gebhart/patrepeval huggingface dataset:
Control of Directionality in Lambda Site Specific Recombination (1985)

The simple relation between the substrates and products of site-specific recombination raises questions about the control of directionality often observed in this class of DNA transactions. For bacteriophage lambda, viral integration and excision proceed by discrete pathways, and DNA substrates with the intrinsic property of recombining in only one direction can be constructed. These pathways display an asymmetric reliance on a complex array of protein binding sites, and they respond differently to changes in the concentrations of the relevant proteins. The Escherichia coli protein integration host factor (IHF) differentially affects integrative and excisive recombination, thereby influencing directionality. A four- to eightfold increase in intracellular IHF coincides with the transition from exponential to stationary phase; this provides a mechanism for growth phase-dependent regulation of recombination that makes the cellular physiology an intrinsic part of the recombination reaction.
A High Proportion of DNA Variants of BRCA1 and BRCA2 Is Associated with Aberrant Splicing in Breast/Ovarian Cancer Patients (2010)

An important fraction of DNA variants of BRCA1/2 presents splicing aberrations that may represent a relevant disease-causing mechanism in HBOC. The identification of splicing disruptions by functional assays is a valuable tool to discriminate between benign polymorphisms and pathogenic mutations.
Integrin αVβ3 Contains a Cell Surface Receptor Site for Thyroid Hormone that Is Linked to Activation of Mitogen-Activated Protein Kinase and Induction of Angiogenesis (2005)

Integrin alpha(V)beta(3) is a heterodimeric plasma membrane protein whose several extracellular matrix protein ligands contain an RGD recognition sequence. This study identifies integrin alpha(V)beta(3) as a cell surface receptor for thyroid hormone [L-T(4) (T(4))] and as the initiation site for T(4)-induced activation of intracellular signaling cascades. Integrin alpha(V)beta(3) dissociably binds radiolabeled T(4) with high affinity, and this binding is displaced by tetraiodothyroacetic acid, alpha(V)beta(3) antibodies, and an integrin RGD recognition site peptide. CV-1 cells lack nuclear thyroid hormone receptor, but express plasma membrane alpha(V)beta(3); treatment of these cells with physiological concentrations of T(4) activates the MAPK pathway, an effect inhibited by tetraiodothyroacetic acid, RGD peptide, and alpha(V)beta(3) antibodies. Inhibitors of T(4) binding to the integrin also block the MAPK-mediated proangiogenic action of T(4). T(4)-induced phosphorylation of MAPK is inhibited by small interfering RNA knockdown of alpha(V) and beta(3). These findings suggest that T(4) binds to alpha(V)beta(3) near the RGD recognition site and show that hormone-binding to alpha(V)beta(3) has physiological consequences.
Rapid progression of familial amyloidotic polyneuropathy (2015)

In a multinational population of patients with FAP, rapid neuropathic progression is observed and the severity of neuropathy is associated with functional scales of locomotion.
Space-frequency coded broadband OFDM systems (2002)

Space-time coding for fading channels is a communication technique that realizes the diversity benefits of multiple transmit antennas. Previous work in this area has focused on the narrowband flat fading case where spatial diversity only is available. We investigate the use of space-time coding in OFDM-based broadband systems where both spatial and frequency diversity are available. We consider a strategy which basically consists of coding across OFDM tones and is therefore called space-frequency coding. For a spatial broadband channel model taking into account physical propagation parameters and antenna spacing, we derive the design criteria for space-frequency codes and we show that space-time codes designed to achieve full spatial diversity in the narrowband case will in general not achieve full space-frequency diversity. Specifically, we show that the Alamouti (see IEEE J. Sel. Areas Comm., vol.16, p.1451-58, 1998) scheme across tones fails to exploit frequency diversity. For a given set of propagation parameters and given antenna spacing, we establish the maximum achievable diversity order. Finally, we provide simulation results studying the influence of delay spread, propagation parameters, and antenna spacing on the performance of space-frequency codes.
Bile Acid Derivatives as Ligands of the Farnesoid X Receptor. Synthesis, Evaluation, and Structure−Activity Relationship of a Series of Body and Side Chain Modified Analogues of Chenodeoxycholic Acid (2004)

