gebhart/patrepeval huggingface dataset:
New Aspects of the Setting of Glass-ionomer Cements (1993)

For many years, glass-ionomer cements have been described as setting by the formation of a poly(acrylate) matrix. Recent research has suggested that a second reaction may be involved, namely, the formation of a silica matrix. So that this hypothesis could be tested, non-polymer cements, based on an ionomer glass plus acetic acid, were prepared and stored for up to six months. They were insoluble in water, and their compressive strength was found to increase rapidly over the period of storage. By contrast, the product of the reaction between ZnO and acetic acid was soluble in water. These results support the idea that there is a secondary setting reaction in glass ionomers and suggest that it is responsible for the increase in strength observed.
X-ray structure of p38α bound to TAK-715: comparison with three classic inhibitors (2012)

The p38α mitogen-activated protein kinase regulates the synthesis of pro-inflammatory cytokines in response to stimulation by a diverse set of stress signals. Various different chemotypes and clinical candidates that inhibit p38α function have been reported over the years. In this publication, the novel structure of p38α cocrystallized with the clinical candidate TAK-715 is reported. Owing to the impact of crystallization conditions on the conformation of protein kinases (and in particular p38α), the structures of complexes of p38α with SB-203580, SCIO-469 and VX-745 have also been determined to enable in-depth comparison of ligand-induced protein conformations. The impact of experimental conditions on p38α-inhibitor complex structures, most importantly soaking versus cocrystallization, is discussed. Analysis of the structures and quantification of the protein-ligand interactions couples ligand-induced protein conformations to the number of interactions and to inhibitor selectivity against the human kinome. This shows that for the design of novel kinase inhibitors, selectivity is best obtained through maximization of the number of interactions throughout the ATP pocket and the exploitation of specific features in the active site.
Functional nanoparticle architectures for sensoric, optoelectronic, and bioelectronic applications (2002)

Abstract Tailored sensoric, electronic, photoelectrochemical, and bioelectrocatalytic functions can be designed by organized molecular or biomolecular nanoparticle hybrid configurations on surfaces. Layered receptor-cross-linked Au nanoparticle assemblies on electrodes act as specific sensors of tunable sensitivities. Layered DNA-cross-linked CdS nanoparticles on electrode supports reveal organized assemblies of controlled electronic and photoelectrochemical properties. Au nanoparticle-FAD semisynthetic cofactor units are reconstituted into apo-glucose oxidase (GOx) and assembled onto electrodes. The resulting enzymes reveal effective electrical contacting with the electrodes, and exhibit bioelectrocatalytic functions toward the oxidation of glucose to gluconic acid. Magneto-switchable electrocatalysis and bioelectrocatalysis are accomplished by the surface modification of magnetic particles with redox-relay units. By the attraction of the modified magnetic particles to the electrode support, or their retraction from the electrode, by means of an external magnet, the electrochemical functions of the magnetic particle-tethered relays can be switched between "ON" and "OFF" states, respectively. The magneto-switchable redox functionalities of the modified particles activate electrocatalytic transformations, such as a biocatalytic chemoluminescence cascade that leads to magneto-switchable light emission or the activation of bioelectrocatalytic processes.
Combinatorial Synthesis of Natural Product-Based Libraries (2006)

Chemistry on the Interface of Natural Products and Combinatorial Chemistry Armen M. Boldi and Dean R. Dragoli Natural Products and Combinatorial Chemistry - An Uneasy Past but a Glorious Future A. Ganesan Computational Analysis of Natural Molecules and Strategies for the Design of Natural Product-Based Compound Libraries Florence L. Stahura and Jurgen Bajorath Accessing Expanded Molecular Diversity through Engineered Biosynthesis of Natural Products Steven D. Dong and David C. Myles Natural Product-Based, Chemically and Functionally Diverse Libraries Peter Eckard, Ulrich Abel, Hans-Falk Rasser, Werner Simon, Bernd Sontag, and Friedrich G. Hansske The Use of Polymer-Supported Reagents and Scavengers in the Synthesis of Natural Products Steven V. Ley, Ian R. Baxendale, and Rebecca M. Myers Carbohydrate-Derived Small-Molecule Libraries Armen M. Boldi In Search of Novel Antibiotics Using a Natural Product Template Approach Michael J. Sofia Synthetic Libraries of Fungal Natural Products Michael C. Pirrung, Zhitao Li, and Hao Liu Solid-Phase Combinatorial Synthesis Based on Natural Products Takayuki Doi and Takashi Takahashi Employing Natural Product-Like Combinatorial Libraries in the Discovery of Lead Libraries Pedro M. Abreu, Paula S. Branco, and Susan Matthew Index
β-Peptides: a surprise at every turn (1997)

