gebhart/patrepeval huggingface dataset:
President's page (2014)

Abstract EDITOR'S SUMMARY As Association president, Harry Bruce attended a meeting of the Council of Scientific Society Presidents (CSSP) where, despite varied focus areas, the shared goals and challenges of participating research organizations became evident. These association leaders are concerned about member satisfaction and engagement and making the most of online technologies for member support. ASIS&amp;T's name change to reflect its international membership caught the attention of many. ASIS&amp;T continues service to the membership by gathering data on member attitudes to better understand the perceived value of membership. To promote engagement and conversation the Association is also pursuing a social media initiative and website overhaul. The CSSP meeting was a reminder of the central role of information science linking scientific disciplines and the support of the professional societies. In closing, Bruce notes the passing of Professor Eliza Dresang, colleague, scholar and professor at the University of Washington iSchool.
Recombinant immunotoxins specific for a mutant epidermal growth factor receptor: Targeting with a single chain antibody variable domain isolated by phage display (1996)

EGFRvIII is a mutant epidermal growth factor receptor found in glioblastoma, and in carcinoma of the breast, ovary, and lung. The mutant receptor has a deletion in its extracellular domain that results in the formation of a new, tumor-specific extracellular sequence. Mice were immunized with a synthetic peptide corresponding to this sequence and purified EGFRvIII. A single chain antibody variable domain (scFv) phage display library of 8 x 10(6) members was made from the spleen of one immunized mouse. A scFv specific for EGFRvIII was isolated from this library by panning with successively decreasing amounts of synthetic peptide. This was used to make an immunotoxin by fusing the scFv DNA sequence to sequences coding for domains II and III of Pseudomonas exotoxin A. Purified immunotoxin had a Kd of 22 nM for peptide and a Kd of 11 nM for cell-surface EGFRvIII. The immunotoxin was very cytotoxic to cells expressing EGFRvIII, with an IC50 of 1 ng/ml (16 pM) on mouse fibroblasts transfected with EGFRvIII and an IC50 of 7-10 ng/ml (110-160 pM) on transfected glioblastoma cells. There was no cytotoxic activity at 1000 ng/ml on the untransfected parent glioblastoma cell line. The immunotoxin was completely stable upon incubation at 37 degrees C for 24 h in human serum. The combination of good affinity, cytotoxicity and stability make this immunotoxin a candidate for further preclinical evaluation.
X-ray computed tomography (2006)

X-ray computed tomography (CT), introduced into clinical practice in 1972, was the first of the modern slice-imaging modalities. To reconstruct images mathematically from measured data and to display and to archive them in digital form was a novelty then and is commonplace today. CT has shown a steady upward trend with respect to technology, performance and clinical use independent of predictions and expert assessments which forecast in the 1980s that it would be completely replaced by magnetic resonance imaging. CT not only survived but exhibited a true renaissance due to the introduction of spiral scanning which meant the transition from slice-by-slice imaging to true volume imaging. Complemented by the introduction of array detector technology in the 1990s, CT today allows imaging of whole organs or the whole body in 5 to 20 s with sub-millimetre isotropic resolution. This review of CT will proceed in chronological order focussing on technology, image quality and clinical applications. In its final part it will also briefly allude to novel uses of CT such as dual-source CT, C-arm flat-panel-detector CT and micro-CT. At present CT possibly exhibits a higher innovation rate than ever before. In consequence the topical and most recent developments will receive the greatest attention.
Establishment and Characterization of a Human Primitive Neuroectodermal Tumor Cell Line from the Cerebral Hemisphere (1992)

