gebhart/patrepeval huggingface dataset:
AZT induces high frequency, rapid amplification of centromeric DNA (1997)

The reverse transcriptase inhibitor 3'-azido-deoxythymidine (AZT) has previously been shown to be incorporated into specific regions near the telomeres and centromeres of Chinese hamster ovary cell chromosomes. Our investigation of the effects of AZT on chromosome stability has led to the discovery of a high frequency amplification of telomere-like centromeric DNA. The amplified structures, when analyzed cytogenetically, appear as tandem arrays of tightly clustered blocks of centromeric repeats containing telomeric sequences (TTAGGG)n. There were 5-13 blocks of amplified DNA per structure. These structures form rapidly within one or two cell cycles and can be observed with an incidence as high as 2%. Because the amplification was so rapid, we tested whether the amplification structures could be the result of aberrant overreplication by analyzing BrdU incorporation. Our results indicate that the amplified DNA does not undergo abnormal replication during its formation, but appears to form from existing centromeric regions. We propose a model that involves the excision of multiple centromeric DNA regions from other chromosomes and their relocalization to a new site.
Recent developments and future strategies for immunotherapy of insect venom allergy (2003)

Purpose of review Hymenoptera venom allergy may cause life-threatening, sometimes even fatal, allergic reactions and thus may be associated with a serious reduction in the quality of life. Venom immunotherapy is effective in the majority of patients with this allergy. Treatment failures do however occur and immunotherapy may cause frequent systemic allergic side effects, especially in honeybee venom-allergic patients. New strategies to improve safety and efficacy of this treatment are therefore of general interest. Recent findings Among these new strategies are premedication with antihistamines: this definitely reduces side effects and based on recent in-vitro experiments and one clinical controlled study may even improve efficacy by modulating the T-cell response through interference with histamine receptors on these cells. Furthermore, during recent years the cDNA of most major allergens of bee and vespid venoms has been cloned and these allergens have been expressed in recombinant form. This allows for the preparation of patient-tailored extracts, with or without reduction of their allergenicity, for example by using unrefolded or point-mutated recombinant allergens. Yet another approach is the use of non IgE binding peptide fragments of the allergen with preserved T-cell epitopes for immunotherapy. Such preparations of bee venom phospholipase A2 have been used successfully in pilot studies. Finally, DNA vaccination with phospholipase A2 sequence plasmids has proved effective in one experimental study in sensitized mice. Summary A number of new strategies for venom immunotherapy, mostly based on genetic engineering, have been described and we await their use in clinical medicine.
The laser welding of thin metal sheets: an integrated keyhole and weld pool model with supporting experiments (1994)

An integrated mathematical model for laser welding of thin metal sheets under a variety of laser material processing conditions has been developed and tested against the results of experiments. Full account is taken in the model of the interaction of the laser-generated keyhole with the weld pool. Results calculated from the model are found to agree well with experiment for appropriate values of the keyhole radius. The analysis yields values for power absorption in the metal. In a complementary calculation the total absorption of the laser energy is determined from detailed consideration of the inverse Bremsstrahlung absorption in the plasma and Fresnel absorption at the keyhole walls. To test these results, experiments were performed on 1 mm mild steel using a high-speed video camera, which measured the surface dimensions of the melt pool. Processing parameters were varied to study the effect on the melt pool; parameters considered included traverse speed, laser power and shroud gas species. The general shape of the weld pool was found to depend on whether penetration was full, partial or blind; only the results for full penetration were compared with the theory, which is for complete penetration only.
CD167 Acts as a Novel Costimulatory Receptor in T-Cell Activation (2009)

Optimal T-cell activation requires both an antigen-specific and a costimulatory signal. CD167 is a tyrosine kinase receptor for native type I collagen, its physiologic functions include matrix homeostasis and cell growth, adhesion, branching, and migration, but the specific role of CD167 in T cells has not yet been characterized. In this study, we found that CD167 expression on T cells was up-regulated after activation. Cooperation of CD167 engagement with suboptimal TCR/CD3 signals induced T-cell proliferation, enhanced expression of activation markers such as CD25 and CD69, elevated intracellular calcium mobilization and tyrosine phosphorylation, and introduced a bias toward a TH1/Tc1 immune response. Cooperation of CD167 engagement also enhanced mixed lymphocyte responses to alloantigens. Moreover, CD167 rapidly localized to the aggregated lipid rafts upon T-cell activation, this provided a molecular base for the signaling machinery of CD167. Together these findings, we demonstrate for the first time that CD167 could serve as a novel costimulatory receptor for T-cell activation.
Generation of bioreagents for protein chips (2003)

