gebhart/patrepeval huggingface dataset:
Linkage structures strongly influence the binding cooperativity of DNA intercalators conjugated to triplex forming oligonucleotides (1994)

Conjugation of DNA intercalators to triple helix forming oligodeoxynucleotides (ODN's) can enhance ODN binding properties and consequently their potential ability to modulate gene expression. To test the hypothesis that linkage structure could strongly influence the binding enhancement of intercalator conjugation with triplex forming ODN's, we have used a model system to investigate binding avidity of short oligomers conjugated to DNA intercalators through various linkages. Using a dA10.T10 target sequence imbedded in a 20 bp duplex, binding avidities of a T10 ODN joined to the DNA intercalator 6,9-diamino, 3-methoxy acridine (DAMA) by 8 different 5' linkages were measured using an electrophoretic mobility shift assay. Although unmodified T10 has a very limited capacity for stable binding under these conditions (apparent Kd > 250 microM at 4 degrees C), conjugation to DAMA using flexible linkers of certain lengths and chemical compositions greatly enhanced binding (Kd of 1 microM at 4 degrees C). Other linkers, however, modestly enhanced binding or had no effect on binding at all. Thus, the length, flexibility, and chemical composition of linker structures all substantially influence intercalator conjugated oligodeoxynucleotide binding avidity.
Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency (2014)

Embryonic stem cells (ESCs) of mice and humans have distinct molecular and biological characteristics, raising the question of whether an earlier, "naive" state of pluripotency may exist in humans. Here we took a systematic approach to identify small molecules that support self-renewal of naive human ESCs based on maintenance of endogenous OCT4 distal enhancer activity, a molecular signature of ground state pluripotency. Iterative chemical screening identified a combination of five kinase inhibitors that induces and maintains OCT4 distal enhancer activity when applied directly to conventional human ESCs. These inhibitors generate human pluripotent cells in which transcription factors associated with the ground state of pluripotency are highly upregulated and bivalent chromatin domains are depleted. Comparison with previously reported naive human ESCs indicates that our conditions capture a distinct pluripotent state in humans that closely resembles that of mouse ESCs. This study presents a framework for defining the culture requirements of naive human pluripotent cells.
[Risk factors for bronchopulmonary dysplasia in neonates with respiratory distress syndrome]. (2007)

The risk for BPD is multifactorial. Preventing small gestational age and low birth weight prematurity, decreasing the duration of mechanical ventilation and treatment of pulmonary infection are necessary to prevent BPD.
Charge Detection Mass Spectrometry for the Characterization of Mass and Surface Area of Composite Nanoparticles (2014)

Binary colloidal particles of polyhedral morphology, obtained by an emulsion polymerization of styrene in the presence of silica seeds, are studied. Because of kinetic effects, composite particles usually exhibit polydispersity in size, shape, and composition. Thus, accurate techniques aiming at characterizing the size and the shape, as well as the composition and surface properties of such objects, are required. In this work, we use charge detection mass spectrometry (CD-MS) as a tool for the characterization of nanometer-sized composite (clusters of) particles. CD-MS measures both the mass and the charge for each ion. This single ion mass spectrometry technique enables one to construct a histogram of mass, yielding the mass distribution. CD-MS for molar mass determination and composition of composite particles is demonstrated to be complementary to transmission electron microscopy. The study of the charging capacity of these composite particles in the gas phase also appears as a valuable approach to probe the surface area of such complex nano-objects, thus giving some insight about their structure and morphology.
RNA interference (RNAi) for extracellular signal-regulated kinase 1 (ERK1) alone is sufficient to suppress cell viability in ovarian cancer cells (2005)

