gebhart/patrepeval huggingface dataset:
Selective Platination of Biologically Relevant Polyamines. Linear Coordinating Spermidine and Spermine as Amplifying Linkers in Dinuclear Platinum Complexes (1997)

A new approach to the synthesis of novel bifunctional dinuclear platinum complexes with linear coordinating spermidine and spermine is reported. The synthetic pathway involves first the three-step selective protection of the polyamines, giving bis(trifluoroacetyl)polyamines (1, 4), (tert-butoxycarbonyl)bis(trifluoroacetyl)polyamines (2, 5), and (tert-butoxycarbonyl)polyamines (3, 6), respectively. The platination at desired sites with activated species of cis- or trans-[PtCl2(NH3)2] (CDDP or TDDP, respectively) produces the BOC-protected dinuclear species [{cis- or trans-PtCl(NH3)2}2(μ-L)]X (7, L = BOC-spermidine, X = (NO3)0.75Cl1.25; 9, L = (BOC)2-spermine, X = Cl2; cis spermine species not isolated). Through final deprotection, three different complexes were obtained and further investigated: [{trans-PtCl(NH3)2}2{μ-spermidine-N1,N8}]Cl3 (8), [{trans-PtCl(NH3)2}2{μ-spermine-N1,N12}]Cl4 (10), and [{cis-PtCl(NH3)2}2{μ-spermine-N1,N12}]Cl4 (11). One- and two-dimensional NMR solution studies provided evidence that 11, at physiological pH, forms an inert bis((tetraamine)platinum) species in which each Pt is chelated by a central and a terminal amino group. In contrast, complexes 8 and 10 retain their reactivity, showing only reversible formation of hydroxo bridges. The comparison of in vitro cytotoxicity data for 8, 10, and 11 with data for previously described bifunctional dinuclear complexes shows the enhanced activity particularly of complex 8 in the CDDP-resistant L1210 cell line. The binding of 8 and 10 to poly(dG-dC)·poly(dG-dC) is further increased and also reflected by B → Z conformational changes at lower doses.
Induction of the differentiation and apoptosis of tumor cells in vivo with efficiency and selectivity. (2004)

Hedgehog/smoothened signaling is active in a variety of tumors and is also involved in the maintenance of normal stem cells in vivo. We evaluated the possibility of preferential affection of tumor versus normal cells following inhibition of this signaling. We applied a cream preparation of cyclopamine (an inhibitor of the hedgehog/smoothened signaling) onto skin tumors in patients who were scheduled for the excision of these tumors (four basal cell carcinomas and a trichoepithelioma in four unrelated patients). All of the cyclopamine-treated tumors regressed rapidly. Histological and immunohistochemical analyses showed inhibition of the proliferation and highly efficient induction of the differentiation and apoptosis of tumor cells by a non-genotoxic mechanism. No adverse effects were noted and normal skin tissue and putative stem cells that were exposed to cyclopamine together with tumors were well preserved under the conditions we describe. Our findings show selective and highly efficient induction of the differentiation and apoptosis of tumor cells in vivo by transient inhibition of the hedgehog/ smoothened signaling and provide a rational cancer therapy.
Burkholdines from Burkholderia ambifaria: Antifungal Agents and Possible Virulence Factors (2012)

Burkholdines are cyclic lipopeptides with unusual antifungal potency, making them promising leads as a new class of antifungal agents. However, a recent report using knockout mutagenesis indicates that these and related compounds, such as occidiofungins, xylocandins, and cepacidines, may also be synonymous with the long-known hemolytic virulence factors found in diverse Burkholderia isolates. Because of their possible roles in causing Burkholderia infections or curing fungal infections, it is important to fully define their structures and biological activities using pure compounds. Here, we report the structures of three further burkholdines, Bk-1119, Bk-1213, and Bk-1215, which were elucidated using spectroscopic methods. The absolute configuration of this compound class was determined for the first time using a combination of spectroscopy and chemical degradation techniques. Antifungal and hemolytic activities were assessed for five pure burkholdines, representative of the structural diversity of this lipopeptide class. All of the burkholdines were potent antifungal and hemolytic agents, validating their probable role in virulence. However, one of the burkholdines (Bk-1119) exhibited a >30-fold selectivity for fungi versus sheep erythrocytes and was more than 25-fold more potent than amphotericin against some fungal strains. Therefore, burkholdines have potential to selectively target fungal infections.
Enzyme-Mediated Site-Specific Antibody−Protein Modification Using a ZZ Domain as a Linker (2010)

