gebhart/patrepeval huggingface dataset:
Biophysically Defined and Cytocompatible Covalently Adaptable Networks as Viscoelastic 3D Cell Culture Systems (2013)

Presented here is a cytocompatible covalently adaptable hydrogel uniquely capable of mimicking the complex biophysical properties of native tissue and enabling natural cell functions without matrix degradation. Demonstrated is both the ability to control elastic modulus and stress relaxation time constants by more than an order of magnitude while predicting these values based on fundamental theoretical understanding and the simulation of muscle tissue and the encapsulation of myoblasts.
On the mechanism of the modular primer effect (1995)

Modular primers are strings of three contiguously annealed unligated oligonucleotides (modules) as short as 5- or 6-mers, selected from a presynthesized library. It was previously found that such strings can prime DNA sequencing reactions specifically, thus eliminating the need for the primer synthesis step in DNA sequencing by primer walking. It has remained largely a mystery why modular primers prime uniquely, while a single module, used alone in the same conditions, often shows alternative priming of comparable strength. In a puzzling way, the single module, even in a large excess over the template, no longer primes at the alternative sites, when modules with which it can form a contiguous string are also present. Here we describe experiments indicating that this phenomenon cannot be explained by cooperative annealing of the modules to the template. Instead, the mechanism seems to involve competition between different primers for the available polymerase. In this competition, the polymerase is preferentially engaged by longer primers, whether modular or conventional, at the expense of shorter primers, even though the latter can otherwise prime with similar or occasionally higher efficiency.
Functions of Single-Strand DNA-Binding Proteins in DNA Replication, Recombination, and Repair (2012)

Double-stranded (ds) DNA contains all of the necessary genetic information, although practical use of this information requires unwinding of the duplex DNA. DNA unwinding creates single-stranded (ss) DNA intermediates that serve as templates for myriad cellular functions. Exposure of ssDNA presents several problems to the cell. First, ssDNA is thermodynamically less stable than dsDNA, which leads to spontaneous formation of duplex secondary structures that impede genome maintenance processes. Second, relative to dsDNA, ssDNA is hypersensitive to chemical and nucleolytic attacks that can cause damage to the genome. Cells deal with these potential problems by encoding specialized ssDNA-binding proteins (SSBs) that bind to and stabilize ssDNA structures required for essential genomic processes. SSBs are essential proteins found in all domains of life. SSBs bind ssDNA with high affinity and in a sequence-independent manner and, in doing so, SSBs help to form the central nucleoprotein complex substrate for DNA replication, recombination, and repair processes. While SSBs are found in every organism, the proteins themselves share surprisingly little sequence similarity, subunit composition, and oligomerization states. All SSB proteins contain at least one DNA-binding oligonucleotide/oligosaccharide binding (OB) fold, which consists minimally of a five stranded beta-sheet arranged as a beta barrel capped by a single alpha helix. The OB fold is responsible for both ssDNA binding and oligomerization (for SSBs that operate as oligomers). The overall organization of OB folds varies between bacteria, eukaryotes, and archaea. As part of SSB/ssDNA cellular structures, SSBs play direct roles in the DNA replication, recombination, and repair. In many cases, SSBs have been found to form specific complexes with diverse genome maintenance proteins, often helping to recruit SSB/ssDNA-processing enzymes to the proper cellular sites of action. This clustering of genome maintenance factors can help to stimulate and coordinate the activities of individual enzymes and is also important for dislodging SSB from ssDNA. These features support a model in which DNA metabolic processes have evolved to work on ssDNA/SSB nucleoprotein filaments rather than on naked ssDNA. In this volume, methods are described to interrogate SSB-DNA and SSB-protein binding functions along with approaches that aim to understand the cellular functions of SSB. This introductory chapter offers a general overview of SSBs that focuses on their structures, DNA-binding mechanisms, and protein-binding partners.
High Throughput Parallel Analysis of Hundreds of Patient Samples for More Than 100 Mutations in Multiple Disease Genes (1997)

