gebhart/patrepeval huggingface dataset:
The Genetic and Biochemical Basis of Polyketide Metabolism in Microorganisms and its Role in Drug Discovery and Development (1991)

The possibilities for the design of new drug screening and development strategies directed to a specific objective on the basis of genetic engineering of microorganisms is discussed from two points of view. Firstly, results of work on genetic hybrids of Streptomyces species for the production of new metabolites such as mederrhodin (1) and aloespanoarin II (4) are described. Secondly, the enhanced production of known metabolites such as tetracenomycin A2 (11) and tetracenomycin C (9) by recombinant Streptomyces species is considered. Mechanistic aspects of polyketide metabolism are included.
Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN) (2018)

ClinicalTrials.gov: NCT01538381.
Biological Function of Fucosylation in Cancer Biology (2007)

Fucosylation is one of the most common modifications involving oligosaccharides on glycoproteins or glycolipids. Fucosylation comprises the attachment of a fucose residue to N-glycans, O-glycans and glycolipids. O-Fucosylation, which is a special type of fucosylation, is very important for Notch signalling. The regulatory mechanisms for fucosylation are complicated. Many kinds of fucosyltransferases, the GDP-fucose synthesis pathway and GDP-fucose transporter are involved in the regulation of fucosylation. Increased levels of fucosylation have been reported in a number of pathological conditions, including inflammation and cancer. Therefore, certain types of fucosylated glycoproteins such as AFP-L3 or several kinds of antibodies, which recognize fucosylated oligosaccharides such as sialyl Lewis a/x, have been used as tumour markers. Furthermore, fucosylation of glycoproteins regulates the biological functions of adhesion molecules and growth factor receptors. Changes in fucosylation could provide a novel strategy for cancer therapy. In this review, the biological significance of and regulatory pathway for fucosylation have been described.
Autophagic programmed cell death by selective catalase degradation (2006)

Autophagy plays a central role in regulating important cellular functions such as cell survival during starvation and control of infectious pathogens. Recently, it has been shown that autophagy can induce cells to die; however, the mechanism of the autophagic cell death program is unclear. We now show that caspase inhibition leading to cell death by means of autophagy involves reactive oxygen species (ROS) accumulation, membrane lipid oxidation, and loss of plasma membrane integrity. Inhibition of autophagy by chemical compounds or knocking down the expression of key autophagy proteins such as ATG7, ATG8, and receptor interacting protein (RIP) blocks ROS accumulation and cell death. The cause of abnormal ROS accumulation is the selective autophagic degradation of the major enzymatic ROS scavenger, catalase. Caspase inhibition directly induces catalase degradation and ROS accumulation, which can be blocked by autophagy inhibitors. These findings unveil a molecular mechanism for the role of autophagy in cell death and provide insight into the complex relationship between ROS and nonapoptotic programmed cell death.
The Mitochondrial p55 Accessory Subunit of Human DNA Polymerase γ Enhances DNA Binding, Promotes Processive DNA Synthesis, and Confers N-Ethylmaleimide Resistance (1999)

Human DNA polymerase gamma is composed of a 140-kDa catalytic subunit and a smaller accessory protein variously reported to be 43-54 kDa. Immunoblot analysis of the purified, heterodimeric native human polymerase gamma complex identified the accessory subunit as 55 kDa. We isolated the full-length cDNA encoding a 55-kDa polypeptide, expressed the cDNA in Escherichia coli and purified the 55-kDa protein to homogeneity. Recombinant Hp55 forms a high affinity, salt-stable complex with Hp140 during protein affinity chromatography. Immunoprecipitation, gel filtration, and sedimentation analyses revealed a 190-kDa complex indicative of a native heterodimer. Reconstitution of Hp140.Hp55 raises the salt optimum of Hp140, stimulates the polymerase and exonuclease activities, and increases the processivity of the enzyme by several 100-fold. Similar to Hp140, isolated Hp55 binds DNA with moderate strength and was a specificity for double-stranded primer-template DNA. However, Hp140.Hp55 has a surprisingly high affinity for DNA, and kinetic analyses indicate Hp55 enhances the affinity of Hp140 for primer termini by 2 orders of magnitude. Thus the enhanced DNA binding caused by Hp55 is the basis for the salt tolerance and high processivity characteristic of DNA polymerase gamma. Observation of native DNA polymerase gamma both as an Hp140 monomer and as a heterodimer with Hp55 supports the notion that the two forms act in mitochondrial DNA repair and replication. Additionally, association of Hp55 with Hp140 protects the polymerase from inhibition by N-ethylmaleimide.
Carbonic anhydrase inhibitors and their therapeutic potential (2000)

