gebhart/patrepeval huggingface dataset:
Degradation of Nuclease-Stabilized RNA Oligonucleotides in Mycoplasma-Contaminated Cell Culture Media (2012)

Artificial RNA reagents such as small interfering RNAs (siRNAs) and aptamers often must be chemically modified for optimal effectiveness in environments that include ribonucleases. Mycoplasmas are common bacterial contaminants of mammalian cell cultures that are known to produce ribonucleases. Here we describe the rapid degradation of nuclease-stabilized RNA oligonucleotides in a human embryonic kidney 293 (HEK) cell culture contaminated with Mycoplasma fermentans, a common species of mycoplasma. RNA with 2'-fluoro- or 2'-O-methyl- modified pyrimidines was readily degraded in conditioned media from this culture, but was stable in conditioned media from uncontaminated HEK cells. RNA completely modified with 2'-O-methyls was not degraded in the mycoplasma-contaminated media. RNA zymogram analysis of conditioned culture media and material centrifuged from the media revealed several distinct protein bands (ranging from 30 to 68 kDa) capable of degrading RNA with 2'-fluoro- or 2'-O-methyl-modified pyrimidines. Finally, the mycoplasma-associated nuclease was detected in material centrifuged from the contaminated culture supernatants in as little as 15 minutes with an RNA oligo-containing 2'-O-methyl-modified pyrimidines and labeled with a 5'-fluorescein amidite (FAM) and 3'-quencher. These results suggest that mycoplasma contamination may be a critical confounding variable for cell culture experiments involving RNA-based reagents, with particular relevance for applications involving naked RNA (e.g., aptamer-siRNA chimeras).
An Improved Method for Prenatal Diagnosis of Genetic Diseases by Analysis of Amplified DNA Sequences (1987)

We report the development of a rapid nonradioactive technique for the genetic prediction of human disease and its diagnostic application to hemophilia A. This method is based on enzymatic amplification of short segments of human genes associated with inherited disorders. A novel feature of the procedure is the use of a heat-stable DNA polymerase, which allows the repeated rounds of DNA synthesis to proceed at 63 degrees C. The high sequence specificity of the amplification reaction at this elevated temperature permits restriction-site polymorphisms, contained in the amplified samples, to be analyzed by visual inspection of their digestion products on polyacrylamide gels. By means of this method, we have performed carrier detection and prenatal diagnosis of hemophilia in two families with use of the factor VIII intragenic polymorphisms identified by the restriction enzymes BclI and XbaI. Predictions can be made directly from chorionic villi, without previous DNA extraction, and fetal sex can be determined by amplification of sequences specific for the Y chromosome. Specific amplification of genomic sequences with heat-stable DNA polymerase is applicable to the diagnosis of a wide variety of inherited disorders. These include diseases diagnosed by restriction-site variation, such as Duchenne's muscular dystrophy and sickle cell anemia, those due to a collection of known mutations, such as beta-thalassemia, and those due to gene deletion, such as alpha-thalassemia.
Overview of novel integrated optical ring resonator bio/chemical sensors (2007)

In parallel to a stand-alone microsphere resonator and a planar ring resonator on a wafer, the liquid core optical ring resonator (LCORR) is regarded as the third type of ring resonator that integrates microfluidics with state-of-the-art photonics. The LCORR employs a micro-sized glass capillary with a wall thickness of a few microns. The circular cross section of the capillary forms a ring resonator that supports the whispering gallery modes (WGMs), which has the evanescent field in the core, allowing for repetitive interaction with the analytes carried inside the capillary. Despite the small physical size of the LCORR and sub-nanoliter sensing volume, the effective interaction length can exceed 10 cm due to high Q-factor (10<sup>6</sup>), significantly improving the LCORR detection limit. The LCORR is a versatile system that exhibits excellent fluid handling capability inherent to capillaries and permits non-invasive and quantitative measurement at any location along the capillary. Furthermore, the LCORR uses the refractive index change as a transduction signal, which enables label-free detection. Therefore, the LCORR is a promising technology platform for future sensitive, miniaturized, lab-on-a-chip type sensors. In this paper, we will introduce the concept of the LCORR and present the theoretical analysis and the experimental results related to the LCORR sensor development.
PROTEOLYTIC ACTIVITIES THAT MEDIATE APOPTOSIS (1998)