Protein microarrays have the potential to dramatically increase the throughput of proteomic analysis. Protein expression profiling chips with distinct spots of immobilized protein capture agents will allow the simultaneous measurement of hundreds to thousands of proteins from one sample. In contrast to DNA chips, for which the capture probes are easily designed and synthesized, the development of content for protein biochips is a long and laborious process. Careful consideration must be given to the specificities desired, the format of the assay, and the requirements of the capture agents, as well as to process optimization to minimize development time and cost. Monoclonal antibodies have been the prime choice as protein capture agents for the majority of protein chips developed to date. New technologies for the production of protein capture agents are more amenable to automation than traditional monoclonal antibody production and therefore carry the promise for industrialization.
Expression of a cloned Bacillus thuringiensis crystal protein gene in Escherichia coli (1987)

The expression in Escherichia coli of a cloned crystal protein gene from Bacillus thuringiensis was investigated through the use of fusions of the crystal protein gene promoter to beta-galactosidase and catechol oxidase genes. Analysis of deletion and insertion derivatives of the crystal protein gene promoter showed that a region of B. thuringiensis DNA located between 87 and 258 base pairs upstream from the transcription initiation site caused reduced transcription from this promoter. Insertion of Tn5 145 base pairs upstream from the transcription initiation site resulted in overproduction of the crystal protein. S1 nuclease mapping experiments failed to detect transcription from an outwardly directed promoter in Tn5, indicating that the overproduction resulted from the disruption or repositioning of the transcription-suppressing region.
Identification of an upstream region of the mousep53promoter critical for transcriptional expression (1995)

We have investigated the transcription factor requirements for basal expression of the mouse p53 promoter by using a combination of reporter and electrophoretic mobility shift assays (EMSAs). We have found that only four regions of the promoter bind transcription factors in EMSAs, suggesting that these are the only important factors for basal transcription. These factors are NF1, USF, ETF-like and a novel factor which we have called PF2. Construction of promoter deletion mutants has shown that the absence of the PF2 site completely inactivates the promoter, whereas deletion of other sites, whilst reducing promoter activity, does not. We suggest that this novel transcription factor (PF2) is critical for expression of the mouse p53 promoter.
Botulinum Toxin in the Treatment of Chronic Urinary Retention in Women (1992)

Six women were identified as having difficulty in voiding or complete urinary retention due to abnormal myotonic-like electromyographic (EMG) activity in the striated muscle of the urethral sphincter. An attempt was made to improve voiding by injection of botulinum toxin into the striated sphincter muscle. Although 3 patients then developed transient stress incontinence, demonstrating that sufficient botulinum toxin had been given to cause sphincter weakness, no patient had significant symptomatic benefit.
Oxidation of Metal Surfaces (2002)

Metal oxidation is often unwanted--for example, in the case of corrosion--but under controlled conditions the oxidation of metals can be beneficial for the manufacture and performance of advanced materials9. In their Perspective,
 Over and Seitsonen
 provide a brief overview of the complex oxidation behavior of metal surfaces. They highlight the report by
 ThA¼rmeret al., who demonstrate the crucial role played by surface impurities in the oxidation of lead crystallites.
Microfluidic size separation of cells and particles using a swinging bucket centrifuge (2015)

