gebhart/patrepeval huggingface dataset:
Hybrids of antibiotics inhibiting protein synthesis. Synthesis and biological activity (1993)

Four hybrid antibiotics combining structural features of chloramphenicol (1a), sparsomycin (2b), lincomycin (5c), and puromycin (6d)--lincophenicol (1c), chloramlincomycin (5a), sparsolincomycin (5b), and sparsopuromycin (6b)--were synthesized. They were investigated as inhibitors of several partial reactions of procaryotic and eucaryotic protein synthesis as well as potential antimicrobial agents. Lincophenicol (1c) was active as inhibitor of Escherichia coli ribosomal peptidyltransferase-catalyzed puromycin reaction. Both lincophenicol (1c) and sparsophenicol (1b) inhibited the binding of the iodophenol analogue of sparsomycin to E. coli ribosomes. The results are discussed in terms of a retro-inverso hypothesis advanced earlier for interpretation of biological activity of chloramphenicol (1a) and sparsophenicol (1b). Chloramlincomycin (5a) suppressed the growth of Streptococcus pyogenes with MIC 6.25 micrograms/mL.
ChemInform Abstract: Inhibitors of Cyclic AMP Phosphodiesterase. Part 1. Analogues of Cilostamide and Anagrelide. (1987)

Abstract The compounds (IX) ‐ (XI), which are analogues of cilostamide (I) and anagrelide (II), and the corresponding methoxy‐substituted heterocycles are synthesized.
Uterine inflammation as a noxious visceral stimulus: behavioral characterization in the rat (1998)

We have developed a model of uterine inflammation in the rat. The purpose of this study was to characterize the behavioral manifestations of uterine pain. Mustard oil was injected into one uterine horn to produce chemical inflammation. Control rats were sham-operated. Non-stop videotape recording was performed for 7 days to monitor rat behavior. Rats with uterine inflammation showed abnormal behavior during the first 4 days (hunching, hump-backed position, licking of the lower abdomen, repeated waves of contraction of the ipsilateral oblique musculature with inward turning of the ipsilateral hindlimb, stretching, squashing of the lower abdomen against the floor) suggestive of visceral pain and evidence of flank muscle hyperalgesia over 7 days indicative of referred visceral pain. This model resembles closely a state of inflammatory uterine pain and will allow to gain further insight into the neural processes which contribute to visceral nociception.
Therapeutic use of omeprazole for refractory stress-induced gastric mucosal hemorrhage (1992)

Department of Surgery, Cornell University Medical College, New York Hospital-Cornell Medical Center, New York, NY.
Poly-DL-lactide-co-glycolide microspheres as a controlled release antigen delivery system (1999)

Successful vaccine application means maximum protection with minimal number of administrations. A rational development of vaccines involves studies of the nature of the antigen as well as of the adjuvant to be used to improve the immune responses. This has provided the impetus for studies to design the degradable devices and for different approaches to antigen delivery by different routes of administration. The development of controlled release systems based on polymeric devices that permit a sustained or pulsed release of encapsulated antigens has attracted much interest. Polymeric delivery systems consist of polymers that release their content continuously in a controlled manner over a period of time. The development of a biocompatible delivery system for parenteral administration offers several advantages in terms of immunoadjuvanticity over other compounds. It was found that, in contrast to other carriers, microspheres are more stable, thus permitting administration by the oral or parenteral route. In the present study, we describe the main characteristics and potentialities of this new immunoadjuvant for oral and parenteral administration.
Latent fibronectin‐degrading serine proteinase activity in N‐terminal heparin‐binding domain of human plasma fibronectin (1991)

The N‐terminal 70‐kDa fragment of human plasma fibronectin, purified from a cathepsin D digest, is characterized by lack of stability. It is processed proteolytically during incubation in the presence of Ca 2+ into 27‐kDa N‐terminal heparin‐binding and 45‐kDa collagen‐binding domains. The N‐terminal residue in the 27‐kDa fragment was blocked as in native fibronectin. The 45‐kDa fragments began with the sequences AAVYQP, AVYQP and VYQP (residues 260, 261, 262–265 of fibronectin) that correspond to the beginning of the collagen‐binding domain. In the presence of Ca 2+ the purified 27‐kDa fragment underwent further processing finally leading to the cleavage of the bond K85‐D86 and to the simultaneous appearance of a specific proteolytic activity. Inhibition studies suggests that the newly generated enzyme is a Ca 2+ ‐dependent serine proteinase. Among all assayed matrix proteins, the newly generated enzyme cleaves native fibronectin and its fragments. It is proposed that this fibronectinase may originate from the N‐terminal domain of fibronectin.
ESR1 Mutations in Circulating Plasma Tumor DNA from Metastatic Breast Cancer Patients (2015)