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.
Isolation of RNA Aptamers for Biological Cofactors by In Vitro Selection (1994)

Short RNA sequences with specific secondary structure (see below) are the binding motifs for the cofactors flavin adenine dinucleotide and flavin mononucleotide (FAD and FMN, respectively), according to selection experiments with randomized RNA pools and FAD- and FMN-modified agarose. It was also shown that only the flavin portion plays a role in binding. Analogous experiments were conducted with NAD+ and its mononucleotide.
Glutamate and Depression (2003)

The past decade has seen a steady accumulation of evidence supporting a role for the excitatory amino acid (EAA) neurotransmitter, glutamate, and its receptors in depression and antidepressant activity. To date, evidence has emerged indicating that N-methyl-d-aspartate (NMDA) receptor antagonists, group I metabotropic glutamate receptor (mGluR1 and mGluR5) antagonists, as well as positive modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors have antidepressant-like activity in a variety of preclinical models. Moreover, antidepressant-like activity can be produced not only by drugs modulating the glutamatergic synapse, but also by agents that affect subcellular signaling systems linked to EAA receptors (e.g., nitric oxide synthase). In view of the extensive colocalization of EAA and monoamine markers in nuclei such as the locus coeruleus and dorsal raphe, it is likely that an intimate relationship exists between regulation of monoaminergic and EAA neurotransmission and antidepressant effects. Further, there is also evidence implicating disturbances in glutamate metabolism, NMDA, and mGluR1,5 receptors in depression and suicidality. Finally, recent data indicate that a single intravenous dose of an NMDA receptor antagonist is sufficient to produce sustained relief from depressive symptoms. Taken together with the proposed role of neurotrophic factors in the neuroplastic responses to stressors and antidepressant treatments, these findings represent exciting and novel avenues to both understand depressive symptomatology and develop more effective antidepressants.
Quantitation of pre.beta.-HDL-dependent and nonspecific components of the total efflux of cellular cholesterol and phospholipid (1993)

Both receptor-mediated and diffusional processes have been proposed as mechanisms for the efflux of cellular cholesterol to plasma. The depletion of a minor high-density lipoprotein subfraction (pre beta-1-HDL) from plasma by incubation was associated with a proportional reduction in up to 58% of cholesterol and lecithin efflux from cultured fibroblasts. Pre beta-HDL-dependent efflux was blocked by protease pretreatment of the cells, while residual ("nonspecific") efflux was protease-insensitive. The whole of cholesterol efflux from blood erythrocytes was both pre beta-1-HDL-and protease-independent. These data suggest that two distinct pathways contribute to total efflux from fibroblast monolayers; one of these is directly proportional to plasma pre beta-1-HDL concentration and may involve a cell-surface protein.
Study on HCCI-SI Combustion Using Fuels Ethanol Containing (2007)

&lt;div class="htmlview paragraph"&gt;Bio-ethanol is one of the candidates for automotive alternative fuels. For reduction of carbon dioxide emissions, it is important to investigate its optimum combustion procedure. This study has explored effect of ethanol fuels on HCCI-SI hybrid combustion using dual fuel injection (DFI). Steady and transient characteristics of the HCCI-SI hybrid combustion were evaluated using a single cylinder engine and a four-cylinder engine equipped with two port injectors and a direct injector. The experimental results indicated that DFI has the potential for optimizing ignition timing of HCCI combustion and for suppressing knock in SI combustion under fixed compression ratio. The HCCI-SI hybrid combustion using DFI achieved increasing efficiency compared to conventional SI combustion. Feed-forward and feed-back control systems based on DFI enabled the transient operation including acceleration and deceleration during HCCI combustion, re-ignition of HCCI combustion after fuel cut mode, HCCI-SI-HCCI combustion transition, and suppression of knock in SI combustion.&lt;/div&gt;
Assessment and Calibration of a Low‐Frequency System for Electrical Impedance Tomography (EIT), Optimized for Use in Imaging Brain Function in Ambulant Human Subjects (1999)