The primitive neuroectodermal tumors (PNET) comprise a class of malignant nervous system neoplasms that afflict children. These tumors consist of cells that are morphologically identical to the primitive neuroepithelial cells normally seen in early stages of neural embryogenesis, supporting the notion that PNET result from a disturbance in the process of normal neuronal or glial differentiation. In the central nervous system, PNET occur most commonly in the cerebellum (medulloblastomas), but only occasionally in the cerebral hemispheres. We report here the establishment and characterization of a new human cell line (PFSK) derived from a PNET from the cerebral hemisphere of a child. The growth characteristics of PFSK cells were typical of an immortalized, transformed cell line. Cytogenetic and molecular genetic studies showed that three different sublines were present. In one of these sublines, sequences from chromosome 17 had been lost during establishment in culture. Immunocytochemical studies showed that PFSK cells expressed nestin, an intermediate filament protein normally expressed by neuroepithelial stem cells during neurulation. The PFSK cells did not express antigens typically found in terminally differentiated neurons or glia, indicating that this tumor cell line might represent neuroepithelial stem cells prior to commitment to a neuronal or glial lineage.
Ataxia–telangiectasia mutated kinase‐mediated upregulation of NKG2D ligands on leukemia cells by resveratrol results in enhanced natural killer cell susceptibility (2013)

The powerful activating receptor NKG2D is expressed by natural killer (NK) cells and promotes cytotoxic lysis of cancer cells expressing NKG2D ligands (NKG2D-Ls). We report the effective induction of NKG2D-Ls, achieved with the naturally occurring polyphenol resveratrol, in a broad range of leukemia cells. In this study, resveratrol upregulated the NKG2D-Ls MHC class I chain-related proteins MICA and MICB, and UL16-binding proteins ULBP1, ULBP2, and ULBP3 in most of the leukemia cells analyzed. Ligand upregulation induced by resveratrol was impaired by pharmacological and genetic disruption of ataxia-telangiectasia mutated kinase, the main regulator of NKG2D-L expression. Leukemia cells treated with resveratrol were more susceptible to killing by NK cells than untreated cells, and the enhanced cytotoxicity of NK cells was blocked by treatment of NK cells with anti-NKG2D mAbs. Interestingly, resveratrol consistently upregulated the NKG2D receptor expression and enhanced NKG2D-mediated functions in resting NK cells obtained from healthy individuals. Therefore, resveratrol has attractive immunotherapeutic potential.
Modification of GaN Schottky barrier interfaces probed by ballistic-electron-emission microscopy and spectroscopy (2000)

Ballistic-electron-emission microscopy (BEEM) and spectroscopy have been used to investigate the properties of Au/GaN interfaces. The effects of in situ and ex situ annealing on the starting GaN surface were examined, with the aim of increasing the surprisingly low value of interface electron transmission observed in previous BEEM measurements. BEEM imaging and spectroscopy have demonstrated that much higher, more uniform transmission across the Au/GaN interface can be achieved. However, while methods were identified that increase transmission by more than an order of magnitude, BEEM spectroscopy indicates that annealing can substantially alter the Schottky barrier height. These barrier height changes at moderate temperatures are attributed to vacancy diffusion.
Mechanism, Structure, and Inhibition of O-GlcNAc Processing Enzymes (2010)

The post-translational modification of nucleocytoplasmic proteins with O-linked 2-acetamido-2-deoxy-d-glucopyranose (O-GlcNAc) is a topic of considerable interest and attracts a great deal of research effort. O-GlcNAcylation is a dynamic process which can occur multiple times over the lifetime of a protein, sometimes in a reciprocal relationship with phosphorylation. Several hundred proteins, which are involved in a diverse range of cellular processes, have been identified as being modified with the monosaccharide. The control of the O-GlcNAc modification state on different protein targets appears to be important in the aetiology of a number of diseases, including type II diabetes, neurodegenerative diseases and cancer. Two enzymes are responsible for the addition and removal of the O-GlcNAc modification: uridine diphospho-N-acetylglucosamine:polypeptide beta-N-acetylglucosaminyltransferase (OGT) and O-GlcNAcase (OGA), respectively. Over the past decade the volume of information known about these two enzymes has increased significantly. In particular, mechanistic studies of OGA, in conjunction with structural studies of bacterial homologues of OGA have stimulated the design of inhibitors and offered a rationale for the binding of certain potent and selective inhibitors. Mechanistic information about OGT lags a little way behind OGA, but the recent deduction of the structure of an OGT bacterial homologue should now drive these studies forward.
Antibody vs. HIV in a clash of evolutionary titans (2005)