Carbonic anhydrases (CAs, EC 4.2.1.1) are wide-spread zinc enzymes, present in archaeo- and eubacteria, algae, green plants and animals. Within these organisms CAs are encoded by three distinct, evolutionarily unrelated gene families: the α-CA, the β-CA and the γ-CA families, respectively. These enzymes are very efficient catalysts for the reversible hydration of CO2 to bicarbonate; the α-CAs possess high versatility, being able to catalyse other hydrolytic processes. It is not known whether other reactions catalysed by CAs (than the hydration of CO2/dehydration of HCO-) may have physiological relevance in systems where these enzymes are present. CAs are inhibited primarily by two main classes of compounds: the metal complexing inorganic anions (e.g., cyanide, cyanate, thiocyanate, azide, hydrogensulphide etc.) and the unsubstituted sulphonamides possessing the general formula RSO2NH2 (R = aryl; hetaryl; perhaloalkyl). The first type of inhibitor was important for understanding in detail the catalytic and inhibitory mechanisms, whereas the second led to the development of several classes of pharmacological agents. Inhibitors of both types directly bind to the metal ion within the enzyme active site, either by substituting the zinc-bound H-, or adding to the co-ordination sphere, leading thus to pentaco-ordinated Zn(II). Sulphonamide CA inhibitors (CAIs) are useful as diuretics, or in the treatment and prevention of a variety of diseases such as glaucoma, epilepsy, congestive heart failure, mountain sickness, gastric and duodenal ulcers, neurological disorders and osteoporosis among others, as well as diagnostic tools. Their applications are due to the wide distribution of the different α-CA isozymes (14 are presently known) in higher vertebrates, where they play important physiological functions related to respiration and transport of CO2/HCO3 between metabolising tissues and the lungs, pH and CO2 homeostasis, electrolyte secretion in a variety of tissues/organs, and biosynthetic reactions, such as gluconeogenesis and ureagenesis, among others. CA activators have recently been described and their mechanism of action at molecular level elucidated. Such agents might be useful for developing therapies for the CA deficiency syndrome.
Switching viral latency to viral lysis: a novel therapeutic approach for Epstein-Barr virus-associated neoplasia. (1996)

We describe an EBV-driven lytic system (LySED) that can be used to specifically target therapy to EBV- containing tumors. This system takes advantage of the transactivating properties of EBNA-1, a latency protein expressed in all EBV-containing cells, to drive the expression of Zta, a gene sufficient for inducing the EBV lytic cycle. Thus, EBV provides both the target and the executor for mediating tumor-specific cell death, markedly increasing the specificity of the system. Transfection of EBV-positive cell lines with the LySED construct resulted in a switch to lytic cycle and subsequent cell death, even in the presence of an inhibitor of EBV thymidine kinase (acyclovir) without an increase in virion production. In contrast, growth of EBV-negative B-cell lines was not affected.
Self-forming nanoscale devices (2003)