An EIT system has been produced that has been optimized for imaging impedance changes with scalp electrodes during brain activity in ambulant subjects. It can record from 225 Hz to 65 kHz, has a small headbox on a lead 10 m long, and has software programmable electrode selection. In calibration experiments in a small cylindrical tank filled with potassium chloride solution and samples of cucumber, noise was less than 1% with averaging, and acceptable images were produced at frequencies down to 1800 Hz. This suggests that EIT can be performed at low frequencies, which are likely to give larger signals during brain activity. Future work will include trials in humans and improvement of the current source and isolation.
Survey of the year 2005: literature on applications of isothermal titration calorimetry (2006)

Abstract Isothermal titration calorimetry (ITC) can provide a full thermodynamic characterization of an interaction. Its usage does not suffer from constraints of molecular size, shape or chemical constitution. Neither is there any need for chemical modification or attachment to solid support. This ease of use has made it an invaluable instrumental resource and led to its appearance in many laboratories. Despite this, the value of the thermodynamic parameterization has, only quite recently, become widely appreciated. Although our understanding of the correlation between thermodynamic data and structural details continues to be somewhat naïve, a large number of publications have begun to improve the situation. In this overview of the literature for 2005, we have attempted to highlight works of interest and novelty. Furthermore, we draw attention to those works which we feel have provided a route to better analysis and increased our ability to understand the meaning of thermodynamic change on binding. Copyright © 2006 John Wiley &amp; Sons, Ltd.
2'-Hydroxyflavanone inhibits proliferation, tumor vascularization and promotes normal differentiation in VHL-mutant renal cell carcinoma (2011)

Renal cell carcinoma (RCC) is one of the top ten cancers prevalent in USA. Loss-of-function mutations in the von Hippel-Lindau (VHL) gene constitute an established risk factor contributing to 75% of total reported cases of RCC. Loss-of-VHL leads to a highly vascularized phenotype of renal tumors. Intake of citrus fruits has been proven to reduce the risk of RCC in multicenter international studies. Hence, we studied the effect of 2'-hydroxyflavanone (2HF), an active anticancer compound from oranges, in RCC. Our in vitro investigations revealed that 2HF suppresses VHL-mutant RCC to a significantly greater extent than VHL-wild-type RCC by inhibiting epidermal growth factor receptor signaling, which is increased due to VHL mutations in RCC. Our results also revealed for the first time, that 2HF inhibits glutathione S-transferase pi activity. 2HF reduced cyclin B1 and CDK4 levels and induced G2/M phase arrest in VHL-mutant RCC. Importantly, 2HF inhibited the angiogenesis in VHL-mutant RCC by decreasing vascular endothelial growth factor expression. Our in vivo studies in mice xenografts confirmed our in vitro results as evident by decreased levels of proliferation marker, Ki67 and angiogenic marker, CD31, in 2HF-treated mice xenografts of VHL-mutant RCC. 2HF also increased the expression of E-cadherin in VHL-mutant RCC, which would be of significance in restoring normal epithelial phenotype. Collectively, our in vitro and in vivo results revealed the potent antiproliferative, anti-angiogenic and prodifferentiation properties of 2HF in VHL-mutant RCC, sparing normal cells, which could have significant implications not only in the specific management of VHL-mutant RCC but also towards other VHL syndromes.
Abnormal oxidative metabolism of estradiol in women with breast cancer. (1982)

