gebhart/patrepeval huggingface dataset:
The serum-inducible mouse gene Krox-24 encodes a sequence-specific transcriptional activator. (1990)

The mouse gene Krox-24 is transiently activated during cell cycle reentry. It encodes a protein with three zinc fingers similar to those of the transcription factor Sp1. Here we present a biochemical characterization of the gene products. Krox-24 mRNA is translated into two proteins of 82 and 88 kilodaltons, designated p82Krox-24 and p88Krox-24, respectively. p82Krox-24 is initiated at the first AUG codon of the open reading frame, whereas synthesis of p88Krox-24 starts at a non-AUG codon located upstream. Both proteins were synthesized in HeLa cells infected with recombinant vaccinia viruses expressing Krox-24 cDNAs. Under these conditions, they were found phosphorylated on serine residues and glycosylated. The availability of the proteins made possible the determination of the DNA recognition sequence. In vitro, Krox-24 bound specifically to the sequence 5'-GCG(C/G)GGGCG-3'. This sequence is similar but not identical to the Sp1 target sequence. Insertion of an oligomer for the binding site in cis, close to the herpes simplex virus thymidine kinase promoter, rendered this promoter responsive to Krox-24. Krox-24 is therefore a sequence-specific transcriptional activator. Krox-24-binding sites were found upstream of several serum-inducible genes, raising the possibility that Krox-24 is involved in the regulation of these genes.
Advanced Organic Chemistry. Part B: Reactions and Synthesis. Fourth Edition (2001)

The control of reactivity to achieve specific syntheses is one of the overarching goals of organic chemistry.[...]
Steroid−DNA Interactions Increasing Stability, Sequence-Selectivity, DNA/RNA Discrimination, and Hypochromicity of Oligonucleotide Duplexes (1999)

Cholic acid and its deoxy derivatives were found to increase the melting point of oligonucleotide duplexes when coupled to their 5‘-termini. For duplexes of mixed-sequence octamers, the melting point was 8−11 °C higher with the steroid appendage than without. For the self-complementary hexamer TGCGCA, a 21 °C melting point increase was measured in the presence of steroid appendage and −18 kcal/mol in ΔΔH°. The affinity increases were accompanied by increased discrimination against mismatches at the two terminal base pairs and increased hypochromicity, as well as an improved DNA/RNA discrimination for the non selcomplementary sequence. Cross-peaks in the NOESY spectrum of (chl-T*GCGCA)2, where chl denotes the cholic acid residue and T* a 5‘-amino-5‘-deoxythymidine residue, point toward stacking interactions in which the methyl groups of the steroid face the nucleobases. Our results indicate that bile acids can form a specific complex with terminal T:A base pairs of double-stranded DNA.
Gut and Brain Effects of American Ginseng Root on Brainstem Neuronal Activities in Rats (1998)

Brainstem neurons receiving subdiaphragmatic vagal inputs were recorded in an in vitro neonatal rat brainstem-gastric preparation. Aqueous extracts of American ginseng root (Panax quinquefolium L.) were applied to the gastric compartment or the brainstem compartment of the bath chamber to evaluate the peripheral gut and central brain effects of the extracts on brainstem unitary activity. After Panax quinquefolium L. application to the gastric or brainstem compartment, a concentration-related inhibition in neuronal discharge frequency in the brainstem unitary activity was observed, suggesting that Panax quinquefolium L. may play an important role in regulating the digestive process and modulating brain function. In this study, pharmacological effects of American-cultivated Panax quinquefolium L. and Chinese-cultivated Panax quinquefolium L. were also compared. Our results suggest that American-cultivated Panax quinquefolium L. possesses a significantly stronger gastric modulating effect on brain neuronal activity.
Assignment of resonances in the phosphorus-31 nuclear magnetic resonance spectrum of poly[d(A-T)] from phosphorothioate substitution (1983)