Abstract Purpose: Mutations in the estrogen receptor (ER)α gene, ESR1, have been identified in breast cancer metastases after progression on endocrine therapies. Because of limitations of metastatic biopsies, the reported frequency of ESR1 mutations may be underestimated. Here, we show a high frequency of ESR1 mutations using circulating plasma tumor DNA (ptDNA) from patients with metastatic breast cancer. Experimental Design: We retrospectively obtained plasma samples from eight patients with known ESR1 mutations and three patients with wild-type ESR1 identified by next-generation sequencing (NGS) of biopsied metastatic tissues. Three common ESR1 mutations were queried for using droplet digital PCR (ddPCR). In a prospective cohort, metastatic tissue and plasma were collected contemporaneously from eight ER-positive and four ER-negative patients. Tissue biopsies were sequenced by NGS, and ptDNA ESR1 mutations were analyzed by ddPCR. Results: In the retrospective cohort, all corresponding mutations were detected in ptDNA, with two patients harboring additional ESR1 mutations not present in their metastatic tissues. In the prospective cohort, three ER-positive patients did not have adequate tissue for NGS, and no ESR1 mutations were identified in tissue biopsies from the other nine patients. In contrast, ddPCR detected seven ptDNA ESR1 mutations in 6 of 12 patients (50%). Conclusions: We show that ESR1 mutations can occur at a high frequency and suggest that blood can be used to identify additional mutations not found by sequencing of a single metastatic lesion. Clin Cancer Res; 22(4); 993–9. ©2015 AACR.
Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. (1991)

Liver parenchymal cells continuously extract high amounts of bile acids from portal blood plasma. This uptake process is mediated by a Na+/bile acid cotransport system. A cDNA encoding the rat liver bile acid uptake system has been isolated by expression cloning in Xenopus laevis oocytes. The cloned transporter is strictly sodium-dependent and can be inhibited by various non-bile-acid organic compounds. Sequence analysis of the cDNA revealed an open reading frame of 1086 nucleotides coding for a protein of 362 amino acids (calculated molecular mass 39 kDa) with five possible N-linked glycosylation sites and seven putative transmembrane domains. Translation experiments in vitro and in oocytes indicate that the transporter is indeed glycosylated and that its polypeptide backbone has an apparent molecular mass of 33-35 kDa. Northern blot analysis with the cloned probe revealed crossreactivity with mRNA species from rat kidney and intestine as well as from liver tissues of mouse, guinea pig, rabbit, and man.
Synthesis of halosulfuron‐methyl via selective chlorination at 3‐ and/or 5‐position of pyrazole‐4‐carboxylates (1997)

Abstract Reactions of methyl pyrazole‐4‐carboxylates 4b‐d with N ‐chlorosuccinimide under heating conditions without a solvent gave methyl 3,5‐dichloro‐1‐methylpyrazole‐4‐carboxylate 4a in good yields. The reaction of 4a with sodium hydrosulfide led to a nucleophilic substitution on the 5‐position regioselectively to afford methyl 3‐chloro‐1‐methyl‐5‐mercaptopyrazole‐4‐carboxylate 6a, which was followed by oxidative chlorination and amination to obtain 3‐chloro‐1‐methyl‐5‐sulfamoylpyrazole‐4‐carboxylate 2a. Finally, the reaction of 2a with phenyl 4,6‐dimethoxypyrimidin‐2‐yl carbamate 7 provided methyl 3‐chloro‐5‐(4,6‐dimethoxypyrimidin‐2‐ylcarbamoylsulfamoyl)‐1‐methylpyrazole‐4‐carboxylate (halosulfuron‐methyl) 1a promising herbicide in com.
Molecular Mechanisms Regulating mRNA Stability: Physiological and Pathological Significance (2005)

