gebhart/patrepeval huggingface dataset:
Highly Enantioselective Synthesis of No‐Carrier‐Added 6‐[<sup>18</sup>F]Fluoro‐<scp>L</scp>‐dopa by Chiral Phase‐Transfer Alkylation (2004)

Abstract [ 18 F]Fluoro‐ L ‐dopa, an important radiopharmaceutical for positron emission tomography (PET), has been synthesized using a phase‐transfer alkylation reaction. A chiral quaternary ammonium salt derived from a Cinchona alkaloid served as phase‐transfer catalyst for the enantioselective alkylation of a glycine derivative. The active methylene group of this Schiff‐base substrate was deprotonated with cesium hydroxide and rapidly alkylated by the 2‐[ 18 F]fluoro‐4,5‐dimethoxybenzyl halide (X = Br, I). The reaction proceeded with high yield (> 90%) at 0 °C or room temperature in various solvents such as toluene or dichloromethane. Preparation of the [ 18 F]alkylating agent on a solid support was developed. After labelling, the labeled [ 18 F]fluoroveratraldehyde was trapped on a t C18 cartridge and then converted on the cartridge into the corresponding benzyl halide derivatives by addition of aqueous sodium borohydride and gaseous hydrobromic or ‐iodic acid. Hydrolysis and purification by preparative HPLC made 6‐[ 18 F]fluoro‐ L ‐dopa ready for human injection in a 25−30% decay‐corrected radiochemical yield in a synthesis time of 100 min. The product was found to be chemically, radiochemically and enantiomerically pure ( ee > 95%). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Internal Field Emission at Narrow Silicon and Germanium<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mi>p</mml:mi><mml:mo>−</mml:mo><mml:mi>n</mml:mi></mml:math>Junctions (1960)

A detailed study has been made of the reverse characteristics of several silicon and germanium alloyed $p\ensuremath{-}n$ junctions with breakdown voltages in the range of about 0.1 to 0.8 volt. In these junctions the reverse current is generated almost entirely by internal field emission (tunneling). The reverse bias characteristics are insensitive to the dislocation density present so that the tunneling current occurs mainly in undistorted material. From capacitance studies it is established that these narrow junctions are very close to being ideal step junctions. The room-temperature reverse characteristics are analyzed in terms of the usual tunneling probability expressions and in particular, good agreement, both qualitative and quantitative, is found between experiment and theory. The tunneling probability $\mathrm{exp}(\ensuremath{-}\frac{\ensuremath{\alpha}{\ensuremath{\epsilon}}^{\frac{3}{2}}}{E})$, when compared with experiment, yields values for $\ensuremath{\alpha}{\ensuremath{\epsilon}}^{\frac{3}{2}}$ in agreement with the theoretical ones to within a factor of less than 2 for both silicon and germanium.The critical voltage (the reverse bias voltage necessary to maintain a constant tunneling current) was measured as a function of temperature from 4.2\ifmmode^\circ\else\textdegree\fi{}K up to temperatures as high as 700\ifmmode^\circ\else\textdegree\fi{}K. In germanium, the critical voltage drops monotonically as the temperature increases whereas in silicon, there is considerable structure in the curve. This is shown to be consistant with the tunneling being by direct transitions in germanium and by indirect transitions (involving phonon emission and absorption) in silicon. In germanium, the temperature dependence of the critical voltage arises from that of the direct energy gap while in silicon, it is determined, primarily, by the available phonon density. From an analysis of the temperature data for silicon that invokes the transverse acoustic phonons, the estimate of $\ensuremath{\alpha}{\ensuremath{\epsilon}}^{\frac{3}{2}}$ that is obtained is in excellent agreement with that found, independently, from the analysis of the reverse characteristics.
Examining XML: new concepts and possibilities in Web authoring. (1998)

XML est un metalangage ou ensemble de regles permettant de coder les documents. Comme le HTML, le XML est issu du SGML. Plus complique que le HTML, il se conforme a une DTD. Certaines differences entre les deux langages requierent des changements pour avoir une complete compatibilite mais les navigateurs XML sont capables de lire les documents HTML. Ce nouveau langage va entrainer l'augmentation des varietes des documents. L'edition electronique voit beaucoup d'avantages dans le XML
Identification and Characterization of Severe Acute Respiratory Syndrome Coronavirus Replicase Proteins (2004)

