gebhart/patrepeval huggingface dataset:
Purification and Characterization of Allophanate Hydrolase (AtzF) from Pseudomonas sp. Strain ADP (2005)

AtzF, allophanate hydrolase, is a recently discovered member of the amidase signature family that catalyzes the terminal reaction during metabolism of s-triazine ring compounds by bacteria. In the present study, the atzF gene from Pseudomonas sp. strain ADP was cloned and expressed as a His-tagged protein, and the protein was purified and characterized. AtzF had a deduced subunit molecular mass of 66,223, based on the gene sequence, and an estimated holoenzyme molecular mass of 260,000. The active protein did not contain detectable metals or organic cofactors. Purified AtzF hydrolyzed allophanate with a k(cat)/K(m) of 1.1 x 10(4) s(-1) M(-1), and 2 mol of ammonia was released per mol allophanate. The substrate range of AtzF was very narrow. Urea, biuret, hydroxyurea, methylcarbamate, and other structurally analogous compounds were not substrates for AtzF. Only malonamate, which strongly inhibited allophanate hydrolysis, was an alternative substrate, with a greatly reduced k(cat)/K(m) of 21 s(-1) M(-1). Data suggested that the AtzF catalytic cycle proceeds through a covalent substrate-enzyme intermediate. AtzF reacts with malonamate and hydroxylamine to generate malonohydroxamate, potentially derived from hydroxylamine capture of an enzyme-tethered acyl group. Three putative catalytically important residues, one lysine and two serines, were altered by site-directed mutagenesis, each with complete loss of enzyme activity. The identity of a putative serine nucleophile was probed using phenyl phosphorodiamidate that was shown to be a time-dependent inhibitor of AtzF. Inhibition was due to phosphoroamidation of Ser189 as shown by liquid chromatography/matrix-assisted laser desorption ionization mass spectrometry. The modified residue corresponds in sequence alignments to the nucleophilic serine previously identified in other members of the amidase signature family. Thus, AtzF affects the cleavage of three carbon-to-nitrogen bonds via a mechanism similar to that of enzymes catalyzing single-amide-bond cleavage reactions. AtzF orthologs appear to be widespread among bacteria.
Natural and synthetic cathelicidin peptides with anti-microbial and anti-biofilm activity against Staphylococcus aureus (2011)

The NA-CATH:ATRA1-ATRA1 peptide inhibits the production of biofilm by S. aureus in the presence of salt, exhibiting anti-biofilm activity at lower peptide concentrations than NA-CATH, LL-37 and D-LL-37; and demonstrates low cytoxicity against host cells but does not affect bacterial attachment. The peptides utilized in this anti-biofilm approach may provide templates for a new group of anti-microbials and potential future topical therapeutics for treating chronic wound infections.
Tissue Expression of Sialyl Tn Antigen in Gynecologic Tumors (1995)

These findings indicate different behaviors in the appearance of STN in tumor tissue and blood circulation, and also suggest the possible applicability of STN to immunohistochemical diagnosis of squamous-cell carcinomas.
A Comparison of Compressed and Uncompressed Transmission Modes (1991)

A Comparison of Compressed and Uncompressed Transmission Modes In this paper we address the problem of host to host communication. In particular, we discuss the issue of efficient and adaptive transmission mechanisms over possible physical links. We develop a tool for making decisions regarding the flow of control sequences and data from and to a host. The issue of compression is discussed in details, a decision box and an optimizing tool for finding the appropriate thresholds for a decision are developed. Physical parameters like the data rate, bandwidth of the communication medium, distance between the hosts, baud rate, levels of discretization, signal to noise ratio and propagation speed of the signal are taken into consideration while developing our decision system. Theoretical analysis is performed to develop mathematical models for the optimization algorithm. Simulation models are also developed for testing both the optimization and the decision tool box.
The Preparation of Succinamido Peptides1 (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Preparation of Succinamido Peptides1Casimir Berse, Lucien Piché, Louis Lachance, and Gaétan LaflammeCite this: J. Org. Chem. 1962, 27, 10, 3489–3495Publication Date (Print):October 1, 1962Publication History Published online1 May 2002Published inissue 1 October 1962https://doi.org/10.1021/jo01057a021RIGHTS & PERMISSIONSArticle Views113Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (787 KB) Get e-Alerts Get e-Alerts
Overexpression of Full-Length Human Glucocorticoid Receptor inSpodoptera frugiperdaCells Using the Baculovirus Expression Vector System (1990)