Since the discovery that cells can activate their own suicide program, investigators have attempted to determine whether the events that are associated with this form of cell death are genetically determined. The discovery that the ced-3 gene of Caenorhabditis elegans encodes a cysteine protease essential for developmentally regulated apoptosis ignited interest in this area of research. As a result, we now know that cell death is specified by a number of genes and that this biologic process contributes significantly to development, tumorigenesis, and autoimmune disease. In this review I summarize what is currently known about signaling pathways involved in apoptosis, with particular emphasis on the function of the cysteine proteases known as caspases. However, there is also evidence that protease-independent cell death pathways exist. Is there a relationship between these two distinct mechanisms? If so, how do they communicate? Finally, even though the involvement of tumor necrosis factor/nerve growth factor family of receptors and cysteine proteases has been elegantly established as a component of many apoptotic signaling pathways, what happens downstream of these initial events? Why are only a selected group of cellular proteins--many nuclear--the targets of these proteases? Are nuclear events essential for apoptosis in vivo? Are the cellular genes that encode products involved in apoptotic signaling frequent targets of mutation/alteration during tumorigenesis? These are only a few questions that may be answered in the next ten years.
Loss of the Y chromosome: an age-related or clonal phenomenon in acute myelogenous leukemia/myelodysplastic syndrome? (2008)

Loss of the Y chromosome appears to be primarily an age-related phenomenon. However, in individuals in which all cells on cytogenetic analysis showed loss of the Y chromosome, there was a statistically significant increase in AML/MDS, suggesting that the absence of any normal-dividing cells in a bone marrow analysis may be indicative of AML/MDS.
Effect of Alloying on the Resistance of Cu-10% Ni Alloys to Seawater Impingement (1999)

Cu-Ni castings and wrought pipes nominally contain 1% Fe to 2% Fe, which is added to improve the Cu-Ni alloy’s erosion-corrosion resistance. After fabrication, Cu-Ni products are solution heat-treated to dissolve the iron uniformly and form a single-phase alloy. During welding, however, iron can precipitate from solid solution onto grain boundaries in the heat-affected zones (HAZ). During seawater service, these iron-rich precipitates can dissolve preferentially (galvanically), leading to intergranular corrosion of the HAZ. The present report described 90-10 Cu-Ni alloys in which different soluble elements were substituted for iron. Jet-impingement testing in filtered natural seawater showed that 2% In also promoted improved erosion-corrosion resistance. Because indium is very soluble in copper, it should not precipitate in the HAZ during welding and cause intergranular corrosion of the HAZ during seawater service. The present study reviewed the literature on the mechanisms by which iron is believed to improve the erosion-corrosion resistance, and proposed a different model based on doping of the thin surface oxide film.
Molecular Basis for the Subtype Discrimination of the Estrogen Receptor-β-Selective Ligand, Diarylpropionitrile (2003)

Although the two subtypes of the human estrogen receptor (ER), ERalpha and ERbeta, share only 56% amino acid sequence identity in their ligand binding domain (LBD), the residues that surround the ligand are nearly identical; nevertheless, subtype-selective ligands are known. To understand the molecular basis by which diarylpropionitrile (DPN), an ERbeta-selective ligand, is able to discriminate between the two ERs, we examined its activity on ER mutants and chimeric constructs generated by DNA shuffling. The N-terminal region of the ERbeta LBD (through helix 6) appears to be fully responsible for the ERbeta selectivity of DPN. In fact, a single ERalpha point mutation (L384M) was largely sufficient to switch the DPN response of this ER to that of the ERbeta type, but residues in helix 3 are also important in achieving the full ERbeta selectivity of DPN. Using molecular modeling, we found an energetically favorable fit for the S-DPN enantiomer in ERbeta, in which the proximal phenol mimics the A ring of estradiol, and the nitrile engages in stabilizing interactions with residues in the ligand-binding pocket of ERbeta. Our findings highlight that a limited number of critical interactions of DPN with the ERbeta ligand-binding pocket underlie its ER subtype-selective character.
Targeting the Deregulated Spliceosome Core Machinery in Cancer Cells Triggers mTOR Blockade and Autophagy (2013)