The severe acute respiratory syndrome coronavirus (SARS-CoV) encodes proteins required for RNA transcription and genome replication as large polyproteins that are proteolytically processed by virus-encoded proteinases to produce mature replicase proteins. In this report, we generated antibodies against SARS-CoV predicted replicase protein and used the antibodies to identify and characterize 12 of the 16 predicted mature replicase proteins (nsp1, nsp2, nsp3, nsp4, nsp5, nsp8, nsp9, nsp12, nsp13, nsp14, nsp15, and nsp16) in SARS-CoV-infected Vero cells. Immunoblot analysis of infected-cell lysates identified proteins of the predicted sizes. Immunofluorescence microscopy detected similar patterns of punctate perinuclear and distributed cytoplasmic foci with all replicase antibodies and as early as 6 h postinfection. Dual-labeling studies demonstrated colocalization of replicase protein nsp8 with nsp2 and nsp3 in cytoplasmic complexes and also with LC3, a protein marker for autophagic vacuoles. Antibodies directed against mouse hepatitis virus (MHV) virions and against the putative RNA-dependent RNA polymerase (Pol) detected SARS-CoV nucleocapsid and nsp12 (Pol), respectively, in SARS-CoV-infected Vero cells. These results confirm the predicted protein processing pattern for mature SARS-CoV replicase proteins, demonstrate localization of replicase proteins to cytoplasmic complexes containing markers for autophagosome membranes, and suggest conservation of protein epitopes in the replicase and nucleocapsid of SARS-CoV and the group II coronavirus, MHV. Further, the results demonstrate the ability of replicase antibodies to detect SARS-CoV-infected cells as early as 6 h postinfection and thus represent important tools for studies of SARS-CoV replication, inhibition, and diagnosis.
Optical studies of molecular motions: using fluorescence anisotropy decays to determine the shapes of dye molecules, proteins, and nucleosomes (1991)

Molecules undergo Brownian rotational diffusion, continually tumbling through solution. If a molecule contains a fluorescent chromophore with an appropriate excited-state lifetime, and a solution of such molecules is excited with a brief flash of polarized laser light, then it is possible to measure the rates at which the molecule tumbles. One can measure the anisotropy of the decay of the fluorescence, a measure of the depolarization of the fluorescence in time. The rates of rotational diffusion are sensitive to the shape of the molecule. This paper examines the molecular shape information available from the anisotropy decay. Three systems, which are of interest to our laboratory, are described here. Our studies on the dye rose bengal (molecular weight ~1000) suggest that an approximation used in rotational diffusion theory-that the solvent molecules are very small compared to the solute-is valid even for this relatively small molecule. Next, we examine the effects of calcium concentration on the rotational diffusion ofthe protein calmodulin (molecular weight ~17,000) derivatized by photoinduced crosslinking to form a dityrosine fluorophore. In the presence of sufficiently high calcium ion concentration, this crosslinked calmodulin shows a single exponential anisotropy decay consistent with the rotational diffusion of the extended dumbbell structure found for calmodulin by x-ray crystallography. At low calcium concentrations, the crosslinked calmodulin rotates considerably faster, suggesting a much more compact shape; also, this anisotropy decay shows short correlation times that are interpreted as arising from a segmental flexibility not evident for crosslinked calmodulin at high calcium concentration. Finally, we examine a transition that is observed at very low salt concentrations for nucleosome core particles, relatively large complexes (molecular weight ~204,000) derived from the chromatin of higher organisms and comprised of eight histone molecules and 145 base pairs of DNA.
Identification of RNA Aptamer Specific to Mutant KRAS Protein (2010)

Mutations in the KRAS gene are required for early occurrence and maintenance of tumorigenesis and are the most frequently found in many types of human malignant diseases. Therefore, approaches targeting RAS function have been proposed for cancer therapy. However, no selective and specific inhibitors of KRAS have yet been developed as anticancer agents. In this study, by employing counter-systematic evolution of ligands by exponential enrichment technique, we identified and characterized an RNA aptamer that specifically bound to mutant KRAS protein with a point mutation in codon 12 of the KRAS gene. Real-time polymerase chain reaction analysis, surface plasmon resonance measurements, and competitive precipitation experiments showed that the selected aptamer contained activities of specific and high-affinity binding to the mutant KRAS (K(D) approximately 4.04 nM) but much less binding to the wild type (K(D) approximately 227 nM). This RNA aptamer could be useful as a ligand for specific therapeutics and diagnostics against mutant KRAS-mediated cancers.
THE INFLUENCE OF HIGH PHENYLALANINE AND TYROSINE ON THE CONCENTRATIONS OF ESSENTIAL AMINO ACIDS IN BRAIN (1968)

