gebhart/patrepeval huggingface dataset:
Tautomerism of Uracil and Thymine in Aqueous Solution: Spectroscopic Evidence (1972)

Excitation spectra for triplet state formation and fluorescence emission from uracil and thymine in neutral aqueous solution at room temperature are anomalous when compared to the absorption spectra of uracil and thymine. The experimental data are critically examined with respect to three molecular models; Model 1, which is characterized by increased intersystem crossing from higher vibrational levels of S(1); Model 2, in which fluorescence is attributed to a (pi,pi(*)) state, whereas intersystem crossing occurs from an (npi(*)) state; and Model 3, in which fluorescence is attributed to a tautomer I, while triplet yields originate from tautomer II. Reasons are presented for discarding Models 1 and 2, and it is demonstrated that the observed excitation spectra complement each other with respect to the absorption spectrum, such that the quantum yields of triplet formation and fluorescence emission become independent of exciting wavelength. It is suggested that the fluorescing tautomer I has the N(3)-C(4) enol structure, while the triplet-forming tautomer II is most likely the predominant diketo form.
SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. (1993)

We report the cDNA cloning of SREBP-2, the second member of a family of basic-helix-loop-helix-leucine zipper (bHLH-Zip) transcription factors that recognize sterol regulatory element 1 (SRE-1). SRE-1, a conditional enhancer in the promoters for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A synthase genes, increases transcription in the absence of sterols and is inactivated when sterols accumulate. Human SREBP-2 contains 1141 amino acids and is 47% identical to human SREBP-1a, the first recognized member of this family. The resemblance includes an acidic NH2 terminus, a highly conserved bHLH-Zip motif (71% identical), and an unusually long extension of 740 amino acids on the COOH-terminal side of the bHLH-Zip region. SREBP-2 possesses one feature lacking in SREBP-1a--namely, a glutamine-rich region (27% glutamine over 121 residues). In vitro SREBP-2 bound SRE-1 with the same specificity as SREBP-1a. In vivo it mimicked SREBP-1a in activating transcription of reporter genes containing SRE-1. As with SREBP-1a, activation by SREBP-2 occurred in the absence and presence of sterols, abolishing regulation. Cotransfection of low amounts of pSREBP-1a and pSREBP-2 into human embryonic kidney 293 cells stimulated transcription of promoters containing SRE-1 in an additive fashion. At high levels transcription reached a maximum, and the effects were no longer additive. The reason for the existence of two SREBPs and the mechanism by which they are regulated by sterols remain to be determined.
Deep sequencing of the small RNA transcriptome of normal and malignant human B cells identifies hundreds of novel microRNAs (2010)

A role for microRNA (miRNA) has been recognized in nearly every biologic system examined thus far. A complete delineation of their role must be preceded by the identification of all miRNAs present in any system. We elucidated the complete small RNA transcriptome of normal and malignant B cells through deep sequencing of 31 normal and malignant human B-cell samples that comprise the spectrum of B-cell differentiation and common malignant phenotypes. We identified the expression of 333 known miRNAs, which is more than twice the number previously recognized in any tissue type. We further identified the expression of 286 candidate novel miRNAs in normal and malignant B cells. These miRNAs were validated at a high rate (92%) using quantitative polymerase chain reaction, and we demonstrated their application in the distinction of clinically relevant subgroups of lymphoma. We further demonstrated that a novel miRNA cluster, previously annotated as a hypothetical gene LOC100130622, contains 6 novel miRNAs that regulate the transforming growth factor-β pathway. Thus, our work suggests that more than a third of the miRNAs present in most cellular types are currently unknown and that these miRNAs may regulate important cellular functions.
Role of oxyR in the Oral Anaerobe Porphyromonas gingivalis (2006)

