gebhart/patrepeval huggingface dataset:
Drusen, choroidal neovascularization, and retinal pigment epithelium dysfunction in SOD1-deficient mice: A model of age-related macular degeneration (2006)

Oxidative stress has long been linked to the pathogenesis of neurodegenerative diseases; however, whether it is a cause or merely a consequence of the degenerative process is still unknown. We show that mice deficient in Cu, Zn-superoxide dismutase (SOD1) have features typical of age-related macular degeneration in humans. Investigations of senescent Sod1(-/-) mice of different ages showed that the older animals had drusen, thickened Bruch's membrane, and choroidal neovascularization. The number of drusen increased with age, and exposure of young Sod1(-/-) mice to excess light induced drusen. The retinal pigment epithelial cells of Sod1(-/-) mice showed oxidative damage, and their beta-catenin-mediated cellular integrity was disrupted, suggesting that oxidative stress may affect the junctional proteins necessary for the barrier integrity of the retinal pigment epithelium. These observations strongly suggest that oxidative stress may play a causative role in age-related retinal degeneration, and our findings provide evidence for the free radical theory of aging. In addition, these results demonstrate that the Sod1(-/-) mouse is a valuable animal model to study human age-related macular degeneration.
A 128 x 128 cmos biosensor array for extracellular recording of neural activity (2003)

Sensor arrays are a key tool in the field of neuroscience for noninvasive recording of the activity of biological networks, such as dissociated neurons or neural tissue. A high-density sensor array complementary metal-oxide-semiconductor chip is presented with 16 K pixels, a frame rate of 2 kiloframes per second, and a pitch of 7.8 μm × 7.8 μm for imaging of neural activity. The related circuit and system issues as well as process aspects are discussed. A mismatch-canceling calibration circuitry with current mode signal representation is used. Results from first biological experiments are presented, which prove full functionality of the chip.
Ternary Logic Synthesis with Modified Quine-McCluskey Algorithm (2019)

Logic synthesis has been increasingly important to accelerate the development of high-level systems. However, in multi-valued logic, logic synthesis methods that can process emerging devices are deficient. We propose and automate a method to synthesize ternary logic circuits. Our design of ternary logic circuits is based on static gate design, and exploits carbon nanotube field-effect transistors. We optimize ternary logic circuits by minimizing the number of transistors with a modified Quine-McCluskey algorithm. Our proposed method has improved power-delay product by 52.72 % over the state-of-the-art method for a ternary half adder, and by 68.06 % for a ternary multiplier. We also have improved power-delay product by 37.30 % over the state-of-the-art method for a ternary full adder that has high load capacitance. Our design has an average of 42.43 % fewer transistors than the existing design for circuits that have large number of inputs. As circuits become larger, the improved power-delay product and reduced transistor count are advantageous.
Environmental and Developmental Regulation of the Wound-Induced Cell Wall Protein WI12 in the Halophyte Ice Plant (2001)

A wounded gene WI12 was used as a marker to examine the interaction between biotic stress (wounding) and abiotic stress (high salt) in the facultative halophyte ice plant (Mesembryanthemum crystallinum). The deduced WI12 amino acid sequence has 68% similarity to WUN1, a known potato (Solanum tuberosum) wound-induced protein. Wounding, methyl jasmonate, and pathogen infection induced local WI12 expression. Upon wounding, the expression of WI12 reached a maximum level after 3 h in 4-week-old juvenile leaves, whereas the maximum expression was after 24 h in 8-week-old adult leaves. The temporal expression of WI12 in salt-stressed juvenile leaves was similar to that of adult leaves. The result suggests that a salt-induced switch from C3 to Crassulacean acid metabolism has a great influence on the ice plant's response to wounding. The expression of WI12 and the accumulation of WI12 protein were constitutively found in phloem and in wounded mesophyll cells. At the reproductive stage, WI12 was constitutively found in petals and styles, and developmentally regulated in the placenta and developing seeds. The histochemical analysis showed that the appearance of WI12 is controlled by both environmental and developmental factors. Immunogold labeling showed WI12 preferentially accumulates in the cell wall, suggesting its role in the reinforcement of cell wall composition after wounding and during plant development.
Pharmacokinetic study of S-1, a novel oral fluorouracil antitumor drug. (1999)