Two phosphorothioate analogues of poly[d(A$-T)] have been synthesized enzymatically. In one, poly[d(A$-T)], dTMP is replaced by thymidine 5'-O-phosphorothioate; in the other, poly[d(T$-A)], dAMP is replaced by 2'-deoxyadenosine 5'-O-phosphorothioate. The 31P NMR spectrum of poly[d-(A-T)] in solutions at low salt concentration shows two resonances at 51.80 and -4.25 ppm relative to trimethyl phosphate. The corresponding values for poly[d(T$-A)] are 51.51 and -4.43 ppm. These data allow the assignment of the downfield resonance at -4.23 ppm in poly[d(A-T)] to the phosphate group of d(TpA) and the resonance at -4.41 ppm to that of d(ApT). Thus, strong evidence is provided for a repeating dinucleotide structure. A comparison of the 31P NMR spectra of the various polymers in solutions of 2 M CsF reveals that both resonances are shifted upfield by approximately 0.9 ppm in the case of the phosphorothioates and by 0.2 or 0.4 ppm in the case of the phosphates. An upfield shift of about 0.18 ppm can also be observed for the two corresponding dinucleoside monophosphates. Thus, the upfield shift induced by high concentrations of CsF is not specific for the polymer backbone.
Defense Islands in Bacterial and Archaeal Genomes and Prediction of Novel Defense Systems (2011)

The arms race between cellular life forms and viruses is a major driving force of evolution. A substantial fraction of bacterial and archaeal genomes is dedicated to antivirus defense. We analyzed the distribution of defense genes and typical mobilome components (such as viral and transposon genes) in bacterial and archaeal genomes and demonstrated statistically significant clustering of antivirus defense systems and mobile genes and elements in genomic islands. The defense islands are enriched in putative operons and contain numerous overrepresented gene families. A detailed sequence analysis of the proteins encoded by genes in these families shows that many of them are diverged variants of known defense system components, whereas others show features, such as characteristic operonic organization, that are suggestive of novel defense systems. Thus, genomic islands provide abundant material for the experimental study of bacterial and archaeal antivirus defense. Except for the CRISPR-Cas systems, different classes of defense systems, in particular toxin-antitoxin and restriction-modification systems, show nonrandom clustering in defense islands. It remains unclear to what extent these associations reflect functional cooperation between different defense systems and to what extent the islands are genomic "sinks" that accumulate diverse nonessential genes, particularly those acquired via horizontal gene transfer. The characteristics of defense islands resemble those of mobilome islands. Defense and mobilome genes are nonrandomly associated in islands, suggesting nonadaptive evolution of the islands via a preferential attachment-like mechanism underpinned by the addictive properties of defense systems such as toxins-antitoxins and an important role of horizontal mobility in the evolution of these islands.
The expression of c-myc and c-N-ras in human cirrhotic livers, hepatocellular carcinomas and liver tissue surrounding the tumors. (1990)

To study the possible role of proto-oncogenes in the multistep process of human liver hepatocarcinogenesis, we have examined the expression of c-N-ras and c-myc in human hepatocellular carcinomas and liver tissue surrounding the tumors as well as cirrhotic livers which are generally considered to precede the formation of human hepatocellular carcinoma. One to four-fold higher expression of the c-N-ras proto-oncogene was observed in twelve hepatoma patients as compared to normal liver. Increased expression of c-N-ras was also observed in liver tissue surrounding these tumors. Eight patients exhibited an apparent higher expression of the c-N-ras oncogene in adjacent liver tissue than in their corresponding tumor tissues. Six human liver cirrhosis patients also exhibited a slight increase in c-N-ras expression. Southern blot analysis demonstrated an amplified c-N-ras sequence in these tissues surrounding the tumors. In the study of the c-myc gene, variable degrees of highly enhanced expression were found in all twelve hepatoma patients as compared to normal liver. The c-myc gene was also expressed in the adjacent liver tissue and in some of the human cirrhotic livers. Our studies give further evidence that the expression of c-N-ras and c-myc proto-oncogenes are involved in the process of human hepatocarcinogenesis.
Lithography beyond light: Microcontact printing with monolayer resists (1997)

