of exogenous DNA through the nuclear membrane is a major concern of gene delivery technologies. To take advantage of the cellular import machinery, we have synthesized a capped 3.3-kbp CMVLuciferase-NLS gene containing a single nuclear localization signal peptide (PKKKRKVEDPYC). Transfection of cells with the tagged gene remained effective down to nanogram amounts of DNA. Transfection enhancement (10- to 1,000-fold) as a result of the signal peptide was observed irrespective of the cationic vector or the cell type used. A lysine to threonine mutation of the third NLS amino acid completely abolished these remarkable features, suggesting importin-mediated translocation. Our hypothesis is that the 3-nm-wide DNA present in the cytoplasm is initially docked to and translocated through a nuclear pore by the nuclear import machinery. As DNA enters the nucleus, it is quickly condensed into a chromatin-like structure, which provides a mechanism for threading the remaining worm-like molecule through the pore. A single NLS signal is thus sufficient, whereas many signals on a gene would actually inhibit entry, the same DNA molecule being threaded through adjacent pores.
Hyaluronic acid accumulation and redistribution in rejecting rat kidney graft. Relationship to the transplantation edema. (1990)

By using biotin-labeled proteoglycan core protein and an avidin-enzyme system, hyaluronic acid (HA) was visualized in rat kidney. In the normal kidney, HA was localized in the extracellular space of the inner medulla and increased markedly towards the papillary tip. No staining for HA was seen in the interstitial tissue of the cortex or the outer medulla. During the development of rejection of allogeneic renal grafts, a progressive increase in accumulated HA was seen in the interstitial tissue of the cortex and outer medulla. The extractable amounts of HA increased, on average, 40 times in the cortex and outer medulla; no increase was measured in the inner medulla and papilla. The relative water content of the cortex and outer medulla also increased progressively and correlated with the HA accumulation. The extractable amounts of HA in syngeneic grafts increased by day 2 and then leveled off, indicating that surgical trauma may induce some transient HA accumulation after transplantation. Interstitial accumulation of HA, a glycosaminoglycan with unique water-binding qualities, would presumably influence water transport and osmotic activity and should thereby be implicated in the normal papillary function, but also in the development of the interstitial edema of the cortex and outer medulla during rejection of renal grafts.
Special Delivery (2000)

RETURN TO ISSUEPREVNewsNEXTSpecial DeliveryAlternative methods for delivering drugs improve performance, convenience, and patient complianceCELIA M. HENRYView Author Information C&EN WashingtonCite this: Chem. Eng. News 2000, 78, 38, 49–65Publication Date (Print):September 18, 2000Publication History Published online12 November 2010Published inissue 18 September 2000https://doi.org/10.1021/cen-v078n038.p049Copyright © 2000 American Chemical SocietyArticle Views23Altmetric-Citations9LEARN 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 InReddit PDF (7 MB) SUBJECTS:Drug delivery,Pharmaceuticals Get e-Alerts
Generation of an endogenous DNA-methylating agent by nitrosation in Escherichia coli (1996)

Escherichia coli ada ogt mutants, which are totally deficient in O6-methylguanine-DNA methyltransferases, have an increased spontaneous mutation rate. This phenotype is particularly evident in starving cells and suggests the generation of an endogenous DNA alkylating agent under this growth condition. We have found that in wild-type cells, the level of the inducible Ada protein is 20-fold higher in stationary-phase and starving cells than in rapidly growing cells, thus enhancing the defense of these cells against DNA damage. The increased level of Ada in stationary cells is dependent on RpoS, a stationary-phase-specific sigma subunit of RNA polymerase. We have also identified a potential source of the mutagenic agent. Nitrosation of amides and related compounds can generate directly acting methylating agents and can be catalyzed by bacteria] enzymes. E. coli moa mutants, which are defective in the synthesis of a molybdopterin cofactor required by several reductases, are deficient in nitrosation activity. It is reported here that a moa mutant shows reduced generation of a mutagenic methylating agent from methylamine (or methylurea) and nitrite added to agar plates. Moreover, a moa mutation eliminates much of the spontaneous mutagenesis in ada ogt mutants. These observations indicate that the major endogenous mutagen is not S-adenosylmethionine but arises by bacterially catalyzed nitrosation.
Optimized Method for Preparation of DNA from Pathogenic and Environmental Mycobacteria (2008)