β-Peptides, i.e. oligomers of β-amino acids, containing as few as six residues may form surprisingly stable helices, with half-lives for the H/D exchange of the central NH protons of up to several days. Furthermore, these β-peptides (carrying the side chains of familiar α-amino acids such as Ala, Val, Leu, Phe, Lys in the 2- and/or 3-position of their 3-amino carboxylic moieties) have been shown to be stable to common peptidases for at least two days. In this article, a brief account of the results obtained since we started work in this area in early 1995 is given. The synthesis of enantiopure β-amino acids can be achieved by homologation of α-amino acids. The greater structural variability of β-amino acids leads to an even greater multitude of possible β-peptide primary and secondary structures. Circular dichroism, NMR and X-ray investigations have unveiled helical, pleated-sheet and tubular arrangements of linear and cyclic β-peptides composed of up to twelve β-amino acids. The prospects for the use of β-peptides as drugs, the construction of large, enzymatically-active β-proteins and their interaction with the natural, α-peptidic counterparts are discussed.
Spontaneous production of gamma-interferon in cultures of T lymphocytes obtained from patients with Behçet's disease. (1983)

The spontaneous production of interferon (IFN) in the cultures of peripheral blood mononuclear leukocytes (PBML) obtained from 30 patients with Behçet's disease was investigated. PBML obtained from each of 26 patients in the convalescent stage and four patients in the exacerbation stage were cultured at least twice without stimulation, and IFN activity in the culture fluid 2 to 7 days after the cultivation was assayed. Twenty PBML of normal healthy donors were also cultured simultaneously. PBML of all patients in the convalescent stage spontaneously produced high-titered IFN (60.0 +/- 9.5 IU/ml), but IFN activity produced in PBML cultures of four patients in the exacerbation stage was very low or was undetectable. Similarly, IFN was always detectable in the circulation of the patients whose PBML spontaneously produced IFN. All IFN activity detected both in the circulation and in the fluid of PBML culture from these patients was gamma-IFN, defined by virtue of its acid lability and antigenicity neutralized with antiserum for gamma-IFN and not with antisera for alpha- and beta-IFN. The cellular source of this gamma-IFN in the patients' PMBL was T lymphocytes and not non-T cells or macrophages. T lymphocytes did not require the help of macrophages. It is suggested that T lymphocytes of these patients may be stimulated by unknown causative agents in vivo and may produce gamma-IFN in vivo as well as in in vitro culture of T lymphocytes.
Anti-Cancer Effect of IN-2001 in T47D Human Breast Cancer (2012)

Histone deacetylases (HDACs) are enzymes involved in the remodelling of chromatin, and have a key role in the epigenetic regulation of gene expression. Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anti-cancer agents. In recent years, a number of structurally diverse HDAC inhibitors have been identified and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. However, the underlying molecular mechanisms remain unclear. This study aimed at investigating the anti-tumor activity of various HDAC inhibitors, IN-2001, using T47D human breast cancer cells. Moreover, the possible mechanism by which HDAC inhibitors exhibit anti-tumor activity was also explored. In estrogen receptor positive T47D cells, IN-2001, HDAC inhibitor showed anti-proliferative effects in dose-and time-dependent manner. In T47D human breast cancer cells showed anti-tumor activity of IN-2001 and the growth inhibitory effects of IN-2001 were related to the cell cycle arrest and induction of apoptosis. Flow cytometry studies revealed that IN-2001 showed accumulation of cells at G2/M phase. At the same time, IN-2001 treatment time-dependently increased sub-G1 population, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with induction of cdk inhibitor expression. In T47D cells, IN-2001 as well as other HDAC inhibitors treatment significantly increased p21(WAF1) and p27(KIP1) expression. In addition, thymidylate synthase, an essential enzyme for DNA replication and repair, was down-regulated by IN-2001 and other HDAC inhibitors in the T47D human breast cancer cells. In summary, IN-2001 with a higher potency than other HDAC inhibitors induced growth inhibition, cell cycle arrest, and eventual apoptosis in human breast cancer possibly through modulation of cell cycle and apoptosis regulatory proteins, such as cdk inhibitors, cyclins, and thymidylate synthase.
Alcohol and the intensive care unit: It’s not just an antiseptic* (2007)