The farnesoid X receptor (FXR) is activated by endogenous bile acids (BAs) and plays a variety of physiological roles related to modulation of gene transcription. In particular, FXR positively regulates the cholesterol catabolism while feedback inhibits the BA synthesis by repressing the expression of the CYP7A and CYP8B genes. We have previously shown that 6alpha-ethyl-CDCA (6ECDCA) is a potent and selective FXR agonist. In this paper we report an extensive structure-activity relationship for a series of synthetic bile acids. Our results indicate that the 6alpha position plays a fundamental role in determining affinity and that the side chain of BA is amenable to a variety of chemical modification. Although none of the new derivatives is more potent than 6ECDCA, we show here that a wide variability in efficacy, from full agonists to partial antagonists, can be obtained.
Model for carbohydrase action. Aspergillus oryzae α-amylase degradation of maltotriose (1978)

Aspergillus oryzae alpha-amylase catalyzes degradation of oligosaccharides by a variety of pathways. We present here a quantitative study of the degradation of maltotriose by this amylase. Our results lead to a scheme involving multiple transglycosylation reactions and shifted binding due to simultaneous binding of two substrate molecules. The scheme is able to account for the diverse body of information collected for the enzyme. The effect of substrate concentration on the products of maltotriose degradation is correctly predicted over a 10(4)-fold concentration range, and the time course of maltotriose degradation is closely approximated by this scheme. The initial velocity data, which show deviation from Michaelis-Menton kinetics, are also consistent with the formulated scheme. The scheme is proposed as a general model of carbohydrase action.
Collagen, cross-linking, and advanced glycation end products in aging human skeletal muscle (2007)

We examined intramuscular endomysial collagen, cross-linking, and advanced glycation end products, as well as the general and contractile protein concentration of 20 young (25 +/- 3 yr) and 22 old (78 +/- 6 yr, range: 70-93 yr) sedentary men and women to better understand the underlying basis of changes in skeletal muscle mass and function that occur with aging. The old individuals had an impaired ability (increased time) (P < 0.05) to climb stairs (80%), rise from a chair (56%), and walk (44%), as well as lower (P < 0.05) quadriceps muscle volume (-29%), muscle strength (-35%), muscle power (-48%), and strength (-17%) and power (-33%) normalized to muscle size. Vastus lateralis muscle biopsies revealed that intramuscular endomysial collagen (young: 9.6 +/- 1.1, old: 10.2 +/- 1.2 microg/mg muscle wet wt) and collagen cross-linking (hydroxylysylpyridinoline) (young: 395 +/- 65, old: 351 +/- 45 mmol hydroxylysylpyridinoline/mol collagen) were unchanged (P > 0.05) with aging. The advanced glycation end product, pentosidine, was increased (P < 0.05) by approximately 200% (young: 5.2 +/- 1.3, old: 15.9 +/- 4.5 mmol pentosidine/mol collagen) with aging. While myofibrillar protein concentration was lower (-5%, P < 0.05), the concentration of the main contractile proteins myosin and actin were unchanged (P > 0.05) with aging. These data suggest that the synthesis and degradation of proteins responsible for the generation (myosin and actin) and transfer (collagen and pyridinoline cross-links) of muscle force are tightly regulated in aging muscle. Glycation-related cross-linking of intramuscular connective tissue may contribute to altered muscle force transmission and muscle function with healthy aging.
Expression of BRC Repeats in Breast Cancer Cells Disrupts the BRCA2-Rad51 Complex and Leads to Radiation Hypersensitivity and Loss of G2/M Checkpoint Control (1999)

BRCA2 is a breast tumor suppressor with a potential function in the cellular response to DNA damage. BRCA2 binds to Rad51 through its BRC repeats. In support of the biological significance of this interaction, we found that the complex of BRCA2 and Rad51 in breast cancer MCF-7 cells was diminished upon conditional expression of a wild-type, but not a mutated, BRC4 repeat using the tetracycline-inducible system. Cells expressing a wild-type BRC4 repeat showed hypersensitivity to gamma-irradiation, an inability to form Rad51 radiation-induced foci, and a failure of radiation-induced G(2)/M, but not G(1)/S, checkpoint control. These results strongly suggest that the interaction between BRCA2 and Rad51 mediated by BRC repeats is critical for the cellular response to DNA damage.
A delayless subband active noise control system for wideband noise control (2001)