We have expressed a full-length human glucocorticoid receptor (hGR) in Spodoptera frugiperda (Sf9) cells using the baculovirus expression vector system (BEVS). The level of expression is approximately 100-fold greater than in CEM-C7 cells. Between 0.5-1.0 mg hGR can be generated per liter of Sf9 cell culture. The expressed hGR is capable of binding glucocorticoids with specificity and high affinity. Covalent labeling with 3H-dexamethasone mesylate and Western blot analysis using a polyclonal antibody indicate that the molecular weight of the expressed protein is approximately 94 k. The nonactivated receptor sediments as a 8-9S complex in sucrose gradients and can be heat activated to a 4S form. The activated receptor is capable of retarding the migration of a 23 base-pair DNA fragment containing the glucocorticoid response element from the tyrosine aminotransferase gene. These data indicate that the expressed GR displays characteristics identical to those of GR from mammalian cells. By scaling up this culture we can, for the first time, obtain enough purified full-length receptor for crystallographic and functional studies which could provide new insight into exactly how hGR works.
Serum ionised calcium and its relationship to parathyroid hormone after tibial fracture (1993)

The changes in serum adjusted ionised calcium and parathyroid hormone (PTH) were prospectively studied in 32 patients with isolated tibial fractures, treated conservatively. We measured serum albumin, adjusted total calcium, phosphate, pH, adjusted ionised calcium and PTH at intervals until the fractures had healed. The mean ionised calcium adjusted for pH fell within 24 hours of injury, and then rose to a peak at between four and six weeks. These changes cannot be explained by changes in serum pH or PTH. The restoration of normal ionised calcium levels after fracture coincided with the period when the callus was being calcified. Analysis of the changes in ionised calcium, phosphate and PTH suggests that PTH levels alter in response to changes in ionised calcium levels. PTH is highest immediately after fracture and lowest, often not recordable, at six weeks. The cause of the changes in the ionised calcium level has yet to be elucidated.
Fluorescence Detection in Hydrodynamically Focused Sample Streams: Reduction of Diffusional Defocusing by Association of Analyte with High-Molecular-Weight Species (1998)

Fluorescence methods have been developed for ultra-low-level detection down to the single molecule level. In ultra-low-level analysis, one successful approach to background reduction is to use hydrodynamically focused sample streams coupled with focused laser excitation to reduce detection volumes. However, low-molecular-weight analytes such as fluorescent dyes or fluorescently tagged nucleotides can diffuse radially out of the sample stream before detection, which can cause a significant reduction in the detection efficiency. Diffusional spreading can cause sample stream mixing in multiplexed analyses. Also, axial diffusion can cause misordering of analyte molecules in DNA sequencing at high analysis rates. A new method is presented for reducing diffusion effects by incorporating a high-molecular-weight species that has a strong binding affinity for the analyte (anchor) into the sheath fluid. As the analyte starts to diffuse out of the sample stream, it associates with the anchor and effectively assumes the anchor's molecular weight. This association reduces the analyte's mobility to that of the anchor. Consequently, both radial and axial diffusion are reduced. Further, in favorable cases, this adduct can have significantly increased luminescence yields and photostability compared to the free analyte. Examples of several dye polymer combinations involving electrostatic and other binding modes are given that show the very beneficial effects of this approach. Extension to other systems is described.
Integrative transformation of Candida albicans, using a cloned Candida ADE2 gene. (1986)