Genomic studies on pathogenic and environmental mycobacteria are of growing interest for understanding of their evolution, distribution, adaptation, and host-pathogen interaction. Since most mycobacteria are slow growers, material from in vitro cultures is usually scarce. The robust mycobacterial cell wall hinders both experimental cell lysis and efficient DNA extraction. Here, we compare elements of several DNA preparation protocols and describe a method that is economical and practical and reliably yields large amounts--usually 10-fold increased compared to earlier protocols--of highly pure genomic DNA for sophisticated downstream applications. This method was optimized for cultures of a variety of pathogenic and environmental mycobacterial species and proven to be suitable for direct mycobacterial DNA extraction from infected insect specimens.
Characterization of Nb and W Doped Titania as Catalyst Supports for Proton Exchange Membrane Fuel Cells (2009)

Niobium doped titania and tungsten doped titania prepared using a sol-gel technique were evaluated as possible catalyst support materials for proton exchange membrane fuel cells.  The electrical conductivity of the doped materials prepared under different heat-treatment temperatures and partial oxygen pressures was measured.  Rutile 10Nb-TiO2 was extremely conductive compared to the anatase 10Nb-TiO2.  For the W doped samples the conductivity was found to be extremely low compared to the rutile 10Nb-TiO2, and W segregation was observed when the material was reduced in H2 at temperatures greater than 700dC.  X-ray photoelectron spectroscopy (XPS) analysis was completed on 10Nb-TiO2 calcined at 500dC and on 10Nb-TiO2 calcined and then reduced at a range of temperatures (500dC to 900dC).
Optimal Relay Selection in IEEE 802.16j Multihop Relay Vehicular Networks (2010)

This paper examines the IEEE 802.16j multihop relay (MR) technology that improves vehicle-to-infrastructure communications. We study the selection of optimal relay station (RS) for a vehicular subscriber station (SS) that maximizes the end-to-end capacity, assuming that the locations of vehicular SSs are known. By incorporating a highway mobility model, the problem can be formulated into a nonlinear optimization problem and solved for the optimal locations of RSs that guarantee maximal end-to-end capacities to SSs. Numerical results from a case study show that the selection of the corresponding optimal RS increases the expected end-to-end capacity for individual SSs by 50%, as compared with the method without using relays.
35??C Hypothermia Can Reduce Increased Intracranial Pressure as Well as 33??C Hypothermia in Patients with Severe Traumatic Brain Injury (2006)

de Tommasi, Antonio M.D.; Luzzi, Sabino M.D.; D’Urso, Pietro M.D.; de Tommasi, Claudio M.D.; Ciappetta, Pasqualino M.D.
Two Heads Better Than One: Metric+Active Learning and its Applications for IT Service Classification (2009)

Large IT service providers track service requests and their execution through problem/change tickets. It is important to classify the tickets based on the problem/change description in order to understand service quality and to optimize service processes. However, two challenges exist in solving this classification problem: 1) ticket descriptions from different classes are of highly diverse characteristics, which invalidates most standard distance metrics; 2) it is very expensive to obtain high-quality labeled data. To address these challenges, we develop two seemingly independent methods 1) discriminative neighborhood metric learning (DNML) and 2) active learning with median selection (ALMS), both of which are, however, based on the same core technique: iterated representative selection. A case study on real IT service classification application is presented to demonstrate the effectiveness and efficiency of our proposed methods.
Gp135/podocalyxin and NHERF-2 participate in the formation of a preapical domain during polarization of MDCK cells (2005)

