gebhart/patrepeval huggingface dataset:
Covalent Addition of H2O, Enzyme Substrates and Activators to Pyrrolo‐quinoline Quinone, the Coenzyme of Quinoproteins (1982)

The fluorescence excitation and the adsorption spectrum of 2,7,9-tricarboxy-1H-pyrrolo [2,3-f]quinoline-4,5-dione (pyrrolo-quinoline quinone, PQQ), measured in the pH range 7.0-10.0, are quite different. However, when the temperature of the solution is lowered, the shape and maxima of these spectra become more similar. 1H-NMR in 2H2O revealed a temperature-dependent equilibrium between PQQ and a hydrated form. Evidence is presented that low temperature favours the formation of the fluorescing species which is PQQ, hydrated at the C-5 position. Even further hydration is possible since absorption, fluorescence and NMR spectroscopy of PQQ in borate buffer pH 10.0 reveal additional hydration at the C-4 position, pointing to a dihydrate. PQQ also reacts with quinoprotein enzyme substrates and activators. Spectroscopic measurements showed the existence of 5-alkoxy-5-hydroxy-PQQ and 5-amino-5-hydroxy-PQQ in the presence of alcohols and 2 M NH4Cl, pH 9.0, respectively. In the latter case, the existence of 5-imino-PQQ could also be demonstrated. Addition compounds with amines appear to be unstable. The amines become probably oxidized because pyrrolo-quinoline quinol (PQQH2) was found as the reaction product. On the other hand, an addition compound containing an imino bond could be isolated after addition of urea to a PQQ solution. Spectral characteristics of PQQ and its addition compounds are presented since these data are necessary for the spectral analysis of quinoproteins and the quantitative estimation of coenzyme.
Analgesic and anti-inflammatory effects of A-286501, a novel orally active adenosine kinase inhibitor (2002)

Adenosine (ADO) is an inhibitory neuromodulator that can increase nociceptive thresholds in response to noxious stimulation. Inhibition of the ADO-metabolizing enzyme, adenosine kinase (AK) increases extracellular ADO concentrations at sites of tissue trauma and AK inhibitors may have therapeutic potential as analgesic and anti-inflammatory agents. N7-((1'R,2'S,3'R,4'S)-2',3'-dihydroxy-4'-amino-cyclopentyl)-4-amino-5-bromo-pyrrolo[2,3-a]pyrimidine (A-286501) is a novel and potent (IC50=0.47 nM) carbocyclic nucleoside AK inhibitor that has no significant activity (IC50 >100 microM) at other sites of ADO interaction (A1, A2A, A3 receptors, ADO transporter, and ADO deaminase) or other (IC50 value >10 microM) neurotransmitter and peptide receptors, ion channel proteins, neurotransmitter reuptake sites and enzymes, including cyclooxygenases-1 and -2. A-286501 showed equivalent potency to inhibit AK from several mammalian species and kinetic studies revealed that A-286501 was a reversible and competitive inhibitor with respect to ADO and non-competitive with respect to MgATP2-. A-286501 was orally effective to reduce nociception in animal models of acute (thermal), inflammatory (formalin and carrageenan), and neuropathic (L5/L6 nerve ligation and streptozotocin-induced diabetic) pain. A-286501 was particularly potent (ED50=1 micromol/kg, p.o.) to reduce carrageenan-induced inflammatory thermal hyperalgesia as compared to its analgesic actions in other pain models (acute and neuropathic) and its ability to alter hemodynamic function and motor performance. A-286501 was also effective to reduce carrageenan-induced paw edema and myeloperoxidase activity, a measure of neutrophil influx (ED50=10 micromol/kg, p.o.), in the injured paw. The anti-nociceptive effects of A-286501 in the L5/L6 nerve injury model of neuropathic pain (ED50=20 micromol/kg, p.o.) were not blocked by the opioid antagonist naloxone, but were blocked by the ADO receptor antagonist, theophylline. Following repeated administration, A-286501 showed less potential to produce tolerance as compared to morphine. Thus, A-286501 is a structurally novel AK inhibitor that effectively attenuates nociception by a non-opioid, non-non-steroidal anti-inflammatory drug ADO, receptor mediated mechanism.
Microsatellite analysis of free tumor DNA in urine, serum, and plasma of patients: a minimally invasive method for the detection of bladder cancer. (2002)