The three dominant oxidative biotransformations of estradiol were examined in 10 normal women and 33 females with breast cancer by using a recently devised radiometric method. Estradiol tracers, labeled with 3H specifically in the 17 alpha, C-2, or 16 alpha position, were used to measure both the rate and extent of 17 beta-ol oxidation (the initial metabolic step) and the subsequent 2- and 16 alpha-oxidative reactions. The mean +/- SEM values for the extent of extradiol metabolism at these three specific sites for the extent of estradiol metabolism at these three specific sites were 76.9 +/- 5.3%, 31.1 +/- 4.0%, and 9.3 +/- 0.8%, respectively in normal subjects. Corresponding data in patients with breast cancer--i.e., 73.0 +/- 4.2%, 32.7 +/- 2.7%, and 14.9 +/- 1.5%--revealed a significantly greater extent of 16 alpha-hydroxylation in the latter population. Because the 16 alpha-hydroxylated compounds (including estriol) are themselves potent estrogens, these changes may have important hyperestrogenic consequences that could have a bearing on the etiology of the disease.
Toying with Enzyme Catalysis (1998)

Research Article| April 01 1998 Toying with Enzyme Catalysis Debbie Richards Debbie Richards Search for other works by this author on: This Site PubMed Google Scholar The American Biology Teacher (1998) 60 (4): 294–295. https://doi.org/10.2307/4450476 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Debbie Richards; Toying with Enzyme Catalysis. The American Biology Teacher 1 April 1998; 60 (4): 294–295. doi: https://doi.org/10.2307/4450476 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentThe American Biology Teacher Search This content is only available via PDF. Copyright The National Association of Biology Teachers Article PDF first page preview Close Modal You do not currently have access to this content.
In vivo and in vitro trans-cleavage activity of hepatitis C virus serine proteinase expressed by recombinant baculoviruses (1995)

By the use of recombinant baculoviruses, the trans-cleavage of hepatitis C virus (HCV) non-structural polyprotein was studied. The viral serine proteinase encoded by the NS3 gene was expressed efficiently in insect cells infected with a baculovirus recombined with HCV cDNA corresponding to amino acids 1046-1243 and the signal sequence of the rabies virus G protein. Coinfection studies showed the in vivo trans-cleavage activity of the expressed protein by the use of a recombinant producing NS5 as a substrate. We also found that the partially purified NS3 serine proteinase prepared from the recombinant-infected cells could cleave NS5A/5B substrate. Characterization of the proteinase obtained wil provide basic knowledge on processing of the HCV polyprotein.
Brief inhalation of low-dose carbon monoxide protects rodents and swine from postoperative ileus* (2005)

These findings demonstrate that inhalation of a low concentration of CO before surgery attenuates postoperative ileus in rodents and, more importantly, in a large animal species without risk to well-being during surgery or perioperatively. Exposures need not be prolonged, with significant benefit occurring with a 3-hr pretreatment.
Genetic analysis of the filamentous bacteriophage packaging signal and of the proteins that interact with it (1989)

The single-stranded DNA of filamentous phages (f1, fd, M13, Ike) contains a region that can fold into a hairpin structure that serves to earmark the DNA for encapsidation. Second-site suppressor mutants of f1 that can compensate for deletion of this packaging signal have been isolated and characterized. The mutations lie in three genes, two that encode virion proteins located at the end of the particle that is first to emerge from the cell, the end at which the packaging signal is located, and the third in a gene whose product is required for assembly but which is not itself a part of the virion. Analysis of base substitution and deletion mutations in the packaging signal suggests that both structural and sequence elements are important to its proper function.
A Computerized System to Manufacture Prostheses for Amputees in Developing Countries (1989)

Walsh, Nicolas E. M.D.; Lancaster, Jack L. Ph.D.; Faulkner, Virgil W. C.P.O.; Rogers, William E. M.S. Author Information
A Comparison of PAM50 Intrinsic Subtyping with Immunohistochemistry and Clinical Prognostic Factors in Tamoxifen-Treated Estrogen Receptor–Positive Breast Cancer (2010)

The PAM50 gene expression test for intrinsic biological subtype can be applied to large series of formalin-fixed, paraffin-embedded breast cancers, and gives more prognostic information than clinical factors and IHC using standard cut points.
Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer (2006)