Epithelial polarization involves the segregation of apical and basolateral membrane domains, which are stabilized and maintained by tight junctions and membrane traffic. We report that unlike most apical and basolateral proteins in MDCK cells, which separate only after junctions have formed, the apical marker gp135 signifies an early level of polarized membrane organization established already in single cells. We identified gp135 as the dog orthologue of podocalyxin. With a series of domain mutants we show that the COOH-terminal PSD-95/Dlg/ZO-1 (PDZ)-binding motif is targeting podocalyxin to the free surface of single cells as well as to a subdomain of the terminally polarized apical membrane. This special localization of podocalyxin is shared by the cytoplasmic PDZ-protein Na+/H+ exchanger regulatory factor (NHERF)-2. Depleting podocalyxin by RNA interference caused defects in epithelial polarization. Together, our data suggest that podocalyxin and NHERF-2 function in epithelial polarization by contributing to an early apical scaffold based on PDZ domain-mediated interactions.
Oxytocin may be useful to increase trust in others and decrease disruptive behaviours in patients with Prader-Willi syndrome: a randomised placebo-controlled trial in 24 patients (2011)

ClinicalTrials.gov: NCT01038570.
The PARP inhibitor AZD2281 (Olaparib) induces autophagy/mitophagy in BRCA1 and BRCA2 mutant breast cancer cells (2015)

PARP inhibitors are considered promising anticancer agents and currently being tested in clinical trials in hereditary breast cancer patients harboring mutations in BRCA1 and BRCA2 genes. In this study, we investigated the antiproliferative effects and mechanism of PARP inhibitors ABT-888 (Veliparib), BSI-201 (Iniparib) and AZD228 (Olaparib) in breast cancer cell lines with BRCA1 or BRCA2 mutations and 9 different BRCA wild-type cell lines with BRCA1 allelic loss. We found that AZD2281 was the most potent in the PARP inhibitors and induces significant growth inhibition (~95%) in BRCA1 mutant (HCC‑1937, MDA-MB-436, and SUM-149PT) and BRCA2 mutant (HCC‑1428) cell lines. AZD2281 treatment also resulted in growth inhibition ranging from 20 to 50% in cells with BRCA1 allelic loss, including ER(+), HER2/Neu(+) and triple-negative breast cancer (TNBC) cells, but showed no effect in cells without with type BRCA without allelic loss. Knocking down of BRCA1 or BRCA2 in TNBC cells with BRCA1 allelic loss by RNA interference significantly enhanced AZD2281-induced growth inhibition and induced significant autophagy that was associated with mitophagy in cells with BRCA mutations. Inhibition of autophagy by gene knockdown significantly diminished AZD2281-induced mitophagy and apoptosis, indicating that autophagic process mediates some of the downstream effects of PARP inhibitors. In conclusion, our data provide the first evidence of PARP inhibitor AZD2281 autophagy and mitophagy in breast cancer cell lines with BRCA mutations or BRCA-allelic loss. In addition, our results indicate that the patients with BRCA1 allelic loss may also benefit from PARP inhibitor therapy if BRCA is further inhibited.
Apolipoprotein E and Alzheimer's Disease (1996)

The apolipoprotein E locus (APOE) is associated with variations in the age of onset and risk of Alzheimer's disease. The APOE4 allele increases the probability of disease at an earlier age. In contrast, the APOE3 and APOE2 alleles decrease the probability of disease and increase the age of onset. Therefore the metabolism of apolipoprotein E is relevant to Alzheimer's disease. Isoform-specific interactions of apolipoprotein E with other molecules may determine the rate of disease expression through molecular pathways that appear unique to the disease. In addition, some isoform-specific interactions of apolipoprotein E have been demonstrated with the defining pathological lesions of Alzheimer's disease, the neurofibrillary tangle and neuritic plaque. Several hypotheses of disease pathogenesis are now based on the relevance of apolipoprotein E.
GLUT4 Is Reduced in Slow Muscle Fibers of Type 2 Diabetic Patients (2001)

