gebhart/patrepeval huggingface dataset:
Synthesis of the ABC Ring System of Manzamine A (2002)

A synthesis of the core ABC ring system of the manzamine alkaloids is described, starting from arecoline. The key steps involve a Claisen rearrangement to set up a 4-substituted-3-methylenepiperidine and a stereoselective azomethine ylide dipolar cycloaddition reaction. Condensation of the aldehyde 6 and sarcosine ethyl ester hydrochloride salt gives an intermediate azomethine ylide, which undergoes an intramolecular cycloaddition reaction to set up two new rings and three new chiral centers stereoselectively. The aldehyde 6 was not a suitable substrate for related azomethine ylide cycloaddition reactions with other amines. However, the related dimethyl acetal 26 could be condensed with a variety of amines to give the desired tricyclic products. The cycloaddition reaction with N-methyl or N-allyl glycine ethyl ester gave almost exclusively the exo adduct, whereas cycloaddition with glycine ethyl ester gave the endo adduct.
Predicting the energetics of osmolyte-induced protein folding/unfolding (2005)

A primary thermodynamic goal in protein biochemistry is to attain predictive understanding of the detailed energetic changes that are responsible for folding/unfolding. Through use of recently determined free energies of side-chain and backbone transfer from water to osmolytes and Tanford's transfer model, we demonstrate that the long-sought goal of predicting solvent-dependent cooperative protein folding/unfolding free-energy changes (m values) can be achieved. Moreover, the approach permits dissection of the folding/unfolding free-energy changes into individual contributions from the peptide backbone and residue side chains.
Induction of tumor necrosis factor-alpha messenger RNA in human and murine cells by the flavone acetic acid analogue 5,6-dimethylxanthenone-4-acetic acid (NSC 640488). (1994)

The investigational antitumor agent, 5,6-dimethylxanthenone-4-acetic acid (5,6-MeXAA; NSC 640488) induced greater expression of tumor necrosis factor-alpha (TNF-alpha) mRNA in murine spleen cells in vivo at its optimal dose of 27.5 mg/kg than flavone acetic acid (FAA; NSC 347512) at its optimal dose of 220 mg/kg. Up-regulation of TNF-alpha mRNA was obtained using 5,6-MeXAA in vitro in cultures of murine splenocytes, the murine J774 macrophage cell line, and the human HL-60 myelomonocytic leukemia cell line. Maximal induction occurred at a 5,6-MeXAA concentration of 200 micrograms/ml for both murine J774 and human HL-60 cells. A direct comparison of FAA and 5,6-MeXAA (100-600 micrograms/ml) to stimulate TNF-alpha mRNA in HL-60 cells showed activity by 5,6-MeXAA at all doses but minimal activity with FAA. The results demonstrate that 5,6-MeXAA is equally potent in up-regulating TNF-alpha mRNA in human and murine cells of the monocyte/macrophage lineage, whereas FAA has demonstrable activity in murine cells only. The results suggest that 5,6-MeXAA would be a more active clinical agent than FAA because TNF-alpha induction appears to be a critical factor in the antitumor effects of this class of compounds.
Magnetic Iron Oxide Nanoparticles: Synthesis and Surface Functionalization Strategies (2008)

Surface functionalized magnetic iron oxide nanoparticles (NPs) are a kind of novel functional materials, which have been widely used in the biotechnology and catalysis. This review focuses on the recent development and various strategies in preparation, structure, and magnetic properties of naked and surface functionalized iron oxide NPs and their corresponding application briefly. In order to implement the practical application, the particles must have combined properties of high magnetic saturation, stability, biocompatibility, and interactive functions at the surface. Moreover, the surface of iron oxide NPs could be modified by organic materials or inorganic materials, such as polymers, biomolecules, silica, metals, etc. The problems and major challenges, along with the directions for the synthesis and surface functionalization of iron oxide NPs, are considered. Finally, some future trends and prospective in these research areas are also discussed.
Nitroimidazoles: Part XIX. Structure-activity relationships (1984)

