gebhart/patrepeval huggingface dataset:
Comparison of a DSB-120 DNA Interstrand Cross-Linked Adduct with the Corresponding Bis-tomaymycin Adduct: An Example of a Successful Template-Directed Approach to Drug Design Based upon the Monoalkylating Compound Tomaymycin (1994)

The interstrand cross-linked DSB-120-d(CICG*ATCICG)2 DNA adduct (*indicates covalently modified guanine) was examined by two-dimensional NMR and compared to the bis-tomaymycin adduct on the same oligomer. Tomaymycin and DSB-120 form self-complementary adducts with the d(CICGATCICG)2 duplex sequence in which the covalent linkage sites occur between C11 of either drug and the exocyclic 2-amino group of the single reactive guanine on each strand of d(CICGATCICG)2. In the case of DSB-120, this is evidence for the formation of a guanine--guanine DNA interstrand cross-link. Both drugs show formation of an S stereo-chemistry at the covalent linkage site with an associated 3' orientation. While the majority of DNA in these adducts appears to be B-form, DSB-120 interstrand cross-linking induces atypical properties in the 8I nucleotide, indicated by broadening of the 8IH2 proton resonance, non-C2' endo sugar geometry, and unusually weak internucleotide NOE connectivity to the 7C nucleotide. Tomaymycin does not produce this regional dislocation. For tomaymycin, while there are strong NOE connectivities from protons on the five-membered ring to the 8IH2 proton on the floor of the minor groove, the equivalent internucleotide connectivities in DSB-120 are weaker. This indicates that the tomaymycin tail is close to the floor of the minor groove, while the five-membered ring of DSB-120 is more shallowly immersed, perhaps due to strain from cross-linking with a very short linker unit. Last, the conformational stresses induced on the duplex by DSB-120 appear to make the region of covalent attachment more accessible to solvent than is the case for tomaymycin. The 4GN2Hb resonance appears in 100% D2O on the tomaymycin adduct but is only observed in 90% H2O/10% D2O for the DSB-120 adduct. On the basis of these results, the strategies for template-directed DNA cross-linker design are assessed.
An In Vitro Comparative Study on the Reactivation of Nerve Agent-Inhibited Guinea Pig and Human Acetylcholinesterases by Oximes (2007)

The reactivation of nerve agent-inhibited acetylcholinesterase (AChE) by oxime is the most important step in the treatment of nerve agent poisoning. Since the evaluation of nerve agent antidotes cannot be conducted in humans, results from animal experiments are extrapolated to humans. Guinea pig is one of the animal models that is frequently used for conducting nerve agent antidote evaluations. Several investigations have demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited AChE. If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Therefore, the goal of this study was to compare the reactivation of guinea pig and human AChEs inhibited by six different G and V type nerve agents. Reactivation kinetic studies with five mono- and bis-pyridinium oximes showed that oxime reactivation of nerve agent-inhibited human AChE in most cases was faster than guinea pig AChE. The most significant enhancement was observed in the reactivation of human AChE inhibited by nerve agents containing bulky side chains GF, GD, and VR, by H-series oximes HLo-7, HI-6, and ICD-585. In these cases, species-related differences observed between the two AChEs, based on the second-order reactivation rate constants, were 90- to over 400-fold. On the other hand, less than 3-fold differences were observed in the rates of aging of nerve agent-inhibited guinea pig and human AChEs. These results suggest that the remarkable species-related differences observed in the reactivation of nerve agent-inhibited guinea pig and human AChEs were not due to differences in the rates of aging. These results also suggest that guinea pig may not be an appropriate animal model for the in vivo evaluation of oxime therapy.
Fabrication of Nano-precision PDMS Replica Using Two-photon Photopolymerization and Vacuum Pressure Difference Technique (2004)