Abstract —High circulating levels of phenylalanine caused depletions of threonine, valine, methionine, isoleucine, leucine, histidine, tryptophan, and tyrosine in immature and adult rat brains. The branched‐chain amino acids were most affected. Their reductions ranged between 38–64 per cent of control values when phenylalanine was administered either parenterally or in the diet. The pattern of cerebral amino acid depletions found in phenylalanine‐injected infant rats was similar to that of the adults. Phenylalanine loading caused depletions in serum amino acid levels in adult rats, but in infant rats the serum levels were either unchanged or somewhat elevated. Tyrosine, when administered to adult rats either parenterally or via the diet, caused cerebral depletions in essential amino acids, but the depletions were not as striking as with phenylalanine. In both the infant and adult rat, brain‐blood ratios of most of the essential amino acids were significantly reduced by phenylalanine loading.
Room-temperature continuous-wave operation of Ti:sapphire buried channel-waveguide lasers fabricated via proton implantation (2006)

Fabrication and laser operation of proton-implanted Ti:sapphire buried channel waveguides is reported for the first time to our knowledge. Without any postimplantation annealing of the structures, continuous laser operation near 780 nm was demonstrated at room temperature at an absorbed pump power threshold of 230 mW. Single-transverse-mode laser emission was observed with measured beam propagation factors M(2)(x) and M(2)(y) of 1.5 and 1.2, respectively. An output power of 12.4 mW for 1 W pump power was obtained with an output coupler of 4.6% transmission at the signal wavelength. Higher output powers were measured in waveguides with larger cross sections exhibiting multimode laser emission.
Interaction of porcine von Willebrand factor with the platelet glycoproteins Ib and IIb/IIIa complex (1992)

Porcine von Willebrand factor (PvWF) induces platelet aggregation which is thought to be responsible for the thrombocytopenia that occurs in haemophilic patients treated with commercial preparations of porcine factor VIII. This study demonstrates that such aggregation can be completely inhibited by a monoclonal antibody against human platelet glycoprotein GPIb and partially inhibited by an antibody directed against platelet GPIIb/IIIa. The interaction of PvWF with GPIb is also demonstrated by the inhibitory effect of purified glycocalycin on aggregation. The binding site of PvWF to GPIb is very close to that of human vWF, since a recombinant peptide blocks the binding of both molecules to GPIb. When platelets are incubated with PvWF, the GPIIb/IIIa receptor is activated and binds fibrinogen. PvWF also binds to GPIIb/IIIa when platelets are stimulated with thrombin, suggesting that the molecule has the same RGD sequence as other adhesive proteins (human vWF, fibrinogen, fibronectin and vitronectin). These findings identify the dual mechanisms responsible for in vivo platelet aggregation induced by PvWF, i.e. binding to GPIb and activation of the GPIIb/IIIa receptor.
Therapy for chemopretreated metastatic urothelial cancer (mUC) with the antibody-drug conjugate (ADC) sacituzumab govitecan (IMMU-132). (2017)

327 Background: Patients (pts) with mUC pre-treated with platinum-containing chemotherapy have limited therapeutic options, with checkpoint-inhibitor immunotherapy (IO) responses in a minority of pts. We present an interim update of the safety and activity of sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 ADC, as therapy for chemotherapy-pretreated mUC pts (ClinicalTrials.gov, NCT01631552). Methods: We enrolled 32 pts with mUC and ECOG PS 0-1 who failed ≥ 1 prior standard therapy (median=3; range, 1-5). IMMU-132 was administered at 8 or 10 mg/kg on days 1 and 8 every 21 days, continued until disease progression (PD) or unacceptable toxicity. Response-evaluable pts received ≥ 2 doses, and had ≥ 1 post-baseline response assessment. Results: Twenty-five pts [median age 68 yrs (range: 50-91), 24 males] are currently assessable for safety and response; 23 had prior platinum-containing therapy; 46% had >2 prior therapies; 4 also had IO agents. Sites of metastases included liver (N=4; 16%), lungs (N=7; 28%), bone (N=4; 16%), and lymph nodes (N=16; 64%). Pts received a median of 7 cycles (range, 2-23) of IMMU-132. ORR was 36% (9/25) [1 complete (CR) and 8 partial responses (PR)]; 44% (11/25) had stable disease (SD). Further, pts with 1 line of prior chemotherapy had an ORR of 53.8% (7/13), and 16.7% for those with 2 to 5 prior therapy lines. Median PFS for all patients is 7.2 mos (95% CI, 4.9-10.7); median survival is not reached yet. Of the 4 pts with progression after prior IO, there were 1 PR and 2 SDs with IMMU-132. Duration of response for CR/PR pts is currently 5.1 mos (95% CI, 4.1-12.9) and 10/11 pts (5 with ≥ 20% tumor reduction) had stable disease > 4 mos. Grade 4 neutropenia (16%) lasted < 7 days, and non-hematological grade 3 AEs included fatigue (12%) and hypophosphatemia (8%). No treatment-related deaths were observed. Analysis of Trop-2 expression revealed 1+ to 3+ positive staining in 95% of 19 archival patient specimens. Conclusions: With an ORR of 36% and a median PFS of 7.2 months in a heavily pretreated population, these interim results suggest that IMMU-132 is a promising agent as 2 nd line or later therapy for platinum- or IO- pretreated mUC pts. Clinical trial information: NCT01631552.
Intranasal Immunization Promotes Th17 Immune Responses (2009)