The study indicates that simultaneous and multiple investigations of microsatellite markers on free DNA of urine and blood could have clinical relevance as a minimally invasive method for diagnosis and screening of bladder cancer.
Structural Preorganization of Peptide Nucleic Acids: Chiral Cationic Analogues with Five- or Six-Membered Ring Structures (2002)

The advent of aminoethylglycyl peptide nucleic acids, aegPNAs, as strong and specific DNA/RNA binding agents has triggered much research activity directed towards the development of PNA-based antisense/antigene therapeutics. These efforts have mainly been directed towards further refinement of aegPNA properties such as water solubility, cellular uptake and discrimination between parallel and antiparallel binding modes. Introduction of chirality and also of positive/negative charges in the PNA backbone has met with some success in this direction. The conformational freedom in the nucleobase linker arm and in the backbone aminoethyl and glycyl segments in the aegPNA backbone were found to be causes of unfavourable entropic loss during complex formation. Suitable clamping in the aegPNA backbone may reduce entropic loss and help produce a conformation appropriate for maximum enthalpic benefits from nucleobase recognition. Introduction of constraint by means of five- or six-membered ring structures in the aegPNA and their contributions to maintaining the balance between rigidity and flexibility in the backbone have shown interesting effects on the overall stability of PNA-DNA/RNA complexes. This review presents an account of the literature in this direction. The significant promise of our approach, which makes use of the naturally occurring trans-4-hydroxy-L-proline to arrive at different chirally pure cyclic PNA analogues, is presented in this review, together with the DNA binding properties of the compounds. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)
Structure of antibiotic A41030A (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure of antibiotic A41030AAnn H. Hunt, Douglas E. Dorman, Manuel Debono, and R. Michael MolloyCite this: J. Org. Chem. 1985, 50, 12, 2031–2035Publication Date (Print):June 1, 1985Publication History Published online1 May 2002Published inissue 1 June 1985https://pubs.acs.org/doi/10.1021/jo00212a005https://doi.org/10.1021/jo00212a005research-articleACS PublicationsRequest reuse permissionsArticle Views97Altmetric-Citations10LEARN 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
The Role of Vascular Endothelial Growth Factor Genetic Variability in Cancer (2009)

Angiogenesis is a hallmark of tumor pathogenesis. Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis and its inhibition has become a successful approach to antitumor therapy across tumor types. The VEGF gene is highly polymorphic with multiple common single nucleotide polymorphisms (SNPs) in the promoter, 5' untranslated region and 3' untranslated region. There is evidence that these SNPs in the regulatory regions can affect VEGF expression. In vitro and in vivo data show that genetic variability affects the activity and expression of VEGF. Case-control and cohort studies suggest that genetic variability may affect risk and outcome of a variety of disease states that are tightly regulated by angiogenesis. Recently, genetic variability in VEGF has been studied as a potential predictive biomarker for bevacizumab. The VEGF-1154 AA and -2578 AA genotypes predicted an improved median overall survival, whereas the VEGF-634 CC and -1498 TT genotypes predicted protection from grade 3-4 hypertension in the pivotal trial, E2100. If validated, these finding could help direct which subgroup of patients should receive bevacizumab.
[General characteristics and problems of the galenic aspects of fat emulsions]. (1983)

