gebhart/patrepeval huggingface dataset:
Phospholipid derivatives of nucleoside analogs as prodrugs with enhanced catabolic stability. (1981)

The nucleoside 5'-diphosphate-L-1,2-dipalmitin derivatives of 1-beta-D-arabinofuranosylcytosine (ara-C), 9-beta-D-arabinofuranosyladenine (ara-A), and tubercidin have been synthesized, and their cytotoxicity has been evaluated against a mouse myeloma cell line (MPC-11) in vitro and against L1210 lymphoid leukemia both in vitro and in vivo. Sonication methods were utilized to solubilize these lipophilic derivatives in aqueous solution in order to facilitate such biological evaluation; the ara-A derivative resisted solubilization by several techniques. The nucleoside:phospholipid conjugates of ara-C and tubercidin both were cytotoxic towards the two cell lines, and detailed experiments were cytotoxic towards the two cell lines, and detailed experiments were carried out to show that the new derivatives (a) were not degraded in the medium prior to cellular uptake and (b) acted as prodrugs or molecular depots of the parent nucleoside analog. In addition, 1-beta-D-arabinofuranosylcytosine 5'-diphosphate'5'-L-1,2-dipalmitin was not a substrate for cytidine deaminase (cytidine aminohydrolase, EC 3.5.4.5), the primary enzyme responsible for the rapid catabolism of ara-C. In in vivo studies against L1210 lymphoid leukemia in mice, the 1-beta-D-arabinofuranosylcytosine 5'-diphosphate-5'-L-1,2-dipalmitin showed an increased efficacy (increased life span, 260%) relative to the parent ara-C (increased life span, 89%) regardless of treatment schedule used, whereas the tubercidin 5'-diphosphate-5'-L-1,2-dipalmitin appeared extremely toxic even at low dosages. That 1-beta-D-arabinofuranosylcytosine 5'-diphosphate-5'-L-1,2-dipalmitin was acting as a sustained release drug in vivo was demonstrated by utilizing a single dose administered on Days -1, 0, +1, and +2 relative to inoculation of the L1210 lymphoid leukemia cells on Day 0. Again, a much increased efficacy relative to the best treatment using ara-C was apparent. The potential advantages and the biochemical rationale for the development of these novel prodrugs are discussed.
GatorShare (2010)

Voluntary Computing systems or Desktop Grids (DGs) enable sharing of commodity computing resources across the globe and have gained tremendous popularity among scientific research communities. Data management is one of the major challenges of adopting the Voluntary Computing paradigm for large data-intensive applications. To date, middleware for supporting such applications either lacks an efficient cooperative data distribution scheme or cannot easily accommodate existing data-intensive applications due to the requirement for using middleware-specific APIs.To address this challenge, in this paper we introduce Gator-Share, a data management framework that offers a file system interface and an extensible architecture designed to support multiple data transfer protocols, including BitTorrent, based on which we implement a cooperative data distribution service for DGs. It eases the integration with Desktop Grids and enables high-throughput data management for unmodified data-intensive applications. To improve the performance of BitTorrent in Desktop Grids, we have enhanced BitTorrent by making it fully decentralized and capable of supporting partial file downloading in an on-demand fashion.To justify this approach we present a quantitative evaluation of the framework in terms of data distribution efficiency. Experimental results show that the framework significantly improves the data dissemination performance for unmodified data-intensive applications compared to a traditional client/server architecture.
Catalytic Hydrolysis of Vasoactive Intestinal Peptide by Human Autoantibody (1989)

Vasoactive intestinal peptide (VIP) labeled with 125I, [Tyr10-125I]VIP, can be hydrolyzed by immunoglobulin G (IgG) purified from a human subject, as judged by trichloroacetic acid precipitation and reversed-phase high-performance liquid chromatography (HPLC). The hydrolytic activity was precipitated by antibody to human IgG, it was bound by immobilized protein G and showed a molecular mass close to 150 kilodaltons by gel filtration chromatography, properties similar to those of authentic IgG. The Fab fragment, prepared from IgG by papain treatment, retained the VIP hydrolytic activity of the IgG. Peptide fragments produced by treatment of VIP with the antibody fraction were purified by reversed-phase HPLC and identified by fast atom bombardment-mass spectrometry and peptide sequencing. The scissile bond in VIP deduced from these experiments was Gln16-Met17. The antibody concentration (73.4 fmol per milligram of IgG) and the Kd (0.4 nM) were computed from analysis of VIP binding under conditions that did not result in peptide hydrolysis. Analysis of the antibody-mediated VIP hydrolysis at varying concentrations of substrate suggested conformity with Michaelis-Menton kinetics (Km). The values for Km (37.9 X 10(-9) M) and the turnover number kcat (15.6 min-1) suggested relatively tight VIP binding and a moderate catalytic efficiency of the antibody.
Magnetic resonance imaging of bone marrow in patients with chronic myeloid leukemia and its clinical value (2005)