The cytoplasmic level of a messenger RNA, and hence protein, depends not only upon its rates of synthesis, processing, and transport, but its decay rate as well. mRNA decay rates are frequently not static, but vary in response to extracellular stimuli and viral infections. Sequence elements within an mRNA, together with the protein and/or small noncoding RNA factors that bind these elements, dictate its decay rate. Not surprisingly, genetic alterations in mRNA stability can lead to various diseases, including cancer, heart disease, and immune disorders. However, we now have the capacity to alter selective aspects of the mRNA decay machinery by design in order to tune expression of any given gene to desired levels as a means of achieving therapeutic results. Our intent in this review is to introduce the reader to the intricacies of regulated gene expression at the level of mRNA stability, describe the roles of mRNA stability in pathology and drug development, and discuss some recent developments in the field of computational biology that are providing novel tools for understanding specific protein-RNA interactions, which drive the mRNA degradation machinery.
A model-based circular binary segmentation algorithm for the analysis of array CGH data (2011)

A novel algorithm, eCBS, was developed in this study. The current implementation of eCBS consistently outperforms the hybrid CBS 4× to 20× in computation time without loss of accuracy. Source codes, supplementary materials, supplementary figures, and supplementary tables can be found at http://ntumaps.cgm.ntu.edu.tw/eCBSsupplementary.
Transcription Factor Nrf2 Regulates Inflammation by Mediating the Effect of 15-Deoxy-Δ12,14-Prostaglandin J2 (2003)

Activated macrophages express high levels of Nrf2, a transcription factor that positively regulates the gene expression of antioxidant and detoxication enzymes. In this study, we examined how Nrf2 contributes to the anti-inflammatory process. As a model system of acute inflammation, we administered carrageenan to induce pleurisy and found that in Nrf2-deficient mice, tissue invasion by neutrophils persisted during inflammation and the recruitment of macrophages was delayed. Using an antibody against 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), it was observed that macrophages from pleural lavage accumulate 15d-PGJ(2). We show that in mouse peritoneal macrophages 15d-PGJ(2) can activate Nrf2 by forming adducts with Keap1, resulting in an Nrf2-dependent induction of heme oxygenase 1 and peroxiredoxin I (PrxI) gene expression. Administration of the cyclooxygenase 2 inhibitor NS-398 to mice with carrageenan-induced pleurisy caused persistence of neutrophil recruitment and, in macrophages, attenuated the 15d-PGJ(2) accumulation and PrxI expression. Administration of 15d-PGJ(2) into the pleural space of NS-398-treated wild-type mice largely counteracted both the decrease in PrxI and persistence of neutrophil recruitment. In contrast, these changes did not occur in the Nrf2-deficient mice. These results demonstrate that Nrf2 regulates the inflammation process downstream of 15d-PGJ(2) by orchestrating the recruitment of inflammatory cells and regulating the gene expression within those cells.
Different Regulatory Regions Are Required for the Vernalization-Induced Repression of FLOWERING LOCUS C and for the Epigenetic Maintenance of Repression (2002)

Vernalization, the promotion of flowering by a prolonged period of low temperature, results in repression of the floral repressor FLOWERING LOCUS C (FLC) and in early flowering. This repression bears the hallmark of an epigenetic event: the low expression state is maintained over many cell division cycles, but expression is derepressed in progeny. We show that the two stages of the response of FLC to vernalization, the repression of FLC and the maintenance of the repression during growth at normal temperatures after vernalization, are mediated through different regions of the FLC gene. Both promoter and intragenic regions are required for the responses. We also identify a 75-bp region in the FLC promoter that, in addition to intragenic sequences, is required for expression in nonvernalized plants.
Block Copolymer-Templated Chemistry on Si, Ge, InP, and GaAs Surfaces (2005)

Patterning of semiconductor surfaces is an area of intense interest, not only for technological applications, such as molecular electronics, sensing, cellular recognition, and others, but also for fundamental understanding of surface reactivity, general control over surface properties, and development of new surface reactivity. In this communication, we describe the use of self-assembling block copolymers to direct semiconductor surface chemistry in a spatially defined manner, on the nanoscale. The proof-of-principle class of reactions evaluated here is galvanic displacement, in which a metal ion, M+, is reduced to M0 by the semiconductor, including Si, Ge, InP, and GaAs. The block copolymer chosen has a polypyridine block which binds to the metal ions and brings them into close proximity with the surface, at which point they undergo reaction; the pattern of resulting surface chemistry, therefore, mirrors the nanoscale structure of the parent block copolymer. This chemistry has the added advantage of forming metal nanostructures that result in an alloy or intermetallic at the interface, leading to strongly bound metal nanoparticles that may have interesting electronic properties. This approach has been shown to be very general, functioning on a variety of semiconductor substrates for both silver and gold deposition, and is being extended to organic and inorganic reactions on a variety of conducting, semiconducting, and insulating substrates.
Palladium-Catalyzed Annulation of Aryl Heterocycles with Strained Alkenes (2007)