The development of a clinically applicable intravenous fat emulsion has a long history. The gain of knowledge about the best lipid and emulsifying system had an intermittent development and led to three generations of distinct fat emulsions. For the evaluation of a fat emulsion it is necessary to compare the results of the same generation only. In the past, many misinterpretations came from mixing the results of different generations. It can be stated that by considering the contraindications, application schedules and basal galenic aspects, only minimal side effects from a parenteral administration of fat emulsions can be seen. Today the most important aspects of parenteral nutrition with fat emulsions are the galenic ones, which are often overlooked. The staining of the liposomes of the fat emulsions with 2% OSO4 make electron microscopic investigations of the liposomes possible after mixing them with carbohydrates, amino acids, electrolytes, vitamins and trace elements. The liposomes of soybean oil emulsions in different "All In One" (AIO) solutions have been under current investigations. The results demonstrated that the liposomes of fresh AIO-solutions carry highly osmiophilic inclusion bodies. Prolonged storage led to further alterations, as change of shape, loss of osmiophility and finally formation of liposomes ghosts. In solutions kept at 4 degrees C those changes developed between the 1st and 2nd month of storage, whereas storage at 22 degrees C was harmless within 48 h only. Therefore, it is recommended that already prepared AIO solutions are kept at 4 degrees C and used as soon as possible.
23.2: Binocular Holographic Waveguide Visor Display (2014)

Abstract This paper documents the development of a prototype binocular, see‐through, monochrome holographic waveguide helmet mounted display (HWVD). The optical system couples a commercial high resolution 1440 times 1080 pixel (1.5Mpixel) 12mm diagonal LCOS microdisplay with a state of the art holographic waveguide. Utilization of the waveguide gives a wide 40‐degree field of view (FOV), while having a large 30times30 mm eyebox. With the advantages obtained by use of the holographic waveguide and the small LCOS microdisplay, the HWVD system enables significant cost, volume, and weight reductions as compared to existing CRT type designs. The design will also address power and efficiency requirements consistent with a pilot HMD system.
Bisphosphonate Inhibition of the Exopolyphosphatase Activity of theTrypanosoma bruceiSoluble Vacuolar Pyrophosphatase (2005)

Trypanosoma brucei, the causative agent of African trypanosomiasis, contains a soluble, vacuolar pyrophosphatase, TbVSP1, not present in humans, which is essential for the growth of bloodstream forms in their mammalian host. Here, we report the inhibition of a recombinant TbVSP1 expressed in Escherichia coli by a panel of 81 bisphosphonates. The IC50 values were found to vary from approximately 2 to 850 microM. We then used 3D QSAR (comparative molecular field and comparative molecular similarity index; CoMFA and CoMSIA) methods to analyze the enzyme inhibition results. The R2 values for the experimental versus the QSAR-predicted activities were 0.78 or 0.61 for CoMFA and 0.79 or 0.68 for CoMSIA, for two different alignments. The root-mean-square (rms) pIC50 error for the best CoMFA model was 0.41 for five test sets of five activity predictions, which translates to a factor of approximately 2.6 error in IC50 prediction. For CoMSIA, the rms pIC50 error and error factors were 0.35 and 2.2, respectively. In general, the most active compounds contained both a single aromatic ring and a hydrogen bond donor feature. Thirteen of the more potent compounds were then tested in vivo in a mouse model of T. brucei infection. The most active compound in vivo provided a 40% protection from death with no apparent side effects, suggesting that further development of such compounds may be of interest.
Identification of a Novel GC-Rich 113-Nucleotide Region To Complete the Circular, Single-Stranded DNA Genome of TT Virus, the First Human Circovirus (1999)

The sequence data (H. Okamoto et al., Hepatol. Res. 10:1-16, 1998) of a newly discovered single-stranded DNA virus, TT virus (TTV), showed that it did not have the terminal structure typical of a parvovirus. Elucidation of the complete genome structure was necessary to understand the nature of TTV. We obtained a 1.0-kb amplified product from serum samples of four TTV carriers by an inverted, nested long PCR targeted for nucleotides (nt) 3025 to 3739 and 1 to 216 of TTV. The sequence of a clone obtained from serum sample TA278 was compared with those registered in GenBank. The complete circular TTV genome contained a novel sequence of 113 nt (nt 3740 to 3852 [=0]) in between the known 3'- and 5'-end arms, forming a 117-nt GC-rich stretch (GC content, 90.6% at nt 3736 to 3852). We found a 36-nt stretch (nt 3816 to 3851) with an 80.6% similarity to chicken anemia virus (CAV) (nt 2237 to 2272 of M55918), a vertebrate circovirus. A putative SP-1 site was located at nt 3834 to 3839, followed by a TATA box at nt 85 to 90, the first initiation codon of a putative VP2 at nt 107 to 109, the termination codon of a putative VP1 at nt 2899 to 2901, and a poly(A) signal at nt 3073 to 3078. The arrangement was similar to that of CAV. Furthermore, several AP-2 and ATF/CREB binding sites and an NF-kappaB site were arranged around the GC-rich region in both TTV and CAV. The data suggested that TTV is circular and similar to CAV in its genomic organization, implying that TTV is the first human circovirus.
Biomedical Applications of Shape Memory Alloys (2011)