Th17 cells are a lineage of CD4+ T cells characterized by IL-17 secretion, which plays a crucial role in immune responses against important respiratory pathogens, such as Mycobacterium tuberculosis. In this study, we demonstrated that intranasal (i.n.) immunization leads per se to Th17-biased immune responses, regardless of the adjuvant used. The activated CD4+ T cells also showed an up-regulated expression of the chemokine receptor CCR6, which is a marker for murine Th17 cells. These results have important implications in the context of optimizing rational vaccine design, since i.n. immunization appears to be the strategy of choice for situations where the induction of a Th17 phenotype would be beneficial.
Raman spectra of diamondlike amorphous carbon films (1988)

Raman spectra of diamondlike amorphous carbon (a-C) films prepared under atmosphere with various hydrogen gas content have been measured as a function of excitation wavelength. The Raman spectral profiles vary with excitation wavelength depending on electronic absorption spectra associated with π-π* electronic transitions. Dependence of Raman spectra on excitation wavelength is interpreted in terms of π-π* resonant Raman scattering from aromatic rings with various sizes rather than polyene chains. The relative intensity of a 1400 cm−1 band against a 1530 cm−1 band is found to decrease with an increase of sp3 content in a-C films. It is shown that the relative intensity can be used as a parameter for sp3 content.
Tunable optical correlator using an optical frequency comb and a nonlinear multiplexer (2013)

We experimentally demonstrate a tunable optical correlator to search for multiple patterns among QPSK symbols. We utilize an optical frequency comb to generate the coherent signals and multiplex them coherently in a single PPLN waveguide. Multiple patterns with different lengths are successfully searched within QPSK symbols in a 40-Gb/s signal.
Practical Advanced Analysis for Steel Frame Design (1996)

This dissertation presents three practical advanced analysis methods for a two-dimensional steel frame design: (1) an explicit imperfection modeling methods; (2) an equivalent notional load method; and (3) a further reduced tangent modulus method. The methods can be used to assess realistically both strength and behavior of a structural system and its individual members in a direct manner. As a result, the methods can be used for design without tedious separate member capacity checks, including the calculations of K-factor. Key factors influencing steel frame behavior are described including: material, geometric, and connection nonlinearity, and simple procedures to enable designers to assess this behavior are provided. The procedures incorporate the refined plastic-hinge concept for spread of plasticity together with practical modeling for geometric imperfections. The magnitudes of geometric imperfections for braced and unbraced frames are proposed. The strengths predicted by the proposed procedures are compared well with those predicted by the exact plastic-zone analysis as well as by the conventional LRFD procedure. The displacement predictions are also compared well with the plastic-zone solutions. Analysis and design principles in using the proposed methods are given in detail, and comparative case studies are made to compare the practical advanced analysis with the LRFD design procedures. The case studies cover various braced, unbraced, and semi-rigid frames. Member sizes determined by the proposed methods are compared with those determined by the LRFD method, and a good agreement is generally observed. The proposed methods have been developed and refined to achieve both simplicity in use and, as far as possible, a realistic representation of actual behavior and strength of members as defined by the LRFD member capacity formulas. It is concluded that the proposed procedures are suitable for adoption in practice.
Association between Receptor Protein-tyrosine Phosphatase RPTPα and the Grb2 Adaptor (1996)