Candida albicans is a diploid dimorphic yeast with no known sexual cycle. The development of a DNA transformation system would greatly improve the prospects for genetic analyses of this yeast. Plasmids were isolated from a Candida Sau3A partial library which complements the ade2-1 and ade2-5 mutations in Saccharomyces cerevisiae. These plasmids contain a common region, part of which, when subcloned, produces ade2 complementation. Among the small number of auxotrophs previously isolated in C. albicans, red adenine-requiring mutants had been identified by several groups. In two of these strains, the cloned Candida DNA transformed the mutants to ADE+ at frequencies of 0.5 to 5 transformants per micrograms of DNA. In about 50% of the transformants, plasmid DNA sequences became stably integrated into the host genome and, in the several cases analyzed by Southern hybridization, the DNA was integrated at the site of the ADE2 gene in one of the chromosomal homologs.
Is T factor of the TNM staging system a predominant prognostic factor in pathologic stage I non-small-cell lung cancer ? A multivariate prognostic factor analysis of 151 patients. (1993)

We attempted to clarify whether the T factor of the TNM staging system should be viewed as a predominant prognostic factor in patients with pathologic stage I non-small-cell lung cancer when analyzed together with various histopathologic factors and deoxyribonucleic acid ploidy pattern of tumors. We studied 151 patients who were in this stage. Histopathologic factors used in the analysis were as follows: histologic cell type (squamous or nonsquamous cell carcinoma), grade of differentiation, and tumor invasion of visceral pleura and vessels. Deoxyribonucleic acid ploidy pattern of tumors was analyzed by flow cytometry, and the tumors were classified as diploid or aneuploid tumors. Significant prognostic factors (p < 0.05) that were demonstrated by univariate analysis of survival curves were as follows: (1) T1 versus T2; (2) well versus moderately or poorly differentiated tumor; (3) the absence versus presence of tumor exposed on pleura, (4) artery invasion, (5) lymphatic vessel invasion; and (6) diploid versus aneuploid tumor. Multivariate prognostic factor analysis showed the grade of differentiation and deoxyribonucleic acid ploidy pattern to be predominant prognostic factors. The T2 tumor group had significantly more cases with tumor invasion of lymphatic vessels that did the T1 tumor group and included 18 cases with tumor exposed on pleura. When these two factors were excluded from multivariate analysis, the T factor was marginally significant (p = 0.08). These observations suggest that the T factor is not necessarily a predominant prognostic factor in pathologic stage I non-small-cell lung cancer.
Low Complexity Partial SLM Technique for PAPR Reduction in OFDM Transmitters (2013)

In wireless OFDM systems, a major cause for signal degradation during transmission is high Peak to Average Power Ratio (PAPR). Selected mapping (SLM) is one efficient technique which reduces the peaks of a signal considerably. One drawback associated with this technique is its computational complexity. The computational complexity is directly related to the complexity of the IFFT block and increases as the number of sub-carriers increases. In this paper, an effort is done to reduce the computational complexity as well as to improve the PAPR performance of the conventional SLM technique. The proposed technique called Partial Selected Mapping in which the IFFT block is divided into smaller blocks and each block is used as a separate SLM block. Partial outputs of all sub-blocks are concatenated to form the final sequence. Simulation results show that the overall computational complexity of the proposed technique is lower than that of the conventional SLM technique with better PAPR performance. A reduction of around 3dB in PAPR performance at CCDF of 10 -3 is achieved.
Long-term dual-color tracking of genomic loci by modified sgRNAs of the CRISPR/Cas9 system (2016)

Visualization of chromosomal dynamics is important for understanding many fundamental intra-nuclear processes. Efficient and reliable live-cell multicolor labeling of chromosomal loci can realize this goal. However, the current methods are constrained mainly by insufficient labeling throughput, efficiency, flexibility as well as photostability. Here we have developed a new approach to realize dual-color chromosomal loci imaging based on a modified single-guide RNA (sgRNA) of the CRISPR/Cas9 system. The modification of sgRNA was optimized by structure-guided engineering of the original sgRNA, consisting of RNA aptamer insertions that bind fluorescent protein-tagged effectors. By labeling and tracking telomeres, centromeres and genomic loci, we demonstrate that the new approach is easy to implement and enables robust dual-color imaging of genomic elements. Importantly, our data also indicate that the fast exchange rate of RNA aptamer binding effectors makes our sgRNA-based labeling method much more tolerant to photobleaching than the Cas9-based labeling method. This is crucial for continuous, long-term tracking of chromosomal dynamics. Lastly, as our method is complementary to other live-cell genomic labeling systems, it is therefore possible to combine them into a plentiful palette for the study of native chromatin organization and genome ultrastructure dynamics in living cells.
SCIDOT-42. FT-2102 – A POTENT AND SELECTIVE BRAIN PENETRANT INHIBITOR OF MUTANT ISOCITRATE DEHYDROGENASE (2019)