Devices that have been beyond the reach of engineers can now be fabricated in new ways. The crucial factor has been the development of a technique by which extremely narrow rods, or nanowires, of a semiconductor can be formed. The bottom-up, self-assembly process enables accurate control of dimension, location, composition, and other properties. The materials are the same semiconductors, like Si and GaAs, that we have, for the last forty or so years, been shaping into devices and circuits. But this process has relied on top-down fabrication techniques. The top-down approach limits the dimensions of devices to what is technically achievable using lithography. This is the means by which patterns can be drawn, either in stone as the Vikings did when they carved messages into granite, or into Si as the electronics industry does today to build integrated circuits. Lithographic techniques can create device features as narrow as 130 nm and the industry sees the road ahead pretty well drawn up for line-widths down to ∼50 nm. This continued progress does not come without a price; the cost of new fabs is growing extremely fast, at a pace that may limit continued progress, simply because devices and circuits become too expensive to be economically viable.
In Vivo X-Ray Fluorescence of Bone Lead in the Study of Human Lead Metabolism: Serum Lead, Whole Blood Lead, Bone Lead, and Cumulative Exposure (1994)

Traditionally, clinical studies of lead's effect on health have relied on blood lead levels to indicate lead exposure. However, this is unsatisfactory because blood lead levels have a half-life of approximately 5 weeks (Rabinowitz et al. , 1976), and thus reflect recent exposure. Over 90% of the lead body burden is in bone, and it is thought to have a long residence time, thus implying that measurements of bone lead reflect cumulative exposure (Barry, 1975). So, measurements of bone lead are useful m understanding the long-term health effects of lead.
ORAL SIZE PERCEPTION OF PARTICLES: EFFECT OF SIZE, TYPE, VISCOSITY AND METHOD (2005)

ABSTRACT We investigated how different parameters affect oral size perception of small particles of SiO 2 and polystyrene particles of varying sizes (2–230 μm). Eighteen healthy subjects assessed the size of the particles by rubbing the sample between the tongue and the palate. The importance of size and type were studied by direct scaling and forced choice ranking and the results of the two methods were compared. To assess the relative importance of the tongue and the palate in oral size perception topical anesthesia was applied. The size and characteristics of particles are of importance for perception of particle size, where hard and irregular particles are perceived as larger than soft and round particles of similar size. The two methods of size perception, direct scaling and forced ranking produce very similar results on oral size perception. Topical anesthesia of either the tongue or the palate had no significant effect.
New methods for analysing DNA make genetics simpler (1982)

Conference Article| February 01 1982 New methods for analysing DNA make genetics simpler EDWIN M. SOUTHERN EDWIN M. SOUTHERN 1MRC Mammalian Genome Unit, Department of Zoology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, Scotland Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1982) 10 (1): 1–4. https://doi.org/10.1042/bst0100001 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation EDWIN M. SOUTHERN; New methods for analysing DNA make genetics simpler. Biochem Soc Trans 1 February 1982; 10 (1): 1–4. doi: https://doi.org/10.1042/bst0100001 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search nav search search input Search input auto suggest search filter All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1982 Biochemical Society1982 Article PDF first page preview Close Modal You do not currently have access to this content.
The ‘headache tree’ via umbellulone and TRPA1 activates the trigeminovascular system (2011)