Objective To describe the magnetic resonance imaging(MRI) characteristics of chronic myeloid leukemia(CML) and to assess its clinical value for diagnosing and staging . Methods MRI of pelvis and femur was performed on 50 adult patients diagnosed as chronic myeloid leukemia based on morphology,immunophenotype and cytogenetic analysis. Disease status was classified as newly diagnosed chronic phase in 16 cases, steady chronic status in 18 cases having accepted effective treatment, accelerated phase in 7 cases, and blast phase in 9 cases after a long chronic phase. Twenty age-matched healthy volunteers were selected as controls. Results MRI patients newly diagnosed as chronic phase and transformation into accelerated or blast phases on T1WI spin echo showed either diffusal and uniform low signal intensity in ilium and femur or only punctate sheet high signal intensity was seen in femoral head and greater trochanter. The distribution of the patterns had no statistical significance(P0.05). The 18 cases in steady chronic status who had accepted long time treatment showed diffusal low or mixed signal intensity in ilium and irregular mixed signal intensity in femur .There was significant difference between this group and the above groups(P0.01). Conclusion The characteristics of MRI reflect the progression of chronic myeloid leukemia. MRI would be beneficial to CML′s diagnosing and staging together with considerations of clinical features. It had important value in monitoring disease and indicating depravation.
G1 phase arrest induced by Wilms tumor protein WT1 is abrogated by cyclin/CDK complexes. (1995)

WT1, the Wilms tumor-suppressor gene, maps to the human chromosomal region 11p13 and encodes a transcriptional repressor, WT1, implicated in controlling normal urogenital development. Microinjection of the WT1 cDNA into quiescent cells or cells in early to mid G1 phase blocked serum-induced cell cycle progression into S phase. The activity of WT1 varied significantly depending on the presence or absence of an alternatively spliced region located upstream of the zinc finger domain. The inhibitory activity of WT1 was abrogated by the overexpression of cyclin E/CDK2 as well as cyclin D1/CDK4. Furthermore, both CDK4- and CDK2-associated kinase activities were downregulated in cells overexpressing WT1, whereas the levels of CDK4, CDK2, and cyclin D1 expression were unchanged. These findings suggest that inhibition of the activity of cyclin/CDK complexes may be involved in mediating the WT1-induced cell cycle block.
Intraoperatively Updated Neuroimaging Using Brain Modeling and Sparse Data (1999)

A strategy by which intraoperative brain deformation may be accounted for has been developed, validated in an animal model, and demonstrated clinically.
Reduction in the Rate of Early Restenosis after Coronary Angioplasty by a Diet Supplemented with n–3 Fatty Acids (1988)

To determine the safety and benefit of n-3 fatty acid therapy in the prevention of early restenosis after coronary angioplasty, we conducted a randomized, unblinded study comparing a conventional antiplatelet regimen (325 mg of aspirin and 225 mg of dipyridamole per day; control group) with a similar regimen supplemented with 3.2 g of eicosapentaenoic acid per day (treatment group). Treatment began seven days before angioplasty and continued for six months afterward. All angiographic analyses were blinded and performed by a method that was validated by comparison with quantitative coronary angiography. In 82 male patients, 103 coronary lesions were dilated. Both groups had similar base-line clinical and angiographic characteristics. The incidence of early vessel restenosis, as determined on a second angiogram three to four months after angioplasty, was 36 percent in the control group and 16 percent in the treatment group (P = 0.026). The incidence of restenosis per patient was also significantly lower in the treatment group (46 vs. 19 percent). Both multiple logistic regression and Mantel-Haenszel statistical analyses demonstrated a significant independent benefit of treatment with n-3 fatty acids. No important bleeding complications developed in the treated patients. These results, in a male population at relatively high risk for restenosis, suggest that a dietary supplement of n-3 fatty acids, administered for one week before and for six months after coronary angioplasty, is safe and reduces the occurrence of early restenosis after that procedure. Whether this beneficial effect also applies to other populations is unknown.
A Self-Excisable Infectious Bacterial Artificial Chromosome Clone of Varicella-Zoster Virus Allows Analysis of the Essential Tegument Protein Encoded by ORF9 (2007)