A ZZ domain (ZZ) and alkaline phosphatase (AP), luciferase (Luc), or glucose oxidase (GOD) were conjugated using Sortase A (SrtA) from Staphylococcus aureus. The specific peptidyl linker for SrtA was genetically fused to the C-terminus of ZZ, and the other linker was fused to the N-terminus of AP, Luc, or GOD, respectively. The resultant proteins were obtained separately by bacterial expression. The recombinant peptide-tagged ZZ and AP, Luc, or GOD were site-specifically conjugated by SrtA through the extra peptidyl linkers in vitro. The SrtA reaction had little influence on either the antibody-binding activity of the ZZ moiety or the enzymatic activity of AP, Luc, or GOD moieties of the conjugates. Additionally, antibody-ZZ-proteins were yielded easily by mixing antibody with ZZ-AP, ZZ-Luc, or ZZ-GOD, allowing their use in an enzyme-linked immunosorbent assay. These results suggest that the enzymatic approach with SrtA facilitates the construction of ZZ-proteins. Furthermore, mixing antibody and ZZ-proteins produces a wide variety of antibody-ZZ-proteins.
Functionalized Poly(ethylene glycol)-Grafted Polysiloxane Monolayers for Control of Protein Binding (2002)

Two new grafted polysiloxane polymers, a copolysiloxane and a terpolysiloxane, have been synthesized. Both polysiloxane backbones are grafted with dialkyl disulfide chains and 600 MW methoxy-terminated poly(ethylene glycol) (PEG) chains, while the terpolysiloxane also has 3400 MW PEG side chains terminated with N-hydroxysuccinimide (NHS) reactive ester groups. The two polymers spontaneously form monolayers on gold surfaces with estimated thicknesses of 23 and 31 Å, respectively. Combined analysis with angle-dependent X-ray photoelectron spectroscopy and static time-of-flight secondary ion mass spectrometry showed that most grafted dialkyl disulfide side chains were bound to the gold surface, forming multiple molecular linkages at the monolayer/gold interface. The PEG-grafted chains were concentrated in the outermost exposed region of the monolayers. Protein adsorption on the two immobilized polymer monolayers was examined with surface plasmon resonance (SPR). The copolymer-covered surface resisted protein adsorption from buffer, while the terpolymer monolayer bound significant amounts of protein. The NHS headgroup in the terpolymer was the primary site for protein binding. These two polymers have potential applications for SPR biosensor surface modification as protein-resistant and protein-immobilizing surfaces, respectively.
Temperature-strain discrimination using a wavelength-division-multiplexed chirped in-fibre-Bragg-grating/extrinsic Fabry-Perot sensor system (2003)

In this letter, we present a novel sensor approach allowing fast measurement of temperature. It consists of a chirped fibre Bragg grating (CFBG) and an extrinsic Fabry-Perot interferometric sensor (EFPI) in series. Both EFPI and CFBG are well integrated to provide local strain and temperature information respectively, using wavelength-division-multiplexed (WDM) technique. As the wavelength-shift of the CFBG is detected via intensity variation, the speed for temperature measurement can be very high (<0.1 ms). Also, there is little cross-talk between the CFBG and the EFPI due to the introduction of WDM.
Novel Cerebral Lesions in the Eker Rat Model of Tuberous Sclerosis: Cortical Tuber and Anaplastic Ganglioglioma (2000)

The Eker rat is a model for human tuberous sclerosis (TSC) caused by a mutation in the Tsc2 gene. We describe here histological and immunohistochemical findings of the brain lesions in Eker rats, with emphasis on 2 novel lesions found in this study: a cortical tuber and an anaplastic ganglioglioma. The rat cortical tuber resembled those of humans, and further confirmed the value of this animal model as a tool for investigating the molecular pathology of tuberous sclerosis. On the other hand, the rat anaplastic ganglioglioma had features of a malignant neoplasm that are absent from human subependymal giant cell astrocytomas.
The singular value decomposition: Its computation and some applications (1980)