Abstract BACKGROUND Iocitrate dehydrogenase mutations (mIDH1) are present in &gt;70% of patients with Grade II/III gliomas resulting in production and accumulation of (R)-2-hydroxyglutarate (2-HG) causing DNA hypermethylation and promoting tumorigenesis. This abstract summarizes the structure-based design of FT-2102, a potent and selective inhibitor of mutated IDH1-R132 with brain distribution (Kpuu) that is in context of minimal effective concentrations required in brain to modulate 2-HG. METHODS The crystal structure of mutated IDH1 in complex with FT-2102 and NADPH cofactor (2.1A resolution) was determined via sitting-drop vapour-diffusion set-ups. HCT116/IDH1 R132H were implanted in Balb/c nude mice and FT-2102 was administered orally twice daily. FT-2102 and 2-HG levels in plasma and xenografts were determined by LC/MS. In silico and in vitro models were used to determine the extent of brain distribution and ex-vivo rat data was generated to validate the projected distribution into brain tissue (Kpuu). RESULTS In tumor Xenograft (HCT116/IDH1-R132H), FT-2102 inhibits tumor 2-HG production with an IC50 of 24nM which is consistent with its in vitro IC50 of 18nM. FT-2102 unbound plasma concentrations of 256nM in xenografted mice were found to achieve 90% reduction of 2-HG in tumor. Rat data showed that FT-2102 partitions into brain with a Kpuu of 0.45. Based on these data, the concentration of FT-2102 in brain to significantly reduce 2HG is predicted to be 115nM. Recent publications (Natsume, et al, ASCO19) propose 90% reduction of 2-HG (90%) is associated with tumor reduction in the brain. CONCLUSION The structure-based design of FT-2102 has facilitated CNS penetration in animal models and is undergoing evaluation in ongoing clinical trials including patients with CNS based IDH1m tumors (NCT: 03684811).
Developing nucleic acid-based electrical detection systems (2006)

Development of nucleic acid-based detection systems is the main focus of many research groups and high technology companies. The enormous work done in this field is particularly due to the broad versatility and variety of these sensing devices. From optical to electrical systems, from label-dependent to label-free approaches, from single to multi-analyte and array formats, this wide range of possibilities makes the research field very diversified and competitive. New challenges and requirements for an ideal detector suitable for nucleic acid analysis include high sensitivity and high specificity protocol that can be completed in a relatively short time offering at the same time low detection limit. Moreover, systems that can be miniaturized and automated present a significant advantage over conventional technology, especially if detection is needed in the field. Electrical system technology for nucleic acid-based detection is an enabling mode for making miniaturized to micro- and nanometer scale bio-monitoring devices via the fusion of modern micro- and nanofabrication technology and molecular biotechnology. The electrical biosensors that rely on the conversion of the Watson-Crick base-pair recognition event into a useful electrical signal are advancing rapidly, and recently are receiving much attention as a valuable tool for microbial pathogen detection. Pathogens may pose a serious threat to humans, animal and plants, thus their detection and analysis is a significant element of public health. Although different conventional methods for detection of pathogenic microorganisms and their toxins exist and are currently being applied, improvements of molecular-based detection methodologies have changed these traditional detection techniques and introduced a new era of rapid, miniaturized and automated electrical chip detection technologies into pathogen identification sector. In this review some developments and current directions in nucleic acid-based electrical detection are discussed.
A Light Water Excess Heat Reaction Suggests That “Cold Fusion” May Be “Alkali-Hydrogen Fusion” (1992)