To gain further insight into the mechanisms underlying muscle insulin resistance, the influence of obesity and type 2 diabetes on GLUT4 immunoreactivity in slow and fast skeletal muscle fibers was studied. Through a newly developed, very sensitive method using immunohistochemistry combined with morphometry, GLUT4 density was found to be significantly higher in slow compared with fast fibers in biopsy specimens from lean and obese subjects. In contrast, in type 2 diabetic subjects, GLUT4 density was significantly lower in slow compared with fast fibers. GLUT4 density in slow fibers from diabetic patients was reduced by 9% compared with the weight-matched obese subjects and by 18% compared with the lean control group. The slow-fiber fraction was reduced to 86% in the obese subjects and to 75% in the diabetic subjects compared with the control group. Estimated GLUT4 contribution from slow fibers was reduced to 77% in the obese subjects and to 61% in type 2 diabetic patients compared with the control subjects. We propose that a reduction in the fraction of slow-twitch fibers, combined with a reduction in GLUT4 expression in slow fibers, may reduce the insulin-sensitive GLUT4 pool in type 2 diabetes and thus contribute to skeletal muscle insulin resistance.
High mobility poly-Si TFT by a new excimer laser annealing method for large area electronics (1991)

A high-mobility (280 cm/sup 2//V-s), high-throughput poly-Si TFT (thin-film transistor) formed using a low-temperature process (<or= 600 degrees C) has been achieved through a novel excimer laser annealing method. The method uses thin, active-layer poly-Si film (500 AA) and involves controlling the solidification process of molten Si by low-temperature (<or= 400 degrees C) substrate heating during laser annealing. Poly-Si film grain formed by this process is radically larger in size, and has minimal internal defects. The maximum grain size is over 5000 AA, and uniformity in field effect mobility was found to be +or-10% within the effective laser irradiation area.<<ETX>>
Accumulation of MDSC subsets in renal cell carcinoma correlates with grade and progression free survival, and is associated with intratumoral expression of IL-1β, IL-8 and CXCL5 (2014)

Meeting abstracts Myeloid derived suppressor cells (MDSC, CD33+CD11b+ HLA-DR low/-) play a major role in tumor-mediated immune evasion and are composed of at least 3 subsets PMN (CD15+), monocytic (CD14+) and lineage-negative (CD15-CD14-), and each has been shown to be significantly increased in
Current surgical strategies to treat fecal incontinence (2015)

Fecal incontinence is a devastating condition, vastly under-reported, and may affect up to 18% of the population. While conservative management may be efficacious in a large portion of patients, those who are refractory will likely benefit from appropriate surgical intervention. There are a wide variety of surgical approaches to fecal incontinence management, and knowledge and experience are crucial to choosing the appropriate procedure and maximizing functional outcome while minimizing risk. In this article, we provide a comprehensive description of surgical options for fecal incontinence to help the clinician identify an appropriate intervention.
Ophthalmological Aspects in Allogenic Bone Marrow Transplantation: Sjögren-Like Syndrome in Graft-Versus-Host Disease (1997)

The possible etiology of SLS includes three factors: total body irradiation, ocular toxicity of chemotherapy and GVHD. A correlation was found between poor-prognosis GVHD and the occurrence of SLS.
On the Absorption Spectra of Complex Ions II (1954)

The secular determinants obtained in the previous paper are solved for the energy levels which are important in the absorption spectra of the normal complex ions, leaving the crystalline field strength as a parameter. The values of B and C (Racah's parameters) there needed are determined from the observed spectra of free ions or in some cases by extrapolation. The f -values of the transitions which connect the energy levels calculated are estimated and compared with the observed intensities. The difference of the spectral width among absorption bands and lines is also considered using the energy diagram obtained. Following the assignments determined by the above considerations, the calculated positions of lines and bands are rather in good agreement with the experimental data in divalent ions [MX 6 ] 2+ (M=Cr, Mn, Fe, Co, Ni), when we adjust the crystalline field parameter D q suitably. In trivalent ions [MX 6 ] 3+ (M=Ti, V, Cr, Mn, Fe), it is necessary besides the adjustment of D q to use smaller values of B and C than those of the free ions to obtain better agreement with experiments. The values of D q thus determined are of reasonable magnitude close to those obtained in other ways. The decrease of B and C compared with those of the free ions might be connected with the recent Stevens' suggestion. It is interesting that, though the agreement is poor about, [Co(H 2 O) 6 ] 3+ and [Co(NH 3 ) 6 ] 3+ whose bindings are usually considered covalent, the qualitative explanation of their spectra is found possible in the crystalline field approximation.