We provide a tutorial introduction to certain numerical computations both in linear algebra and linear systems in the context of bounded arithmetic. The essential characteristics of bounded arithmetic are discussed in an introductory section followed by a review of the fundamental concepts of numerical stability and conditioning. The singular value decomposition (SVD) is then presented along with some related comments on the numerical determination of rank. A variety of applications of the SVD in linear algebra and linear systems is then outlined. A final section discusses some details of the implementation of the SVD on a digital computer. An Appendix is provided which contains a number of useful illustrative example.
Modulation by applied electric fields of Purkinje and stellate cell activity in the isolated turtle cerebellum. (1986)

Quasi steady-state electric fields were applied across the isolated turtle cerebellum to study the relationship between applied field, neuronal morphology and the modulation of the neuronal spike firing pattern. Spiking elements were identified electrophysiologically using extracellular recording methods and by subsequent horseradish peroxidase injection, which revealed their dendritic morphology and orientation. The electric field was precisely defined by measuring the voltage gradients induced in the cerebellum by 40 s constant-current pulses. The field was constant in the vertical (dorso-ventral) axis and zero in the horizontal plane, in agreement with theory. Neurones were modulated by applying a sinusoidal field at frequencies between 0.05 and 1.0 Hz. Modulated cells exhibited an increase in firing frequency and fell into one of four classes, depending on the direction of the field that produced the modulation. Thus neurones were excited by: ventricle-directed fields (V modulation), pia-directed fields (P modulation), both of the above (V/P modulation) or showed no consistent modulation (non-modulation). Most Purkinje somata and primary dendrites (nineteen out of twenty-eight) and most Purkinje dendrites (eighteen out of thirty), were V modulated with maximum rate proportional to the peak field intensity. The dendrites of these cells were consistently oriented toward the pia. Among the stellate cells, the lower molecular layer stellates, with dendrites extending predominantly towards the pia, were mostly (nineteen out of thirty-two) V modulated. The mid-molecular layer stellates, which showed much variability in dendritic orientation, were distributed among all four of the modulation classes. The upper molecular layer stellates, with a mostly horizontal dendritic alignment, were mainly (nine out of sixteen) non-modulated. All groups of spiking elements showed a correlation between patterns of modulation by applied fields and dendritic orientation, which suggests the degree of differential polarization of the extended cable elements of the neurone by the applied field as the basic mechanism for field-induced excitation or inhibition. The threshold for modulation among all neurones was 15-20 mV/mm, which is similar to the fields that modulate other nervous tissues. This suggests that many neurones can be modulated by fields of the order of 10-20 mV/mm.
Conductive diamond tips with sub‐nanometer electrical resolution for characterization of nanoelectronics device structures (2009)

Abstract Over the past decade, boron‐doped diamond tips have become the ultimate choice for electrically characterizing microelectronics devices using scanning probe methods such as scanning spreading resistance microscopy (SSRM). Although nanometer‐scale electrical resolution has been demonstrated, the development of a reliable probe process remained a challenge. Therefore, we did develop in this work solid diamond tips with sub‐nanometer electrical resolution and integrated them into metal cantilevers using a peel‐off approach. It is shown that the ultra‐high tip resolution is achieved by diamond nanocrystals protruding from the apex of the diamond pyramid. The yield for sub‐nanometer probes is 20–30% in air and 40–60% in vacuum. This paper describes the fabrication scheme, discusses probe characterization, and shows SSRM measurements obtained with these probes. Our probes are routinely used for SSRM measurements and current efforts are focusing on increasing the yield for sub‐nanometer tips further.
Conformation and Optical Rotation of Restricted Biphenyls. Configurational Correlation of Biaryls by Optical Displacement. The Absolute Configuration of Restricted 1,1'-Binaphthyls1 (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformation and Optical Rotation of Restricted Biphenyls. Configurational Correlation of Biaryls by Optical Displacement. The Absolute Configuration of Restricted 1,1'-Binaphthyls1Donald D. Fitts, Maurice Siegel, and Kurt MislowCite this: J. Am. Chem. Soc. 1958, 80, 2, 480–486Publication Date (Print):January 1, 1958Publication History Published online1 May 2002Published inissue 1 January 1958https://pubs.acs.org/doi/10.1021/ja01535a057https://doi.org/10.1021/ja01535a057research-articleACS PublicationsRequest reuse permissionsArticle Views345Altmetric-Citations36LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Long distance electron transfer (1988)