[reaction: see text] An annulation reaction proceeding by the intermolecular addition of an arylpalladium(II) halide across a strained alkene, followed by an intramolecular C-H functionalization of a pendant heterocycle is described. A variety of polycyclic heterocycles have been prepared from readily accessible haloaryl heterocycles by annulation with a range of strained alkene partners.
Building a robust software-based router using network processors (2001)

Recent efforts to add new services to the Internet have increased interest in software-based routers that are easy to extend and evolve. This paper describes our experiences using emerging network processors---in particular, the Intel IXP1200---to implement a router. We show it is possible to combine an IXP1200 development board and a PC to build an inexpensive router that forwards minimum-sized packets at a rate of 3.47Mpps. This is nearly an order of magnitude faster than existing pure PC-based routers, and sufficient to support 1.77Gbps of aggregate link bandwidth. At lesser aggregate line speeds, our design also allows the excess resources available on the IXP1200 to be used robustly for extra packet processing. For example, with 8 × 100Mbps links, 240 register operations and 96 bytes of state storage are available for each 64-byte packet. Using a hierarchical architecture we can guarantee line-speed forwarding rates for simple packets with the IXP1200, and still have extra capacity to process exceptional packets with the Pentium. Up to 310Kpps of the traffic can be routed through the Pentium to receive 1510 cycles of extra per-packet processing.
[Construction of a phage antibody library and screening of anti-epidermal growth factor receptor variant III single chain antibody]. (2010)

An immune phage ScFv library is successfully constructed, and the ScFv antibody fragment is capable of specific binding to EGFRvIII.
Clinical trial risk in castration‐resistant prostate cancer: immunotherapies show promise (2013)

Currently, one in 33 compounds that enters clinical testing will be awarded US Food and Drug Administration approval. This appears to be the highest risk indication investigated to date, based on clinical trial studies alone, with an average cost of $1.411bn to bring a new drug to market when adjusted for risk. Development of radical therapeutics such as immunotherapies may also be warranted instead of classic antineoplastic therapeutics. Given the high clinical trial risk, efforts may have to shift to biomarker and surrogate endpoints to manage future clinical trial risk in prostate cancer.
Overexpression of manganese superoxide dismutase suppresses tumor formation by modulation of activator protein-1 signaling in a multistage skin carcinogenesis model. (2001)

Manganese superoxide dismutase (MnSOD) is a nuclear encoded primary antioxidant enzyme localized in mitochondria. Because expression of MnSOD plays a major role in maintaining cellular redox status and reactive oxygen species are known to play a role in signal transduction and carcinogenesis, we investigated the role of MnSOD in the development of cancer using a two-stage [7,12-dimethylbenz(a)-anthracene plus 12-O-tetradecanoylphorbol-13-acetate (TPA)] skin carcinogenesis model. Female transgenic mice expressing the human MnSOD gene in the skin and their nontransgenic counterparts were used in this study. Pathological examination demonstrated significant reduction of papilloma formation in transgenic mice. Quantitative analysis of 4-hydroxy-2-nonenal-modified proteins showed greater accumulation of oxidative damage products in nontransgenic compared with transgenic mice, and this oxidative damage was demonstrated to be present in both mitochondria and nucleus. TPA increased activator protein-1 (AP-1) binding activity within 6 h in nontransgenic mice, but increased AP-1 binding activity was delayed in the transgenic mice. Electrophoretic mobility shift assay, transcription of the target genes, and Western analysis studies indicated that the increased AP-1 binding activity was attributable to induction of the Jun but not the Fos protein families. Overexpression of MnSOD selectively inhibited the TPA-induced activation of protein kinase Cepsilon and prevented subsequent activation of c-Jun NH(2)-terminal kinase in response to TPA. Overall, these results indicate that MnSOD regulates both cellular redox status and selectively modulates PKCepsilon signaling, thereby delaying AP-1 activation and inhibiting tumor promotion, resulting in reduction of tumors in MnSOD transgenic mice.
Dronedarone: A new antiarrhythmic agent (2006)