We describe high-resolution lithography based on transfer of a pattern from an elastomeric “stamp” to a solid substrate by conformal contact: a nanoscale interaction between substrate and stamp on macroscopic scales that allows transport of material from stamp to substrate. The stamp is first formed by curing poly(dimethyl siloxane) (PDMS) on a master with the negative of the desired surface, resulting in an elastomeric solid with a pattern of reliefs, typically a few microns deep, on its surface. The stamp provides an “ink” that forms a self-assembled monolayer (SAM) on a solid surface by a covalent, chemical reaction. Because SAMs act as highly localized and efficient barriers to some wet etches, microcontact printing forms part of a convenient lithographic system not subject to diffraction or depth of focus limitations while still providing simultaneous transfer of patterned features. Our study helps to define the strengths and limitations of microcontact printing with SAMs, a process that is necessary to assess its worth to technology. We used lithography based on scanning tunneling microscopy (STM) to demonstrate that disruption of SAMs on gold allowed the formation of etched features as small as 20 nm using a CN <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−</sup> /O <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> etch. This result implied that etching occurred where damage of a few molecules in the ordered SAM allowed passage of cyanide, whereas adjacent molecules in the SAM remained unperturbed at this scale. Features as small as 30 nm etched in gold over areas greater than 1 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> resulted from microcontact printing with replicas of electron-beam-formed masters, with the transfer of these printed SAMs requiring only ≈1 s. STM studies of these transferred SAMs revealed an achievable order indistinguishable from that found for SAMs prepared from solution. Facile alignment of printing steps at submicron scales may result from new designs of stamps that exploit their limited deformability and lock-and-key-type approaches to mate stamp and substrate.
Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage (2006)

Topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and meiosis and is a highly attractive target for chemotherapeutic agents. We have identified previously topoisomerase II and heat shock protein 90 (Hsp90) as part of a complex. In this paper we demonstrate that drug combinations targeting these two enzymes cause a synergistic increase in apoptosis. The objective of our study was to identify the mode of cell killing and the mechanism behind the increase in topoisomerase II mediated DNA damage. Importantly we demonstrate that Hsp90 inhibition results in an increased topoiosmerase II activity but not degradation of topoisomerase II and it is this, in the presence of a topoisomerase II poison that causes the increase in cell death. Our results suggest a novel mechanism of action where the inhibition of Hsp90 disrupts the Hsp90-topoisomerase II interaction leading to an increase in and activation of unbound topoisomerase II, which, in the presence of a topoisomerase II poison leads to the formation of an increased number of cleavable complexes ultimately resulting in rise in DNA damage and a subsequent increase cell death.
A Ras by Any Other Name (2001)

Ras proteins are now well recognized for their essential function in transducing extracellular signals that regulate cell growth, survival, and differentiation. Although ras genes were originally identified in the mid-1960s as the transforming elements of the Harvey and Kirsten strains of rat sarcoma viruses, investigation of the biological properties of their protein products did not gain momentum until the early 1980s, when mutated alleles of cellular ras genes were identified as dominant oncogenes in various types of human tumors. The mammalian ras gene family consists of three members: H-ras, K-ras, and N-ras, which are located on different chromosomes. The H-ras and K-ras genes are the cellular counterparts of the viral Harvey and Kirsten genes, respectively, and the N-ras gene is derived from a human neuroblastoma cell line. Are the different ras genes functionally redundant or does each ras gene have a specific role? This review briefly recounts results from biochemical and genetic studies supporting the unanticipated possibility that the answer to both questions may be yes.
A controlled trial of smart infusion pumps to improve medication safety in critically ill patients* (2005)

Intravenous medication errors and adverse drug events were frequent and could be detected using smart pumps. We found no measurable impact on the serious medication error rate, likely in part due to poor compliance. Although smart pumps have great promise, technological and nursing behavioral factors must be addressed if these pumps are to achieve their potential for improving medication safety.
Antiproliferative Properties of Type I and Type II Interferon (2010)