Werner syndrome (WS) is an inherited disorder characterized by premature onset of aging, genomic instability, and increased cancer incidence. The disease is caused by loss of function mutations of the WRN gene, a RecQ family member with both helicase and exonuclease activities. However, despite its putative tumor-suppressor function, little is known about the contribution of WRN to human sporadic malignancies. Here, we report that WRN function is abrogated in human cancer cells by transcriptional silencing associated with CpG island-promoter hypermethylation. We also show that, at the biochemical and cellular levels, the epigenetic inactivation of WRN leads to the loss of WRN-associated exonuclease activity and increased chromosomal instability and apoptosis induced by topoisomerase inhibitors. The described phenotype is reversed by the use of a DNA-demethylating agent or by the reintroduction of WRN into cancer cells displaying methylation-dependent silencing of WRN. Furthermore, the restoration of WRN expression induces tumor-suppressor-like features, such as reduced colony formation density and inhibition of tumor growth in nude mouse xenograft models. Screening a large collection of human primary tumors (n = 630) from different cell types revealed that WRN CpG island hypermethylation was a common event in epithelial and mesenchymal tumorigenesis. Most importantly, WRN hypermethylation in colorectal tumors was a predictor of good clinical response to the camptothecin analogue irinotecan, a topoisomerase inhibitor commonly used in the clinical setting for the treatment of this tumor type. These findings highlight the importance of WRN epigenetic inactivation in human cancer, leading to enhanced chromosomal instability and hypersensitivity to chemotherapeutic drugs.
Treatment of Sydenham's Chorea with Intravenous Immunoglobulin, Plasma Exchange, or Prednisone (2005)

Sydenham's chorea has been established as a postinfectious autoimmune neuropsychiatric disorder. Corticosteroids have been used to treat patients with severe disease but are not always effective, and relapses are frequent after cessation. Eighteen subjects were entered into this randomized-entry controlled trial designed to determine if intravenous immunoglobulin or plasma exchange would be superior to prednisone in decreasing the severity of chorea. Mean chorea severity for the entire group was significantly lower at the 1-month follow-up evaluation (overall 48% improvement). Although the between-group differences were not statistically significant, clinical improvements appeared to be more rapid and robust in the intravenous immunoglobulin and plasma exchange groups than in the prednisone group (mean chorea severity scores decreased by 72% in the intravenous immunoglobulin group, 50% in the plasma exchange group, and 29% in the prednisone group). Larger studies are required to confirm these clinical observations and to determine if these treatments are cost-effective for this disorder.
New Model for the Study of Angiogenesis and Antiangiogenesis in the Chick Embryo Chorioallantoic Membrane: The Gelatin Sponge/ Chorioallantoic Membrane Assay (1997)

Several methods for the in vivo study of angiogenesis are available, and each angiogenic assay presents distinct advantages and disadvantages. In this study, we present a new method for the quantitation of angiogenesis and antiangiogenesis in the chick embryo chorioallantoic membrane (CAM), based on the implantation of gelatin sponges on the top of growing CAM, on day 8 of incubation. After implantation, the sponges were treated with a stimulator (recombinant human basic fibroblast growth factor, FGF2) or an inhibitor (a rabbit polyclonal anti-FGF2 antibody) of blood vessel formation. Blood vessels growing vertically into the sponge and at the boundary between sponge and surrounding CAM mesenchyme were counted by a morphometric method on day 12. In addition, to assess whether the gelatin sponge is an appropriate vehicle to deliver cultured cells and evaluate their angiogenic potential, mouse aortic endothelial cells were cotransfected with human FGF2 and the Escherichia coli beta-galactosidase (beta-GAL) reporter gene. Stable transfectants were absorbed by the sponge, and evaluation of the angiogenic response was paralleled by beta-GAL staining to visualize implanted cells. This technique may facilitate the discovery and development of agonists or antagonists of angiogenesis.