In order to facilitate the generation of mutant viruses of varicella-zoster virus (VZV), the agent causing varicella (chicken pox) and herpes zoster (shingles), we generated a full-length infectious bacterial artificial chromosome (BAC) clone of the P-Oka strain. First, mini-F sequences were inserted into a preexisting VZV cosmid, and the SuperCos replicon was removed. Subsequently, mini-F-containing recombinant virus was generated from overlapping cosmid clones, and full-length VZV DNA recovered from the recombinant virus was established in Escherichia coli as an infectious BAC. An inverted duplication of VZV genomic sequences within the mini-F replicon resulted in markerless excision of vector sequences upon virus reconstitution in eukaryotic cells. Using the novel tool, the role in VZV replication of the major tegument protein encoded by ORF9 was investigated. A markerless point mutation introduced in the start codon by two-step en passant Red mutagenesis abrogated ORF9 expression and resulted in a dramatic growth defect that was not observed in a revertant virus. The essential nature of ORF9 for VZV replication was ultimately confirmed by restoration of the growth of the ORF9-deficient mutant virus using trans-complementation via baculovirus-mediated gene transfer.
Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family. (1987)

A family of genes coding for proteins homologous to the alpha subunit of the muscle nicotinic acetylcholine receptor has been identified in the rat genome. These genes are transcribed in the central and peripheral nervous systems in areas known to contain functional nicotinic receptors. In this paper, we demonstrate that three of these genes, which we call alpha 3, alpha 4, and beta 2, encode proteins that form functional nicotinic acetylcholine receptors when expressed in Xenopus oocytes. Oocytes expressing either alpha 3 or alpha 4 protein in combination with the beta 2 protein produced a strong response to acetylcholine. Oocytes expressing only the alpha 4 protein gave a weak response to acetylcholine. These receptors are activated by acetylcholine and nicotine and are blocked by Bungarus toxin 3.1. They are not blocked by alpha-bungarotoxin, which blocks the muscle nicotinic acetylcholine receptor. Thus, the receptors formed by the alpha 3, alpha 4, and beta 2 subunits are pharmacologically similar to the ganglionic-type neuronal nicotinic acetylcholine receptor. These results indicate that the alpha 3, alpha 4, and beta 2 genes encode functional nicotinic acetylcholine receptor subunits that are expressed in the brain and peripheral nervous system.
Arachidonic acid-induced secretion in the rat colon. Indomethacin-resistant neuronal and epithelial actions. (1990)

The effect of arachidonic acid on short-circuit current (Isc) was studied in two preparations of the rat colon descendens, one with and one without the submucosal plexus. In both preparations, arachidonic acid (10(-7)-5 x 10(-5) mol.l-1) increased Isc concentration-dependently. The cyclooxygenase blocker, indomethacin, inhibited its action only partially. The lipoxygenase inhibitor, nordihydroguaiaretic acid, was an ineffective inhibitor of the response to arachidonic acid. Tetrodotoxin (TTX), atropine, and hexamethonium blocked the effect of arachidonic acid in the preparation with the submucosal plexus. Inhibition by neuronal blockers was also observed in the presence of indomethacin. After removal of the submucosal plexus, TTX no longer affected the Isc response evoked by arachidonic acid. This epithelial action of arachidonic acid was inhibited by the calmodulin antagonist, trifluoperazine, and the intra-cellular Ca2(+)-antagonist, TMB-8. Inhibition by these drugs was also found in the presence of indomethacin. Consequently, for the secretion induced by arachidonic acid two sites of action, the submucosal plexus and the epithelium, and two mechanisms of action, prostaglandin-mediated and non-mediated, could be distinguished.
A novel c-fgr exon utilized in Epstein-Barr virus-infected B lymphocytes but not in normal monocytes. (1991)