The clinical possibilities of interferon (IFN) became apparent with early studies demonstrating that it was capable of inhibiting tumor cells in culture and in vivo using animal models. IFN gained the distinction of being the first recombinant cytokine to be licensed in the USA for the treatment of a malignancy in 1986, with the approval of IFN-α2a (Hoffman-La Roche) and IFN-α2b (Schering-Plough) for the treatment of Hairy Cell Leukemia. In addition to this application, other approved antitumor applications for IFN-α2a are AIDS-related Kaposi's Sarcoma and Chronic Myelogenous Leukemia (CML) and other approved antitumor applications for IFN-α2b are Malignant Melanoma, Follicular Lymphoma, and AIDS-related Kapoisi's Sarcoma. In the ensuing years, a considerable number of studies have been conducted to establish the mechanisms of the induction and action of IFN's anti-tumor activity. These include identifying the role of Interferon Regulatory Factor 9 (IRF9) as a key factor in eliciting the antiproliferative effects of IFN-α as well as identifying genes induced by IFN that are involved in recognition of tumor cells. Recent studies also show that IFN-activated human monocytes can be used to achieve >95% eradication of select tumor cells. The signaling pathways by which IFN induces apoptosis can vary. IFN treatment induces the tumor suppressor gene p53, which plays a role in apoptosis for some tumors, but it is not essential for the apoptotic response. IFN-α also activates phosphatidylinositol 3-kinase (PI3K), which is associated with cell survival. Downstream of PI3K is the mammalian target of rapamycin (mTOR) which, in conjunction with PI3K, may act in signaling induced by growth factors after IFN treatment. This paper will explore the mechanisms by which IFN acts to elicit its antiproliferative effects and more closely examine the clinical applications for the anti-tumor potential of IFN.
RNA Sequencing and Analysis (2015)

RNA sequencing (RNA-Seq) uses the capabilities of high-throughput sequencing methods to provide insight into the transcriptome of a cell. Compared to previous Sanger sequencing- and microarray-based methods, RNA-Seq provides far higher coverage and greater resolution of the dynamic nature of the transcriptome. Beyond quantifying gene expression, the data generated by RNA-Seq facilitate the discovery of novel transcripts, identification of alternatively spliced genes, and detection of allele-specific expression. Recent advances in the RNA-Seq workflow, from sample preparation to library construction to data analysis, have enabled researchers to further elucidate the functional complexity of the transcription. In addition to polyadenylated messenger RNA (mRNA) transcripts, RNA-Seq can be applied to investigate different populations of RNA, including total RNA, pre-mRNA, and noncoding RNA, such as microRNA and long ncRNA. This article provides an introduction to RNA-Seq methods, including applications, experimental design, and technical challenges.
Transplantation of Polymer Encapsulated Neurotransmitter Secreting Cells: Effect of the Encapsulation Technique (1991)

Deficits associated with neurological diseases may be improved by the transplantation within the brain lesioned target structure of polymer encapsulated cells releasing the missing neurotransmitter. Surrounding cells with a permselective membrane of appropriate molecular weight cut-off allows inward diffusion of nutrients and outward diffusion of neurotransmitters, but prevents immunoglobulins or immune cells from reaching the transplant. This technique therefore allows transplantation of post-mitotic cells across species. It also permits neural grafting of transformed cell lines since the polymer capsule prevents the formation of tumors by physically sequestering the transplanted tissue. In the present study, we compared the ability of dopamine-secreting cells, encapsulated by 2 different methods, to reverse experimental Parkinson's disease, a neurodegenerative disease characterized by motor disturbances due to a lack of dopamine within the striatum following degeneration of the dopaminergic nigro-striatal pathway. PC12 cells were loaded in polyelectrolyte-based microcapsules or thermoplastic-based macrocapsules and maintained in vitro or transplanted in a rat experimental Parkinson model for 4 weeks. Chemically-induced depolarization increased the in vitro release of dopamine from macrocapsules over time, while no increase in release was observed from microcapsules. Encapsulated PC12 cells were able to reduce lesion-induced rotational asymmetry in rats for at least 4 weeks, regardless of the encapsulation technique used. With both encapsulation methods, PC12 cell viability was greater in vivo than in vitro which suggests that the striatum releases trophic factors for PC12 cells. More brain tissue damage was observed with microcapsules than macrocapsules, possibly the result of the difficulty of manipulating the more fragile microcapsules.(ABSTRACT TRUNCATED AT 250 WORDS)
Structure of two fungal β‐1,4‐galactanases: Searching for the basis for temperature and pH optimum (2003)