While ovarian cancer is a leading cause of death in females today, the molecular, genetic, and environmental factors that initiate and support the progression of this disease are still only partially understood. The extracellular signal-regulated kinase (ERK) signaling pathway is a major contributor to cellular growth, differentiation and survival. Recently, we reported that this pathway is constitutively activated in ovarian cancer cells, and that by using RNA interference (RNAi) for ERK1 and ERK2, we were able to significantly suppress the number of viable tumor cells. In the present study, we have further investigated the mechanisms by which RNAi for the ERK kinases decreased viability in these cancer cells. It was determined that treatment of the cancer cells with small inhibitory RNAs (siRNAs) directed against ERK1 and ERK2 leads to the induction of apoptosis and necrosis by four hours following treatment. Additionally, we found that primary, nonmalignant ovarian cells do not respond similarly to ERK siRNA treatment and that these cells fail to die following treatment. Data presented show that ERK2 expression is more difficult to silence, depending upon cell type being examined and that silencing ERK1 expression alone is sufficient to significantly decrease tumor cell viability.
Novel AAV serotypes for improved ocular gene transfer (2008)

Some of the most successful gene therapy results have been obtained using recombinant viral vectors to treat animal models of inherited and acquired ocular diseases. Clinical trials using adenovirus vector systems have been initiated for two ocular diseases. Adeno-associated viruses (AAVs) represent an attractive alternative to adenoviral vector systems as they enable stable and long-term expression and can target a variety of different ocular cell types depending on the capsid serotype; recently clinical trails for congenital blindness was initiated with a vector-based AAV serotype 2. High levels of retinal gene transfer have been achieved using vectors based on AAV serotypes 1, 2, 4 and 5. This report compares the gene transfer efficacy and stability of expression of vector systems based on three novel AAV serotypes: AAV7, 8, 9, with the established vectors AAV1, 2, 5. We show here that AAV7 and 8 enable superior long-term transduction of retinal and also anterior chamber structures.
Tree-structured nonlinear signal modeling and prediction (1999)

We develop a regression tree approach to identification and prediction of signals that evolve according to an unknown nonlinear state space model. In this approach, a tree is recursively constructed that partitions the p-dimensional state space into a collection of piecewise homogeneous regions utilizing a 2/sup p/-ary splitting rule with an entropy-based node impurity criterion. On this partition, the joint density of the state is approximately piecewise constant, leading to a nonlinear predictor that nearly attains minimum mean square error. This process decomposition is closely related to a generalized version of the thresholded AR signal model (ART), which we call piecewise constant AR (PCAR). We illustrate the method for two cases where classical linear prediction is ineffective: a chaotic "double-scroll" signal measured at the output of a Chua-type electronic circuit and a second-order ART model. We show that the prediction errors are comparable with the nearest neighbor approach to nonlinear prediction but with greatly reduced complexity.
Identification of Human and Mouse Hematopoietic Stem Cell Populations Expressing High Levels of mRNA Encoding Retrovirus Receptors (1998)

One obstacle to retrovirus-mediated gene therapy for human hematopoietic disorders is the low efficiency of gene transfer into pluripotent hematopoietic stem cells (HSC). We have previously shown a direct correlation between retrovirus receptor mRNA levels in mouse HSC and the efficiency with which they are transduced. In the present study, we assayed retrovirus receptor mRNA levels in a variety of mouse and human HSC populations to identify HSC which may be more competent for retrovirus transduction. The highest levels of amphotropic retrovirus receptor (amphoR) mRNA were found in cryopreserved human cord blood HSC. The level of amphoR mRNA in Lin−CD34+ CD38− cells isolated from frozen cord blood was 12-fold higher than the level in fresh cord blood Lin− CD34+ CD38− cells. In mice, the level of amphoR mRNA in HSC from the bone marrow (BM) of mice treated with stem cell factor and granulocyte-colony stimulating factor was 2.8- to 7.8-fold higher than in HSC from the BM of untreated mice. These findings suggest that HSC from frozen cord blood and cytokine-mobilized BM may be superior targets for amphotropic retrovirus transduction compared with HSC from untreated adult BM.
Rupe and Meyer-Schuster rearrangements (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRupe and Meyer-Schuster rearrangementsS. Swaminathan and K. V. NarayananCite this: Chem. Rev. 1971, 71, 5, 429–438Publication Date (Print):October 1, 1971Publication History Published online1 May 2002Published inissue 1 October 1971https://pubs.acs.org/doi/10.1021/cr60273a001https://doi.org/10.1021/cr60273a001research-articleACS PublicationsRequest reuse permissionsArticle Views3435Altmetric-Citations373LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Reflectance spectroscopy of clotting blood: a description of the time-dependent behavior. (2004)