Receptor protein-tyrosine phosphatase RPTPalpha is found associated in vivo with the adaptor protein Grb2. Formation of this complex, which contains no detectable levels of Sos, is known to depend on a C-terminal phosphorylated tyrosine residue (Tyr798) in RPTPalpha and on the Src homology (SH) 2 domain in Grb2 (, ). We show here that association of Grb2 with RPTPalpha also involves a critical function for the C-terminal SH3 domain of Grb2. Furthermore, Grb2 SH3 binding peptides interfere with RPTPalpha-Grb2 association in vitro, and the RPTPalpha protein can dissociate the Grb2-Sos complex in vivo. These observations constitute a novel mode of Grb2 association and suggest a model in which association with a tyrosine-phosphorylated protein restricts the repertoire of SH3 binding proteins with which Grb2 can simultaneously interact. The function of the Tyr798 tyrosine phosphorylation/Grb2 binding site in RPTPalpha was studied further by expression of wild type or mutant RPTPalpha proteins in PC12 cells. In these cells, wild type RPTPalpha interferes with acidic fibroblast growth factor-induced neurite outgrowth; this effect requires both the catalytic activity and the Grb2 binding Tyr798 residue in RPTPalpha. In contrast, expression of catalytically active RPTPalpha containing a mutated tyrosine phosphorylation/Grb2 association site enhances neurite outgrowth. Our observations associate a functional effect with tyrosine phosphorylation of, and ensuing association of signaling proteins with, a receptor protein-tyrosine phosphatase and raise the possibility that RPTPalpha association may modulate Grb2 function and vice versa.
Experimental evidence for the regiospecific primary mode of styrene insertion into metal‐carbon bonds of an isospecific Ziegler‐Natta catalyst (1987)

Abstract Styrene/1‐hexene copolymers of different chemical composition were prepared with a classical isospecific Ziegler‐Natta catalyst, TiCl 3 (H)‐AlEt 3 . Their structure and the distribution of the monomeric unites was analyzed by GPC double detection and 1 H and 13 C NMR. The chemical arrangement of isolated and blocked styrene monomeric units between sequences of hexene monomeric units was also investigated. 13 C chemical shifts of carbon atoms in the copolymers and in addition in model molecules of the two modes of styrene addition indicate that styrene insertion into carbon‐metal bonds of the catalyst proceeds according to a primary mode. Mechanistic implications of these results are discussed.
Identification of Distinct Populations of Prostasomes That Differentially Express Prostate Stem Cell Antigen, Annexin A1, and GLIPR2 in Humans1 (2011)

In addition to sperm cells, seminal fluid contains various small membranous vesicles. These include prostasomes, membrane vesicles secreted by prostate epithelial cells. Prostasomes have been proposed to perform a variety of functions, including modulation of (immune) cell activity within the female reproductive tract and stimulation of sperm motility and capacitation. How prostasomes mediate such diverse functions, however, remains unclear. In many studies, vesicles from the seminal plasma have been categorized collectively as a single population of prostasomes; in fact, they more likely represent a heterogeneous mixture of vesicles produced by different reproductive glands and secretory mechanisms. We here characterized membranous vesicles from seminal fluid obtained from vasectomized men, thereby excluding material from the testes or epididymides. Two distinct populations of vesicles with characteristic sizes (56 ± 13 nm vs. 105 ± 25 nm) but similar equilibrium buoyant density (∼1.15 g/ml) could be separated by using the distinct rates with which they floated into sucrose gradients. Both types of vesicle resembled exosomes in terms of their buoyant density, size, and the presence of the ubiquitous exosome marker CD9. The protein GLIPR2 was found to be specifically enriched in the lumen of the smaller vesicles, while annexin A1 was uniquely associated with the surface of the larger vesicles. Prostate stem-cell antigen (PSCA), a prostate-specific protein, was present on both populations, thereby confirming their origin. PSCA was, however, absent from membrane vesicles in the seminal fluid of some donors, indicating heterogeneity of prostasome characteristics between individuals.
An improved OTSU method based on Genetic Algorithm (2016)

Image segmentation is required to be studied in detail some particular features (areas of interest) of a digital image. It forms an important and exigent part of image processing and requires an exhaustive and robust search technique for its implementation. In the present work we have studied working of image thresholding based on genetic algorithm. The proposed variant in this paper is tested on a set of images and the results are compared with original Otsu method.