The fgr proto-oncogene encodes a nonreceptor protein-tyrosine kinase, designated p55c-fgr. In this study, we have isolated human fgr cDNA molecules from normal monocyte mRNA templates. Nucleotide sequence analysis of the longest fgr cDNA revealed a 5' untranslated region of 927 bp which included two Alu-like repeats as well as three translation stop codons immediately upstream of the initiator for p55c-fgr synthesis. Within genomic DNA, these sequences were distributed over 13 kbp as three distinct 5' untranslated exons. Previous studies have shown that Epstein-Barr virus (EBV) increases c-fgr mRNA levels in B lymphocytes. By comparing the nucleotide sequence reported for transcripts isolated from EBV-infected B lymphocytes with those of our monocyte cDNA as well as genomic DNA, we identified a novel untranslated exon utilized only in EBV-infected cells. The transcriptional initiation sites of fgr mRNA expressed in EBV-converted cells were mapped and shown to reside within a region identified as an intron for fgr mRNA that is expressed in normal myelomonocytic cells. Furthermore, the region of the fgr locus upstream of the novel exon displayed properties of a transcriptional promoter when transfected into heterologous cells. We conclude from all of these findings that activation of the fgr gene by EBV is achieved by mechanisms distinct from those normally regulating its programmed expression in myelomonocytic cells.
Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver (2013)

Rapamycin (Rapa) and dietary restriction (DR) have consistently been shown to increase lifespan. To investigate whether Rapa and DR affect similar pathways in mice, we compared the effects of feeding mice ad libitum (AL), Rapa, DR, or a combination of Rapa and DR (Rapa + DR) on the transcriptome and metabolome of the liver. The principal component analysis shows that Rapa and DR are distinct groups. Over 2500 genes are significantly changed with either Rapa or DR when compared with mice fed AL; more than 80% are unique to DR or Rapa. A similar observation was made when genes were grouped into pathways; two-thirds of the pathways were uniquely changed by DR or Rapa. The metabolome shows an even greater difference between Rapa and DR; no metabolites in Rapa-treated mice were changed significantly from AL mice, whereas 173 metabolites were changed in the DR mice. Interestingly, the number of genes significantly changed by Rapa + DR when compared with AL is twice as large as the number of genes significantly altered by either DR or Rapa alone. In summary, the global effects of DR or Rapa on the liver are quite different and a combination of Rapa and DR results in alterations in a large number of genes and metabolites that are not significantly changed by either manipulation alone, suggesting that a combination of DR and Rapa would be more effective in extending longevity than either treatment alone.
Clinical Indications for Probiotics: An Overview (2008)

Probiotic bacteria are used to treat or prevent a broad range of human diseases, conditions, and syndromes. In addition, there are areas of medical use that have been proposed for future probiotic applications. Randomized double-blind studies have provided evidence of probiotic effectiveness for the treatment and prevention of acute diarrhea and antibiotic-induced diarrhea, as well as for the prevention of cow milk-induced food allergy in infants and young children. Research studies have also provided evidence of effectiveness for the prevention of traveler's diarrhea, relapsing Clostridium difficile-induced colitis, and urinary tract infections. There are also studies indicating that probiotics may be useful for prevention of respiratory infections in children, dental caries, irritable bowel syndrome, and inflammatory bowel disease. Areas of future interest for the application of probiotics include colon and bladder cancers, diabetes, and rheumatoid arthritis. The probiotics with the greatest number of proven benefits are Lactobacillus rhamnosus strain GG and Saccharomyces boulardii.
Bevacizumab terminates homeobox B9-induced tumor proliferation by silencing microenvironmental communication (2014)

HOXB9 promotes the secretion of angiogenic factors, including VEGF, to induce tumor proliferation through microenvironmental production of cytokines including IL6 signaling. Moreover, silencing of VEGF or IL6 terminates cytokine release in tumor microenvironment. Thus, HOXB9 and IL6 may be potential biomarkers for bevacizumab treatment.
Glutamate Transporter GLAST Is Expressed in the Radial Glia–Astrocyte Lineage of Developing Mouse Spinal Cord (1997)

