gebhart/patrepeval huggingface dataset:
Aryl-bridged polysilsesquioxanes--new microporous materials (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAryl-bridged polysilsesquioxanes--new microporous materialsKenneth J. Shea, Douglas A. Loy, and Owen W. WebsterCite this: Chem. Mater. 1989, 1, 6, 572–574Publication Date (Print):November 1, 1989Publication History Published online1 May 2002Published inissue 1 November 1989https://pubs.acs.org/doi/10.1021/cm00006a003https://doi.org/10.1021/cm00006a003research-articleACS PublicationsRequest reuse permissionsArticle Views528Altmetric-Citations137LEARN 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
Cell Cycle-dependent Phosphorylation, Nuclear Localization, and Activation of Human Condensin (2004)

Condensin, one of the most abundant components of mitotic chromosomes, is a conserved protein complex composed of two structural maintenance of chromosomes (SMC) subunits (SMC2- and SMC4-type) and three non-SMC subunits, and it plays an essential role in mitotic chromosome condensation. Purified condensin reconfigures DNA structure using energy provided by ATP hydrolysis. To know the regulation of condensin in somatic cells, the expression level, subcellular localization, and phosphorylation status of human condensin were examined during the cell cycle. The levels of condensin subunits were almost constant throughout the cell cycle, and the three non-SMC subunits were phosphorylated at specific sites in mitosis and dephosphorylated upon the completion of mitosis. Subcellular fractionation studies revealed that a proportion of condensin was tightly bound to mitotic chromosomes and that this form was phosphorylated at specific sites. Condensin purified from mitotic cells had much stronger supercoiling activity than that purified from interphase cells. These results suggest that condensin functions in somatic cells are regulated by phosphorylation in two ways during the cell cycle; the phosphorylation of specific sites correlates with the chromosomal targeting of condensin, and its biochemical activity is stimulated by phosphorylation.
Sip1, a Novel RS Domain-Containing Protein Essential for Pre-mRNA Splicing (1998)

Previous studies have shown that protein-protein interactions among splicing factors may play an important role in pre-mRNA splicing. We report here identification and functional characterization of a new splicing factor, Sip1 (SC35-interacting protein 1). Sip1 was initially identified by virtue of its interaction with SC35, a splicing factor of the SR family. Sip1 interacts with not only several SR proteins but also with U1-70K and U2AF65, proteins associated with 5' and 3' splice sites, respectively. The predicted Sip1 sequence contains an arginine-serine-rich (RS) domain but does not have any known RNA-binding motifs, indicating that it is not a member of the SR family. Sip1 also contains a region with weak sequence similarity to the Drosophila splicing regulator suppressor of white apricot (SWAP). An essential role for Sip1 in pre-mRNA splicing was suggested by the observation that anti-Sip1 antibodies depleted splicing activity from HeLa nuclear extract. Purified recombinant Sip1 protein, but not other RS domain-containing proteins such as SC35, ASF/SF2, and U2AF65, restored the splicing activity of the Sip1-immunodepleted extract. Addition of U2AF65 protein further enhanced the splicing reconstitution by the Sip1 protein. Deficiency in the formation of both A and B splicing complexes in the Sip1-depleted nuclear extract indicates an important role of Sip1 in spliceosome assembly. Together, these results demonstrate that Sip1 is a novel RS domain-containing protein required for pre-mRNA splicing and that the functional role of Sip1 in splicing is distinct from those of known RS domain-containing splicing factors.
Substances That Inhibit the Actions of Prostaglandins (1974)