It is undoubtingly believed that a revolution in miniaturization, in the field of microelectromechanical systems (MEMS), nano- and biotechnology etc., is under way. Multidimensional micro structures are fabricated by mainly two methods, such as laser rapid prototyping and lithography. Since it is a process that builds features layer by layer, rapid prototyping is a very slow process and is difficult to fabricate smaller objects. 1 On the other hand, the conventional lithographic technique requires an etching process that limits to build complicated figures. Recently, two-photon photopolymerization has attracted increasing attention as an innovative tool for micro- and nanofabrication due to its intrinsic multi-dimensional fabrication capability and subdiffraction limited spatial resolution. 2,3 Two-photon absorption probability strongly depends quadratically on excitation beam intensity confining the process at the vicinity of the focus. Thus, by using two-photon excitation one can activate chemical and physical processes only for a tightly focused spot in the bulk medium with high spatial resolution. This substantial increase in structural complexity was only possible by using chromophores with high two-photon absorption cross-sections (σ ). It is apparent that the synthesis of chromophores with even larger two-photon activity will unleash improvements in the capability and performance of a variety of two-photon absorption application including multi-dimensional nano- and microfabrication. In this paper, we describe the synthesis of newly designed highly efficient two-photon chromophore and fabrication of three-dimensional nano-precision PDMS replica using vacuum pressure difference technique (VPDT) and twophoton photopolymerization. The two-photon absorbing chromophore 3 with long alkyl chain for improved solubility was synthesized using palladium catalyzed coupling reaction designed by Heck 4 from compound 1 and 2. The compound 1 was obtained from Vilsmeier-Haack fomylation of triphenylamine followed by Wittig raction, and the 2,7dibromofluorene was reacted with excess amount of ethylhexylbromide to give compound 2. The resulting twophoton chromophore 3 was extensively purified before use as a light sensitizer/photoinitiator in two-photon photopolymerization. 5 The optical transparency of a chromophore at the wavelength of operation is crucial for successful 3D microfabrication with two-photonpolymerzation. As shown in steady-state absorption and emission spectra (Figure 1), the two-photon chromophore 3 has no absorption beyond 475 nm making itself ideal for two-photon application at the wavelength of 780 nm which is wavelength of our interest. Two-photon absorption cross-section of chromophore 3 at 780 nm was found to be σ = 4.7 × 10 −48 cm 4 s/photon with
Fumaric acid overproduction in yeast mutants deficient in fumarase (1992)

A nuclear mutant of Saccharomyces cerevisiae deficient in mitochondrial fumarase has been identified through the in vitro biochemical assay of enzyme activity after visual selection due to an increased acidification ability of its colonies. Cells of the fumarase-deficient mutant fermenting glucose accumulated extracellular fumaric acid. This accumulation was observed only in growing cultures and required functional mitochondrial electron transport from succinate dehydrogenase to oxygen.
Highly Conductive and Transparent Silicon Doped Zinc Oxide Thin Films Prepared by RF Magnetron Sputtering (1986)

Highly conductive and transparent films of Si-doped ZnO have been prepared by rf magnetron sputtering of a ZnO target with SiO 2 or SiO dopant added. Films with resistivity as low as 3.8×10 -4 Ω cm and average transmittance above 85% in the visible region can be produced on low temperture substrates at below 250°C. Great improvement in the stability of the resistivity for use at high temperatures was obtained for Si-doped ZnO films in comparison with undoped films.
A microfluidic analysis of thrombus formation in reconstituted whole blood samples comparing spray‐dried plasma versus fresh frozen plasma (2020)

Spray-dried plasma is not inferior in supporting haemostasis compared with fresh frozen plasma in a paired analysis. It offers advantages with respect to portability and ease of preparation over frozen plasma in the pre-hospital setting. This study supports development of clinical studies to evaluate the efficacy and safety of spray-dried plasma in trauma patients.
The Relationship between Muscle Mass and Muscle Strength in the Elderly (1991)