The spliceosome is a large ribonucleoprotein complex that guides pre-mRNA splicing in eukaryotic cells. Here, we determine whether the spliceosome could constitute an attractive therapeutic target in cancer. Analysis of gene expression arrays from lung, breast, and ovarian cancers datasets revealed that several genes encoding components of the core spliceosome composed of a heteroheptameric Sm complex were overexpressed in malignant disease as compared with benign lesions and could also define a subset of highly aggressive breast cancers. siRNA-mediated depletion of SmE (SNRPE) or SmD1 (SNRPD1) led to a marked reduction of cell viability in breast, lung, and melanoma cancer cell lines, whereas it had little effect on the survival of the nonmalignant MCF-10A breast epithelial cells. SNRPE or SNRPD1 depletion did not lead to apoptotic cell death but autophagy, another form of cell death. Indeed, induction of autophagy was revealed by cytoplasmic accumulation of autophagic vacuoles and by an increase in both LC3 (MAP1LC3A) protein conversion and the amount of acidic autophagic vacuoles. Knockdown of SNRPE dramatically decreased mTOR mRNA and protein levels and was accompanied by a deregulation of the mTOR pathway, which, in part, explains the SNRPE-dependent induction of autophagy. These findings provide a rational to develop new therapeutic agents targeting spliceosome core components in oncology.
Ligand Synthesis and Metal Complex Formation of 1,2,3-Triaminopropane (1998)

A series of linear primary polyamines H2N–CH2–(CH–NH2)n–CH2–NH2 (1 ≤ n ≤ 3) was prepared from the corresponding polyalcohols. The polyamines were isolated as HCl adducts and the acidity constants in aqueous solution were determined. The crystal structure of the fully protonated tetraamine (n = 2) was elucidated by an X-ray diffraction study. Complex formation of the triamine (n = 1) with Ni2+, Cu2+, Zn2+, Cd2+ was re-investigated in aqueous solution. The pH-dependent formation of a variety of species MxLyHz was established by potentiometric titrations and was compared with previous reports. The crystal structure of the Cu complex [CuL2]Cl2 exhibited a chain structure with a five-coordinate CuII centre in which two amino groups of the triamine ligands are coordinated to one Cu centre, while the third amino group of one of the ligands is bonded to a neighbouring Cu atom. The compound shows weak antiferromagnetic coupling interactions between the CuII centres within the chain.
Structural Probing of a Protein Phosphatase 2A Network by Chemical Cross-Linking and Mass Spectrometry (2012)

The identification of proximate amino acids by chemical cross-linking and mass spectrometry (XL-MS) facilitates the structural analysis of homogeneous protein complexes. We gained distance restraints on a modular interaction network of protein complexes affinity-purified from human cells by applying an adapted XL-MS protocol. Systematic analysis of human protein phosphatase 2A (PP2A) complexes identified 176 interprotein and 570 intraprotein cross-links that link specific trimeric PP2A complexes to a multitude of adaptor proteins that control their cellular functions. Spatial restraints guided molecular modeling of the binding interface between immunoglobulin binding protein 1 (IGBP1) and PP2A and revealed the topology of TCP1 ring complex (TRiC) chaperonin interacting with the PP2A regulatory subunit 2ABG. This study establishes XL-MS as an integral part of hybrid structural biology approaches for the analysis of endogenous protein complexes.
Polyhydroxyalkanoates: biodegradable polymers with a range of applications (2007)

Abstract Increased and accelerated global economic activities over the past century have led to interlinked problems that require urgent attention. The current patterns of production and consumption have raised serious concerns. In this context, greater emphasis has been put on the concept of sustainable economic systems that rely on technologies based on and supporting renewable sources of energy and materials. Average UK households produce around 3.2 million tonnes of packaging waste annually whereas 150 million tonnes of packaging waste is generated annually by industries in the UK. Hence, the development of biologically derived biodegradable polymers is one important element of the new economic development. Key among the biodegradable biopolymers is a class known as polyhydroxyalkanoates. Polyhydroxyalkanoates (PHAs) are a family of polyhydroxyesters of 3‐, 4‐, 5‐ and 6‐hydroxyalkanoic acids, produced by a variety of bacterial species under nutrient‐limiting conditions with excess carbon. These water‐insoluble storage polymers are biodegradable, exhibit thermoplastic properties and can be produced from renewable carbon sources. Thus, there has been considerable interest in the commercial exploitation of these biodegradable polyesters. In this review various applications of polyhydroxyalkanoates are discussed, covering areas such as medicine, agriculture, tissue engineering, nanocomposites, polymer blends and chiral synthesis. Overall this review shows that polyhydroxyalkanoates are a promising class of new emerging biopolymers. Copyright © 2007 Society of Chemical Industry
Tripeptide Structure of Bursin, a Selective B-Cell-Differentiating Hormone of the Bursa of Fabricius (1986)