AbstractMills and Kneizys presented data in support of a light water “excess heat” reaction obtained with an electrolytic cell highly reminiscent of the Fleischmann-Pons “cold fusion” cell. The claim of Mills and Kneizys that their excess heat reaction can be explained on the basis of a novel chemistry, which supposedly also explains cold fusion, is rejected in favor of their reaction being, instead, a light water cold fusion reaction. If it is the first known light water cold fusion reaction to exhibit excess heat, it may serve as a prototype to expand our understanding of cold fusion. From this new hypothetical vantage point, a number of potential nuclear reactions are deduced, including those common to past cold fusion studies.This broader pattern of nuclear reactions is typically seen to involve a fusion of the nuclides of the alkali atoms with the simplest of the alkali-type nuclides, namely, protons, deuterons, and tritons. Thus, the term “alkali-hydrogen fusion” seems appropriate for this new type of reaction with three subclasses: alkali-hydrogen fusion, alkali-deuterium fusion, and alkali-tritium fusion. A significant part of the difference between alkali-hydrogen fusion and thermonuclear fusion is hypothesized to involve an effect that is essentially the opposite of the well-known Mössbauer effect. Transfer of energy to the lattice is shown to be consistent with the uncertainty principle and special relativity. The implications of alkali-hydrogen fusion for theoretical models for cold fusion are considered. Boson properties are suggested to be unimportant for alkali-hydrogen fusion, which apparently rules out the prospect that a Bose-Einstein condensation could be involved in cold fusion.A new three-dimensional transmission resonance model (TRM) is sketched that avoids Jände’s criticism of the one-dimensional TRM. When the new TRM is coupled with the alkali-hydrogen fusion hypothesis for cold fusion, it suggests a solution for the surface, or near-surface, excess heat effect for cold fusion in the form of a reaction between 6Li and a deuteron to produce 4He, or between two deuterons to produce predominantly 4He. A lattice effect essentially opposite to an “umklapp” process suggests that energy should be given to the lattice in the reaction.Finally, preliminary experimental evidence in support of the hypothesis o f a light water nuclear reaction and alkali-hydrogen fusion is reported. Excess heat has been detected with light water-based electrolytes for the separate cases of K2CO3, Na2CO3, Rb2CO3, and RbOH. Preliminary evidence for a correlation between the amount of elemental strontium produced in the case of Rb2CO3 as the electrolyte, or of elemental calcium produced in the case of K2CO3 as the electrolyte, and the total excess heats produced in the respective cells has been mixed. Evidence is presented that appears to strongly implicate the transmission resonance phenomenon of the new TRM.
Clinical Applications of Recent Molecular Advances in Urologic Malignancies (2013)

As our understanding of the molecular events leading to the development and progression of genitourologic malignancies, new markers of detection, prognostication, and therapy prediction can be exploited in the management of these prevalent tumors. The current review discusses the recent advances in prostate, bladder, renal, and testicular neoplasms that are pertinent to the anatomic pathologist.
Synthesis and Characterization of a Uranium(III) Complex Containing a Redox-Active 2,2′-Bipyridine Ligand (2010)

Hydrotris(3,5-dimethylpyrazolyl)borate uranium(III) diiodide derivatives have been prepared as an entry into low-valent uranium chemistry with these ligands. The bis(tetrahydrofuran) adduct, Tp*UI(2)(THF)(2) (1) (Tp* = hydrotris(3,5-dimethylpyrazolyl)borate), was synthesized by addition of sodium hydrotris(3,5-dimethylpyrazolyl)borate (NaTp*) to an equivalent of UI(3)(THF)(4). Addition of 2,2'-bipyridine (2,2'-bpy) to 1 displaced the THF molecules producing Tp*UI(2)(2,2'-bpy) (2). Both derivatives were characterized by (1)H NMR and IR spectroscopies, magnetic measurements, and X-ray crystallography. Reduction of both species was attempted with two equivalents of potassium graphite. The reduction of 1 did not result in a clean product, but rather decomposition and ligand redistribution. However, compound 2 was reduced to form Tp*(2)U(2,2'-bpy), 3, which is composed of a uranium(III) ion with a radical monoanionic bipyridine ligand. This was confirmed by X-ray crystallography, which revealed distortions in the bond lengths of the bipyridine consistent with reduction. Further support was obtained by (1)H NMR spectroscopy, which showed resonances shifted far upfield, consistent with radical character on the 2,2'-bipyridine ligand. Future studies will explore the reactivity of this compound as well as the consequences for redox-activity in the bipyridine ligand.