A variety of nitroimidazoles, mostly 1,2-disubstituted-5-nitroderivatives were examined for in vitro activity against E. histolytica and in early hepatic infection of infected golden hamsters. Many preparations carried a functionalised N atom at position 2. In vivo activity was found widely among 1-alkyl-5-nitroimidazoles carrying a substituted imidazolidinone (1) or imidazole (2). Out of these derivatives, l-methyl-sulphonyl-3-(1-methyl-5-nitro-2-imidazolyl)-2-irnidazolidinone(la;C 10213-Go) was found to be the best and to be superior to marketed nitroimidazoles against hepatic and caecal infections of E. histolytica ip the golden hamster and T. foetus infections in mice, and has been developed as a drug for treatment of amoebiasis, giardiasis and trichomoniasis.
The Pseudomonas syringae Hrp pathogenicity island has a tripartite mosaic structure composed of a cluster of type III secretion genes bounded by exchangeable effector and conserved effector loci that contribute to parasitic fitness and pathogenicity in plants (2000)

The plant pathogenic bacterium Pseudomonas syringae is divided into pathovars differing in host specificity, with P. syringae pv. syringae (Psy) and P. syringae pv. tomato (Pto) representing particularly divergent pathovars. P. syringae hrp/hrc genes encode a type III protein secretion system that appears to translocate Avr and Hop effector proteins into plant cells. DNA sequence analysis of the hrp/hrc regions in Psy 61, Psy B728a, and Pto DC3000 has revealed a Hrp pathogenicity island (Pai) with a tripartite mosaic structure. The hrp/hrc gene cluster is conserved in all three strains and is flanked by a unique exchangeable effector locus (EEL) and a conserved effector locus (CEL). The EELs begin 3 nt downstream of the stop codon of hrpK and end, after 2.5-7.3 kb of dissimilar intervening DNA with tRNA(Leu)-queA-tgt sequences that are also found in Pseudomonas aeruginosa but without linkage to any Hrp Pai sequences. The EELs encode diverse putative effectors, including HopPsyA (HrmA) in Psy 61 and proteins similar to AvrPphE and the AvrB/AvrC/AvrPphC and AvrBsT/AvrRxv/YopJ protein families in Psy B728a. The EELs also contain mobile genetic element sequences and have a G + C content significantly lower than the rest of the Hrp Pai or the P. syringae genome. The CEL carries at least seven ORFs that are conserved between Psy B728a and Pto DC3000. Deletion of the Pto DC3000 EEL slightly reduces bacterial growth in tomato, whereas deletion of a large portion of the CEL strongly reduces growth and abolishes pathogenicity in tomato.
Organ Selective Delivery Using a Tissue-Directed Sreptavidin-Biotin System: Targeting 5-Fluorouridine via TNP-Streptavidin (1999)

Trinitrophenyl (TNP) modification of streptavidin (St) resulted in high and prolonged accumulation in mouse liver following intravenous administration of radioiodinated TNP streptavidin (TNP-St). Uptake, which is correlated with increased TNP substitution, was first observed at 2-3 h, increased to 40-50% of injected dose/gram tissue (%/g) at 24 h and slowly declined later on. A low degree of accumulation (10%/g) was observed in the spleen. TNP substitution of other proteins such as bovine serum albumin (BSA) or ovalbumin (Ova) led to a transient short-term liver uptake. The enzyme-resistance property of streptavidin and its biotin binding sites render TNP-modified streptavidin a potential targeting vehicle to the liver. 5-Fluorouridine (FUR) was attached to high molecular weight carrier carboxymethyldextran (CMdex, derived from 40 kDa dextran) and the dextran FUR conjugate was charged with 2-4 biotinyl groups (in the form of biotinyl-diaminopropionyl-tyrosine, BDT) for complexing to TNP-St. Biodistribution monitoring of the BDT-CMdex-FUR ligand, radiolabeled at the tyrosyl residue of BDT and targeted via non-radiolabeled TNP-St, showed that ligand accumulation in the liver was similar to TNP-St itself. Liver targeting of FUR was demonstrated by trace-labeling FUR with its structural analog 5,6-[3H]uridine prior to conjugation to dextran hydrazide. Specific liver accumulation of [3H] radioactivity occurred following administration of the conjugate only when complexed to TNP-St. Hepatic levels of [3H] radioactivity were in the range of 25%/g or 35% per whole liver during a period of at least 8 h, as compared to the rapid elimination of free FUR+[3H]uridine (4%/g at 20 min). [3H]-drug radioactivity disappeared at a faster rate as compared to 125I-dextran radioactivity, suggesting that metabolic processes required to generate the 5,6-[3H]uracil-containing active metabolites took place.
Detection of Single Base Substitutions by Ribonuclease Cleavage at Mismatches in RNA:DNA Duplexes (1985)