Several substances have been found to inhibit some actions of prostaglandins. Three principal types have shown characteristics of specific, competitive prostaglandin antagonism. These are dibenzoxazepine derivatives (especially SC-19220), 7-oxa-prostaglandin analogs (especially 7-oxa-13-prostynoic acid), and phosphorylated polymers of phloretin (especially polyphloretin phosphate). As more is learned about prostaglandins, more evidence is accumulating that they may be involved in certain pathological conditions. This has led to suggestions that prostaglandin antagonists may be useful therapeutic agents for treating conditions such as habitual abortion, premature labor, diarrhea, cerebral vasospasm, fever, bone resorption, sickle cell anemia, obstructive lung diseases, inflammation, uveitis, and glaucoma. No proved therapeutic utility has been established for prostaglandin antagonists, but research in animals has indicated that some of the suggested uses may be practical.
Selective Monocationic Inhibitors of Neuronal Nitric Oxide Synthase. Binding Mode Insights from Molecular Dynamics Simulations (2012)

The reduction of pathophysiologic levels of nitric oxide through inhibition of neuronal nitric oxide synthase (nNOS) has the potential to be therapeutically beneficial in various neurodegenerative diseases. We have developed a series of pyrrolidine-based nNOS inhibitors that exhibit excellent potencies and isoform selectivities (J. Am. Chem. Soc. 2010, 132, 5437). However, there are still important challenges, such as how to decrease the multiple positive charges derived from basic amino groups, which contribute to poor bioavailability, without losing potency and/or selectivity. Here we present an interdisciplinary study combining molecular docking, crystallography, molecular dynamics simulations, synthesis, and enzymology to explore potential pharmacophoric features of nNOS inhibitors and to design potent and selective monocationic nNOS inhibitors. The simulation results indicate that different hydrogen bond patterns, electrostatic interactions, hydrophobic interactions, and a water molecule bridge are key factors for stabilizing ligands and controlling ligand orientation. We find that a heteroatom in the aromatic head or linker chain of the ligand provides additional stability and blocks the substrate binding pocket. Finally, the computational insights are experimentally validated with double-headed pyridine analogues. The compounds reported here are among the most potent and selective monocationic pyrrolidine-based nNOS inhibitors reported to date, and 10 shows improved membrane permeability.
Frações orgânicas e índice de manejo de carbono do solo em diferentes sistemas de produção orgânica Organic fractions and carbon management index of soil under different organic production systems (2011)

O efeito do manejo orgânico pode influenciar positivamente nas fracoes da materia orgânica do solo. Este estudo objetivou avaliar as fracoes orgânicas do solo e o indice de manejo do carbono em areas submetidas a manejo orgânico sob diferentes sistemas de uso do solo. As areas selecionadas apresentavam os seguintes sistemas de uso do solo: preparo convencional (PC) com cultivo de milho, plantio direto (PD) com cultivo de berinjela, preparo reduzido (PR) com cultivo de figo, consorcio maracuja - Desmodium sp e um sistema agroflorestal (SAF). Uma area de floresta secundaria foi tomada como referencia da condicao original do solo. As amostras de terra foram coletadas nas profundidades de 0-5 e 5-10 cm. Foi quantificado o carbono orgânico total (COT), o carbono orgânico particulado (COp) e o carbono orgânico associado aos minerais (COam). Em seguida calcularam-se os respectivos estoques (EstCOT, EstCOp e EstCOam) e o indice de manejo de carbono (IMC). Na profundidade de 0-5 cm observaram-se maiores teores de COT na area de figo (PR) seguido de berinjela (PD), sendo na profundidade de 5-10 cm verificado maiores diferencas entre as areas avaliadas para este atributo. O EstCOp foi maior na area sob plantio direto (0-5 cm), sendo observado diferencas entre todas as areas nesta profundidade. Esta area tambem apresentou o maior IMC. Os maiores valores de EstCOam foram observados na area de figo (PR), nas duas profundidades, sendo constatadas diferencas entre as demais areas. Os resultados encontrados indicam que o COT foi mais eficiente para identificar mudancas provenientes do manejo adotado na profundidade de 5-10 cm, sendo este comportamento observado para o EstCOp em superficie (0-5 cm). O IMC encontrado na area de berinjela sob PD, manejado organicamente e com uso de leguminosas na forma de adubacao verde, demonstra a maior sustentabilidade do sistema em relacao as demais areas avaliadas. Palavras chave: Materia orgânica, fracionamento granulometrico, residuos vegetais, adubacao verde, agricultura orgânica.
Thrombospondin-1, PECAM-1, and regulation of angiogenesis. (1999)