Quantum mechanical models to treat long distance electron transfer are being developed. The model is based on the theory of R.A. Marcus. Our contribution is in the calculation of the electron coupling factor k. Estimations of the latter number, as well as the bond and solvent relaxation energies, λi and λo, respectively, are necessary to be able to calculate the rate constant for a reaction of the conductivity in an electric field. k may be approximately calculated from orbital energy differences at avoided crossings between orbitals localized in different parts of the system. A novel spectroscopic NDO method is suggested in which one may include any atom of the periodic table. Another problem discussed is the inclusion of electronic relaxation effects of the solvent or protein in the calculation. Applications are made to systems where metal ions are connected by organic bridges of different kinds such as dipyridine with coplanar and perpendicular pyridyl groups. As expected the electronic factor depends strongly on the conformation of the bridge. A strong conformational dependence is also obtained for a saturated bridge of the type NH2 · (CH2)n · NH2. In another study we use an α helix as a bridge between two metal ions. If one glycine in this α-helix is substituted by phenylalanine the electronic factor increases by factors of 1.5–10. It is suggested, however, that larger enhancement factors are possible if an aromatic group is positioned in a favorable way. The CNDO/S method is used to study the charge separation process in a bichromophoric molecule and in the reaction center (RC) of Rhodopseudomonas viridis. In those cases where the electronic coupling is large enough for the charge transfer states to be seen in the spectrum, the calculated results agree well with the experimental ones, but suggest a novel assignment. The CNDO/S results verify that electron transfer is possible through saturated spacers. In the special pair of RC the S1 state is calculated at approximately the correct position. Like the ground state, it has a delocalized character.
Improved Method for Fluorescence Labeling of Sugar Chains with Sialic Acid Residues (1990)

Journal Article Improved Method for Fluorescence Labeling of Sugar Chains with Sialic Acid Residues Get access Akihiro Kondo, Akihiro Kondo Department of Chemistry, Osaka University College of Science, Toyonaka, Osaka 560, Japan Present address: Biotechnology Research Laboratories, Takara Shuzo Co., Ltd., Otsu, Shiga 520-21, Japan Search for other works by this author on: Oxford Academic Google Scholar Jun Suzuki, Jun Suzuki Department of Chemistry, Osaka University College of Science, Toyonaka, Osaka 560, Japan Present address: Biotechnology Research Laboratories, Takara Shuzo Co., Ltd., Otsu, Shiga 520-21, Japan Search for other works by this author on: Oxford Academic Google Scholar Nahoki Kuraya, Nahoki Kuraya Department of Chemistry, Osaka University College of Science, Toyonaka, Osaka 560, Japan Search for other works by this author on: Oxford Academic Google Scholar Sumihiro Hase, Sumihiro Hase Department of Chemistry, Osaka University College of Science, Toyonaka, Osaka 560, Japan To whom correspondence should be addressed. Search for other works by this author on: Oxford Academic Google Scholar Ikunoshin Kato, Ikunoshin Kato Biotechnology Research Laboratories, Takara Shuzo Co., Ltd., Otsu, Shiga 520-21, Japan Search for other works by this author on: Oxford Academic Google Scholar Tokuji Ikenaka Tokuji Ikenaka Department of Chemistry, Osaka University College of Science, Toyonaka, Osaka 560, Japan Present address: Tezukayama Gakuin Junior College, Harumidai, Sakai, Osaka 590-01, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 54, Issue 8, 1 August 1990, Pages 2169–2170, https://doi.org/10.1080/00021369.1990.10870232 Published: 01 August 1990 Article history Received: 05 March 1990 Published: 01 August 1990
Flavobacterium heparinum 2-O-sulphatase for 2-O-sulphato-Delta4,5-glycuronate-terminated oligosaccharides from heparin (1984)