S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), which is a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits dihydropyrimidine dehydrogenase (DPD) activity; and potassium oxonate (Oxo), which reduces gastrointestinal toxicity. Phase I and early Phase II clinical trials have already been completed. On the basis of the results of these trials, 80 mg/m2/day, given daily in two divided doses after breakfast and supper, a 28-day consecutive oral regimen is recommended. In this study, we investigated the pharmacokinetics of 5-FU, intact FT, CDHP, and Oxo, after administration of S-1, at a standard dose of 80 mg/m2/day, in advanced cancer patients. Twelve patients were recruited to the study; 5 patients with gastric cancer, 4 with colorectal cancer, and 3 with breast cancer. Among them, analysis was conducted on 12 patients for single administration and on 10 patients for consecutive administration. The initial dose of S-1 for each patient was determined according to his/her body surface area (BSA) as follows: for BSA < 1.25 m2, 80 mg/body/day; for 1.25 m2 < or = BSA < 1.5 m2, 100 mg/day; and for 1.5 m2 < or = BSA, 120 mg/day. For single administration, half of the standard dose was used. For 28-day consecutive administration, the standard dose was given daily in two divided doses. The average single dose per BSA was 35.9 mg/m2 (31.7-39.7 mg/m2). Pharmacokinetic parameters of plasma 5-FU were as follows: Cmax, 128.5 +/- 41.5 ng/ml; Tmax, 3.5 +/- 1.7 h; AUC(0-14), 723.9 +/- 272.7 ng x h/ml; and T(1/2), 1.9 +/- 0.4 h. In the 28-day consecutive regimen, there were no fluctuations in pharmacokinetics nor any drug accumulation. Because the pharmacokinetics of orally administered S-1 is almost similar to that of continuous i.v. infusion of 5-FU, we concluded that S-1 may improve patients' quality of life.
ChemInform Abstract: SYNTHESIS AND BIOLOGICAL ACTIVITY OF SOME NEW 2‐(N‐SUBSTITUTED CARBAMOYLMETHYLTHIO)NAPHTH(1,2‐D)OXAZOLES. PART V (1982)

Abstract Die Umsetzung des Mercaptonaphthoxazols (I) mit Chloracetamiden (II) liefert die Thiomethylacetamide (III), die zu den Sulfonen (IV) oxidiert werden.
Specificity of short interfering RNA determined through gene expression signatures (2003)

Short interfering RNA (siRNA) is widely used for studying gene function and holds great promise as a tool for validating drug targets and treating disease. A critical assumption in these applications is that the effect of siRNA on cells is specific, i.e., limited to the specific knockdown of the target gene. In this article, we characterize the specificity of siRNA by applying gene expression profiling. Several siRNAs were designed against different regions of the same target gene for three different targets. Their effects on cells were compared by using DNA microarrays to generate gene expression signatures. When the siRNA design and transfection conditions were optimized, the signatures for different siRNAs against the same target were shown to correlate very closely, whereas the signatures for different genes revealed no correlation. These results indicate that siRNA is a highly specific tool for targeted gene knockdown, establishing siRNA-mediated gene silencing as a reliable approach for large-scale screening of gene function and drug target validation.
Immunogenicity and Protection Efficacy of Replication-Deficient Influenza A Viruses with Altered NS1 Genes (2004)

