gebhart/patrepeval huggingface dataset:
Pancreatic Cancer and MicroRNAs (2012)

MicroRNAs (miRNAs) are recently discovered non-coding small RNAs that play a role as regulators of genetic expressions in eukaryotic cells. It comprises about 20 nucleotides, which contains seed sequence to bind 3'-untranslated lesion of specific target mRNA. It regulates self-renewal, proliferation and differentiation via post-transcriptional gene slicing in normal situation. Aberrant expressions of miRNAs are observed in many cancers as well. miRNAs in cancer cells have been investigated extensively to have a role in tumorigenesis, invasion, metastasis and chemoresistance. In cancer cells, miRNAs act both as tumor suppressors or oncogenes by doing down-regulation of oncogenes or up-regulation of tumor suppressors, respectively. This suggests miRNAs can be potential therapeutic and diagnostic targets in cancers. Pancreatic cancer is one of the most lethal tumors. In spite of many efforts, overall 5-year survival rate of pancreatic cancer is still very low (<5%). Recently, several miRNAs as an oncomir (acting like oncogenes or tumor suppressor genes) are discovered in pancreatic cancer. Here, the role of miRNAs in pancreatic cancer will be discussed and its possibility of diagnostic/therapeutic target will be also mentioned.
The visibility of color breakup and a means to reduce it (2014)

Color breakup is an artifact seen on displays that present colors sequentially. When the eye tracks a moving object on such a display, different colors land on different places on the retina, and this gives rise to visible color fringes at the object's leading and trailing edges. Interestingly, color breakup is also observed when the eye is stationary and an object moves by. Using a novel psychophysical procedure, we measured breakup both when viewers tracked and did not track a moving object. Breakup was somewhat more visible in the tracking than in the non-tracking condition. The video frames contained three subframes, one each for red, green, and blue. We spatially offset the green and blue stimuli in the second and third subframes, respectively, to find the values that minimized breakup. In the tracking and non-tracking conditions, spatial offsets of Δx/3 in the second subframe (where Δx is the displacement of the object in one frame) and 2Δx/3 in the third eliminated breakup. Thus, this method offers a way to minimize or even eliminate breakup whether the viewer is tracking or not. We suggest ways to implement the method with real video content. We also developed a color-breakup model based on spatiotemporal filtering in color-opponent pathways in early vision. We found close agreement between the model's predictions and the experimental results. The model can be used to predict breakup for a wide variety of conditions.
Killing of gram-negative bacteria by polymorphonuclear leukocytes: role of an O2-independent bactericidal system. (1982)

Previous studies have suggested that a cationic bactericidal/permeability-increasing protein (BPI) present in both rabbit and human polymorphonuclear leukocytes is the principal O2-independent bactericidal agent of these cells toward several strains of Escherichia coli and Salmonella typhimurium (1978. J. Biol. Chem. 253: 2664--2672; 1979. J. Biol. Chem. 254: 11000--11009). To further evaluate the possible role of this protein in the killing of gram-negative bacteria by polymorphonuclear leukocytes, we have measured the bactericidal activity of intact rabbit peritoneal exudate leukocytes under aerobic or anaerobic conditions and of intact human leukocytes from a patient with chronic granulomatous disease. Anaerobic conditions were created by flushing the cells under a nitrogen stream. Effective removal of oxygen was demonstrated by the inability of nitrogen-flushed leukocytes to mount a respiratory burst (measured as increased conversion of 1-[14C]glucose leads to 14CO2 or by superoxide production) during bacterial ingestion. At a bacteria/leukocyte ratio of 10:1, killing of gram-positive, BPI-resistant, Staphylococcus epidermidis is markedly impaired in the absence of oxygen (76.4 +/- 3.3% killing in room air, 29.2 +/- 8.2% killing in nitrogen). Essentially all increased bacterial survival is intracellular. In contrast, both a nonopsonized rough strain (MR-10) and an opsonized smooth strain (MS) of S. typhimurium 395 are killed equally well in room air and nitrogen. A maximum of 70--80 MR-10 and 30--40 MS are killed per leukocyte either in the presence or absence of oxygen. There is no intracellular bacterial survival in either condition indicating that intracellular O2-independent bactericidal system(s) of rabbit polymorphonuclear leukocytes can at least match the leukocyte's ingestive capacity. Whole homogenates and crude acid extracts manifest similar bactericidal capacity toward S. typhimurium 395. This activity can be accounted for by the BPI content of these cell fractions and is virtually eliminated by immune (anti-BPI), but not by preimmune goat IgG-rich fractions. Opsonization of smooth MS, required for bacterial killing by intact leukocytes, does not alter bacterial sensitivity to BPI in crude or purified form. Leukocytes of a patient with chronic granulomatous disease killed ingested S. typhimurium 396 MS nearly as well as did normal leukocytes. The bactericidal activity toward E. coli (J5) of crude acid extracts of the CGD and normal human leukocytes was virtually the same and was nearly completely inhibited by anti-BPI IgG-rich fractions, but not by preimmune IgG-rich fractions. These findings suggest that the killing of gram-negative bacteria such as S. typhimurium by intact polymorphonuclear leukocytes may also be attributed to the action of BPI.
Increased plasma levels of IL‐6 in bacteremic periodontis patients after scaling (2006)