Division of Burns, Trauma, Critical Care, University of Texas Southwestern Medical School, Dallas, TX
Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. (1985)

A series of human carcinoma cell lines was examined for human papillomavirus (HPV) DNA sequences with the use of HPV-6, HPV-11, HPV-16, and HPV-18 DNA probes. Six of eight cell lines derived from human cervical carcinomas were shown to contain integrated HPV DNA sequences. In five of these six lines, HPV-specific polyadenylated RNA species could also be identified. The expression of HPV sequences was detected in three lines with a HPV-18 DNA probe and in two lines with a HPV-16 DNA probe. Of the two lines which contained HPV-16 specific RNA, one contained HPV DNA sequences which hybridized only to an HPV-16 probe, and the other contained HPV DNA sequences which hybridized to both HPV-16 and HPV-18 DNA probes. Six cell lines established from human squamous-cell carcinomas of the bladder, pharynx, lung, esophagus, and vulva were negative for HPV-6, HPV-11, HPV-16, and HPV-18 DNA sequences under stringent hybridization conditions.
Factors Affecting Recombinant Frequency in Protoplast Fusions of Streptomyces coelicolor (1979)

The optimum concentration of polyethylene glycol 1000 (PEG) for the production of recombinants through protoplast fusion in Streptomyces coelicolor was about 50% (w/v). The addition of 14% (v/v) dimethyl sulphoxide to the fusion mixture enhanced recombination frequencies, but only at sub-optimal PEG concentrations. After treatment of protoplasts with 50% PEG for 1 min, the frequency of recombinants in a multi-factor 'cross' sometimes exceeded 20% of the total progeny. The frequency of recombinants in the progeny could be significantly enhanced by ultraviolet irradiation of the parental protoplast suspensions immediately before fusion.
IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo (2006)

IL-2 plays a critical role in the maintenance of CD4+CD25+ FOXP3(+) regulatory T cells (Tregs) in vivo. We examined the effects of IL-2 signaling in human Tregs. In vitro, IL-2 selectively up-regulated the expression of FOXP3 in purified CD4+CD25+ T cells but not in CD4+CD25- cells. This regulation involved the binding of STAT3 and STAT5 proteins to a highly conserved STAT-binding site located in the first intron of the FOXP3 gene. We also examined the effects of low-dose IL-2 treatment in 12 patients with metastatic cancer and 9 patients with chronic myelogenous leukemia after allogeneic hematopoietic stem cell transplantation. Overall, IL-2 treatment resulted in a 1.9 median fold increase in the frequency of CD4+CD25+ cells in peripheral blood as well as a 9.7 median fold increase in FOXP3 expression in CD3+ T cells. CD56+CD3- natural killer (NK) cells also expanded during IL-2 therapy but did not express FOXP3. In vitro treatment of NK cells with 5-aza-2'-deoxycytidine restored the IL-2 signaling pathway leading to FOXP3 expression, suggesting that this gene was constitutively repressed by DNA methylation in these cells. Our findings support the clinical evaluation of low-dose IL-2 to selectively modulate CD4+CD25+ Tregs and increase expression of FOXP3 in vivo.
An ocean-bottom seismometer capsule (1974)

abstract An ocean-bottom seismometer capsule containing a 1-Hz vertical seismometer and triggered digital recording system has been developed and tested off the coast of San Diego. The output of the seismometer is continuously digitized at 64, 128, or 256 samples per second. The digital data is mixed with a time code and passed through a 256 sample shift register which acts as a delay line. It is then mixed with synchronization characters, serialized, encoded, and recorded on a SONY TC800B tape recorder which is turned on when a seismic event occurs. The event trigger occurs when the seismic signal jumps to at least twice the time-averaged input signal. Data are recovered using the same recorder for playback and a decoder which provides an analog output for field data interpretation or a digital output for computer analysis. The capsule itself falls freely to the ocean bottom. After a predetermined time it is released from a 150-lb steel tripod and floats to the surface. A dual timer and explosive bolt system provides a high recovery reliability. A number of seismic events have been measured in field tests and the system has proven to be extremely simple to check out, diagnose, and deploy.
A 20-GHz Phase-Locked Loop for 40Gb/s Serializing Transmitter in 0.13μm CMOS (2005)