Porphyromonas gingivalis is an anaerobic microorganism that inhabits the oral cavity, where oxidative stress represents a constant challenge. A putative transcriptional regulator associated with oxidative stress, an oxyR homologue, is known from the P. gingivalis W83 genome sequence. We used microarrays to characterize the response of P. gingivalis to H2O2 and examine the role of oxyR in the regulation of this response. Most organisms in which oxyR has been investigated are facultative anaerobes or aerobes. In contrast to the OxyR-regulated response of these microorganisms to H2O2, the main feature of the response in P. gingivalis was a concerted up-regulation of insertion sequence elements related to IS1 transposases. Common OxyR-regulated genes such as dps and ahpFC were not positively regulated in P. gingivalis in response to H2O2. However, their expression was dependent on the presence of a functional OxyR, as revealed by microarray comparison of an oxyR mutant to the wild type. Phenotypic characterization of the oxyR mutant showed that OxyR plays a role in both the resistance to H2O2 and the aerotolerance of P. gingivalis. Escherichia coli and other bacteria with more complex respiratory requirements use OxyR for regulating resistance to H2O2 and use a separate regulator for aerotolerance. In P. gingivalis, the presence of a single protein combining the two functions might be related to the comparatively smaller genome size of this anaerobic microorganism. In conclusion, these results suggest that OxyR does not act as a sensor of H2O2 in P. gingivalis but constitutively activates transcription of oxidative-stress-related genes under anaerobic growth.
P4–415: The effect of moxibustion on spatial memory of aging rats and the underlying mechanisms (2006)

Moxibustion is one important clinical therapeutic method in the Traditional Chinese Medicine and has been widely used in the prevention of aging and related diseases, e.g. Alzheimer's disease. The acupoints, Baihui (DU20) and Shenshu (BL23), have been proved to be the most effective acupoints in aging prevention with moxibustion by large clinical investigation. But the underlying mechanism is still unknown. To evaluate the effect of Baihui (DU20) and Shenshu (BL23) with moxibustion on the learning and memory of natural aging rats and the underlying mechenism. 30 aging SD rats (18–months old) were involved in this research and divided in 2 groups, control group (n=15) and the moxibustion group (n=15). The rats in the latter group have been treated with Baihui (DU20), Shenshu (BL23) by 10 minutes' moxibustion each time for 40 days with an interval every five days. Then the spatial learning and memory of rats were detected by Morris water maze. The ratio of apoptosis, the mitochondrial membrance electro–bit (ΔΨmt), the levels of Caspase–3, Bcl–2 and 14–3–3ξ protein and the ultrastructure of hippocampal neuron were also investigated. It was observed that the aging rats with moxibustion showed significantly shorter latency to find the hidden platform in Morris water maze than the control rats. The significantly decreased number of apoptotic neuron and the caspase–3 level, the significantly increased levels of Bcl–2 and 14–3–3ξ and the obviously improved ultrastructure of hippocampal neuron and ΔΨmt were found in moxibustion group. Moxibustion on Baihui (DU20) and Shenshu (BL23) could significantly improve the spatial learning and memory of aging rats. Improving the structure and function of mitochondria and anti–apoptosis may be the underlying mechanism.
115. Bio-Engineering of Adeno-Associated Virus Serotype (AAV)-2 Capsid at Serine/Threonine Residues Improves Its Transduction Efficiency Both In Vitro and In Vivo (2012)

Sangeetha Hareendran,1 Mansoor Hussain,1 Rupali A. Gadkari,2 Sudha Govindarajan,2 Dwaipayan Sen,3 Balaji Balakrishnan,3 Yesupatham SathishKumar,1 Vaani Kalaivani,3 Banumathi Ramakrishna,4 Arun Srivastava,5 Alok Srivastava,1,3 Giridhara Rao Jayandharan.1,3
New findings about human dipeptidyl peptidase III based on mutations found in cancer (2017)

In this work we investigated the role of two highly conserved residues in the peptidase family M49, whose mutations G313W and R510W were detected in human cancer, using combined experimental and computational approaches.
Comparison of the Gene Transfer Efficiency of mRNA/GL67 and pDNA/GL67 Complexes in Respiratory Cells (2012)