To determine the extent that muscle mass is predictive of muscle strength in the elderly, anthropomorphic estimates of muscle area and impedance measurements of muscle mass and peak isometric muscle strength were obtained in a relatively healthy older population over 65 years of age (mean age = 71.7; n = 218). Midarm muscle area correlated strongly with upper arm strength (r = 0.68, P less than 0.0001) while midthigh muscle area had a much lower correlation with thigh muscle strength (r = 0.29, P less than 0.0001). These muscle area calculations also include bone area. Lean body mass calculated by bioelectric impedance correlated highly with cumulative muscle strength measured by summing all muscle groups (r = 0.79, P less than 0.0001). To determine whether aging alters muscle strength per unit of muscle mass, additional middle-aged subjects were included, and three groups, middle-aged (55-64) (n = 78), young-old (65-74) (n = 161), and old-old (75+) (n = 57), were compared. A significant age-related trend of decreasing muscle strength per unit of lean body mass was noted. It is concluded that although muscle mass correlates with muscle strength in a healthy older population, use of simple age-independent clinical measurements of body mass should not be used to predict muscle strength.
Expression of vascular endothelial growth factor isoforms and their receptors Flt‐1, KDR, and neuropilin‐1 in synovial tissues of rheumatoid arthritis (2000)

Angiogenesis is an indispensable process in the chronic proliferative synovitis and pannus formation of rheumatoid arthritis (RA). This study examined the expression of vascular endothelial growth factor (VEGF) isoforms and VEGF receptors, Flt-1, KDR and neuropilin-1, in RA and osteoarthritis (OA) synovia, and studied the relationship between their expression and the synovial angiogenesis. By RT-PCR analysis, the isoform VEGF121 was constitutively expressed in all the RA (17/17 patients) and OA (8/8 patients) synovia. In contrast, the expression of the isoform VEGF165 was observed in 41% of the RA synovia (7/17 patients), but was undetectable in the OA samples (0/8 patients). The receptor Flt-1 was almost constitutively expressed in RA (15/17 patients) and OA (8/8 patients) synovia, while the expression of KDR was detected in the synovia of six RA patients (6/17 patients; 35%) but none of the OA patients (0/8 patients). The expression of neuropilin-1, an isoform-specific receptor for VEGF165 which enhances the binding of VEGF165 to KDR, was also up-regulated in the same RA synovia that expressed KDR. Furthermore, there was a close correlation between the expression of isoform VEGF165 and that of its receptors KDR and neuropilin-1. Morphometric analysis demonstrated that the vascular density is significantly higher in the RA synovial tissues with expression of VEGF165, KDR, and neuropilin-1 than in those without their expression (p<0.01). In situ hybridization and immunohistochemical studies indicated that the cells expressing VEGF are macrophage-like synovial lining cells and spindle-shaped cells in the sublining cell layer. These results suggest that the selective up-regulation of the isoform VEGF165 and its signalling via KDR and neuropilin-1 play an important role in the synovial angiogenesis which occurs in RA. Copyright © 2000 John Wiley & Sons, Ltd.
Strain Differences in the Somnogenic Effects of Interferon Inducers in Mice (1996)

Increased slow-wave sleep accompanies influenza infection in C57BL/6 mice but not BALB/c mice. These strains of mice possess different alleles of the genetic lucus If-1, which codes for high (If-1h; C57BL/6) and low (If-1(1); BALB/c) production of interferon (IFN), a putative sleep-inducing cytokine. To evaluate the contribution of the If-1 gene to differences in murine sleep propensity, sleep patterns were evaluated in mice treated with the IFN inducers polyinosinic:polycytidilic acid (pIC) or Newcastle disease virus (NDV), with influenza virus, or with murine interferon (IFN-alpha) or IFN-alpha/beta. As compared with baseline values, C57BL/6 mice exhibited increased slow-wave sleep after all three challenges, but BALB/c mice did not. Congenic B6.C-H28c mice, which bear the BALB/c allele for low IFN production on the C57BL/6 genetic background, showed enhanced slow-wave sleep after influenza infection but not after NDV. Exogenous IFN did not enhance slow-wave sleep in either C57BL/6 or BALB/c mice. These data suggest that the If-1 allele may influence the somnogenic responsiveness of mice under some conditions but that additional mechanisms may contribute to sleep enhancement during infectious disease.
Serotype Distribution and Antimicrobial Resistance Patterns of Invasive Isolates ofStreptococcus pneumoniae:Alaska, 1991–1998 (2000)