A 20GHz phase-locked loop with 4.9ps/sub pp//0.65ps/sub rms/ jitter and -101.2dBc/Hz phase noise at 1MHz offset is presented. A half-duty sampled-feedforward loop filter that simply replaces the resistor with a switch and an inverter suppresses the reference spur down to -44.0dBc. A design iteration procedure is outlined that minimizes the phase noise of a negative-g/sub m/ oscillator with a coupled-microstrip resonator. Static frequency dividers made of pulsed latches operate faster than a flip-flop based divider and achieve near 2:1 frequency range. The PLL fabricated in 0.13/spl mu/m CMOS operates from 17.6GHz to 19.4GHz and dissipates 480mW.
Delivery of bioactive molecules to mitochondria in vivo (2003)

Mitochondrial dysfunction contributes to many human degenerative diseases but specific treatments are hampered by the difficulty of delivering bioactive molecules to mitochondria in vivo. To overcome this problem we developed a strategy to target bioactive molecules to mitochondria by attachment to the lipophilic triphenylphosphonium cation through an alkyl linker. These molecules rapidly permeate lipid bilayers and, because of the large mitochondrial membrane potential (negative inside), accumulate several hundredfold inside isolated mitochondria and within mitochondria in cultured cells. To determine whether this strategy could lead to the development of mitochondria-specific therapies, we investigated the administration and tissue distribution in mice of simple alkyltriphenylphosphonium cations and of mitochondria-targeted antioxidants comprising a triphenylphosphonium cation coupled to a coenzyme Q or vitamin E derivative. Significant doses of these compounds could be fed safely to mice over long periods, coming to steady-state distributions within the heart, brain, liver, and muscle. Therefore, mitochondria-targeted bioactive molecules can be administered orally, leading to their accumulation at potentially therapeutic concentrations in those tissues most affected by mitochondrial dysfunction. This finding opens the way to the testing of mitochondria-specific therapies in mouse models of human degenerative diseases.
Camphor Activates and Strongly Desensitizes the Transient Receptor Potential Vanilloid Subtype 1 Channel in a Vanilloid-Independent Mechanism (2005)

Camphor is a naturally occurring compound that is used as a major active ingredient of balms and liniments supplied as topical analgesics. Despite its long history of common medical use, the underlying molecular mechanism of camphor action is not understood. Capsaicin and menthol, two other topically applied agents widely used for similar purposes, are known to excite and desensitize sensory nerves by acting on two members of transient receptor potential (TRP) channel superfamily: heat-sensitive TRP vanilloid subtype 1 (TRPV1) and cold-sensitive TRP channel M8, respectively. Camphor has recently been shown to activate TRPV3, and here we show that camphor also activates heterologously expressed TRPV1, requiring higher concentrations than capsaicin. Activation was enhanced by phospholipase C-coupled receptor stimulation mimicking inflamed conditions. Similar camphor-activated TRPV1-like currents were observed in isolated rat DRG neurons and were strongly potentiated after activation of protein kinase C with phorbol-12-myristate-13-acetate. Camphor activation of rat TRPV1 was mediated by distinct channel regions from capsaicin, as indicated by camphor activation in the presence of the competitive inhibitor capsazepine and in a capsaicin-insensitive point mutant. Camphor did not activate the capsaicin-insensitive chicken TRPV1. TRPV1 desensitization is believed to contribute to the analgesic actions of capsaicin. We found that, although camphor activates TRPV1 less effectively, camphor application desensitized TRPV1 more rapidly and completely than capsaicin. Conversely, TRPV3 current sensitized after repeated camphor applications, which is inconsistent with the analgesic role of camphor. We also found that camphor inhibited several other related TRP channels, including ankyrin-repeat TRP 1 (TRPA1). The camphor-induced desensitization of TRPV1 and block of TRPA1 may underlie the analgesic effects of camphor.
An Assessment of Phenotype Selection for Linolenic Acid Using Genetic Markers (2006)