In this paper, we present an efficient noise control algorithm based on the delayless subband adaptive filter. The algorithm reduces the computational complexity of the delayless subband filter by decomposing the secondary path response into a set of subband functions. In this new algorithm, the filtered reference signal is generated for each subband by using a short impulse response filter that models the secondary path transfer function in a subband-decomposed form. Computational efficiency of the presented method originates from the fact that the filtering process occurs only in one subband for each reference input sample. Furthermore, computational efficiency is enhanced when the presented algorithm is combined with an online identification of the secondary path transfer function. We also propose a frequency-domain implementation of the presented algorithm. In this implementation, it is shown that the computational complexity is further reduced by employing the block-processing approach.
New Hydrolyzable pH‐Responsive Cationic Polymers for Gene Delivery: A Preliminary Study (2004)

Here we want to report the synthesis and the characterization of 2-methylacrylic acid 2-(3-imidazol-1-yl-propionyloxy)ethyl ester (IPEMA), a new methacrylate derivative monomer bearing an hydrolyzable side chain terminated by an imidazole group. The kp/kt(1/2) value for its homopolymerization in N,N-dimethylformamide at 60 degrees C was found to be 0.120 mol(-1/2) x L(1/2) x s(-1/2). The free radical copolymerization of N,N-dimethylaminoethyl methacrylate and this monomer was studied in N,N-dimethylformamide at 60 degrees C, the reactivity ratios of this couple of monomers were determined to be r(DMAEMA) = 1.13 +/- 0.09 and r(IPEMA) = 0.82 +/- 0.09 (using distinct calculation methods). Molecular weights analysis, parallely with refractive index increments measurements, were performed to characterize the obtained polymers. Potentiometric titrations showed the ability of these copolymers to act as a 'proton sponge'. Preliminary study of the copolymers hydrolysis proved that imidazole units could be slowly cleaved from the polymer backbone at 37 degrees C in neutral aqueous buffer. Agarose gel electrophoresis of plasmid DNA/polymer complexes demonstrated the DNA complexing properties of these imidazole-based copolymers.
사회정책사상과 불평등 문제 (2003)

현대 복지국가의 사회정책은 빈곤문제의 해결뿐만 아니라 사회적 재분배 효과, 즉 불평등의 완화를 기대한다. 그러나 과연 사회정책과 사회복지제도가 불평등을 감소시키고 있는지는 의문이다. 왜냐하면 사회정책적 관점에 따라 각기 운영방식이 다르기 때문이다. 이에 따라 본 연구에서는 사회정책사상과 사회불평등간의 관계를 분석하였다.
사회정책사상은 자유주의, 수정자유주의, 사회민주주의, 맑스주의로 구분하였으며, 사회불평등에 대한 관점은 기능주의이론, 비판적 기능주의이론, 갈등이론, 맑스주의이론으로 구분하여 살펴보았다. 분석 결과 현실적으로 사회불평등의 완화에 관련을 맺고 있는 것은 갈등이론과 불평등을 바라보는 시각을 공유하고 있는 사회민주주의 사회정책을 통해 전반적인 불평등의 크기 내지는 격차는 완화시킬 수 있지만, 자본주의사회의 기본적 고나계인 구조화된 불평등체계로서의 계급구조에는 별 영향을 미치고 있지 못한 듯하다.
계급간 불평등이 폐지될 수 없는 것이라면, 사회정책은 보다 강한 재분배 및 교육권 등의 실질적 보장, 그리고 자유권, 정치권 등의 실질적 평등을 구현하는 사회권의 확보로 나아가야 한다.
Biosensors for Measuring Pesticide Residues in the Environment: Past, Present, and Future (1996)

Abstract Inexpensive, fast, reliable, sensitive biosensors and automated devices are being developed for broad-spectrum analysis or specific analysis of single analytes. This paper discusses biosensor research in environmental analysis, focusing on pesticide analysis. Examples are presented from major research fields to serve as a starting point for information about trends and to encourage more research in this interdisciplinary field
Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine. (2001)