Shape memory alloys, and in particular NiTi alloys, are characterized by two unique behaviors, thermally or mechanically activated: the shape memory effect and pseudo-elastic effect . These behaviors, due to the peculiar crystallographic structure of the alloys, assure the recovery of the original shape even after large deformations and the maintenance of a constant applied force in correspondence of significant displacements. These properties, joined with good corrosion and bending resistance, biological and magnetic resonance compatibility, explain the large diffusion, in the last 20 years, of SMA in the production of biomedical devices, in particular for mini-invasive techniques. In this paper a detailed review of the main applications of NiTi alloys in dental, orthopedics, vascular, neurological, and surgical fields is presented. In particular for each device the main characteristics and the advantages of using SMA are discussed. Moreover, the paper underlines the opportunities and the room for new ideas able to enlarge the range of SMA applications. However, it is fundamental to remember that the complexity of the material and application requires a strict collaboration between clinicians, engineers, physicists and chemists for defining accurately the problem, finding the best solution in terms of device design and accordingly optimizing the NiTi alloy properties.
Synchronization and communication in the T3E multiprocessor (1996)

This paper describes the synchronization and communication primitives of the Cray T3E multiprocessor, a shared memory system scalable to 2048 processors. We discuss what we have learned from the T3D project (the predecessor to the T3E) and the rationale behind changes made for the T3E. We include performance measurements for various aspects of communication and synchronization.The T3E augments the memory interface of the DEC 21164 microprocessor with a large set of explicitly-managed, external registers (E-registers). E-registers are used as the source or target for all remote communication. They provide a highly pipelined interface to global memory that allows dozens of requests per processor to be outstanding. Through E-registers, the T3E provides a rich set of atomic memory operations and a flexible, user-level messaging facility. The T3E also provides a set of virtual hardware barrier/eureka networks that can be arbitrarily embedded into the 3D torus interconnect.
Symmetry-based presentation for stem-cell image segmentation (2011)

Cancer stem cells have been isolated from many tumors, including breast, brain, colon, head and neck, lung, pancreas, and prostate tumors. Advances in stem cell biology and animal models help better characterization of cancer stem cells, including the cells of origin, molecular and cellular properties, functions in cancer initiation and development, treatment response, and drug resistance. An important and challenging task in image analysis of stem cells is the image segmentation. A difficulty is to segment aggregated cells that are deformed and occluded. Watershed transform and multiscale morphological operation are the common methods for this purpose, as they are robust against arbitrary shaping and the occlusion of cells. Notwithstanding their high robustness, the two methods are still limited in their applications in the cases with cells suffering perturbations and deformation during cell growth. In this paper, we propose a novel symmetry axis transformation for stem-cell image segmentation. Our algorithm was validated by its comparison with both watershed transform and multiscale morphological operation. Improved segmentation performance in terms of precision (up to 2.2% comparing to watershed; and up to 0.6% comparing to multiscale morphological operation) was achieved using 5197 cell images in which 291 cells are three mutually touching.
Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765 (2011)