Reflectance spectroscopy generates unique information about clotting blood. It is feasible to use anticoagulated blood to elucidate the events underlying the time course and to investigate the effects of COX-2 inhibitors.
Predominant antitumor effects by fully human anti-TRAIL-receptor2 (DR5) monoclonal antibodies in human glioma cells in vitro and in vivo (2010)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2 L) preferentially induces apoptosis in human tumor cells through its cognate death receptors DR4 or DR5, thereby being investigated as a potential agent for cancer therapy. Here, we applied fully human anti-human TRAIL receptor monoclonal antibodies (mAbs) to specifically target one of death receptors for TRAIL in human glioma cells, which could also reduce potential TRAIL-induced toxicity in humans. Twelve human glioma cell lines treated with several fully human anti-human TRAIL receptor mAbs were sensitive to only anti-DR5 mAbs, whereas they were totally insensitive to anti-DR4 mAb. Treatment with anti-DR5 mAbs exerted rapid cytotoxicity and lead to apoptosis induction. The cellular sensitivity was closely associated with cell-surface expression of DR5. Expression of c-FLIP(L), Akt, and Cyclin D1 significantly correlated with sensitivity to anti-DR5 mAbs. Primary cultures of glioma cells were also relatively resistant to anti-DR5 mAbs, exhibiting both lower DR5 and higher c-FLIP(L) expression. Downregulation of c-FLIP(L) expression resulted in the sensitization of human glioma cells to anti-DR5 mAbs, whereas overexpression of c-FLIP(L) conferred resistance to anti-DR5 mAb. Treatment of tumor-burden nude mice with the direct agonist anti-DR5 mAb KMTR2 significantly suppressed growth of subcutaneous glioma xenografts leading to complete regression. Similarly, treatment of nude mice bearing intracerebral glioma xenografts with KMTR2 significantly elongated lifespan without tumor recurrence. These results suggest that DR5 is the predominant TRAIL receptor mediating apoptotic signals in human glioma cells, and sensitivity to anti-DR5 mAbs was determined at least in part by the expression level of c-FLIP(L) and Akt. Specific targeting of death receptor pathway through DR5 using fully human mAbs might provide a novel therapeutic strategy for intractable malignant gliomas.
The complement factsbook (1999)

Abbreviations. Preface. Section 1: The Introductory Chapters B.J. Morley and M. Walport, Introduction. B.J. Morely and M. Walport, The Complement System. Section II: The Complement Proteins Part 1: C1q and the Collectins F. Petry and M. Loos, C1q. P. Lawson and K.B.M. Reid, Mannose-binding Lectin. P. Lawson and K.B.M. Reid, Bovine Conglutinin. R.B. Sim, SP-A. R.B. Sim, SP-D. Part 2: Serine Proteases N. Thielens and G.J. Arlaud, C1r. N. Thielens and G.J. Arlaud, C1s. T. Fujita, MASP-1. S. Petersen and J. Jensenius, MASP-2. J. Schifferli and S. Niot, Factor D. Y. Xu Ma and J.E. Volanakis, C2. A. Circolo and H.R. Colten, Factor B. B.J. Morley, Factor I. Part 3: C3 Family M. Botto, C3. R.A. Wetsel, C5. Part 4: Terminal Pathway Components M. Hobart, C6. M. Hobart, C7. F. Tedesco, M.E. Plumb, and J.M. Sodetz, C8. B.P. Morgan, C9. Part 5: Regulations of Complement Activation (RCA) L.B. Klickstein, CR1. J.M. Guthridge and V.M. Holers, CR2. L. Kuttner-Kondo, W.G. Brodbeck, and M.E. Medof, Decay-accelerating Factor. M.K. Liszewski and J.P. Atkinson, Membrane Cofactor Protein. S. Rodriguez de Cordoba, O. Criado Garcia, and P. Sanchez-Corral, C4b-binding Protein. R.G. DiScipio, Factor H. Part 6: Cell Surface Receptors A.J. Tenner, C1qRp. R.S. Ames, C3aReceptor. A. Klos and W. Bautsch, C5a Receptor. Y. Xia and G. Ross, CR3. A. Law, CR4. Part 7: Miscellaneous Complement Components R. Zahedi and A.E. Davis III, C1 Inhibitor. M.E. Rosenberg, Apolipoprotein J (Clusterin). T. Farries, Properdin. B.P. Morgan, CD59. Index.
Protein kinase C activity modulates myelin gene expression in enriched oligodendrocytes (1993)