We explored the immunogenic properties of influenza A viruses with altered NS1 genes (NS1 mutant viruses). NS1 mutant viruses expressing NS1 proteins with an impaired RNA-binding function or insertion of a longer foreign sequence did not replicate in murine lungs but still were capable of inducing a Th1-type immune response resulting in significant titers of virus-specific serum and mucosal immunoglobulin G2 (IgG2) and IgA, but with lower titers of IgG1. In contrast, replicating viruses elicited high titers of serum and mucosal IgG1 but less serum IgA. Replication-deficient NS1 mutant viruses induced a rapid local release of proinflammatory cytokines such as interleukin-1beta (IL-1beta) and IL-6. Moreover, these viruses also elicited markedly higher levels of IFN-alpha/beta in serum than the wild-type virus. Comparable numbers of virus-specific primary CD8(+) T cells were determined in all of the groups of immunized mice. The most rapid onset of the recall CD8(+)-T-cell response upon the wild-type virus challenge was detected in mice primed with NS1 mutant viruses eliciting high levels of cytokines. It is noteworthy that there was one NS1 mutant virus encoding NS1 protein with a deletion of 40 amino acids predominantly in the RNA-binding domain that induced the highest levels of IFN-alpha/beta, IL-6 and IL-1beta after infection. Mice that were immunized with this virus were completely protected from the challenge infection. These findings indicate that a targeted modification of the RNA-binding domain of the NS1 protein is a valuable technique to generate replication-deficient, but immunogenic influenza virus vaccines.
Method for Reducing Metal Salts Complexed in a Polymer Host with a Laser (1985)

We describe a novel method for generating fine metal lines with a laser. The laser radiation is focused onto the surface of a nonconductive silver nitrate‐doped polymer film to reduce silver. By translating the surface relative to the laser beam, a highly conductive silver line is formed. The measured resistance agrees well with the computed value for a silver conductor of comparable dimensions.
PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction (2016)

Cyclic nucleotide phosphodiesterase 1C (PDE1C) represents a major phosphodiesterase activity in human myocardium, but its function in the heart remains unknown. Using genetic and pharmacological approaches, we studied the expression, regulation, function, and underlying mechanisms of PDE1C in the pathogenesis of cardiac remodeling and dysfunction. PDE1C expression is up-regulated in mouse and human failing hearts and is highly expressed in cardiac myocytes but not in fibroblasts. In adult mouse cardiac myocytes, PDE1C deficiency or inhibition attenuated myocyte death and apoptosis, which was largely dependent on cyclic AMP/PKA and PI3K/AKT signaling. PDE1C deficiency also attenuated cardiac myocyte hypertrophy in a PKA-dependent manner. Conditioned medium taken from PDE1C-deficient cardiac myocytes attenuated TGF-β-stimulated cardiac fibroblast activation through a mechanism involving the crosstalk between cardiac myocytes and fibroblasts. In vivo, cardiac remodeling and dysfunction induced by transverse aortic constriction, including myocardial hypertrophy, apoptosis, cardiac fibrosis, and loss of contractile function, were significantly attenuated in PDE1C-knockout mice relative to wild-type mice. These results indicate that PDE1C activation plays a causative role in pathological cardiac remodeling and dysfunction. Given the continued development of highly specific PDE1 inhibitors and the high expression level of PDE1C in the human heart, our findings could have considerable therapeutic significance.
A survey of static analysis methods for identifying security vulnerabilities in software systems (2007)

In this paper we survey static analysis methods for identifying security vulnerabilities in software systems. We cover three areas that have been associated with sources of security vulnerabilities: access-control, information-flow, and application-programming-interface conformance. Because access control mechanisms fall into two major categories, stack-based access control and role-based access control, we discuss static analysis techniques for these two areas of access control separately. Similarly, security violations pertaining to information flow consist of integrity violations and confidentiality violations, and consequently, our discussion of static analysis techniques for information-flow vulnerabilities includes these two topics. For each type of security vulnerability we present our findings in two parts: in the first part we describe recent research results, and in the second part we illustrate implementation techniques by describing selected static analysis algorithms.
Circular dichroism study of chiral biomolecules conjugated with silver nanoparticles (2004)

Chiral biomolecules conjugated with silver nanoparticles were investigated by circular dichroism (CD) spectroscopy. Silver nanoparticles were prepared by the citrate reduction method and were characterized by UV spectroscopy and TEM. Conjugation of thiol group-containing biomolecules, such as cysteine, glutathione and penicillamine, with silver nanoparticles resulted in the generation of new characteristic CD signals in the region of 240–400 nm, whereas no CD signal changes were found with lysine or glutamine. Association through hydrogen bonding among the biomolecules is considered to be essential for CD signal generation, which was confirmed by experiment with cysteine methyl ester. Interestingly, Au nanoparticles were not found to generate CD signals in the wavelength region tested, indicating that this phenomenon is a unique feature of silver nanoparticles, distinguished from gold nanoparticles.
c-Jun Associates with the Oncoprotein Ski and Suppresses Smad2 Transcriptional Activity (2002)