Single base substitutions can be detected and localized by a simple and rapid method that involves ribonuclease cleavage of single base mismatches in RNA:DNA heteroduplexes. A 32P-labeled RNA probe complementary to wild-type DNA is synthesized in vitro and annealed to a test DNA containing a single base substitution. The resulting single base mismatch is cleaved by ribonuclease A, and the location of the mismatch is then determined by analyzing the sizes of the cleavage products by gel electrophoresis. Analysis of every type of mismatch in many different sequence contexts indicates that more than 50 percent of all single base substitutions can be detected. The feasibility of this method for localizing base substitutions directly in genomic DNA samples is demonstrated by the detection of single base mutations in DNA obtained from individuals with beta-thalassemia, a genetic disorder in beta-globin gene expression.
Nitric oxide attenuates normal and sickle red blood cell adherence to pulmonary endothelium (2000)

Increased adherence of sickle red blood cells (RBC) to endothelium is implicated as an initiating event of vaso-occlusion in sickle cell disease. Although much is known about the humoral influences of this interaction, there has been little investigation regarding endothelial contributions. Endothelial derived nitric oxide (NO) inhibits adhesion of platelets and leukocytes to endothelium and decreases expression of VCAM-1, an endothelial adhesion site implicated in sickle RBC/endothelial adherence. However, whether NO inhibits RBC adherence to endothelium is unexplored. We tested this hypothesis with endothelial monolayers exposed to RBC from normal (Hb AA) and sickle cell (Hb SS) volunteers in a parallel plate flow chamber. To decrease NO production, endothelial monolayers were exposed to 100 microM nitro-L-arginine (NLA), an inhibitor of nitric oxide synthase, resulting in an 87% increase in normal RBC adherence (P = 0.002). Because adherence of normal RBC to endothelium was low, the effect of DETA-NO, an NO donor, was tested after activation of endothelium with TNF-alpha increased adherence by 130% (P < 0.001). Subsequent addition of 2 mM DETA-NO produced a 75% decrease in adherence of normal RBC to endothelium (P = 0.03). At baseline, sickle RBC were significantly more adherent than normal RBC (P < 0.001) and DETA-NO decreased sickle RBC adherence by 54% (P = 0.04). Thus, NO inhibits both normal and sickle RBC adherence to endothelium. Strategies that enhance NO activity may be therapeutic in sickle cell disease.
Authoritative sources in a hyperlinked environment (1998)

The network structure of a hyperlinked environment can be a rich source of information about the content of the environment, provided we have eective means for understanding it. We develop a set of algorithmic tools for extracting information from the link structures of such environments, and report on experiments that demonstrate their eectiveness in a variety of contexts on the World Wide Web. The central issue we address within our framework is the distillation of broad search topics, through the discovery of \authoritative information sources on such topics. We propose and test an algorithmic formulation of the notion of authority, based on the relationship between a set of relevant authoritative and the set of \hub pages that join them together in the link structure. Our formulation has connections to the eigenvectors of certain matrices associated with the link graph; these connections in turn motivate additional heuristics for link-based analysis.
The T Cell-directed CC Chemokine TARC Is a Highly Specific Biological Ligand for CC Chemokine Receptor 4 (1997)

Thymus and activation-regulated chemokine (TARC) is a recently identified CC chemokine that is expressed constitutively in thymus and transiently in stimulated peripheral blood mononuclear cells. TARC functions as a selective chemoattractant for T cells that express a class of receptors binding TARC with high affinity and specificity. To identify the receptor for TARC, we produced TARC as a fusion protein with secreted alkaline phosphatase (SEAP) and used it for specific binding. By stably transfecting five orphan receptors and five known CC chemokine receptors (CCR1 to -5) into K562 cells, we found that TARC-SEAP bound selectively to cells expressing CCR4. TARC-SEAP also bound to K562 cells stably expressing CCR4 with a high affinity (Kd = 0.5 nM). Only TARC and not five other CC chemokines (MCP-1 (monocyte chemoattractant protein-1), RANTES (regulated upon activation, normal T cells expressed and secreted), MIP-1alpha (macrophage inflammatory protein-1alpha), MIP-1beta, and LARC (liver and activation-regulated chemokine)) competed with TARC-SEAP for binding to CCR4. TARC but not RANTES or MIP-1alpha induced migration and calcium mobilization in 293/EBNA-1 cells stably expressing CCR4. K562 cells stably expressing CCR4 also responded to TARC in a calcium mobilization assay. Northern blot analysis revealed that CCR4 mRNA was expressed strongly in human T cell lines and peripheral blood T cells but not in B cells, natural killer cells, monocytes, or granulocytes. Taken together, TARC is a specific functional ligand for CCR4, and CCR4 is the specific receptor for TARC selectively expressed on T cells.
Photosynthesis nuclear genes generally lack TATA‐boxes: a tobacco photosystem I gene responds to light through an initiator (2002)