Protein kinase C (PKC) and its potential role in myelin gene expression were investigated in primary cultured rat oligodendrocytes. The major myelin genes were expressed in a developmentally coordinated manner in cultured oligodendrocytes. PKC activity in these cells was similarly regulated with differential expression of PKC isozyme mRNAs. PKC-gamma mRNA was expressed transiently and was most abundant in 9-day cells in vitro. PKC-alpha and PKC-beta mRNAs were present at low levels throughout development in these cells, and their expression increased in 18-25 day cells. Immunocytochemical colocalization of PKC with oligodendrocyte-specific markers--O4, galactosyl cerebroside, MBP, and PLP--in enriched oligodendrocyte cultures suggested that the PKC enzyme activities assayed in these cultures were predominantly contributed by oligodendrocytes. PKC inhibition resulting from long-term exposure to 4 beta-phorbol-12,13-dibutyrate (4 beta-PDB) reduced steady-state levels of MBP, PLP, MAG, CNP, and PKC-alpha mRNAs, as detected by slot blots or in situ hybridization, and downregulated the oligodendrocyte-specific markers O4, galactosyl cerebroside, and the major constituent proteins MBP and PLP, as detected by immunocytochemistry. PKC-mediated downmodulation of myelin gene expression was most profound in normally differentiating oligodendrocytes at or before the onset of myelin protein synthesis. Six-day oligodendrocytes were most susceptible to such modulation. To elucidate the mechanism of reduction in various myelin gene messages upon modulation of PKC, we analyzed mRNA levels in oligodendrocytes, which were pretreated with either the transcriptional inhibitor actinomycin D or the protein synthesis blocker cycloheximide before exposure to 4 beta-PDB. Our results demonstrate that the PKC inhibition-mediated loss in myelin mRNA levels did not require the transcription of any genes, but appeared to be at least partially dependent on continuous protein synthesis.
Strokes in Children (1996)

Stroke denotes the sudden onset of a focal neurologic deficit and most often includes the abrupt appearance of weakness. Interruption of blood flow to a part of the central nervous system (CNS) usually underlies the resultant weakness. Because most strokes in children are related to focal cerebral involvement, the most common clinical manifestation is the abrupt appearance of hemiparesis. Less frequently, the cause of stroke involves the brain stem, cerebellum, or spinal cord. The functional consequences always reflect the neuroanatomic features of the affected CNS region.EpidemiologyChildhood stroke occurs with an annual incidence of 2.5 cases per 100,000 population and has been reported in all racial and ethnic groups. The sequelae are not trivial. In addition to lasting lateralized weakness, cognitive deficits, disturbances of language, visual deficits, and seizures may persist long after the acute event has concluded.The causes of stroke in children differ from those in adults. Stroke in adults is associated largely with hypertension or atherosclerosis and their respective hemorrhagic and ischemic consequences. Stroke in children more commonly is caused by or related to congenital heart disease, infection, metabolic disorders, hematologic diatheses, and vasculitic disorders, frequently due to autoimmune processes (Table 1). Nonetheless, despite the most thorough of evaluations, etiology escapes detection in approximately 30% of the pediatric patients in whom stroke occurs.
On-Chip Integrated Label-Free Optical Biosensing (2013)