The Smad proteins are key intracellular effectors of transforming growth factor-beta (TGF-beta) cytokines. The ability of Smads to modulate transcription results from a functional cooperativity with the coactivators p300/cAMP-response element-binding protein-binding protein (CBP), or the corepressors TGIF and Ski. The c-Jun N-terminal kinase (JNK) pathway, another downstream target activated by TGF-beta receptors, has also been suggested to inhibit TGF-beta signaling through interaction of c-Jun with Smad2 and Smad3. Here we show that c-Jun directly interacts with Ski to enhance the association of Ski with Smad2 in the basal state. Interestingly, TGF-beta signaling induces dissociation of c-Jun from Ski, thereby relieving active repression by c-Jun. Moreover, activation of JNK pathway suppressed the ability of TGF-beta to induce dissociation of c-Jun from ski. Thus, the formation of a c-Jun/Ski complex maintains the repressed state of Smad2-responsive genes in the absence of ligand and participates in negative feedback regulation of TGF-beta signaling by the JNK cascade.
Comparison of Interleukin-22 and Interleukin-10 Soluble Receptor Complexes (2002)

Interleukin-22 (IL-22) is a cellular homolog of IL-10 that stimulates the production of acute-phase reactants. IL-22 and IL-10 require different ligand-specific receptor chains (IL-22R and IL-10R1) but share a second receptor chain (IL-10R2) to initiate cellular responses. The quaternary structures and the ability of IL-22 and IL-10 to engage soluble (s) IL-10R1, IL-22R, IL-10R2 receptor chains were analyzed using size exclusion chromatography and surface plasmon resonance techniques. In contrast to IL-10, which is a homodimer, IL-22 is a monomer in solution that forms a 1:1 interaction with sIL-22R. Kinetic binding data reveal sIL-22R and sIL-10R1 exhibit specific nanomolar binding constants for IL-22 (k(on)/k(off) = 14.9 nM) and a monomeric isomer of IL-10 (IL-10M1) (k(on)/k(off) = 0.7 nM), respectively. In contrast, IL-10R2 exhibits essentially no affinity for IL-22 (K(eq) approximately 1 mM) or IL-10M1 (K(eq) approximately 2 mM) alone but displays a substantial increase in affinity for the IL-10/sIL-10R1 (K(eq) approximately 350 microM) and IL-22/sIL-22R (K(eq) approximately 45 microM) complexes. Three-dimensional models of IL-22 and IL-10 receptor complexes suggest two receptor residues (Gly-44 and Arg-96) are largely responsible for the marked differences in ligand affinity observed for sIL-10R1 and sIL-22R vs. sIL-10R2.
Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents (2018)

Antibiotic resistance threatens effective treatment of microbial infections globally. This situation has spurred the hunt for new antimicrobial compounds in both academia and the pharmaceutical industry. Here, we report how the widely used antitumor drug cisplatin may be repurposed as an effective antimicrobial against the nosocomial pathogen <i>Pseudomonas aeruginosa</i>. Cisplatin was found to effectively kill strains of <i>P. aeruginosa</i>. In such experiments, transcriptomic profiling showed upregulation of the <i>recA</i> gene, which is known to be important for DNA repair, implicating that cisplatin could interfere with DNA replication in <i>P. aeruginosa</i>. Cisplatin treatment significantly repressed the type III secretion system (T3SS), which is important for the secretion of exotoxins. Furthermore, cisplatin was also demonstrated to eradicate in vitro biofilms and in vivo biofilms in a murine keratitis model. This showed that cisplatin could be effectively used to eradicate biofilm infections which were otherwise difficult to be treated by conventional antibiotics. Although cisplatin is highly toxic for humans upon systemic exposure, a low toxicity was demonstrated with topical treatment. This indicated that higher-than-minimal inhibitory concentration (MIC) doses of cisplatin could be topically applied to treat persistent and recalcitrant <i>P. aeruginosa</i> infections.
Molecular Mechanisms Mediating Proliferation/Differentiation Interrelationships During Progressive Development of the Osteoblast Phenotype (1993)