Complexes between mRNA and GL67:DOPE:DMPE-PEG5000 (GL67) liposomes were formulated and characterized. Subsequently, the in vitro and in vivo expression characteristics of mRNA/GL67 complexes and pDNA/GL67 complexes, each produced at their optimal ratio, were compared in respiratory cells. Transfection of A549 cells with mRNA/GL67 complexes resulted in a much faster expression than after transfection with pDNA/GL67 complexes. The percentage of GFP-positive cells after mRNA and pDNA transfection peaked after 8 and 24 h, respectively. At these time points the percentage of GFP-positive cells was two times higher after mRNA transfection than after pDNA transfection. Furthermore, the efficacy of mRNA/GL67 complexes was independent of the cell cycle. This was in sharp contrast with pDNA/GL67 complexes that caused only a weak expression in nondividing cells. This confirms that the nuclear barrier is a crucial obstacle for pDNA but not for mRNA. Finally, mRNA/GL67 and pDNA/GL67 complexes encoding luciferase were administered intranasally to the lungs of mice. The mRNA/GL67 complexes did not give rise to a measurable luciferase expression in the murine lungs. In contrast, a detectable bioluminescent signal was present in the lungs of mice that received the pDNA/GL67 complexes. We showed that mRNA/GL67 complexes have a lower stability in biological fluids. Consequently, this may be an explanation for their lower performance in vivo.
Vitamin D — Solar Rays, the Milky Way, or Both? (1992)

Adequate vitamin D stores are essential for normal skeletal mineralization and growth. The vitamin is now known to be a prohormone that undergoes successive hydroxylation in the liver and kidney. The first hydroxylation yields 25-hydroxyvitamin D (25(OH)D), and the second the active hormone, 1,25-dihydroxyvitamin D (l,25(OH)2nd). This hormone travels in blood to intracellular receptors that regulate gene transcription and thereby stimulates intestinal absorption of calcium and enterocyte differentiation, regulates osteoblast and hematopoietic-cell functions, and suppresses the activity of the parathyroid gland.1 Without adequate reserves of the vitamin, insufficient l,25(OH)2D is produced, leading to poor calcium absorption, soft (undermineralized) . . .
Synthesis of Functional Polydepsipeptides via Direct Ring‐Opening Polymerization and Post‐Polymerization Modification (2010)

Abstract This contribution explores different strategies for the synthesis of side chain functional polydepsipeptides. First, the ring‐opening polymerization of side chain functional morpholine‐2,5‐diones is revisited and the optimized reaction conditions used for the polymerization of (Z)‐ L ‐Lys, (Boc)‐ L ‐Lys and L ‐allylglycine based morpholine‐2,5‐diones. As a first approach towards side chain functional polydepsipeptides, the deprotection of poly(Glc‐ alt ‐(Z)‐ L ‐Lys) and poly(Glc‐ alt ‐(Boc)‐ L ‐Lys) is evaluated. Although under appropriate conditions, the side chain protecting groups can be quantitatively removed, the reaction conditions used here were found to lead to backbone degradation. As an alternative approach, the thiol‐ene post‐polymerization modification of poly(Glc‐ alt ‐allylglycine) is explored. Free radical addition of various ω ‐functional thiols was found to proceed without backbone degradation and in several cases with quantitative allyl group conversion. The post‐polymerization modification strategy is attractive as it obviates the need for protecting group chemistry and facilitates the synthesis of diverse libraries of side chain functional polydepsipeptides. magnified image
Antithrombotic Properties of a Truncated Recombinant Tissue Factor Pathway Inhibitor in an Experimental Venous Thrombosis Model (1993)

The aim of this study was to investigate whether a truncated recombinant tissue factor pathway inhibitor (rTFPI1-161) had an antithrombotic effect comparable to low-molecular-weight (LMW) heparin. A randomized double-dummy study was conducted with 40 rabbits in 6 groups. An experimental thrombosis was induced in the jugular veins by a combination of destroyed endothelium and restricted blood flow. Group 1 was given placebo; group 2, LMW heparin 60 anti-factor Xa units/kg; group 3, rTFPI1-161 0.1 mg/kg; group 4, rTFPI1-161 1.0 mg/kg and group 5, rTFPI1-161 10.0 mg/kg. rTFPI1-161 reduced the thrombus weights in all treated groups, with a significant effect in doses between 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis was significantly reduced in all treated groups. No hemorrhagic side effects were noted. In conclusion, rTFPI1-161 (1.0-10.0 mg/kg) has an antithrombotic effect comparable to that of LMW heparin.
Identification of Novel β1 Integrin Binding Sites in the Type 1 and Type 2 Repeats of Thrombospondin-1 (2004)