This thesis investigates the design and implementation of a label-free optical biosensing system utilizing a robust on-chip integrated platform. The goal has been to transition optical micro-resonator based label-free biosensing from a laborious and delicate laboratory demonstration to a tool for the analytical life scientist. This has been pursued along four avenues: (1) the design and fabrication of high-$Q$ integrated planar microdisk optical resonators in silicon nitride on silica, (2) the demonstration of a high speed optoelectronic swept frequency laser source, (3) the development and integration of a microfluidic analyte delivery system, and (4) the introduction of a novel differential measurement technique for the reduction of environmental noise. The optical part of this system combines the results of two major recent developments in the field of optical and laser physics: the high-$Q$ optical resonator and the phase-locked electronically controlled swept-frequency semiconductor laser. The laser operates at a wavelength relevant for aqueous sensing, and replaces expensive and fragile mechanically-tuned laser sources whose frequency sweeps have limited speed, accuracy and reliability. The high-$Q$ optical resonator is part of a monolithic unit with an integrated optical waveguide, and is fabricated using standard semiconductor lithography methods. Monolithic integration makes the system significantly more robust and flexible compared to current, fragile embodiments that rely on the precarious coupling of fragile optical fibers to resonators. The silicon nitride on silica material system allows for future manifestations at shorter wavelengths. The sensor also includes an integrated microfluidic flow cell for precise and low volume delivery of analytes to the resonator surface. We demonstrate the refractive index sensing action of the system as well as the specific and nonspecific adsorption of proteins onto the resonator surface with high sensitivity. Measurement challenges due to environmental noise that hamper system performance are discussed and a differential sensing measurement is proposed, implemented, and demonstrated resulting in the restoration of a high performance sensing measurement. The instrument developed in this work represents an adaptable and cost-effective platform capable of various sensitive, label-free measurements relevant to the study of biophysics, biomolecular interactions, cell signaling, and a wide range of other life science fields. Further development is necessary for it to be capable of binding assays, or thermodynamic and kinetics measurements; however, this work has laid the foundation for the demonstration of these applications.
The source and significance of DNA damage in human spermatozoa; a commentary on diagnostic strategies and straw man fallacies (2013)

This article considers the origins of DNA damage in human spermatozoa, the methods that are available to monitor this aspect of semen quality and the clinical significance of such measurements. DNA damage in spermatozoa appears to be largely oxidative in nature, inversely correlated with levels of nuclear protamination and frequently associated with the activation of a truncated apoptotic pathway. DNA base adducts formed as a result of oxidative attack are released from the spermatozoa into the extracellular space through the action of a glycosylase, OGG1. This creates an abasic site, which is not resolved until fertilization because spermatozoa do not possess the molecular machinery needed to continue the base excision repair pathway. The abasic sites so generated in human spermatozoa are readily detected by SCSA or the Comet assay; however, no signal is detectable with TUNEL. This is because spermatozoa lack the enzyme (APE1) needed to create the free 3' hydroxyl groups required by this detection system. Nevertheless, spermatozoa do eventually become TUNEL positive as they enter the perimortem. The American Society of Reproductive Medicine Practice Committee has suggested that DNA damage in spermatozoa should not be assessed because the correlation with pregnancy is inconsistent across independent studies. However, this is a straw man argument. The reason why such assays should be undertaken is not just that they reflect the underlying quality of spermatogenesis but, more importantly, that the DNA damage they reveal may have detrimental effects on the developmental normality of the embryo and the health of possible future children.
A vertical-flow bioreactor array compacts hepatocytes for enhanced polarity and functions (2016)

Although hepatocytes in vivo experience intra-abdominal pressure (IAP), pressure is typically not incorporated in hepatocyte culture systems. The cuboidal cell shape and extent of intercellular contact between cultured hepatocytes are critical parameters that influence the differentiated hepatic phenotype. Using a microfluidic device, the application of pressure to artificially compact cells and forge cell-cell interactions was previously demonstrated to be effective in accelerating hepatic repolarization. In seeking to implement this approach to higher throughput culture platforms for potential drug screening applications, we specifically designed a vertical-flow compaction bioreactor array (VCBA) that compacts hepatocytes within the range of IAP and portal pressure in vivo in a multi-well setup. As a result of vertical perfusion-generated forces, hepatocytes not only exhibited accelerated repolarization, an in vivo-like cuboidal morphology, but also better maintained hepatic functions in long-term culture as compared to the same cells cultured under static conditions. As a novel engineering tool to modulate cell compaction and intercellular interactions, this platform is a promising approach to confer tight control over hepatocyte repolarization for in vitro culture.