From January 1991 through December 1998, a total of 1046 pneumococcal isolates were received from 23 laboratories participating in the statewide surveillance system. Of these, 1037 were recovered from normally sterile sites (blood and cerebrospinal and pleural fluid) and were available for serotyping and susceptibility testing. Ninety-two percent of these isolates were serotypes represented in the 23-valent pneumococcal polysaccharide vaccine. Serotypes in the 7-valent pneumococcal conjugate vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) were recovered from 72% of Alaska Natives and 84% of non-Native children <5 years old with invasive disease. Statewide, 7.3% and 3.2% of isolates had intermediate and high levels of resistance to penicillin, respectively; 9.2% were resistant to erythromycin (minimal inhibitory concentration, >/=1 microg/mL) and 19% to trimethoprim/sulfamethoxazole (minimal inhibitory concentration, >/=4/76 microg/mL). Twelve percent of invasive isolates were resistant to >/=2 classes of antibiotics; of these, serotype 6B accounted for 33%, and 63% were recovered from children <5 years old.
Region X, the cell‐wall‐attachment part of staphylococcal protein A (1984)

The sequence of region X of staphylococcal protein A has been determined. The hypothesis has been put forward that this region spans the Staphylococcus aureus cell wall and is responsible for the binding to the peptidoglycan. The primary amino acid sequence of region X was determined for two strains exhibiting cell-wall-bound protein A, Cowan I and 8325-4. The sequence determination of the Cowan I material is partial and was performed by Edman degradation, in contrast to the sequence of the 8325-4 material which was completely analyzed by nucleotide sequencing of the corresponding gene. The region consists of two structurally different domains, a highly repetitive region (Xr), with an octapeptide structure repeated approximately 12 times, and a C-terminal domain (Xc) with an unique sequence. A comparison between the two strains reveals a high mutual homology as well as a high internal homology between the octapeptide structures. Six out of eight amino acids are identical in the repetition of this structure throughout region Xr in both proteins and the other two are changed in a rather regular pattern.
Automated Protein Identification Using Microcolumn Liquid Chromatography-Tandem Mass Spectrometry (2003)

The sequencing of complete genomes is providing an enormous resource for understanding the biology of organisms (). A complete genome sequence, however, will still leave many unanswered questions about the basic biology of the organism. Which open reading frames are authentic genes? What genes express highly abundant proteins in the cell? How well do the observed physical properties of a protein agree with the predictions of the genomic sequence? Which proteins are covalently processed? Analysis of the proteins encoded in the genome or “the proteome” can answer many of these questions, and will help in understanding the physiology of the organism.
Simultaneous Multianalyte ELISA Performed on a Microarray Platform (2001)

Multiplexed ELISA arrays are a feasible option for analyte quantification in complex biologic samples.
Molecular analysis of the modulatory factors of the response to HBsAg in mice as an approach to HBV vaccine enhancement (1996)

Mice were injected with immune complexes containing the recombinant hepatitis B surface antigen (HBsAg) vaccine (S + preS2) bound to different monoclonal antibodies (mAbs), in order to determine whether an enhancement of the response to a human vaccine could be obtained and observed. Enhancement and indifference were observed, as well as a decrease in immunogenicity. N relationship could be established between any effect and affinity or isotypy of the bound mAbs. The preS2 region was rendered more immunogenic when an IgG2a mAb was bound to the S region of the HBsAg. The response to the S region was not modulated, whereas immunogenicity of the preS2 collinear region was decreased by antibody shielding. The mAb which was the most efficient as an enhancer of the antibody response also increased binding of the complexed immunogen to antigen presenting cells. The binding of a human mAb to the sole S region, but not to the preS2 region, should be tested as a potentiating agent of the anti-preS2 human immune response.
Inhibition of the Sodium Potassium Adenosine Triphosphatase Pump Sensitizes Cancer Cells to Anoikis and Prevents Distant Tumor Formation (2009)