Bacteremia frequently occurs after dental treatment. Periodontal inflammation may influence the incidence, magnitude and duration of bacteremia. The presence of circulating oral bacteria or bacterial components may induce cytokine synthesis in blood cells, which may contribute to the development or exacerbation of atherosclerosis. The present study tested the hypothesis that bacteremia occurring after scaling in periodontitis patients results in altered plasma levels of cytokines. Twenty periodontitis patients were subjected to scaling. Blood samples at baseline and at 0.5, 10 and 30 minutes postscaling were examined for bacteremia whereas baseline and eight-hour postscaling blood samples were examined for the levels of IL-1beta, TNF-alpha, IL-6, IL-8, IL-10 and IL-12p70. IL-6 levels were significantly increased eight hours after scaling, while IL-8 was significantly decreased. No systematic changes occurred in the levels of IL-1beta, TNF-alpha, IL-10 and IL-2p70. IL-6 levels may be increased while IL-8 may be decreased due to scaling, which may have implications for general health.
Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1. (1989)

The effects on human immunodeficiency virus type 1 virion morphogenesis and on virus replication of mutations that affect posttranslational processing of the capsid precursor protein are described. A change in the glycine residue at position two from the N terminus abolishes the myristoylation of the precursor proteins and also prevents virus particle release. Mutations in the viral protease gene abolish proteolytic cleavage of the capsid precursor but do not prevent the formation and budding of virion particles of immature appearance. Mutations that alter the sequence of the sites normally used for cleavage of the major capsid protein p24 from the capsid precursor alter virion morphogenesis and prevent virus replication.
Synthesis and Biological Evaluation of 1-Aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one Inhibitors of Cyclin-Dependent Kinases (2004)

Using a high-throughput screening strategy, a series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation of a protein substrate with IC(50)s in the low micromolar range. On the basis of preliminary structure-activity relationships (SAR), a model was proposed in which these inhibitors occupy the ATP-binding site of the enzyme, forming critical hydrogen bonds to the same residue (Val96) to which the amino group in ATP is presumed to bind. X-ray diffraction studies on a later derivative bound to CDK2 support this binding mode. Iterative cycles of synthesis and screening lead to a novel series of potent, CDK2-selective 6-(arylmethyl)pyrazolopyrimidinones. Placement of a hydrogen-bond donor in the meta-position on the 6-arylmethyl group resulted in approximately 100-fold increases in CDK4 affinity, giving ligands that were equipotent inhibitors of CDK4 and CDK2. These compounds exhibit antiproliferative effects in the NCI HCT116 and other cell lines. The potency of these antiproliferative effects is enhanced in anilide derivatives and translates into tumor growth inhibition in a mouse xenograft model.
Analysis of uncoupling protein and its mRNA in adipose tissue deposits of adult humans. (1992)