Differentiation of lymphoid precursor cells in a variety of species is induced by polypeptide hormones such as thymopoietin for T cells and bursin for B cells. In the present experiments, bursin isolated from the bursa of Fabricius of chicken was found to induce the phenotypic differentiation of mammalian and avian B precursor cells but not of T precursor cells in vitro. Similarly, bursin increased cyclic guanosine monophosphate in cells of the human B-cell line Daudi but not in cells of the human T-cell line CEM. These inducing properties of bursin are the reverse of the inducing properties of thymopoietin produced by the thymus and are appropriate to a physiological B-cell-inducing hormone. A tripeptide sequence (lysyl-histidyl-glycyl-amide) was determined for bursin and confirmed by synthesizing this proposed structure and demonstrating chemical identity of the natural and synthetic peptides. Similarity of biological action was indicated in induction assays by elevation of cyclic adenosine monophosphate and guanosine monophosphate in Daudi B cells but not in CEM T cells.
Coronary artery stent infection (2000)

This paper aimed to examine the literature for cases of coronary artery stent infection in order to provide comprehensive data to clinicians regarding its prevalence, clinical presentations, and possible treatments. Coronary artery stenting was initially reported in 1987. Stenting of the coronary arteries is now used in 40-60% of all interventional coronary artery procedures. The understanding of the pathophysiology of coronary artery disease is evolving. It has been suggested that atherosclerosis may be a complication of an infectious etiology. By using a stent to treat coronary artery disease, a foreign body is directly juxtaposed with an area of inflammation. The first reported case of an infected coronary artery stent was in 1993. Although this is an exceedingly rare event, the associated mortality is alarmingly high. Analysis of the literature reveals a total of four reported cases of coronary artery stent infection. Symptoms of stent infection present days to weeks after the initial coronary intervention. All four patients developed fevers and at least two patients developed postintervention angina. In patients who have had a coronary artery stented, the presence of angina and fevers should make the clinician suspicious for a stent-related infection. Two of the patients had infection with Pseudomonas aeruginosa, which seems to be an unusual organism for a catheter-related infection. Surgical removal of the infected stent and artery complex was performed on nearly all cases. Despite aggressive measures, the majority of patients died. Few data are available on the long-term risk for coronary artery stent infection. In a patient who has undergone coronary artery stent placement, the clinician must be very sensitive to fever, return of angina, and bacteremia. The complication rate at the present time does not warrant the use of prophylactic antibiotics prior to high-risk procedures (e.g., dental procedures). Furthermore, the low infection rate of coronary artery stents may be a result of the inflammatory nature of atherosclerosis, which may provide a protective benefit against bacterial infection of the stent.
COMBINATION OF BORANE-DIMETHYL SULFIDE COMPLEX WITH CATALYTIC SODIUM TETRAHYDROBORATE AS A SELECTIVE REDUCING AGENT FOR α-HYDROXY ESTERS. VERSATILE CHIRAL BUILDING BLOCK FROM (S)-(−)-MALIC ACID (1984)

Abstract Borane-dimethyl sulfide complex has proven to be an efficient and selective reducing agent in the presence of catalytic sodium tetrahydroborate for α-hydroxy esters as exemplified in the reduction of dimethyl (S)-(−)-malate, providing the versatile chiral building block of four-carbon backbone.
Feline herpesvirus (2007)