Biomolecular separation is crucial for downstream analysis. Separation technique mainly relies on centrifugal sedimentation. However, minuscule sample volume separation and extraction is difficult with conventional centrifuge. Furthermore, conventional centrifuge requires density gradient centrifugation which is laborious and time-consuming. To overcome this challenge, we present a novel size-selective bioparticles separation microfluidic chip on a swinging bucket minifuge. Size separation is achieved using passive pressure driven centrifugal fluid flows coupled with centrifugal force acting on the particles within the microfluidic chip. By adopting centrifugal microfluidics on a swinging bucket rotor, we achieved over 95% efficiency in separating mixed 20 μm and 2 μm colloidal dispersions from its liquid medium. Furthermore, by manipulating the hydrodynamic resistance, we performed size separation of mixed microbeads, achieving size efficiency of up to 90%. To further validate our device utility, we loaded spiked whole blood with MCF-7 cells into our microfluidic device and subjected it to centrifugal force for a mere duration of 10 s, thereby achieving a separation efficiency of over 75%. Overall, our centrifugal microfluidic device enables extremely rapid and label-free enrichment of different sized cells and particles with high efficiency.
Synthesis of an Estrogen Receptor β-Selective Radioligand:  5-[18F]Fluoro-(2R*,3S*)-2,3-bis(4-hydroxyphenyl)pentanenitrile and Comparison of in Vivo Distribution with 16α-[18F]Fluoro-17β-estradiol (2005)

Estrogen receptor beta (ERbeta), a less active ER subtype that appears to have a restraining effect on the more active ERalpha, could be a factor that determines the level of estrogen action in certain estrogen target tissues. ERbeta is found in breast cancer, and its levels relative to ERalpha decline with disease progression. Thus, the independent quantification of ERalpha and ERbeta levels in breast cancer by imaging might be predictive of responses to different hormone therapies. To develop an imaging agent for ERbeta, we synthesized a fluoroethyl analogue of DPN (2,3-bis(4-hydroxyphenyl)propanonitrile), a known ERbeta-selective ligand. This analogue, FEDPN (5-fluoro-(2R,3S)-2,3-bis(4-hydroxyphenyl)pentanenitrile), has an 8.3-fold absolute affinity preference for ERbeta. [18F]Fluoride-labeled FEDPN was prepared from a toluenesulfonate precursor, which provided [18F]FEDPN with a specific activity greater than 3100 Ci/mmol after HPLC purification. Biodistribution studies in immature female rats using estradiol as a blocking agent revealed specific uptake of [18F]FEDPN in the uterus and ovaries. Experiments using ERalpha- and ERbeta-knockout mice demonstrated the expected ERalpha-subtype dependence in the tissue uptake of the known 16alpha-[18F]fluoro-17beta-estradiol ([18F]FES), which has a 6.3-fold preference for ERalpha. The tissue uptake of [18F]FEDPN in the ER knockout mice showed some evidence of mediation by ERbeta, but the levels of specific uptake of this agent were relatively modest. Based on our results, imaging of ERalpha can be done effectively with [18F]FES, but imaging of ERbeta will likely require agents with more optimized ERbeta binding affinity and selectivity than [18F]FEDNP.
Primary Structure of Anti-Lipopolysaccharide Factor from American Horseshoe Crab, Limulus polyphemus1 (1987)

The complete amino acid sequence of anti-lipopolysaccharide (LPS) factor purified from the hemocytes lysate of the American horseshoe crab, Limulus polyphemus, was determined by characterization of the NH2-terminal sequence and the peptides generated after digestion of the protein with lysyl endopeptidase, clostripain, and Staphylococcus aureus V8 protease. Upon sequencing the peptides by the automated Edman method, the following primary structure was obtained: (Sequence: in text). During the sequence analysis, two species of the protein, which differed from each other at one locus, were found and characterized. L. polyphemus anti-LPS factor was a basic protein consisting of a single polypeptide chain of 101 residues and a calculated molecular weight of 11,786 or 11,800. The hydrophobic NH2-terminal sequence and the clustering of positive charges found in the disulfide loop yielded a typical amphipathic character of this protein. Moreover, L. polyphemus anti-LPS factor showed 83% sequence identity with the Tachypleus tridentatus protein, and the sequence similar to that observed in the EF-hand structure was found to contain in the COOH terminal portions of these proteins, although its function is unknown.
Evidence for a self-associating equilibrium intermediate during folding of human growth hormone (1993)