beta-1,4-Galactanases hydrolyze the galactan side chains that are part of the complex carbohydrate structure of the pectin. They are assigned to family 53 of the glycoside hydrolases and display significant variations in their pH and temperature optimum and stability. Two fungal beta-1,4-galactanases from Myceliophthora thermophila and Humicola insolens have been cloned and heterologously expressed, and the crystal structures of the gene products were determined. The structures are compared to the previously only known family 53 structure of the galactanase from Aspergillus aculeatus (AAGAL) showing approximately 56% identity. The M. thermophila and H. insolens galactanases are thermophilic enzymes and are most active at neutral to basic pH, whereas AAGAL is mesophilic and most active at acidic pH. The structure of the M. thermophila galactanase (MTGAL) was determined from crystals obtained with HEPES and TRIS buffers to 1.88 A and 2.14 A resolution, respectively. The structure of the H. insolens galactanase (HIGAL) was determined to 2.55 A resolution. The thermostability of MTGAL and HIGAL correlates with increase in the protein rigidity and electrostatic interactions, stabilization of the alpha-helices, and a tighter packing. An inspection of the active sites in the three enzymes identifies several amino acid substitutions that could explain the variation in pH optimum. Examination of the activity as a function of pH for the D182N mutant of AAGAL and the A90S/ H91D mutant of MTGAL showed that the difference in pH optimum between AAGAL and MTGAL is at least partially associated with differences in the nature of residues at positions 182, 90, and/or 91.
Effects of grapefruit juice and orange juice components on P‐glycoprotein‐ and MRP2‐mediated drug efflux (2004)

We investigated the effects of grapefruit juice (GFJ) and orange juice (OJ) on drug transport by MDR1 P-glycoprotein (P-gp) and multidrug resistance protein 2 (MRP2), which are efflux transporters expressed in human small intestine. We examined the transcellular transport and uptake of [(3)H]vinblastine (VBL) and [(14)C]saquinavir in a human colon carcinoma cell line (Caco-2) and in porcine kidney epithelial cell lines transfected with human MDR1 cDNA and human MRP2 cDNA, LLC-GA5-COL150, and LLC-MRP2, respectively. In Caco-2 cells, the basal-to-apical transports of [(3)H]VBL and [(14)C]saquinavir were greater than those in the opposite direction. The ratio of basal-to-apical transport to apical-to-basal transport of [(3)H]VBL and [(14)C]saquinavir by Caco-2 cells was reduced in the presence of MK571 (MRPs inhibitor), verapamil (P-gp inhibitor), cyclosporin A (inhibitor of both), 50% ethyl acetate extracts of GFJ and OJ, or their components (6',7'-dihydroxybergamottin, bergamottin, tangeretin, hepatomethoxyflavone, and nobiletin). Studies of transport and uptake of [(3)H]VBL and [(14)C]saquinavir with MDR1 and MRP2 transfectants showed that VBL and saquinavir are transported by both P-gp and MRP2. GFJ and OJ components inhibited the transport by MRP2 as well as P-gp. However, their inhibitory potencies for P-gp or MRP2 were substrate-dependent. The present study has revealed that GFJ and OJ interact with not only P-gp but also MRP2, both of which are expressed at apical membranes and limit the apical-to-basal transport of VBL and saquinavir in Caco-2 cells.
Asynchronous processor survey (1997)

Virtually all computers today are synchronous. As systems grow increasingly large and complex the clock can cause big problems with clock skew, a timing delay that can create havoc with the overall design. It can also increase the circuit silicon and power dissipation, which can affect overheating and power supplies. Computer architecture researchers are actively considering asynchronous processor design. Asynchronous architectures permit modular design. Each subsystem or functional block can be optimized without being synchronized to a global clock, which simplifies interfacing. Moreover, an asynchronous system exhibits the average performance of all the individual components, rather than the synchronous system's worst-case performance of a single component. Furthermore, asynchronous processors may yet prove to offer reduced power dissipation by inherently shutting down unused portions of the circuit. This article examines the key architecture issues that concern designers and compares six developmental asynchronous architectures: CAP, the Caltoch Asynchronous Processor; FAM, the Fully Asynchronous Microprocessor; NSR, the Nonsynchronous RISC; CFPP, the Counterflow Pipeline Processor; Strip, a Self-Assured RISC Processor; and Amulet 1.