The California bay laurel or Umbellularia californica (Hook. & Arn.) Nutt., is known as the 'headache tree' because the inhalation of its vapours can cause severe headache crises. However, the underlying mechanism of the headache precipitating properties of Umbellularia californica is unknown. The monoterpene ketone umbellulone, the major volatile constituent of the leaves of Umbellularia californica, has irritating properties, and is a reactive molecule that rapidly binds thiols. Thus, we hypothesized that umbellulone stimulates the transient receptor potential ankyrin 1 channel in a subset of peptidergic, nocioceptive neurons, activating the trigeminovascular system via this mechanism. Umbellulone, from µM to sub-mM concentrations, selectively stimulated transient receptor potential ankyrin 1-expressing HEK293 cells and rat trigeminal ganglion neurons, but not untransfected cells or neurons in the presence of the selective transient receptor potential ankyrin 1 antagonist, HC-030031. Umbellulone evoked a calcium-dependent release of calcitonin gene-related peptide from rodent trigeminal nerve terminals in the dura mater. In wild-type mice, umbellulone elicited excitation of trigeminal neurons and released calcitonin gene-related peptide from sensory nerve terminals. These two responses were absent in transient receptor potential ankyrin 1 deficient mice. Umbellulone caused nocioceptive behaviour after stimulation of trigeminal nerve terminals in wild-type, but not transient receptor potential ankyrin 1 deficient mice. Intranasal application or intravenous injection of umbellulone increased rat meningeal blood flow in a dose-dependent manner; a response selectively inhibited by systemic administration of transient receptor potential ankyrin 1 or calcitonin gene-related peptide receptor antagonists. These data indicate that umbellulone activates, through a transient receptor potential ankyrin 1-dependent mechanism, the trigeminovascular system, thereby causing nocioceptive responses and calcitonin gene-related peptide release. Pharmacokinetics of umbellulone, given by either intravenous or intranasal administration, suggest that transient receptor potential ankyrin 1 stimulation, which eventually results in meningeal vasodilatation, may be produced via two different pathways, depending on the dose. Transient receptor potential ankyrin 1 activation may either be caused directly by umbellulone, which diffuses from the nasal mucosa to perivascular nerve terminals in meningeal vessels, or by stimulation of trigeminal endings within the nasal mucosa and activation of reflex pathways. Transient receptor potential ankyrin 1 activation represents a plausible mechanism for Umbellularia californica-induced headache. Present data also strengthen the hypothesis that a series of agents, including chlorine, cigarette smoke, formaldehyde and others that are known to be headache triggers and recently identified as transient receptor potential ankyrin 1 agonists, utilize the activation of this channel on trigeminal nerves to produce head pain.
Continuous liquid interface production of 3D objects (2015)

Fast, continuous, 3D printing Although three-dimensional (3D) printing is now possible using relatively small and low-cost machines, it is still a fairly slow process. This is because 3D printers require a series of steps to cure, replenish, and reposition themselves for each additive cycle. Tumbleston et al. devised a process to effectively grow solid structures out of a liquid bath. The key to the process is the creation of an oxygen-containing “dead zone” between the solid part and the liquid precursor where solidification cannot occur. The precursor liquid is then renewed by the upward movement of the growing solid part. This approach made structures tens of centimeters in size that could contain features with a resolution below 100 µm. Science , this issue p. 1349
Thermal uniformity of 12-in silicon wafer during rapid thermal processing by inverse heat transfer method (2000)

Through an inverse heat transfer method, this paper presents a finite difference formulation for determination of incident heat fluxes to achieve thermal uniformity in a 12-in silicon wafer during rapid thermal processing. A one-dimensional thermal model and temperature-dependent thermal properties of a silicon wafer are adopted in this study. Our results show that the thermal nonuniformity can he reduced considerably if the incident heat fluxes on the wafer are dynamically controlled according to the inverse-method results. An effect of successive temperature measurement errors on thermal uniformity is discussed. The resulting maximum temperature differences are only 0.618, 0.776, 0.981, and 0.326/spl deg/C for 4-, 6-, 8- and 12-in wafers, respectively. The required edge heating compensation ratio for thermal uniformity in 4-, 6-, 8and 12-in silicon wafers is also evaluated.
Dystrophin-associated proteins are greatly reduced in skeletal muscle from mdx mice. (1991)

Dystrophin, the protein product of the human Duchenne muscular dystrophy gene, exists in skeletal muscle as a large oligomeric complex that contains four glycoproteins of 156, 50, 43, and 35 kD and a protein of 59 kD. Here, we investigated the relative abundance of each of the components of the dystrophin-glycoprotein complex in skeletal muscle from normal and mdx mice, which are missing dystrophin. Immunoblot analysis using total muscle membranes from control and mdx mice of ages 1 d to 30 wk found that all of the dystrophin-associated proteins were greatly reduced (80-90%) in mdx mouse skeletal muscle. The specificity of the loss of the dystrophin-associated glycoproteins was demonstrated by the finding that the major glycoprotein composition of skeletal muscle membranes from normal and mdx mice was identical. Furthermore, skeletal muscle membranes from the dystrophic dy/dy mouse exhibited a normal density of dystrophin and dystrophin-associated proteins. Immunofluorescence microscopy confirmed the results from the immunoblot analysis and showed a drastically reduced density of dystrophin-associated proteins in mdx muscle cryosections compared with normal and dy/dy mouse muscle. Therefore, our results demonstrate that all of the dystrophin-associated proteins are significantly reduced in mdx skeletal muscle and suggest that the loss of dystrophin-associated proteins is due to the absence of dystrophin and not due to secondary effects of muscle fiber degradation.
Human Metapneumovirus Detection in Patients with Severe Acute Respiratory Syndrome (2003)