Thrombospondin-1 (TSP1) is a multidomain glycoprotein expressed by many cell types. It is a multifunctional protein with important roles in regulation of vascular cell functions. Mutation or loss of tumor suppressor genes results in down regulation of TSP1 expression during malignant transformation. Thus, suggesting that down regulation of TSP1 may contribute to development of the tumor angiogenic phenotype and perhaps tumor metastasis. TSP1 was demonstrated to be a natural inhibitor of angiogenesis. Peptides from procollagen-like domain and type 1 repeats of TSP1, like whole TSP1, inhibit the angiogenic response to a variety of angiogenic stimuli in vivo and endothelial cell (EC) migration in vitro by directly acting on ECs. The molecular mechanisms which mediate these inhibitory effects of TSP1 and its peptides are not understood. TSP1 expression is down regulated in the Polyoma middle T transformed mouse brain ECs (bEND.3). This may remove the TSP1 inhibitory effects allowing ECs to rapidly proliferate in culture and form hemangiomas in vivo. Re-expression of TSP1 in bEND.3 cells restores a normal phenotype and suppresses their ability to form hemangiomas. This is mediated by modulating expression of several genes in concert favoring a differentiated state of endothelium. TSP1 transfected bEND.3 cells down regulate expression of PECAM-1, a multifunctional endothelial cell adhesion molecule with essential roles in angiogenesis. A similar phenotype to that of TSP1 transfected cells was observed when endogenous PECAM-1 levels were down regulated by anti-sense transfection of bEND.3 cells. The anti-sense PECAM-1 transfected cells turn on expression of endogenous TSP1 and its angioinhibitory receptor, CD36. Expression of other genes with potential roles in regulation of EC phenotype were also affected in patterns very similar to those observed in TSP1 transfected bEND.3 cells. Therefore, it appears that a reciprocal relationship exists between TSP1 and PECAM-1 such that they are constituents of a "switch" that regulates in concert many components of the angiogenic and differentiated phenotype of ECs.
Enthalpy of Transformation of a High-Pressure Polymorph of Titanium Dioxide to the Rutile Modification (1967)

The enthalpy of transformation of a high-pressure form of titanium dioxide, which has the alpha lead dioxide structure, to the rutile modification was measured by the method of "transposed temperature-drop calorimetry." For the reaction, titanium dioxide (alpha lead dioxide form) transforming to rutile, the change in the heat content is -0.76 +/- 0.17 kilocalorie per mole. From this value and the volume change (+ 2.8 percent) associated with the transformation, we estimate the equilibrium pressure at 294 degrees K to be 60 +/- 20 kilobars.
Respiratory infections in the first year of life in children at risk of developing atopy. (1982)

Ninety-two infants, each of whom had one parent with asthma or hay fever, were followed up from birth to age of 1 year and 72 to the age of three years. During the first year of life respiratory symptoms, eczema, and respiratory viral infections were all reported. Within the first year 24 babies developed eczema; 28 had a wheal of 1 mm in diameter or more on prick skin testing with cutaneous allergens. Forty-three children had one or both of these characteristics and formed an atopic subgroup; by the same criteria, 49 children were non-atopic. The number of respiratory infections in the two groups was not significantly different; similar viruses were isolated from both groups. These viruses were associated with both upper and lower respiratory tract infections. Wheezing was a clinical feature in 12 children during lower respiratory tract infections. Of these babies six were atopic in the first year of life. Of the six non-atopic babies, one had eczema in the second year and five children developed raised total serum IgE values within the 3 years.
CSF-1 Receptor Signaling in Myeloid Cells (2014)