The glycosulphatase which hydrolyses the 2-O-sulphate of the disaccharide, 4-deoxy-2-O-sulphato-alpha-L-threohex-4-enopyranosyl uronic acid-(1----4)-2-deoxy-2-sulphamido-6-O-sulphato-D-glucose (delta UA-2S----GlcNS-6S), has been isolated from the soluble fraction of disrupted Flavobacterium heparinum. The activity was purified 3300-fold by chromatography on CM-Sepharose CL-6B, hydroxyapatite, taurine-Sepharose CL-4B and blue-Sepharose CL-6B. From sodium dodecylsulphate/polyacrylamide gel electrophoresis, the enzyme was homogeneous and of 62000 Mr. A novel assay was devised using the de-N-sulphonated [1-3H]alditol, 4-deoxy-2-O-sulphato-alpha-L-threo-hex-4-enopyranosyl uronic acid-(1----4)-2-amino-2-deoxy-6-O-sulphato-D-[1-3H]glucitol (delta UA-2S----[1-3H]GlcNH2-ol-6S). This alditol was shown by 13C-NMR to be desulphated in the analogous manner to the original reducing trisulphated disaccharide. The purified 2-O-sulphatase was completely free of heparinase I, heparinase II (heparitinase), chondroitinases AC, chondroitinase B, the delta 4,5-glycuronidase for heparin delta 4,5-disaccharides, the 6-O-sulphatase and the 2-sulphamidase. It was optimally active over the range pH 5.5-6.5 and was practically unaffected by Na, K, Ca or Mg ions. Inorganic phosphate inhibited the activity. The Km value for the alditol substrate was 1.22 mmol dm-3. Using 13C-NMR, the 2-O-sulphatase was found to hydrolyse the analogous esters of higher delta 4,5-oligosaccharides from heparin. This contrasts with the findings of other authors [Dietrich, C. P., Silva, M. E., and Michelacci, Y. M. (1973) J. Biol. Chem. 248, 6408-6415].
Developing adenoviral‐mediated in vivo gene therapy for ornithine transcarbamylase deficiency (1998)

There are a number of reasons for choosing ornithine transcarbamylase (OTC) deficiency as a candidate for gene therapy: the gene has been cloned; the disorder is relatively common; the current clinical outcome is poor; and there are authentic animal models. In considering the development of gene therapy for OTC deficiency, we focused on the use of in vivo gene therapy with an adenoviral vector. Using the partially OTC-deficient sparse fur mouse we found transduction and expression could be achieved using an intravenous infusion of a recombinant adenovirus containing the OTC cDNA. The results were transient as a result of immune activation in response to the vector and vector-transduced cells. By modifying the adenoviral construct, creating an E1 deletion-E2 temperature-sensitive mutation, we blunted the cytotoxic T lymphocyte immune response and achieved correction of biochemical abnormalities for 2-3 months. We also found that transduction and expression following gene transfer occurred sufficiently rapidly to protect against acute hyperammonaemia within 24 h. Subsequent preclinical studies in mice and non-human primates demonstrated that E1-E4-deleted vectors had a substantially improved safety profile and similar efficacy. With this evidence of efficacy and safety of adenoviral vectors, we are embarking on a phase I trial of intravascular gene transfer using an E1-E4-deleted vector in adults with partial OTC deficiency.
Analysis of Coupled Phase-Locked Loops With Independent Oscillators for Beam Control Active Phased Arrays (2004)

Phase dynamics and phase noise of N coupled phase-locked loops (PLLs) with N independent oscillators are analyzed. The phase noise of coupled PLLs with independent oscillators is analyzed by using the signal flow graph and Mason's gain rules. The near-carrier phase noise of PLL elements in the array can be reduced to 1/N that of a single independent (without coupling) VCO of the PLL element, and return to its free-running phase noise far from the carrier frequency, provided the coupling network is reciprocal, the feedback loop gain of the PLL elements is large, and the phase detector and amplifier noise are neglected. The phase dynamics and noise improvement of coupled PLL arrays are verified by using two coupled PLLs with independent GaAs MESFET oscillators operating at X-band.