HIV has evolved many strategies to avoid neutralizing antibody responses, particularly to conserved regions on the external glycoprotein spikes of the virus. Nevertheless, a small number of antibodies have been evolved by the human immune system to recognize conserved parts of the glycoproteins, and therefore, have broadly neutralizing cross-strain activities. These antibodies constitute important tools in the quest to design immunogens that can elicit broadly neutralizing antibodies in humans and hence contribute to an effective HIV vaccine. Crystallographic analyses of the antibodies, in many cases in an antigen-complexed form, have revealed novel and, in some instances, remarkable structural adaptations to attain virus recognition. Antibodies, like HIV, can evolve relatively rapidly through mutation and selection. It seems that the structures of these broadly neutralizing antibodies bear witness to a heroic struggle between two titans of rapid evolution.
Functional Downregulation of P2X3Receptor Subunit in Rat Sensory Neurons Reveals a Significant Role in Chronic Neuropathic and Inflammatory Pain (2002)

The excitation of nociceptive sensory neurons by ATP released in injured tissue is believed to be mediated partly by P2X3 receptors. Although an analysis of P2X3 knock-out mice has revealed some deficits in nociceptive signaling, detailed analysis of the role of these receptors is hampered by the lack of potent specific pharmacological tools. Here we have used antisense oligonucleotides (ASOs) to downregulate P2X3 receptors to examine their role in models of chronic pain in the rat. ASOs and control missense oligonucleotides (180 microg/d) were administered intrathecally to naive rats for up to 7 d via a lumbar indwelling cannula attached to an osmotic minipump. Functional downregulation of the receptors was confirmed by alphabeta-methylene ATP injection into the hindpaw, which evoked significantly less mechanical hyperalgesia as early as 2 d after treatment with ASOs relative to controls. At this time point, P2X3 protein levels were significantly downregulated in lumbar L4 and L5 dorsal root ganglia. After 7 d of ASO treatment, P2X3 protein levels were reduced in the primary afferent terminals in the lumbar dorsal horn of the spinal cord. In models of neuropathic (partial sciatic ligation) and inflammatory (complete Freund's adjuvant) pain, inhibition of the development of mechanical hyperalgesia as well as significant reversal of established hyperalgesia were observed within 2 d of ASO treatment. The time course of the reversal of hyperalgesia is consistent with downregulation of P2X3 receptor protein and function. This study demonstrates the utility of ASO approaches for validating gene targets in in vivo pain models and provides evidence for a role of P2X3 receptors in the pathophysiology of chronic pain.
High-Throughput Metabolic Engineering: Advances in Small-Molecule Screening and Selection (2010)

Metabolic engineering for the overproduction of high-value small molecules is dependent upon techniques in directed evolution to improve production titers. The majority of small molecules targeted for overproduction are inconspicuous and cannot be readily obtained by screening. We provide a review on the development of high-throughput colorimetric, fluorescent, and growth-coupled screening techniques, enabling inconspicuous small-molecule detection. We first outline constraints on throughput imposed during the standard directed evolution workflow (library construction, transformation, and screening) and establish a screening and selection ladder on the basis of small-molecule assay throughput and sensitivity. An in-depth analysis of demonstrated screening and selection approaches for small-molecule detection is provided. Particular focus is placed on in vivo biosensor-based detection methods that reduce or eliminate in vitro assay manipulations and increase throughput. We conclude by providing our prospectus for the future, focusing on transcription factor-based detection systems as a natural microbial mode of small-molecule detection.
Text Chunking using Transformation-Based Learning (1995)

Eric Brill introduced transformation-based learning and showed that it can do part-of-speech tagging with fairly high accuracy. The same method can be applied at a higher level of textual interpretation for locating chunks in the tagged text, including non-recursive ``baseNP'' chunks. For this purpose, it is convenient to view chunking as a tagging problem by encoding the chunk structure in new tags attached to each word. In automatic tests using Treebank-derived data, this technique achieved recall and precision rates of roughly 92% for baseNP chunks and 88% for somewhat more complex chunks that partition the sentence. Some interesting adaptations to the transformation-based learning approach are also suggested by this application.
Dual-bed catalyst system for C–C coupling of biomass-derived oxygenated hydrocarbons to fuel-grade compounds (2010)