Normal epithelial cells undergo apoptosis upon detachment from the extracellular matrix, a process termed "anoikis." However, malignant epithelial cells with metastatic potential resist anoikis and can survive in an anchorage-independent fashion. Molecules that sensitize resistant cells to anoikis will be useful chemical probes to understand this pathway. To identify novel anoikis sensitizers in anoikis-resistant PPC-1 prostate adenocarcinoma cells, a library of 2,000 off-patent drugs and natural products was screened for their ability to preferentially induce cell death in suspension over adherent culture conditions. This screen identified five members of the family of cardiac glycosides as anoikis sensitizers, including ouabain, peruvoside, digoxin, digitoxin, and strophanthidin. We conducted further studies with ouabain to discern the mechanism of cardiac glycoside-induced anoikis sensitization. Ouabain initiated anoikis through the mitochondrial pathway of caspase activation. In addition, ouabain sensitized cells to anoikis by inhibiting its known target, the Na(+)/K(+) ATPase pump, and inducing hypoosmotic stress. Resistance to anoikis permits cancer cells to survive in the circulation and facilitates their metastasis to distant organs, so we tested the effects of Na(+)/K(+) ATPase inhibition on distant tumor formation in mouse models. In these mouse models, ouabain inhibited tumor metastases but did not alter the growth of subcutaneous tumors. Thus, we have identified a novel mechanism to sensitize resistant cells to anoikis and decrease tumor metastasis. These results suggest a potential mechanism for the observed clinical reduction in metastasis and relapse in breast cancer patients who have undergone treatments with cardiac glycosides.
The role of anemia in the progression of congestive heart failure. Is there a place for erythropoietin and intravenous iron? (2004)

Anemia is found in about one-third of all cases of congestive heart failure (CHF). The most likely common cause is chronic kidney insufficiency (CKI), which is present in about half of all CHF cases. The CKI is likely to be due to the renal vasoconstriction that often accompanies CHF and can cause long-standing renal ischemia. This reduces the amount of erythropoietin (EPO) produced in the kidney and leads to anemia. However, anemia can occur in CHF without CKI and is likely to be due to excessive cytokine production (for example, tumor necrosis factor-alfa (TNF-alfa) and interleukin-6 (IL-6)), which is common in CHF and can cause reduced EPO secretion, interference with EPO activity in the bone marrow and reduced iron supply to the bone marrow. The anemia itself can worsen cardiac function, both because it causes cardiac stress through tachycardia and increased stroke volume, and because it can cause a reduced renal blood flow and fluid retention, adding further stress to the heart. Long-standing anemia of any cause can cause left ventricular hypertrophy (LVH), which can lead to cardiac cell death through apoptosis and worsen the CHF. Therefore, a vicious circle is set up wherein CHF causes anemia, and the anemia causes more CHF and both damage the kidneys worsening the anemia and the CHF further. We have termed this vicious circle the cardio renal anemia (CRA) syndrome. Patients with CHF who are anemic are often resistant to all CHF medications resulting in being hospitalized repeatedly. Many studies also demonstrate that these patients die more rapidly than their non-anemic counterparts do. In addition, they have a more rapid deterioration in their renal function and can end up on dialysis. There is now evidence from both uncontrolled and controlled studies that early correction of the CHF anemia with subcutaneous EPO and intravenous (i.v.) iron improves shortness of breath and fatigue, cardiac function, renal function and exercise capability, dramatically reducing the need for hospitalization. For these reasons, it is not surprising that quality of life has also been shown to improve. As both CHF and end-stage renal disease (ESRD) are rapidly increasing, the possibility that these twin conditions can be improved by the adequate treatment of anemia offers new hope for slowing the progression of both conditions.
The Preparation of Heterocyclic Fluorine Compounds by the Schiemann Reaction. III. Some Monofluoroisoquinolines1 (1951)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Preparation of Heterocyclic Fluorine Compounds by the Schiemann Reaction. III. Some Monofluoroisoquinolines1Arthur Roe and Claude E. Teague Jr.Cite this: J. Am. Chem. Soc. 1951, 73, 2, 687–688Publication Date (Print):February 1, 1951Publication History Published online1 May 2002Published inissue 1 February 1951https://doi.org/10.1021/ja01146a054Request reuse permissionsArticle Views353Altmetric-Citations18LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (306 KB) Get e-Alertsclose Get e-Alerts