The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). It plays important roles in development and in innate immunity by regulating the development of most tissue macrophages and osteoclasts, of Langerhans cells of the skin, of Paneth cells of the small intestine, and of brain microglia. It also regulates the differentiation of neural progenitor cells and controls functions of oocytes and trophoblastic cells in the female reproductive tract. Owing to this broad tissue expression pattern, it plays a central role in neoplastic, inflammatory, and neurological diseases. In this review we summarize the evolution, structure, and regulation of expression of the CSF-1R gene. We discuss the structures of CSF-1, IL-34, and the CSF-1R and the mechanism of ligand binding to and activation of the receptor. We further describe the pathways regulating macrophage survival, proliferation, differentiation, and chemotaxis downstream from the CSF-1R.
Modification of Tumor Microenvironment by Cytokine Gene Transfer (1995)

The tumor microenvironment is determined by the interactions between host and tumor cells, a process in which cytokines play a major role. We have used retroviral vectors to insert and express cytokine genes in tumor cells so as to induce predictable changes in the host cells that infiltrate tumors. This frequently caused changes in tumor cell phenotype through autocrine/intracrine pathways. We reasoned that cytokine-induced alterations in tumor cell phenotype and/or in infiltrating host cells might alter the in vitro and in vivo cellular response to irradiation. In the present paper we document some of the effects of expression of interleukin-6 (IL-6) and IL-7 genes in tumor cells in this regard. The studies support the hypothesis that cytokines may play a role in determining both intrinsic tumor radioresponsiveness and the tumor microenvironment and in these ways may influence in vivo tumor irradiation responses. Possible cytokine gene-mediated approaches to radiotherapy cancer are discussed.
Massive ex Vivo Expansion of Human Natural Regulatory T Cells (T regs ) with Minimal Loss of in Vivo Functional Activity (2011)

Graft-versus-host disease (GVHD) is a frequent and severe complication after hematopoietic cell transplantation. Natural CD4(+)CD25(+) regulatory T cells (nT(regs)) have proven highly effective in preventing GVHD and autoimmunity in murine models. Yet, clinical application of nT(regs) has been severely hampered by their low frequency and unfavorable ex vivo expansion properties. Previously, we demonstrated that umbilical cord blood (UCB) nT(regs) could be purified and expanded in vitro using good manufacturing practice (GMP) reagents; however, the initial number of nT(regs) in UCB units is limited, and average yield after expansion was only 1 × 10(9) nT(regs). Therefore, we asked whether yield could be increased by using peripheral blood (PB), which contains far larger quantities of nT(regs). PB nT(regs) were purified under GMP conditions and expanded 80-fold to yield 19 × 10(9) cells using anti-CD3 antibody-loaded, cell-based artificial antigen-presenting cells (aAPCs) that expressed the high-affinity Fc receptor and CD86. A single restimulation increased expansion to ~3000-fold and yield to >600 × 10(9) cells while maintaining Foxp3 expression and suppressor function. nT(reg) expansion was ~50 million-fold when flow sort-purified nT(regs) were restimulated four times with aAPCs. Indeed, cryopreserved donor nT(regs) restimulated four times significantly reduced GVHD lethality induced by the infusion of human T cells into immune-deficient mice. The capability to efficiently produce donor cell banks of functional nT(regs) could transform the treatment of GVHD and autoimmunity by providing an off-the-shelf, cost-effective, and proven cellular therapy.
Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice (1999)

Delta9-Tetrahydrocannabinol (Delta9-THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications. To study the role of the major known target of cannabinoids in the CNS, the CB1 cannabinoid receptor, we have produced a mouse strain with a disrupted CB1 gene. CB1 knockout mice appeared healthy and fertile, but they had a significantly increased mortality rate. They also displayed reduced locomotor activity, increased ring catalepsy, and hypoalgesia in hotplate and formalin tests. Delta9-THC-induced ring-catalepsy, hypomobility, and hypothermia were completely absent in CB1 mutant mice. In contrast, we still found Delta9-THC-induced analgesia in the tail-flick test and other behavioral (licking of the abdomen) and physiological (diarrhea) responses after Delta9-THC administration. Thus, most, but not all, CNS effects of Delta9-THC are mediated by the CB1 receptor.
Multiprocessor system development for high performance signal processing applications (2002)