We used a combination approach of conventional virus isolation and molecular techniques to detect human metapneumovirus (HMPV) in patients with severe acute respiratory syndrome (SARS). Of the 48 study patients, 25 (52.1%) were infected with HMPV; 6 of these 25 patients were also infected with coronavirus, and another 5 patients (10.4%) were infected with coronavirus alone. Using this combination approach, we found that human laryngeal carcinoma (HEp-2) cells were superior to rhesus monkey kidney (LLC-MK2) cells commonly used in previous studies for isolation of HMPV. These widely available HEp-2 cells should be included in conjunction with a molecular method for cell culture followup to detect HMPV, particularly in patients with SARS.
Nonreciprocal Exchanges of Information Between DNA Duplexes Coinjected into Mammalian Cell Nuclei (1985)

We have examined the mechanism of homologous recombination between plasmid molecules coinjected into cultured mammalian cells. Cell lines containing recombinant DNA molecules were obtained by selecting for the reconstruction of a functional Neor gene from two plasmids that bear different amber mutations in the Neor gene. In addition, these plasmids contain restriction-length polymorphisms within and near the Neor gene. These polymorphisms did not confer a selectable phenotype but were used to identify and categorize selected and nonselected recombinant DNA molecules. The striking conclusion from this analysis is that the predominant mechanism for the exchange of information between coinjected plasmid molecules over short distances (i.e., less than 1 kilobase) proceeds via nonreciprocal homologous recombination. The frequency of homologous recombination between coinjected plasmid molecules in cultured mammalian cells is extremely high, approaching unity. We demonstrate that this high frequency requires neither a high input of plasmid molecules per cell nor a localized high concentration of plasmid DNA within the nucleus. Thus, it appears that plasmid molecules, once introduced into the nucleus, have no difficulty seeking each other out and participating in homologous recombination even in the presence of a vast excess of host DNA sequences. Finally, we show that most of the homologous recombination events occur within a 1-h interval after the introduction of plasmid DNA into the cell nucleus.
Database analytics acceleration using FPGAs (2012)

Business growth and technology advancements have resulted in growing amounts of enterprise data. To gain valuable business insight and competitive advantage, businesses demand the capability of performing real-time analytics on such data. This, however, involves expensive query operations that are very time consuming on traditional CPUs. Additionally, in traditional database management systems (DBMS), the CPU resources are dedicated to mission-critical transactional workloads. Offloading expensive analytics query operations to a co-processor can allow efficient execution of analytics workloads in parallel with transactional workloads.
Iron-catalysed cross-coupling of halohydrins with aryl aluminium reagents: a protecting-group-free strategy attaining remarkable rate enhancement and diastereoinduction (2012)

Non-protected halohydrins are cross-coupled with aryl aluminium reagents to produce aryl alkanols in the presence of the iron-bisphosphine catalysts. Remarkable reaction rate enhancement and diastereoinduction are realized by the in situ generated aluminium alkoxides, offering a new method for the reactivity and selectivity control of the iron-catalysed cross-coupling reaction.
(tmp)2Zn⋅2 MgCl2⋅2 LiCl: A Chemoselective Base for the Directed Zincation of Sensitive Arenes and Heteroarenes (2007)

Positive zincing: A wide range of polyfunctional aryl and heteroaryl zinc reagents were efficiently prepared in THF by direct zincation using (tmp)2Zn⋅2 MgCl2⋅2 LiCl (1), an exceptionally active base. Ester and cyano functions as well as aldehydes and nitro groups are tolerated. dba=dibenzylideneacetone, tmp=2,2,6,6-tetramethylpiperidide.