Feline herpesvirus (FHV-1; felid herpesvirus 1 (FeHV-1)) is an alphaherpesvirus of cats closely related to canine herpesvirus-1 and phocine herpesvirus-1. There is only one serotype of the virus and it is relatively homogenous genetically. FeHV-1 is an important cause of acute upper respiratory tract and ocular disease in cats. In addition, its role in more chronic ocular disease and skin lesions is increasingly being recognised. Epidemiologically, FeHV-1 behaves as a typical alphaherpesvirus whereby clinically recovered cats become latently infected carriers which undergo periodic episodes of virus reactivation, particularly after a stress. The primary site of latency is the trigeminal ganglion. Conventional inactivated and modified-live vaccines are available and protect reasonably well against disease but not infection, although viral shedding may be reduced. Genetically engineered vaccines have also been developed, both for FeHV-1 and as vector vaccines for other pathogens, but none is as yet marketed.
Intense Furosemide-Sensitive Potassium Accumulation in Astrocytes in the Presence of Pathologically High Extracellular Potassium Levels (1984)

An intense K+ accumulation in primary cultures of astrocytes, occurring when external K+ was increased from 5.4 to 54 mM, was investigated. This increase resulted in a doubling of the K+ content within 10 s. Thirty percent of the accumulation was inhibited by furosemide (2 mM). This drug had no effect on the unidirectional influx of K+ at 5.4 mM K+, but when the extracellular K+ concentration was increased, there appeared to be a furosemide-sensitive component of the influx. This component increased with increasing external K+ levels, reaching 44% of the total influx at 72 mM. These results show that astrocytes exhibit an intense furosemide-sensitive K+ accumulation which is activated by K+ levels resembling those occurring in the extracellular compartment during pathological events. Previous studies on a furosemide-sensitive Cl- pump in cultured astrocytes suggest that this accumulation might be via KCl cotransport, which in other systems is involved in volume control.
Experimental Carcinogenicity and Acute Toxicity Of Representative Epoxides (1963)

Abstract Carcinogenic and acute toxicity potential were assayed while more than 60 epoxy compounds were being studied for commercial utility. Range-finding toxicity data are presented for 60; lifetime mouse skin painting results are given for 28, and mouse sebaceous gland suppression results are listed for 26 of these compounds. None of the 11 monoepoxides produced tumors while 5 of the 17 diepoxides were tumorigenic during lifetime skin painting of mice. The median latent period for tumor production with the diepoxides was 15 to 23 months. No generalities about the toxic, irritative or carcinogenic hazards are justified by the presently known facts. Each compound must be individually studied to determine toxicity and carcinogenicity potential.
Intervention of Thymus and Activation-Regulated Chemokine Attenuates the Development of Allergic Airway Inflammation and Hyperresponsiveness in Mice (2001)

Thymus- and activation-regulated chemokine (TARC; CCL17) is a lymphocyte-directed CC chemokine that specifically chemoattracts CC chemokine receptor 4-positive (CCR4(+)) Th2 cells. To establish the pathophysiological roles of TARC in vivo, we investigated here whether an mAb against TARC could inhibit the induction of asthmatic reaction in mice elicited by OVA. TARC was constitutively expressed in the lung and was up-regulated in allergic inflammation. The specific Ab against TARC attenuated OVA-induced airway eosinophilia and diminished the degree of airway hyperresponsiveness with a concomitant decrease in Th2 cytokine levels. Our results for the first time indicate that TARC is a pivotal chemokine for the development of Th2-dominated experimental allergen-induced asthma with eosinophilia and AHR. This study also represents the first success in controlling Th2 cytokine production in vivo by targeting a chemokine.
Molecular cloning and sequence analysis of the crtB gene of Thermus thermophilus HB27, an extreme thermophile producing carotenoid pigments (1993)

We have cloned and sequenced a 1.5-kb chromosomal fragment of Thermus thermophilus which promoted the overproduction of carotenoids in T. thermophilus. An open reading frame (ORF-A) coding for a polypeptide with 289 amino acids was responsible for carotenoid overproduction. The putative ORF-A protein showed significant homology with the amino acid sequences of crtB gene products (phytoene syntheses) of other microorganisms. The clone containing the ORF-A on a multicopy plasmid produced about three times as much carotenoid as that produced by the host strain, suggesting that the crtB gene product is a rate-limiting enzyme for carotenoid biosynthesis in T. thermophilus.