Mono-functional intermediates produced by catalytic conversion of sugars and polyols over Pt–Re/C catalysts (consisting of alcohols, ketones, carboxylic acids, and heterocyclic compounds) can be upgraded to fuel-grade compounds using two catalytic reactors operated in a cascade mode. The first reactor achieves C–C coupling of mono-functional intermediates using a dual-bed catalyst system, where the upstream catalyst bed (Ce1Zr1Ox) is employed to carry out ketonization of carboxylic acids, and the downstream catalyst bed (Pd/ZrO2) is used to achieve aldol condensation/hydrogenation of alcohols and ketones. This second bed is not significantly inhibited by CO2 and H2O produced during ketonization. The high molecular weight ketones produced by C–C coupling reactions in the dual-bed catalyst system are subsequently converted to alkanes by hydrodeoxygenation (i.e., dehydration/hydrogenation) over a Pt/SiO2–Al2O3 catalyst. Using the aforementioned approach, an aqueous feed containing 60 wt% sorbitol was converted to a liquid stream of alkanes, 53% of which consisted of C7+ alkanes with minimal branching, desirable for Diesel fuel.
Isolation and characterization of Bacillus subtilis genes involved in siderophore biosynthesis: relationship between B. subtilis sfpo and Escherichia coli entD genes (1993)

In response to iron deprivation, Bacillus subtilis secretes a catecholic siderophore, 2,3-dihydroxybenzoyl glycine, which is similar to the precursor of the Escherichia coli siderophore enterobactin. We isolated two sets of B. subtilis DNA sequences that complemented the mutations of several E. coli siderophore-deficient (ent) mutants with defective enterobactin biosynthesis enzymes. One set contained DNA sequences that complemented only an entD mutation. The second set contained DNA sequences that complemented various combinations of entB, entE, entC, and entA mutations. The two sets of DNA sequences did not appear to overlap. AB. subtilis mutant containing an insertion in the region of the entD homolog grew much more poorly in low-iron medium and with markedly different kinetics. These data indicate that (i) at least five of the siderophore biosynthesis genes of B. subtilis can function in E. coli, (ii) the genetic organization of these siderophore genes in B. subtilis is similar to that in E. coli, and (iii) the B. subtilis entD homolog is required for efficient growth in low-iron medium. The nucleotide sequence of the B. subtilis DNA contained in plasmid pENTA22, a clone expressing the B. subtilis entD homolog, revealed the presence of at least two genes. One gene was identified as sfpo, a previously reported gene involved in the production of surfactin in B. subtilis and which is highly homologous to the E. coli entD gene. We present evidence that the E. coli entD and B. subtilis sfpo genes are interchangeable and that their products are members of a new family of proteins which function in the secretion of peptide molecules.
Detection of dengue virus RNA by reverse transcription-polymerase chain reaction in the liver and lymphoid organs but not in the brain in fatal human infection. (1999)

Autopsy tissues from 18 children believed to have died of dengue hemorrhagic fever were tested for the presence of dengue virus RNA by reverse transcription-polymerase chain reaction (RT-PCR). Such RNA was found in 14 of 18 liver specimens, 13 of 18 spleen specimens and 7 of 16 mesenteric lymph node specimens. No dengue virus RNA was detected in 44 samples of brain tissue from 15 individuals, 1 or more of whose other tissues yielded such RNA. All tissues had been tested previously for dengue virus by mosquito inoculation. In those tests, virus was recovered from 5 of 18 liver and 2 of 18 spleen specimens. Thus, the RT-PCR is more sensitive than the most sensitive virus isolation technique for detecting dengue virus or its components in human tissue. Failure to isolate virus from most of spleen and all mesenteric lymph node specimens may indicate that those tissues contained primarily degraded virus undergoing inactivation.
Structure of the murine serum amyloid A gene family. Gene conversion. (1986)