A polyvalent melanoma vaccine prepared from shed antigens stimulates humoral and cellular immune responses and improves survival compared with historical controls. We conducted a double-blind, prospectively randomized, placebo-controlled trial to assess whether this vaccine could slow the progression of resected melanoma. Thirty-eight patients with resected melanoma metastatic to regional nodes (American Joint Committee on Cancer stage III) who had a particularly poor prognosis on the basis of the nodes being clinically positive or two or more histologically positive nodes were randomly assigned in a 2:1 ratio to treatment with 40 microg of melanoma or placebo (human albumin) vaccine, both of which were bound to alum as an adjuvant. Immunizations were given intradermally into the extremities every 3 weeks x 4, monthly x 3, every 3 months x 2, and then every 6 months for 5 years or until disease progression. Twenty-four patients were treated with the melanoma, and 14 patients were treated with the placebo vaccine. The groups were evenly balanced with respect to prognostic factors. Median length of observation was 2.5 years. There was no local or systemic toxicity. By Kaplan-Meier analysis, median time to disease progression was two and a half times longer in patients treated with melanoma vaccine compared with that in patients treated with placebo vaccine, i.e., 1.6 years (95% confidence interval, 1.0-3.0 years) compared with 0.6 year [95% confidence interval, 0.3-1.9 year(s)]. By Cox proportional hazards analysis, this difference was significant at P = 0.03. Overall survival was 40% longer in the melanoma vaccine-treated group (median overall survival of 3.8 years versus 2.7 years), but this difference was not statistically significant. In a double-blind and placebo-controlled trial, these results suggest that immunization with a melanoma vaccine may be able to slow the progression of melanoma. Although statistically significant, these results must be interpreted with caution because they are based on a small number of patients.
Epitope mapping of polyclonal clotting factor VIII-inhibitory antibodies using phage display (2004)

Clotting factor VIII (fVIII)-inhibitory antibodies represent a major problem in the treatment of haemophilia A. To understand the inactivation mechanisms and to pave the way towards modifications of recombinant clotting factors that reduce their immunogenicity, the exact localization of immunodominant epitopes is required. Here, a random peptide phage display library was employed to identify epitopes of polyclonal fVIII antibodies isolated from patient's plasma by affinity chromatography. FVIII-binding specificity and inhibitory activity of the isolated fVIII antibodies were confirmed by ELISA and Bethesda assays. Phage selection on the individual samples yielded several phages which were displaced from binding to the respective antibody preparation by fVIII. Their homology with amino acid motifs of human fVIII and immunoprecipitation results with radioactively labelled fVIII fragments suggested putative epitopes in the A1, A2 and C1 domains of fVIII for one and in the C2 domain for another patient. Synthetic peptides corresponding to the A2, C1 and C2 domain epitopes blocked antibody binding to fVIII and partially neutralized the inhibitory activity of the respective plasma in Bethesda assays. These results provide the proof of principle that random peptide libraries can be used for the mapping of epitopes in a polyclonal antibody preparation.
Use and Application of Stem Cells in Toxicology (2004)

In recent years, stem cells have been the subject of increasing scientific interest because of their utility in numerous biomedical applications. Stem cells are capable of renewing themselves; that is, they can be continuously cultured in an undifferentiated state, giving rise to more specialized cells of the human body such as heart, liver, bone marrow, blood vessel, pancreatic islet, and nerve cells. Therefore, stem cells are an important new tool for developing unique, in vitro model systems to test drugs and chemicals and a potential to predict or anticipate toxicity in humans. The following review provides an overview of the applications of stem cell technology in the area of toxicology. Specifically, this review addresses core technologies that are emerging in the field and how they could fulfill critical safety issues such as QT prolongation and hepatotoxicity, two leading causes of failures in preclinical development of new therapeutic drugs. We report how adult stem cells derived from various sources, such as human bone marrow and placenta, can potentially generate suitable models for cardiotoxicity, hepatotoxicity, genotoxicity/epigenetic and reproductive toxicology screens. Additionally, this review addresses the role and advantages of embryonic stem cells in the aforementioned models for toxicity and how genetic selection is employed to overcome major limitations to the implementation of stem cell-based in vitro models for toxicology.
Zinc‐induced Structural Effects Enhance Oxygen Consumption and Superoxide Generation in Synthetic Pheomelanins on UVA/Visible Light Irradiation† (2010)

The abnormal susceptibility of red-haired individuals to UV-induced inflammation and skin cancers is commonly attributed to the marked photoreactivity of pheomelanin pigments, which would be responsible for the sustained generation of reactive oxygen species in the skin following sun exposure. The structural factors determining pheomelanin photolability remain mostly unknown. Here, we describe the effects of zinc ions, typically found at high levels in red hair, in enhancing both oxygen consumption and superoxide production in model pheomelanin pigments following irradiation with UVA and visible light. Electron paramagnetic resonance (EPR) oximetry and EPR-spin trapping experiments with synthetic pheomelanins, prepared by oxidation of dopa and cysteine or isomeric cysteinyldopas under different conditions, indicate a higher photoreactivity of the pigments prepared in the presence of zinc ions compared with those obtained in the absence of the metal. Quantitative analysis of thiazole-containing structural markers of the synthetic pheomelanins provides evidence that the effect of zinc ions is due to modification of the formation pathway and structural features of the pigments. Overall, these results point to a hitherto unrecognized critical role of zinc ions in pheomelanogenesis, which may affect the intrinsic photoreactivity of the pigment.
Evidence for Immune-Mediated Destruction as Mechanism for LCMV-Induced Anemia in Persistently Infected Mice (1991)