Brown adipose tissue (BAT) is a specialized adipose tissue whose specific marker is the uncoupling protein (UCP). UCP and its mRNA were previously detected in the perirenal fat of several adult subjects undergoing surgery for pheochromocytoma. We have investigated the possible association of the presence of UCP and its mRNA with pathological conditions other than pheochromocytoma. We obtained adipose tissue from both the periadrenal and the perirenal regions of 36 subjects: group A: human infants (n = 6); group B: adult subjects (n = 11) undergoing surgery for pheochromocytoma; group C: adult subjects (n = 9) undergoing surgery for other endocrine pathologies; group D: adult patients (n = 10) operated for non-endocrine pathologies. In all subjects of group A UCP was detectable by Western analysis. Interestingly, in two newborns, we also found a positive signal for UCP in the peristernal and the retroperitoneal adipose tissues as well as in the perirenal fat. We also identified UCP in eight cases in group B, in five cases in group C and six cases in group D. The human H-UCP-0.5 genomic probe detected a typical BAT mRNA in the periadrenal adipose tissue of all subjects of groups B, C and D showing a positive Western blot. Our results confirm the presence of well-developed BAT in human infants, as well as in adults with pheochromocytoma. They also suggest that human BAT UCP and UCP mRNA are present in adult subjects in pathological conditions other than pheochromocytoma. It might be argued that certain hormones distinct from catecholamine could activate BAT development in human adults.(ABSTRACT TRUNCATED AT 250 WORDS)
CXCR4 dimerization and β-arrestin–mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome (2008)

WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome is an immune deficiency linked in many cases to heterozygous mutations causing truncations in the cytoplasmic tail of CXC chemokine receptor 4 (CXCR4). Leukocytes expressing truncated CXCR4 display enhanced responses to the receptor ligand CXCL12, including chemotaxis, which likely impair their trafficking and contribute to the immunohematologic clinical manifestations of the syndrome. CXCR4 desensitization and endocytosis are dependent on beta-arrestin (betaarr) recruitment to the cytoplasmic tail, so that the truncated CXCR4 are refractory to these processes and so have enhanced G protein-dependent signaling. Here, we show that the augmented responsiveness of WHIM leukocytes is also accounted for by enhanced betaarr2-dependent signaling downstream of the truncated CXCR4 receptor. Indeed, the WHIM-associated receptor CXCR4(1013) maintains association with betaarr2 and triggers augmented and prolonged betaarr2-dependent signaling, as revealed by ERK1/2 phosphorylation kinetics. Evidence is also provided that CXCR4(1013)-mediated chemotaxis critically requires betaarr2, and disrupting the SHSK motif in the third intracellular loop of CXCR4(1013) abrogates betaarr2-mediated signaling, but not coupling to G proteins, and normalizes chemotaxis. We also demonstrate that CXCR4(1013) spontaneously forms heterodimers with wild-type CXCR4. Accordingly, we propose a model where enhanced functional interactions between betaarr2 and receptor dimers account for the altered responsiveness of WHIM leukocytes to CXCL12.
Protecting Group Chemistry (2000)

<italic>Protecting Group Chemistry</italic> provides an overview of the general methods that are used to block the reactivity ofi.e. protectspecific functional groups, thus allowing others, present within the same molecule, to be manipulated unambiguously. An introductory chapter outlines protecting group strategy, relevant aspects of functional group reactivity, temporary protection, and introduces the concept of protecting group devices as an aid to unifying the wide range of available methods. The rest of the book is divided on the basis of broad classes of the experimental conditions that lead to cleavage of each protecting group (acid/electrophile, base/nucleophile, oxidising or reducing agent).
Effect of phenyl ring torsional rigidity on the photophysical behavior of tetraphenylethylenes (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffect of phenyl ring torsional rigidity on the photophysical behavior of tetraphenylethylenesDavid A. Shultz and Marye Anne FoxCite this: J. Am. Chem. Soc. 1989, 111, 16, 6311–6320Publication Date (Print):August 1, 1989Publication History Published online1 May 2002Published inissue 1 August 1989https://pubs.acs.org/doi/10.1021/ja00198a049https://doi.org/10.1021/ja00198a049research-articleACS PublicationsRequest reuse permissionsArticle Views934Altmetric-Citations97LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Multitarget-ribozyme directed to cleave at up to nine highly conserved HIV-1 env RNA regions inhibits HIV-1 replication—potential effectiveness against most presently sequenced HIV-1 isolates (1992)