Dronedarone (SR 33589; N,N-dibutyl-3-[4-([2-butyl-5-methylsulphonamido] benzofuran-3-yl-carbonyl) phenoxy]propylamine) is a new synthetic noniodinated derivative of amiodarone that is currently undergoing phase III clinical trials. It demonstrates electrophysiologic patterns similar to amiodarone and shows equivalent efficacy in preventing or converting various ventricular and atrial arrhythmias in laboratory animals. Two phase III trials demonstrated that dronedarone is safe and effective for the maintenance of normal sinus rhythm in patients with atrial fibrillation or atrial flutter. Dronedarone at the dose of 400 mg twice daily was effective in preventing both symptomatic and asymptomatic recurrences of atrial fibrillation or atrial flutter and had a safety profile similar to that of placebo. Further studies are needed to determine the long-term effectiveness and safety of dronedarone in various groups of patients with atrial fibrillation. Other clinical applications of this novel antiarrhythmic drug need to be determined in future clinical trials.
Role of water‐soluble amyloid‐β in the pathogenesis of Alzheimer's disease (2005)

Water-soluble amyloid-beta (wsAbeta) is present in cerebral cortex of subjects at risk of Alzheimer's disease (AD) as well as in normal elderly subjects as a mixture of three major amyloid-beta (Abeta) species: 1-42, py3-42 and py11-42. The three wsAbeta species are nondetectable in brains of young people, free of immunohistochemically detectable amyloid plaques. In the brains of Down's syndrome and APP-mutant transgenic mice, wsAbeta appears long time before amyloid deposition, indicating that it represent the first form of Abeta aggregation and accumulation. In normal brain, wsAbeta is bound to apolipoprotein E that favours its degradation by proteases. The composition of wsAbeta, in terms of the ratio between the full-length 1-42 and the py3-42 peptides, correlates with the severity of clinical and pathological phenotype in familial early onset AD. Water-soluble Abeta is the native counterpart of the Abeta small aggregates (soluble oligomers) that show in vitro an early and high neuronal toxicity.
Two-Dimensional Simulations of Relativistic Jet—Cloud Collisions (1999)

We have investigated the processes of both nonrelativistic and relativistic jet-cloud collisions using a relativistic hydrodynamic simulation code. Several runs were performed to study different aspects of these kinds of collisions. Simulations show that the collisions involve two kinds of processes: reflection and bending. Collisions of relativistic jets and high-Mach-number nonrelativistic jets appear as reflections, while the collisions of low-Mach-number nonrelativistic jets show a reflection feature at their early stage and a bending feature at their late stage. Downstream of the collisions point the flow is still supersonic. In the bending cases, the original supersonic state is maintained all the time, while in the reflection processes, the supersonic condition of the downstreams flow is re-established by high pressure. The deflection angle is not fixed; it depends on almost all parameters involved in the collisions. Even for a particular collision process, its deflection angle is not fixed, but rather changes with time. Two results are noticeable: (1) the deflection angle can be greater than 90°; (2) in the collision region of a reflection process, the temperature is high and the jet material suffers rapid deceleration and reacceleration.
Prevention of obesity in mice by antisense oligonucleotide inhibitors of stearoyl-CoA desaturase–1 (2005)

Effective therapies for the treatment of obesity, a key element of metabolic syndrome, are urgently needed but currently lacking. Stearoyl-CoA desaturase-1 (SCD1) is the rate-limiting enzyme catalyzing the conversion of saturated long-chain fatty acids into monounsaturated fatty acids, which are major components of triglycerides. In the current study, we tested the efficacy of pharmacological inhibition of SCD1 in controlling lipogenesis and body weight in mice. SCD1-specific antisense oligonucleotide inhibitors (ASOs) reduced SCD1 expression, reduced fatty acid synthesis and secretion, and increased fatty acid oxidization in primary mouse hepatocytes. Treatment of mice with SCD1 ASOs resulted in prevention of diet-induced obesity with concomitant reductions in SCD1 expression and the ratio of oleate to stearoyl-CoA in tissues and plasma. These changes correlated with reduced body adiposity, hepatomegaly and steatosis, and postprandial plasma insulin and glucose levels. Furthermore, SCD1 ASOs reduced de novo fatty acid synthesis, decreased expression of lipogenic genes, and increased expression of genes promoting energy expenditure in liver and adipose tissues. Thus, SCD1 inhibition represents a new target for the treatment of obesity and related metabolic disorders.