It has been previously shown, by equilibrium denaturation, that human growth hormone (hGH) folds by a cooperative two-state process. This is in contrast to the folding pathways of other nonhuman growth hormones that contain stable monomeric and multimeric equilibrium intermediates. We have reinvestigated the equilibrium denaturation of hGH at higher protein concentrations and found smooth transitions from the native to denatured state, but the calculated free energy for unfolding, delta G, decreases with increasing protein concentration. The effect of protein concentration on the delta G of unfolding is due to the presence of folding intermediates that have a tendency to self-associate. A correlation was found between the equilibrium denaturation data and the observation of precipitation that occurs upon refolding, suggesting that the presence of self-associated folding intermediates leads to precipitation. Direct evidence for the existence of a soluble, associated intermediate was obtained by dynamic light scattering (DLS) and equilibrium analytical ultracentrifugation. Peptide fragments from the third helix of either hGH or bovine growth hormone (bGH) were capable of inhibiting the formation of this aggregated species and prevent precipitation during refolding. The data show that the folding pathway of hGH is similar to that of nonhuman growth hormones except for differences in the tendency for intermediates to self-associate. These findings are relevant to the design and interpretation of equilibrium folding experiments, and may be important to understanding mechanistic details of protein folding and aggregation in vivo.
Structure, Sequence and Polymorphism in the HLA‐D Region (1985)

Molecular analysis of the HLA-D region has uncovered a complex array of related genes encompassing a minimum of 6 alpha and 7 beta chain sequences. A high level of polymorphism is characteristic of the DQ alpha and beta genes, as well as DR beta. The DP genes, both alpha and beta, are also polymorphic, though to a lesser extent. The genes fit into the previously established loci: DP, DQ and DR, except for a newly-discovered sequence, DZ alpha, which is approximately equally related to all of the other alpha chain genes. Analysis of the polymorphism and evolution of the HLA-D region, by examination of the sequences, calls for several independent duplication events in the generation of this family of genes.
Three Biomarkers Identified from Serum Proteomic Analysis for the Detection of Early Stage Ovarian Cancer (2004)

Early detection remains the most promising approach to improve long-term survival of patients with ovarian cancer. In a five-center case-control study, serum proteomic expressions were analyzed on 153 patients with invasive epithelial ovarian cancer, 42 with other ovarian cancers, 166 with benign pelvic masses, and 142 healthy women. Data from patients with early stage ovarian cancer and healthy women at two centers were analyzed independently and the results cross-validated to discover potential biomarkers. The results were validated using the samples from two of the remaining centers. After protein identification, biomarkers for which an immunoassay was available were tested on samples from the fifth center, which included 41 healthy women, 41 patients with ovarian cancer, and 20 each with breast, colon, and prostate cancers. Three biomarkers were identified as follows: (a) apolipoprotein A1 (down-regulated in cancer); (b) a truncated form of transthyretin (down-regulated); and (c) a cleavage fragment of inter-alpha-trypsin inhibitor heavy chain H4 (up-regulated). In independent validation to detect early stage invasive epithelial ovarian cancer from healthy controls, the sensitivity of a multivariate model combining the three biomarkers and CA125 [74% (95% CI, 52-90%)] was higher than that of CA125 alone [65% (95% CI, 43-84%)] at a matched specificity of 97% (95% CI, 89-100%). When compared at a fixed sensitivity of 83% (95% CI, 61-95%), the specificity of the model [94% (95% CI, 85-98%)] was significantly better than that of CA125 alone [52% (95% CI, 39-65%)]. These biomarkers demonstrated the potential to improve the detection of early stage ovarian cancer.
Functional inhibition of endogenously produced urokinase decreases cell proliferation in a human melanoma cell line. (1989)