A docile substrain of lymphocytic choriomeningitis virus (LCMV) causes a persistent infection in adult C3HeB mice and induces a severe anemia, which, unlike the viremia, eventually resolves. Measurements of red blood cell (RBC) survival rates demonstrated an increased rate of RBC clearance in these animals, indicating a hemolytic process for the anemia. Normal clearance rates of RBCs from infected mice transfused into control mice suggested that there was not an intrinsic defect in these cells. It also appeared that RBC destruction was immune-mediated, as cyclophosphamide treatments prevented the onset of anemia in infected mice, whereas adoptive transfer (AT) of immune splenocytes into immunocompromised mice reestablished the condition. The AT experiments also demonstrated that the onset of anemia correlated with the functional state of the immune cells. In addition, opsonization of RBCs was demonstrated by macrophage phagocytosis, and the appearance of opsonized RBCs corresponded with the course of the anemia. These findings support a hypothesis of RBC opsonization and subsequent phagocytosis by macrophages of the reticuloendothelial system as the mechanism for RBC destruction in LCMV-induced hemolytic anemia.
NORMAL VALEROLACTONE. III. ITS PREPARATION BY THE CATALYTIC REDUCTION OF LEVULINIC ACID WITH HYDROGEN IN THE PRESENCE OF PLATINUM OXIDE (1930)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNORMAL VALEROLACTONE. III. ITS PREPARATION BY THE CATALYTIC REDUCTION OF LEVULINIC ACID WITH HYDROGEN IN THE PRESENCE OF PLATINUM OXIDEH. A. Schuette and Ralph W. ThomasCite this: J. Am. Chem. Soc. 1930, 52, 7, 3010–3012Publication Date (Print):July 1, 1930Publication History Published online1 May 2002Published inissue 1 July 1930https://pubs.acs.org/doi/10.1021/ja01370a069https://doi.org/10.1021/ja01370a069research-articleACS PublicationsRequest reuse permissionsArticle Views642Altmetric-Citations84LEARN 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
Generation and Characterization of E1/E2a/E3/E4-Deficient Adenoviral Vectors Encoding Human Factor VIII (2001)

The use of adenoviral vectors for gene therapy has been limited due to host immune responses directed toward the vector and/or transgene and vector toxicity. To decrease adenoviral vector immunogenicity and toxicity, we attenuated viral gene expression by eliminating E1, E2a, E3, and E4 early genes from the adenoviral backbone. Two highly attenuated, fourth-generation (Av4) E1/E2a/E3/E4-deficient adenoviral vectors encoding human factor VIII (FVIII) under the control of a liver-specific albumin promoter were generated. One Av4 vector (Av4DeltaE4FVIII) was deficient in the entire E4 coding region and the second vector contained a deletion of the E4 region, except for open reading frame 3 (orf 3; Av4orf3FVIII). The Av4 vectors were compared to an E1/E2a/E3-deficient third-generation vector (Av3H8101) containing an analogous transgene expression cassette in vitro and in vivo following intravenous administration in hemophiliac mice. In vitro transduction of Hep3B cells revealed at all three vectors expressed functional FVIII. However, the Av4DeltaE4FVIII vector could not be scaled-up for in vivo studies. Both Av3H8101 and Av4orf3FVIII initially expressed similar levels of FVIII in hemophiliac mice. However, at 3 months, animals treated with the Av4orf3FVIII vector no longer expressed FVIII while Av3H8101-treated mice displayed persistent FVIII expression. Liver enzyme analyses of plasma samples revealed that the Av4orf3FVIII vector was significantly less hepatotoxic than the Av3H8101 vector. These data demonstrate that further attenuation of the adenoviral vector backbone by removal of the majority of the E4 coding region significantly diminished vector toxicity; however, the duration of transgene expression was reduced.