Several mono-, di-, tetra-, penta- and nonaribozymes were developed. These multitarget-ribozymes were targeted to cleave HIV-1 env RNA at up to nine different conserved sites. Each multitarget-ribozyme consisted of a chain of up to nine hammerhead motifs, each flanked by a different targeting sequence. The multitarget-ribozymes were functional in vitro and gave rise to multiple, specific partial and/or complete RNA digestion products. Per RNA copy, multitarget-ribozymes were more efficient than monoribozymes or ribozymes targeting a subset of the same sites. In contrast to monoribozymes, a 400nt nonaribozyme, targeted to cleave at nine different sites within a 1.3kb HIV-1 env RNA substrate, was active and showed the same specificity of cleavage when it was part of a large 3.3kb transcript. We conclude that multitarget-ribozymes retain the specificity of monoribozymes, but they are more efficient per ribozyme RNA copy and they remain active when they are part of a large transcript. A tetra-, penta- or nonaribozyme under control of the SV40 late promoter, the beta-actin gene promoter or the HIV-1 LTR, respectively, were cotransfected with the infectious HIV-1 DNA clone pNL4-3 into permissive HeLa T4 cells. Each cotransfection resulted in a specific inhibition of HIV-1 replication as determined by syncytia formation and p24 antigen release. In addition, coexpression of the nonaribozyme with an HIV-1 env RNA transcript resulted in the specific dramatic reduction of the env transcript. We conclude that the multitarget-ribozymes are also functional intracellularly. A nucleotide sequence comparison of the target sites indicates that the multitarget-ribozymes could potentially be effective against all thirty HIV-1 isolates presently sequenced. Their use may help to slow the selection of viral escape mutants and thereby prolong their effectiveness. We anticipate that multitarget-ribozymes will also be more effective in the successful targeting of less variable cellular RNAs.
Space-Time Completion of Video (2007)

This paper presents a new framework for the completion of missing information based on local structures. It poses the task of completion as a global optimization problem with a well-defined objective function and derives a new algorithm to optimize it. Missing values are constrained to form coherent structures with respect to reference examples. We apply this method to space-time completion of large space-time "holes" in video sequences of complex dynamic scenes. The missing portions are filled in by sampling spatio-temporal patches from the available parts of the video, while enforcing global spatio-temporal consistency between all patches in and around the hole. The consistent completion of static scene parts simultaneously with dynamic behaviors leads to realistic looking video sequences and images. Space-time video completion is useful for a variety of tasks, including, but not limited to: 1) Sophisticated video removal (of undesired static or dynamic objects) by completing the appropriate static or dynamic background information. 2) Correction of missing/corrupted video frames in old movies. 3) Modifying a visual story by replacing unwanted elements. 4) Creation of video textures by extending smaller ones. 5) Creation of complete field-of-view stabilized video. 6) As images are one-frame videos, we apply the method to this special case as well.
Dye-sensitized solar cells based on composite solid polymer electrolytes (2004)

The ionic conductivity of polymer electrolytes and their interfacial contact with dye-attached TiO2 particles were enhanced markedly by the addition of amorphous oligomer into polymer electrolytes, resulting in very high overall energy conversion efficiency.
Role of the IκB Kinase Complex in Oncogenic Ras- and Raf-Mediated Transformation of Rat Liver Epithelial Cells (2000)