The promoter architecture of the nuclear-encoded photosystem I genes was studied using a tobacco gene, psaDb, as a model case. Linker scanning mutations revealed that the psaDb promoter does not have a TATA box. Instead, pyrimidine-rich Initiator (Inr) elements that overlap the transcription start sites are essential for light-responsive transcription of this gene. When the psaDb promoter was mutated to have a TATA-box but no Inr, light-responsive transcription was impaired, indicating that the regulatory system of this gene prefers Inr to a TATA box. As very little is known about plant TATA-less promoters, we subsequently examined whether this promoter architecture is unique to psaDb. Computer analysis of 232 plant promoters revealed surprising features; the majority of photosynthesis nuclear genes lacked TATA boxes, although the frequency of the TATA-less promoters in non-photosynthesis genes was less than 10%. These results strongly suggest that TATA-independent transcription mechanisms play important roles in the regulated expression of photosynthesis nuclear genes.
Modelling speech prosodics for synthesis - perspectives and trials (2000)

Our paper is about syllable-based synthesis and prosodics. It considers perspective carefully and suggests that a particular way of looking at the overall communication system (speaker and perceiver together) prompts a special approach to speech production. We use this idea to give examples of a synthesis strategy in the prosodics area resulting in demonstrably improved naturalness. Our perspective in approaching speech synthesis is to set as goal the creation of a good percept in the mind of the listener-a percept which truly represents the speaker's plan and which minimises the work the listener must do to achieve the right repairs to our relatively poor synthetic signal. By systematically observing listeners' reactions to progressively improved or degraded signals we are gradually building a model of the repair processes. The idea is to introduce into our synthetic speech special repair-oriented cues which, we hope, will cause the listener to report an improvement in the quality of the signal, although the signal itself is no closer to a human signal than it was before. What we are doing is creating synthetic speech to be perceived, not synthetic speech which is to be tested against a natural signal. While we wait for a perfect production model geared to the needs of synthesis, we feel that we can make significant progress with this alternative approach.
Complement resistance of human carcinoma cells depends on membrane regulatory proteins, protein kinases and sialic acid (2003)

Nucleated cells employ several strategies to evade killing by homologous complement. We studied complement resistance in the human carcinoma cell lines (CA) T47D (mammary), SKOV3 (ovarian), and PC-3 (prostate) with emphasis on the following mechanisms of defense: 1. Expression and shedding of the membrane complement regulatory proteins (mCRP) CD46, CD55 and CD59; 2. Resistance based on protein phosphorylation; 3. Cell surface expression of sialic acid residues; 4. Desensitization to complement upon exposure to sublytic complement doses. Anti-mCRP antibody blocking experiments demonstrated that CD59 is the main mCRP protecting these CA from complement. Soluble CD59 was also found in supernates of PC-3> SKOV3 > T47D cells. Second, inhibitors of PKC, PKA and MEK sensitized the CA to lysis, thus implicating these protein kinases in CA complement resistance. Third, removal of sialic acid residues with neuraminidase also sensitized CA to lysis. Finally, exposure of CA to sublytic doses of complement conferred on them enhanced resistance to lytic complement doses in a PKC-dependent process. Combined treatment of CA with anti-CD59 antibodies, PD98059 (a MEK inhibitor) and neuraminidase produced a large enhancement in CA sensitivity to complement. Our results show that CD59 and sialic acid residues present on the cell surface, and intracellular processes involving protein phosphorylation act additively to secure CA resistance to complement-mediated lysis. Therefore, the effectiveness of antibody- and complement-based cancer immunotherapy will markedly improve by suppression of the various complement resistance mechanisms.
Molecular Basis of Human Cardiac Troponin T Isoforms Expressed in the Developing, Adult, and Failing Heart (1995)