B-cell receptor (BCR) signaling is aberrantly activated in chronic lymphocytic leukemia (CLL). Bruton tyrosine kinase (BTK) is essential to BCR signaling and in knockout mouse models its mutation has a relatively B cell-specific phenotype. Herein, we demonstrate that BTK protein and mRNA are significantly over expressed in CLL compared with normal B cells. Although BTK is not always constitutively active in CLL cells, BCR or CD40 signaling is accompanied by effective activation of this pathway. Using the irreversible BTK inhibitor PCI-32765, we demonstrate modest apoptosis in CLL cells that is greater than that observed in normal B cells. No influence of PCI-32765 on T-cell survival is observed. Treatment of CD40 or BCR activated CLL cells with PCI-32765 results in inhibition of BTK tyrosine phosphorylation and also effectively abrogates downstream survival pathways activated by this kinase including ERK1/2, PI3K, and NF-κB. In addition, PCI-32765 inhibits activation-induced proliferation of CLL cells in vitro, and effectively blocks survival signals provided externally to CLL cells from the microenvironment including soluble factors (CD40L, BAFF, IL-6, IL-4, and TNF-α), fibronectin engagement, and stromal cell contact. Based on these collective data, future efforts targeting BTK with the irreversible inhibitor PCI-32765 in clinical trials of CLL patients is warranted.
Translationally controlled tumor protein is a target of tumor reversion (2004)

By analyzing the gene expression profile between tumor cells and revertant counterparts that have a suppressed malignant phenotype, we previously reported a significant down-regulation of translationally controlled tumor protein (TCTP) in the revertants. In the present study, we derived, by using the H1 parvovirus as a selective agent, revertants from three major solid cancers: colon, lung, and melanoma cell lines. These cells have a strongly suppressed malignant phenotype both in vitro and in vivo. The level of TCTP is decreased in most of the revertants. To verify whether inhibition of TCTP expression induces changes in the malignant phenotype, in the classical, well established model of "flat reversion," v-src-transformed NIH3T3 cells were transfected with antisense TCTP. By inhibiting the expression of TCTP, the number of revertant cells was raised to 30%, instead of the reported rate for spontaneous flat revertants of 10(-6). Because TCTP encodes for a histamine-releasing factor, we tested the hypothesis that inhibitors of the histaminic pathway could be effective against tumor cells. We show that some antihistaminic compounds (hydroxyzine and promethazine) and other pharmacological compounds with a related structure (including thioridazine and sertraline) kill tumor cells and significantly decrease the level of TCTP. All together, these data suggest that, with tumor reversion used as a working model, TCTP was identified as a target and drugs were selected that decrease its expression and kill tumor cells.
Caryl–Calkyl bond formation from Cu(ClO4)2-mediated oxidative cross coupling reaction between arenes and alkyllithium reagents through structurally well-defined Ar–Cu(iii) intermediates (2012)

The stable and structurally well-defined Ar-Cu(III) intermediates, that are prepared almost quantitatively from the reaction of azacalix[1]arene[3]pyridines with Cu(ClO(4))(2)·6H(2)O under aerobic conditions, reacted smoothly with a number of alkyllithium reagents under mild conditions to form C(aryl)-C(alkyl) bonds.
2015年盟情咨文：此时此刻,需要我们诚实、团结和大局观 (2015)

欧盟委员会主席容克于今年9月9日在法国斯特拉斯堡发表讲话。他在讲话中强调,应对难民危机是欧盟的当务之急,也是他接下来的工作重点之一。容克此次在欧洲议会发表讲话,是他担任欧盟委员会主席一年来首次发表盟情咨文,重要性可想而知。而对于英语学习者来说,本文也是极好的学习素材。
Cut-off analysis of 19-cell Yb-doped double-cladding rod-type photonic crystal fibers (2011)

Yb-doped double-cladding large mode area rod-type photonic crystal fibers are a key component for power scaling in fiber laser systems. Recently, designs with 19-cell core defect, that is with 19 missing air-holes in the center of the photonic crystal cladding, have been proposed, with reported core diameter up to 100 μm. In this paper an analysis of the cut-off wavelength of the first high-order mode in such low-NA fibers is reported, accounting for different approaches for the definition of the cladding effective index. Results have shown that taking into account the finite fiber cross-section and considering the first cladding mode of the actual fiber is mandatory to obtain a correct estimate of the cut-off wavelength.