Serum amyloid A (SAA) is an apolipoprotein produced by the liver in response to inflammation; the levels of SAA mRNA and SAA protein increase at least 500-fold within 24 h. We have obtained clones of all three genes and pseudogene that make up the murine SAA gene family. Two of the genes have 96% sequence homology over their entire length, including introns and flanking sequences 288 base pairs (bp) 5' and 443 bp 3' to the genes: an overall length of 3215 bp. The sharp boundaries between homologous and nonhomologous sequences and the absence of interspersed repeated sequences there suggest that conversion has occurred between these two genes. The homologous regions are bounded by short inverted repeats containing alternating purine and pyrimidine residues, as described for other gene conversion units. The third SAA gene has evolved separately, although all are closely linked on chromosome 7. Comparison of the upstream regions of the SAA genes with those of the rat fibrinogen genes, whose expression is also induced by inflammation, reveals sequences common to all six genes which are very improbable on a random basis.
Tuftelin mRNA is Expressed in a Human Ameloblastoma Tumor (1998)

RT-PCR, Southern blotting and DNA sequencing have established for the first time that tuftelin mRNA is expressed in human ameloblastoma tumor. The expression of amelogenin mRNA in ameloblastoma was also established, confirming earlier reports by Snead et al. These results corroborate, on a molecular level, the enamel organ epithelial origin of ameloblastoma. In view of the present results, it is interesting that previous studies have indicated that although ameloblastoma, a non-mineralized odontogenic tumor, transcribes amelogenin mRNA, amelogenin (and enamelin) proteins are not expressed in this tissue. However, in mineralizing odontogenic tumors, both these classes of proteins are expressed.
Identification and characterization of genes for a second anthranilate synthase in Pseudomonas aeruginosa: interchangeability of the two anthranilate synthases and evolutionary implications (1990)

Two anthranilate synthase gene pairs have been identified in Pseudomonas aeruginosa. They were cloned, sequenced, inactivated in vitro by insertion of an antibiotic resistance gene, and returned to P. aeruginosa, replacing the wild-type gene. One anthranilate synthase enzyme participates in tryptophan synthesis; its genes are designated trpE and trpG. The other anthranilate synthase enzyme, encoded by phnA and phnB, participates in the synthesis of pyocyanin, the characteristic phenazine pigment of the organism. trpE and trpG are independently transcribed; homologous genes have been cloned from Pseudomonas putida. The phenazine pathway genes phnA and phnB are cotranscribed. The cloned phnA phnB gene pair complements trpE and trpE(G) mutants of Escherichia coli. Homologous genes were not found in P. putida PPG1, a non-phenazine producer. Surprisingly, PhnA and PhnB are more closely related to E. coli TrpE and TrpG than to Pseudomonas TrpE and TrpG, whereas Pseudomonas TrpE and TrpG are more closely related to E. coli PabB and PabA than to E. coli TrpE and TrpG. We replaced the wild-type trpE on the P. aeruginosa chromosome with a mutant form having a considerable portion of its coding sequence deleted and replaced by a tetracycline resistance gene cassette. This resulted in tryptophan auxotrophy; however, spontaneous tryptophan-independent revertants appeared at a frequency of 10(-5) to 10(6). The anthranilate synthase of these revertants is not feedback inhibited by tryptophan, suggesting that it arises from PhnAB. phnA mutants retain a low level of pyocyanin production. Introduction of an inactivated trpE gene into a phnA mutant abolished residual pyocyanin production, suggesting that the trpE trpG gene products are capable of providing some anthranilate for pyocyanin synthesis.
Protein families and TRIBES in genome sequence space (2003)

Accurate detection of protein families allows assignment of protein function and the analysis of functional diversity in complete genomes. Recently, we presented a novel algorithm called TribeMCL for the detection of protein families that is both accurate and efficient. This method allows family analysis to be carried out on a very large scale. Using TribeMCL, we have generated a resource called TRIBES that contains protein family information, comprising annotations, protein sequence alignments and phylogenetic distributions describing 311 257 proteins from 83 completely sequenced genomes. The analysis of at least 60 934 detected protein families reveals that, with the essential families excluded, paralogy levels are similar between prokaryotes, irrespective of genome size. The number of essential families is estimated to be between 366 and 426. We also show that the currently known space of protein families is scale free and discuss the implications of this distribution. In addition, we show that smaller families are often formed by shorter proteins and discuss the reasons for this intriguing pattern. Finally, we analyse the functional diversity of protein families in entire genome sequences. The TRIBES protein family resource is accessible at http://www.ebi.ac.uk/research/cgg/tribes/.