Cardiac troponin T (cTnT), a protein essential for calcium-regulated myofibrillar ATPase activity, is expressed in the human heart as four isoforms (cTnT1 through cTnT4, numbered in the order of decreasing molecular size). The expression of these isoforms at the protein level has previously been found by us to differ in the normal and failing adult and fetal human heart. In the present study, we have cloned and sequenced four full-length cDNAs corresponding to the four native cTnT protein isoforms and have expressed these cDNAs in an in vitro transcription and translation system. The cDNAs differ by the variable inclusion of a 15- and a 30-nt exon in the 5' half of the coding region. These cDNAs yielded proteins that comigrate with the native isoforms, cTnT1 through cTnT4. Polyclonal antisera, raised against a synthetic peptide corresponding to the 10-residue peptide encoded by the 30-nt exon, reacted with the two human isoforms largest in molecular size (cTnT1 and cTnT2) and the two largest cTnT isoforms of the rabbit and rat. The isoforms cTnT1 and cTnT2, containing either both peptides encoded by the 30- and 15-nt exons or the peptide encoded by the 30-nt exon alone, are expressed in the fetal heart, with cTnT2 being expressed at a very low level. cTnT4, lacking both of these sequences, is expressed in the fetal heart and is reexpressed in the failing adult heart, whereas cTnT3, containing the 5-residue peptide, is the dominant isoform in the adult heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Monitoring of minimal residual disease in acute myeloid leukemia (2009)

Studies of MRD should provide us the opportunity to generate comprehensive prognostic algorithms which take into account conventional parameters, such as cytogenetic and genetic profile, and those strictly inherent to the quality of response, such as determination of residual leukemia. This will greatly enhance development of personalized therapeutic approaches, avoiding the situation of under or over drug exposure.
Gallbladder cancer. (2014)

Gallbladder cancer is the fifth most common cancer involving gastrointestinal tract, but it is the most common malignancy of the biliary tract, accounting for 80-95% of biliary tract cancers. This tumor is a highly lethal disease with an overall 5-year survival of less than 5% and mean survival mere than 6 months. An early diagnosis is essential as this malignancy progresses silently with a late diagnosis. The percentage of patients diagnosed to have gallbladder cancer after simple cholecystectomy for presumed gallbladder stone disease is 0.5-1.5%. Patients with preoperative suspicion of gallbladder cancer should not be treated by laparoscopy. Epidemiological studies have identified striking geographic and ethnic disparities-inordinately high occurrence in American Indians, elevated in Southeast Asia, yet quite low elsewhere in the Americas and the world. Environmental triggers play a critical role in eliciting cancer developing in the gallbladder, best exemplified by cholelithiasis and chronic inflammation from biliary tract and parasitic infections. Improved imaging modalities and improved radical aggressive surgical approach in the last decade has improved outcomes and helped prolong survival in patients with gallbladder cancer. The overall 5-year survival for patients with gallbladder cancer who underwent R0 curative resection was from 21% to 69%. In the future, the development of potential diagnostic markers for disease will yield screening opportunities for those at risk either with ethnic susceptibility or known anatomic anomalies of the biliary tract.
Identification of Salmonella typhi in faecal specimens by an antiserum-agar method (1980)

An antiserum-agar technique was evaluated as a method for detecting Salmonella typhi in faeces. Thirty-one laboratory strains of S. typhi produced immunoprecipitate haloes during overnight growth on SS agar and blood-agar-base infusion agar (BAB) containing donkey antiserum to a vaccine strain of S. typhi. Other salmonella species sharing O serogroup antigens with S. typhi also produced haloes when streaked in pure culture on SS-antiserum agar but not on BAB-antiserum agar. One hundred and forty-one consecutive faecal specimens were cultured on SS-antiserum agar. Results with this method were concordant with those of established isolation techniques on specimens from six of seven suspected carriers of S. typhi. Ten other salmonellas were isolated from the faecal specimens but only S. javiana, like S. typhi a serogroup-D organism, yielded false-positive haloes on antiserum agar. The antiserum-agar technique offers promise as a means of screening for S. typhi in faecal cultures.