In addition to the three known beta(1) integrin recognition sites in the N-module of thrombospondin-1 (TSP1), we found that beta(1) integrins mediate cell adhesion to the type 1 and type 2 repeats. The type 1 repeats of TSP1 differ from typical integrin ligands in that recognition is pan-beta(1)-specific. Adhesion of cells that express one dominant beta(1) integrin on immobilized type 1 repeats is specifically inhibited by antagonists of that integrin, whereas adhesion of cells that express several beta(1) integrins is partially inhibited by each alpha-subunit-specific antagonist and completely inhibited by combining the antagonists. beta(1) integrins recognize both the second and third type 1 repeats, and each type 1 repeat shows pan-beta(1) specificity and divalent cation dependence for promoting cell adhesion. Adhesion to the type 2 repeats is less sensitive to alpha-subunit antagonists, but a beta(1) blocking antibody and two disintegrins inhibit adhesion to immobilized type 2 repeats. beta(1) integrin expression is necessary for cell adhesion to the type 1 or type 2 repeats, and beta(1) integrins bind in a divalent cation-dependent manner to a type 1 repeat affinity column. The widely used TSP1 function blocking antibody A4.1 binds to a site in the third type 2 repeat. A4.1 proximally inhibits beta(1) integrin-dependent adhesion to the type 2 repeats and indirectly inhibits integrin-dependent adhesion mediated by the TSP1 type 1 repeats. Although antibody A4.1 is also an antagonist of CD36 binding to TSP1, these data suggest that some biological activities of A4.1 result from antagonism of these novel beta(1) integrin binding sites.
Human CC chemokine liver-expressed chemokine/CCL16 is a functional ligand for CCR1, CCR2 and CCR5, and constitutively expressed by hepatocytes (2001)

Liver-expressed chemokine (LEC)/CCL16 is a human CC chemokine selectively expressed in the liver. Here, we investigated its receptor usage by calcium mobilization and chemotactic assays using mouse L1.2 pre-B cell lines stably expressing a panel of 12 human chemokine receptors. At relatively high concentrations, LEC induced calcium mobilization and chemotaxis via CCR1 and CCR2. LEC also induced calcium mobilization, but marginal chemotaxis via CCR5. Consistently, LEC was found to bind to CCR1, CCR2 and CCR5 with relatively low affinities. The binding of LEC to CCR8 was much less significant. In spite of its binding to CCR5, LEC was unable to inhibit infection of an R5-type HIV-1 to activated human peripheral blood mononuclear cells even at high concentrations. In human liver sections, hepatocytes were strongly stained by anti-LEC antibody. HepG2, a human hepatocarcinoma cell line, was found to constitutively express LEC. LEC was also present in the plasma samples from healthy adult donors at relatively high concentrations (0.3-4 nM). Taken together, LEC is a new low-affinity functional ligand for CCR1, CCR2 and CCR5, and is constitutively expressed by liver parenchymal cells. The presence of LEC in normal plasma at relatively high concentrations may modulate inflammatory responses.
Folate Receptors (1996)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
CYCLINS AND CELL CYCLE CHECKPOINTS (1999)

The eucaryotic cell cycle is regulated by the periodic synthesis and destruction of cyclins that associate with and activate cyclin-dependent kinases. Cyclin-dependent kinase inhibitors, such as p21 and p16, also play important roles in cell cycle control by coordinating internal and external signals and impeding proliferation at several key checkpoints. Understanding how these proteins interact to regulate the cell cycle has become increasingly important to researchers and clinicians with the discovery that many of the genes that encode cell cycle regulatory activities are targets for alterations that underlie the development of cancer. Several therapeutic agents, such as DNA-damaging drugs, microtubule inhibitors, antimetabolites, and topoisomerase inhibitors, take advantage of this disruption in normal cell cycle regulation to target checkpoint controls and ultimately induce growth arrest or apoptosis of neoplastic cells. Other therapeutic drugs being developed, such as UCN-01, specifically inhibit cell cycle regulatory proteins.
Effect on caries of self‐application of a zirconium silicate paste containing 9% stannous fluoride (1976)