The glutamate transporter GLAST is localized on the cell membrane of mature astrocytes and is also expressed in the ventricular zone of developing brains. To characterize and follow the GLAST-expressing cells during development, we examined the mouse spinal cord by in situ hybridization and immunohistochemistry. At embryonic day (E) 11 and E13, cells expressing GLAST mRNA were present only in the ventricular zone, where GLAST immunoreactivity was associated with most of the cell bodies of neuroepithelial cells. In addition, GLAST immunoreactivity was detected in radial processes running through the mantle and marginal zones. From this characteristic cytology, GLAST-expressing cells at early stages were judged to be radial glia cells. At E15, cells expressing GLAST mRNA first appeared in the mantle zone, and GLAST-immunopositive punctate or reticular protrusions were formed along the radial processes. From E18 to postnatal day (P) 7, GLAST mRNA or its immunoreactivity gradually decreased from the ventricular zone and disappeared from radial processes, whereas cells with GLAST mRNA spread all over the mantle zone and GLAST-immunopositive punctate/reticular protrusions predominated in the neuropils. At P7, GLAST-expressing cells were immunopositive for glial fibrillary acidic protein, an intermediate filament specific to astrocytes. Therefore, the glutamate transporter GLAST is expressed from radial glia through astrocytes during spinal cord development. Furthermore, the distinct changes in the cell position and morphology suggest that both the migration and transformation of radial glia cells begin in the spinal cord between E13 and E15, when the active stage of neuronal migration is over.
Six new metal–organic frameworks with multi-carboxylic acids and imidazole-based spacers: syntheses, structures and properties (2011)

Six new metal-organic frameworks [Cu(obba)(bimb)·(obbaH(2))](n) (1), [Cu(obba)(bimb)](n) (2), [Zn(2)(obba)(2)(bimb)(2)(DMF)(2)(H(2)O)(3.5)](n) (3), [Ni(3)(2,2',4,4'-bptcH)(2)(bimb)(2)(H(2)O)(2)·(H(2)O)(2)](n) (4), [Ni(2)(bimb)(3)(H(2)O)(6)·(aobtc)·(DMF)(2)·(H(2)O)(2)](n) (5) and [Cd(3,3',4,4'-bptcH(2))(H(2)O)·(bimb)](n) (6), were obtained by reactions of 4,4'-bis(1-imidazolyl)biphenyl (bimb) and multi-carboxylic acids of 4,4'-oxybis(benzoic acid) (obbaH(2)), 2,2',4,4'-biphenyltetracarboxylate acid (2,2',4,4'-bptcH(4)), azoxybenzene-3,3',5,5'-tetracarboxylic acid (aobtcH(4)), and 3,3',4,4'-biphenyltetracarboxylate acid (3,3',4,4'-bptcH(4)) with corresponding metal salts under hydro/solvothermal conditions, respectively. Complexes 1-3 have entangled structures with different topologies: 1 is a 3-fold interpenetrating NbO three-dimensional (3D) network; 2 is a 3-fold interpenetrating dmp 3D net; 3 is a 6-fold interpenetrating dia 3D chiral net containing rare 1D helical chains with the same handedness. Complex 4 is an uninodal 6-connected network with a Schäfli symbol of (4(8)6(4)8(3)) based on the trinuclear Ni(II) subunits, while complexes 5 and 6 are 1D chains. Interestingly, compound 6 represents the rare example of MOFs that exhibit high photocatalytic activity for dye degradation under visible light and shows good stability towards photocatalysis. Complexes 3 and 6 exhibit intense blue emissions in the solid state at room temperature whereas 3 appears to be a good candidate of novel hybrid inorganic-organic NLO material.
Cytosolic acetyl‐CoA synthetase affected tumor cell survival under hypoxia: the possible function in tumor acetyl‐CoA/acetate metabolism (2009)

Understanding tumor-specific metabolism under hypoxia is important to find novel targets for antitumor drug design. Here we found that tumor cells expressed higher levels of cytosolic acetyl-CoA synthetase (ACSS2) under hypoxia than normoxia. Knockdown of ACSS2 by RNA interference (RNAi) in tumor cells enhanced tumor cell death under long-term hypoxia in vitro. Our data also demonstrated that the ACSS2 suppression slowed tumor growth in vivo. These findings showed that ACSS2 plays a significant role in tumor cell survival under hypoxia and that ACSS2 would be a potential target for tumor treatment. Furthermore, we found that tumor cells excreted acetate and the quantity increased under hypoxia: the pattern of acetate excretion followed the expression pattern of ACSS2. Additionally, the ACSS2 knockdown led to a corresponding reduction in the acetate excretion in tumor cells. These results mean that ACSS2 can conduct the reverse reaction from acetyl-CoA to acetate in tumor cells, which indicates that ACSS2 is a bi-directional enzyme in tumor cells and that ACSS2 might play a buffering role in tumor acetyl-CoA/acetate metabolism.