A FUNCTIONAL relationship between cell growth and the initiation and progression of events associated with differentiation has been a fundamental question challenging developmental biologists for more than a century. In the case of bone, as observed with other cells and tissue, the relationship of growth and differentiation must be maintained and stringently regulated, both during development and throughout the life of the organism, to support tissue remodeling. For many years, bone was defined anatomically and examined largely in a descriptive manner by ultrastructural analysis and by biochemical and histochemical methods. These studies provided the basis for our understanding of bone tissue organization and orchestration of the progressive recruitment, proliferation, and differentiation of the various cellular components of bone tissue. Now, complemented by an increased knowledge of molecular mechanisms that are associated with and regulate expression of genes encoding phenotypic components of bone, and those that may control the progressive development and maturation of the bone cell phenotype, our understanding of bone cell and tissue differentiation is rapidly expanding.
Biologic Determinants of Tumor Recurrence in Stage II Colon Cancer: Validation Study of the 12-Gene Recurrence Score in Cancer and Leukemia Group B (CALGB) 9581 (2013)

The 12-gene RS predicts recurrence in stage II colon cancer in CALGB 9581. This is consistent with the importance of stromal response and cell cycle gene expression in colon tumor recurrence. RS appears to be most discerning for patients with T3 MMR-I tumors, although markers such as grade and lymphovascular invasion did not add value in this subset of patients.
Association of three single nucleotide polymorphisms of the E-cadherin gene with endometriosis in a Chinese population (2007)

Endometriosis, one of the most frequent diseases in gynecology, is a benign but invasive and metastatic disease. The altered expression of E-cadherin may play an important role in developing endometriosis. In this paper, we discuss the association of three single nucleotide polymorphisms (SNPs) on the E-cadherin gene and risk of endometriosis. We examined the genotype frequency of three polymorphisms in 152 endometriosis patients and 189 control women. There was a significant difference in the frequency of the E-cadherin 3'-UTR C --> T genotypes between endometriosis and controls (P = 0.01). The frequency of the C allele in patients (71.1%) was significantly higher than in the controls (63.8%; P = 0.04). When compared with the T/T + T/C genotypes, the C/C genotype had a significantly increased susceptibility to endometriosis, with an adjusted odds ratio of 1.79 (95% confidence interval = 1.17-2.76). No significant difference was found between endometriosis and control women on two polymorphisms (-160 C --> A, -347 G --> GA) at the gene promoter region of E-cadherin. The -160 C --> A and -347 G --> GA polymorphisms displayed linkage disequilibrium (D' = 0.999). The -160 A/-347 GA haplotype was only detected in endometriosis patients (2%). These data show a relation between the E-cadherin 3'-UTR C --> T polymorphism, the -160 A/-347 GA haplotype of two promoter polymorphisms and risk of endometriosis, suggesting a potential role in endometriosis development, at least in North Chinese women.
[Psychological care of children and family in the critical care setting]. (2008)

Admission to the critical care setting can be a traumatic experience for a child and his or her parents. Besides providing physical care, the nurses should assess the psychological and emotional responses of the children and their parents. By integrating the child's psychosocial development and the principles of family-centered care into critical care nursing, the impacts of emergency admission on hospitalized children and their families can be reduced in order to facilitate adaptation on the part of the families.
An "expanded porphyrin": the synthesis and structure of a new aromatic pentadentate ligand (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn "expanded porphyrin": the synthesis and structure of a new aromatic pentadentate ligandJonathan L. Sessler, Toshiaki. Murai, Vincent. Lynch, and Michael. CyrCite this: J. Am. Chem. Soc. 1988, 110, 16, 5586–5588Publication Date (Print):August 1, 1988Publication History Published online1 May 2002Published inissue 1 August 1988https://pubs.acs.org/doi/10.1021/ja00224a062https://doi.org/10.1021/ja00224a062research-articleACS PublicationsRequest reuse permissionsArticle Views929Altmetric-Citations104LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Many Pathways to Renewable Hydrogen (Presentation) (2008)

Presentation on the paths to renewable hydrogen presented by Robert Remick at the 2008 PowerGen: Renewable Energy and Fuels 2008 conference.