Marker assisted selection (MAS) procedures potentially can make breeding more efficient, as genotypes can be identified before pollination allowing breeders to cross or backcross only suitable materials. Our objective was to assess the accuracy of our phenotypic selections in soybean [ Glycine max (L.) Merr.] for linolenic acid using molecular markers specific for mutations in two fatty acid desaturase genes, Gm FAD3A and Gm FAD3C The markers were not available earlier in the selection process and were used retrospectively to determine that phenotypic selection for seed linolenic acid ≤ 35 g kg −1 oil was successful in capturing genotypes homozygous for mutant alleles at both loci, but phenotypic selection was not perfect. Chemical analysis for seed linolenic acid concentration was not an accurate predictor of genotype. The advancement of heterozygotes reduced the selection efficiency relative to what would have been possible using molecular markers specific for mutations in the two fatty acid desaturase genes. Errors are thought to have derived from inaccurate sample tracking or identification, contamination, or errors in chemical analyses. Use of mutation‐specific molecular markers to identify F 2 lines homozygous for mutant alleles in Gm FAD3A and Gm FAD3C , combined with diligence in reducing sampling errors, would eliminate the need for chemical testing for linolenic acid content in subsequent generations where screening can emphasize other traits.
Binding characteristics of Hoechst 33258 with calf thymus DNA, poly[d(A-T)] and d(CCGGAATTCCGG): multiple stoichiometries and determination of tight binding with a wide spectrum of site affinities (1990)

Equilibrium binding experiments using fluorescence and absorption techniques have been performed throughout a wide concentration range (1 nM to 30 microM) of the dye Hoechst 33258 and several DNAs. The most stable complexes found with calf thymus DNA, poly[d(A-T)], d(CCGGAATTCCGG), and d(CGCGAATTCGCG) all have dissociation constants in the range (1-3) X 10(-9) M-1. Such complexes on calf thymus DNA occur with a frequency of about 1 binding site per 100 base pairs, and evidence is presented indicating a spectrum of sequence-dependent affinities with dissociation constants extending into the micromolar range. In addition to these sequence-specific binding sites on the DNA, the continuous-variation method of Job reveals distinct stoichiometries of dye-poly[d(A-T)] complexes corresponding to 1, 2, 3, 4, and 6 dyes per 5 A-T base pairs and even up to 1 and 2 (and possibly more) dyes per backbone phosphate. Models are suggested to account for these stoichiometries. With poly[d(G-C)] the stoichiometries are 1-2 dyes per 5 G-C pairs in addition to 1 and 2 dyes per backbone phosphate. Thermodynamic parameters for formation of the tightest binding complex between Hoechst 33258 and poly[d(A-T)] or d-(CCGGAATTCCGG) are determined. Hoechst 33258 binding to calf thymus DNA, chicken erythrocyte DNA, and poly[d(A-T)] exhibits an ionic strength dependence similar to that expected for a singly-charged positive ion. This ionic strength dependence remains unchanged in the presence of 25% ethanol, which decreases the affinity by 2 orders of magnitude. In addition, due to its strong binding, Hoechst 33258 easily displaces several intercalators from DNA.
Structure of the CRISPR Interference Complex CSM Reveals Key Similarities with Cascade (2013)

The Clustered Regularly Interspaced Palindromic Repeats (CRISPR) system is an adaptive immune system in prokaryotes. Interference complexes encoded by CRISPR-associated (cas) genes utilize small RNAs for homology-directed detection and subsequent degradation of invading genetic elements, and they have been classified into three main types (I-III). Type III complexes share the Cas10 subunit but are subclassifed as type IIIA (CSM) and type IIIB (CMR), depending on their specificity for DNA or RNA targets, respectively. The role of CSM in limiting the spread of conjugative plasmids in Staphylococcus epidermidis was first described in 2008. Here, we report a detailed investigation of the composition and structure of the CSM complex from the archaeon Sulfolobus solfataricus, using a combination of electron microscopy, mass spectrometry, and deep sequencing. This reveals a three-dimensional model for the CSM complex that includes a helical component strikingly reminiscent of the backbone structure of the type I (Cascade) family.
The GOD-H2O2-electrode as an approach to implantable glucose sensors. (1988)

The long-term function of glucose sensors under in-vivo conditions is the first prerequisite in the development of glucose-controlled insulin infusion systems. Amperometric enzyme glucose sensors measuring H2O2 from the enzymatic glucose oxidation are defeated to certain poisoning effects of the electrochemical system and to alterations of the diffusional properties, both resulting in unpredictable changes of the sensor signal. To interpret the signal of subcutaneously implanted sensors after reaching a certain balance of the altering processes, the wick-technique has been established as an independent reference method applicable in the interstitial fluid. Based on the comparison of the wick-glucose concentration and the circulating plasma glucose concentration the in vivo-calibration of the sensor current according to plasma glucose concentration is proven.