Binding of urokinase-type plasminogen activator (u-PA) to its receptor has been shown not only to focus proteolytic activity to the cell surface but also to exert a mitogenic effect on the human epidermal tumor cell line CCL 20.2. This report shows that u-PA is an autocrine mitogen in the human melanoma cell line GUBSB and that inhibition of receptor-bound u-PA by specific anti-u-PA antibodies causes a significant suppression of cell proliferation in this system. The GUBSB cell line secretes 70-80% of the u-PA in its active form and expresses high-affinity u-PA receptors with a Kd of 5.2 x 10(-10) M and 2.8 x 10(4) binding sites per cell. Approximately 70% of the u-PA receptors on these cells are occupied by endogenously secreted u-PA. Addition of the monoclonal anti-u-PA antibody MPW5UK (10 nM), directed against the active site of u-PA, twice daily to the cell cultures resulted in a significant decrease of [3H]thymidine incorporation by the tumor cells, whereas a 10 times higher concentration of the monoclonal antibody MPW4UK, which does not inhibit plasminogen activator activity of u-PA, was necessary to achieve the same effect. In addition, diisopropyl fluorophosphate-inactivated u-PA, in a concentration 50-fold higher than the concentration necessary to saturate the u-PA receptor (250 pM), decreased [3H]thymidine incorporation similarly to the specific antibody, proving that active u-PA is required for the mitogenic effect. Inhibition of endogenous u-PA production by cycloheximide reduced [3H]thymidine incorporation significantly; after addition of exogenous u-PA, [3H]thymidine incorporation increased again in the cycloheximide-treated cells. Therefore, inhibition of receptor-bound u-PA might represent a tool not only to inactivate cell-bound proteolytic activity, necessary for invasion, but also to exert a specific antiproliferative effect on certain tumor cells.
Molecular Cloning and Functional Analysis of a Novel P2 Nucleotide Receptor (1995)

The cDNA encoding a novel P2 receptor was isolated from rat aortic smooth muscle cell library and functionally characterized. The cloned P2 receptor exhibits structural features characteristic of the G protein-coupled receptor family and shows 44 and 38% amino acid identity with previously cloned rat P2U and chicken P2Y receptors, respectively. The cloned P2 receptor is functionally coupled to phospholipase C but not to adenylate cyclase in C6 rat glioma cells transfected with the cloned P2 expression vector. The rank order of agonist potency as judged by intracellular Ca2+ mobilization responses is UTP > ADP = 2-methylthioATP > ADP beta S > ATP = ATP gamma S, which is not compatible with any of the previously characterized P2 receptor subtypes. The nonselective P2 antagonists, suramin and reactive blue-2, inhibit nucleotide-induced phospholipase C activation in cells expressing the cloned P2 receptor. The cloned P2 receptor mRNA is abundantly expressed in various rat tissues including lung, stomach, intestine, spleen, mesentery, heart, and, most prominently, aorta. The results indicate that the novel metabotropic P2 receptor has pharmacological characteristics distinct from any of P2 receptor subtypes thus far identified and suggest the existence of a novel regulatory system by extracellular nucleotides of potential significance.
Femtonewton Force Spectroscopy of Single Extended DNA Molecules (2000)

We studied the thermal fluctuations of single DNA molecules with a novel optical tweezer based force spectroscopy technique. This technique combines femtonewton sensitivity with millisecond time resolution, surpassing the sensitivity of previous force measurements in aqueous solution with comparable bandwidth by a hundredfold. Our data resolve long-standing questions concerning internal hydrodynamics of the polymer and anisotropy in the molecular relaxation times and friction coefficients. The dynamics at high extension show interesting nonlinear behavior.
Preparation of Well‐Defined Antibody–Drug Conjugates through Glycan Remodeling and Strain‐Promoted Azide–Alkyne Cycloadditions (2014)

Antibody-drug conjugates hold considerable promise as anticancer agents, however, producing them remains a challenge and there is a need for mild, broadly applicable, site-specific conjugation methods that yield homogenous products. It was envisaged that enzymatic remodeling of the oligosaccharides of an antibody would enable the introduction of reactive groups that can be exploited for the site-specific attachment of cytotoxic drugs. This is based on the observation that glycosyltransferases often tolerate chemical modifications in their sugar nucleotide substrates, thus allowing the installation of reactive functionalities. An azide was incorporated because this functional group is virtually absent in biological systems and can be reacted by strain-promoted alkyne-azide cycloaddition. This method, which does not require genetic engineering, was used to produce an anti-CD22 antibody modified with doxorubicin to selectively target and kill lymphoma cells.