Developing multiprocessor systems to implement high performance signal processing algorithms can be a formidable undertaking. A process for designing multiprocessor systems, using primarily programmable processors, is proposed. This design process starts with algorithm entry and analysis, continues with functional decomposition and architecture entry, which are used to drive the algorithm to architecture mapping. The development process then proceeds with a combination of hardware profiling and performance modeling, followed by the visualization of the results. Since the process is iterative, feedback from later steps are often used to make better design choices in earlier steps, allowing the impact of these decisions to be re-evaluated. Ultimately, the user finishes with an implemented system. Each of these steps are described in detail, as well as some of the tools which support them.
CNS Drug Delivery Systems: Novel Approaches (2009)

The brain is a delicate organ, and nature has very efficiently protected it. The brain is shielded against potentially toxic substances by the presence of two barrier systems: the blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB). Unfortunately, the same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Despite aggressive research, patients suffering from fatal and/or debilitating central nervous system (CNS) diseases, such as brain tumours, HIV encephalopathy, epilepsy, cerebrovascular diseases and neurodegenerative disorders, far outnumber those dying of all types of systemic cancers or heart diseases. The abysmally low number of potential therapeutics reaching commercial success is primarily due to the complexity of the CNS drug development. The clinical failure of many probable candidates is often, ascribable to poor delivery methods which do not pervade the unyielding BBB. It restricts the passive diffusion of many drugs into the brain and constitutes a significant obstacle in the pharmacological treatment of central nervous system (CNS) disorders. General methods that can enhance drug delivery to the brain are, therefore, of great pharmaceutical interest. Various strategies like non-invasive methods, including drug manipulation encompassing transformation into lipophilic analogues, prodrugs, chemical drug delivery, carrier-mediated drug delivery, receptor/vector mediated drug delivery and intranasal drug delivery, which exploits the olfactory and trigeminal neuronal pathways to deliver drugs to the brain, are widely used. On the other hand the invasive methods which primarily rely on disruption of the BBB integrity by osmotic or biochemical means, or direct intracranial drug delivery by intracerebroventricular, intracerebral or intrathecal administration after creating reversible openings in the head, are recognised. Extensive review pertaining specifically, to the patents relating to drug delivery across the CNS is currently available. However, many patents e.g. US63722506, US2002183683 etc., have been mentioned in a few articles. It is the objective of this article to expansively review drug delivery systems for CNS by discussing the recent patents available.
Intracellular neutralization of influenza virus by immunoglobulin A anti-hemagglutinin monoclonal antibodies (1995)

Traditionally, immunoglobulin A (IgA) was thought to neutralize virus by forming complexes with viral attachment proteins, blocking attachment of virions to host epithelial cells. Recently we have proposed an intracellular action for dimeric IgA, which is actively transported through epithelial cells by the polymeric immunoglobulin receptor (pIgR), in that it may be able to bind to newly synthesized viral proteins within the cell, preventing viral assembly. To this effect, we have previously demonstrated that IgA monoclonal antibodies against Sendai virus, a parainfluenza virus, colocalize with the viral hemagglutinin-neuraminidase protein within infected epithelial cells and reduce intracellular viral titers. Here we determine whether IgA can interact with influenza virus hemagglutinin (HA) protein within epithelial cells. Polarized monolayers of Madin-Darby canine kidney epithelial cells expressing the pIgR were infected on their apical surfaces with influenza virus A/Puerto Rico/8-Mount Sinai. Polymeric IgA anti-HA, but not IgG anti-HA, delivered to the basolateral surface colocalized with HA protein within the cell by immunofluorescence. Compared with those of controls, viral titers were reduced in the supernatants and cell lysates from monolayers treated with anti-HA IgA but not with anti-HA IgG. Furthermore, the addition of anti-IgA antibodies to supernatants did not interfere with the neutralizing activity of IgA placed in the basal chamber, indicating that IgA was acting within the cell and not in the extracellular medium to interrupt viral replication. Thus, these studies provide additional support for the concept that IgA can inhibit replication of microbial pathogens intracellularly.