A 2-year clinical trial was conducted using an adolescent population from a low-fluoride area to evaluate the anticaries effect of self-applications of zirconium silicate paste containing 9% stannous fluoride. tthree study groups totaling 464 children, with an initial average of 12.8 years, completed the study. The control group brushed with a non-fluoride zirconium silicate paste (tzircate Prophylaxis Paste) once each year: the first experimental group brushed with zirconium silicate paste containing 9% stannous fluoride (Zircate Treatment Paste) once each year; and the second experimental group brushed every 6 months with Zircate Treatment Paste. After 2 year, the DMFT and DMFS increments were virtually identical for the control group and the group that received one application of fluoride paste per year. The group that received two applications of fluoride paste per year had a DMTF increment that was about 24% less than that of the control group; however, the DMFS increment was only 5% less. These differences were not statistically significant at the P=.05 level.
An Overview of Clinical Cancer Chemoprevention Studies with Emphasis on Positive Phase III Studies (1995)

Cancer prevention aims to halt or reverse the development and progression of precancerous cells through the use of noncytotoxic nutrients and/or pharmacologic agents during the lengthy time period between tumor initiation and frank malignancy. This paper reviews cancer chemoprevention studies and focuses on Phase III trials, which are large, randomized, placebo-controlled studies that usually last several years. Studies may include multiple agents and dose levels, long-term toxicity evaluations or the modulation of surrogate endpoint biomarkers. Sample sizes of individual studies vary depending on statistical concerns and the demographics of the subject population. Recent Phase III trials include several promising agents: retinol; the retinoids 13-cis retinoic acid, all-trans-retinoic acid and 4-hydroxyphenyl retinamide; beta-carotene; finasteride and tamoxifen. Because one of the many actions of retinoids is the induction of epidermal differentiation, clinical trials with this class of agents have largely been conducted in epithelial or squamous cell tumor types. Several Phase III studies that have targeted the reversal of premalignant lesions or the prevention of second primary tumors have shown promising positive results. In contrast, some studies have shown that chemopreventive agents may have limited activity against the recurrence or progression of cells that have already undergone malignant transformation. Thus, the role of chemoprevention appears to lie in reversal of the premalignant process rather than suppression of malignant growth.
Functional expression of the particulate methane mono-oxygenase gene in recombinantRhodococcus erythropolis (2006)

In order to construct an expression system for the particulate methane mono-oxygenase (pMMO) gene (pmo), the structural gene cluster pmoCAB amplified from Methylosinus trichosporium OB3b was inserted into a shuttle vector pBS305 under the control of a dsz promoter and transformed into Rhodococcus erythropolis LSSE8-1. A stable transformant was successfully obtained using ethane as the sole carbon source. Fluorescence in situ hybridization results showed that the dsz promoter allowed the pmo genes to be transcribed in the recombinant strain. The effects of Cu2+ and Zn2+ concentrations on cell growth and pMMO activity in ethane-containing medium were examined. It was discovered that 7.5 microM Cu2+ and 1.8 microM Zn2+ were suitable to achieve high cell concentration and pMMO activity, but the amount of methanol accumulated during methane oxidation by the recombinant strain was still low.
Activation of Oxidative Stress by Acute Glucose Fluctuations Compared With Sustained Chronic Hyperglycemia in Patients With Type 2 Diabetes (2006)

Glucose fluctuations during postprandial periods and, more generally, during glucose swings exhibited a more specific triggering effect on oxidative stress than chronic sustained hyperglycemia. The present data suggest that interventional trials in type 2 diabetes should target not only hemoglobin A1c and mean glucose concentrations but also acute glucose swings.
Risks and Benefits of Repeated Courses of Intravesical Bacillus Calmette-guerin Therapy for Superficial Bladder Cancer (1987)

An actuarial analysis of the risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer was performed for 100 consecutive patients treated for carcinoma in situ (29), prophylaxis against recurrent tumor (51) or residual superficial papillary tumor (21). The risk-to-benefit ratio at entry into bacillus Calmette-Guerin therapy (7 per cent risk of invasive cancer developing, 5 per cent risk of metastases and 77 per cent prospect for status free of tumor) and in patients who had failed only 1 course of bacillus Calmette-Guerin therapy (11 per cent invasive cancer, 14 per cent metastases and 58 per cent free of tumor) were highly favorable. However, among patients who had failed 2 or more courses of bacillus Calmette-Guerin therapy the risks of invasive (30 per cent) or metastatic (50 per cent) cancer developing exceeded the prospects for eradicating the superficial tumor present (20 per cent) with further therapy. The results suggest that patients who have failed 2 courses of bacillus Calmette-Guerin therapy (as given in our treatment protocol) should be considered for alternative treatment.