NF-kappaB/Rel factors have been implicated in the regulation of liver cell death during development, after partial hepatectomy, and in hepatocytes in culture. Rat liver epithelial cells (RLEs) display many biochemical and ultrastructural characteristics of oval cells, which are multipotent cells that can differentiate into mature hepatocytes. While untransformed RLEs undergo growth arrest and apoptosis in response to transforming growth factor beta1 (TGF-beta1) treatment, oncogenic Ras- or Raf-transformed RLEs are insensitive to TGF-beta1-mediated growth arrest. Here we have tested the hypothesis that Ras- or Raf-transformed RLEs have altered NF-kappaB regulation, leading to this resistance to TGF-beta1. We show that classical NF-kappaB is aberrantly activated in Ras- or Raf-transformed RLEs, due to increased phosphorylation and degradation of IkappaB-alpha protein. Inhibition of NF-kappaB activity with a dominant negative form of IkappaB-alpha restored TGF-beta1-mediated cell killing of transformed RLEs. IKK activity mediates this hyperphosphorylation of IkappaB-alpha protein. As judged by kinase assays and transfection of dominant negative IKK-1 and IKK-2 expression vectors, NF-kappaB activation by Ras appeared to be mediated by both IKK-1 and IKK-2, while Raf-induced NF-kappaB activation was mediated by IKK-2. NF-kappaB activation in the Ras-transformed cells was mediated by both the Raf and phosphatidylinositol 3-kinase pathways, while in the Raf-transformed cells, NF-kappaB induction was mediated by the mitogen-activated protein kinase cascade. Last, inhibition of either IKK-1 or IKK-2 reduced focus-forming activity in Ras-transformed RLEs. Overall, these studies elucidate a mechanism that contributes to the process of transformation of liver cells by oncogene Ras and Raf through the IkappaB kinase complex leading to constitutive activation of NF-kappaB.
Inhibition of ERK phosphorylation decreases nociceptive behaviour in monoarthritic rats (2005)

In this study we investigated the role of the activation of the extracellular signal-regulated kinases 1 and 2 (ERK) in chronic inflammatory articular nociception. Monoarthritis was induced in the left ankle of Wistar rats by injection of complete Freund's adjuvant (CFA). Movement of the inflamed joint increased ERK phosphorylation in neurones of the superficial and deep ipislateral dorsal horn laminae of L3-L5 spinal cord segments. Spinal immunoreactivity to phosphoERK was more intense in animals in which the inflammation lasted longer, 7 days or more, than in rats with less time of inflammation. PhosphoERK levels were transient, since 2h after ankle stimulation spinal immunoreaction had almost disappeared. PhosphoERK immunoreactivity was not induced by movement of ankles from non-arthritic control animals, neither in monoarthritic rats in which the inflamed ankle was not stimulated. Intrathecal administration of PD 98059, an inhibitor of ERK phosphorylation, reduced nociceptive behaviour induced by the ankle bend test in monoarthritic rats. The anti-nociceptive effect of PD 98059 was more prominent and in animals with short lasting (4 days) than in animals with longer (14 days) monoarthritis. Taken together, these findings suggest that ERK phosphorylation in spinal cord neurones plays an important role in chronic inflammatory articular pain and that its inhibition may provide significant anti-nociception.
Factors Influencing Psoriasis: An Analysis Based upon the Extent of Involvement and Clinical Type (1998)

A variety of external stimuli are accepted as important in modifying the severity of psoriasis. We sought to determine whether there is any difference in the influence of external factors on psoriasis in relation to extent of involvement or clinical type. A total of 870 psoriasis patients seen between 1982 and 1995 were categorized as mild, moderate, or severe on the basis of extent of the disease, and as guttate, nummular/plaque, or exfoliative/generalized pustular according to clinical type. We then performed a questionnaire survey concerning the influence of external factors such as seasonal changes, sunlight, stress, and pregnancy. These data sets were combined and analysed. The majority of patients stated favorable effects of summer, sunlight, and pregnancy and adverse effects of winter and stress. A statistically significant correlation was noted between the extent of psoriasis and the proportion of patients stating that their disease worsened at times of psychological stress (p < 0.01). We confirmed that psoriasis patients with more extensive involvement experience greater fluctuations in their condition, notice these changes, and therefore relate them to psychological stress.