gebhart/patrepeval huggingface dataset:
Secondary structure conversions of Alzheimer’s Aβ(1–40) peptide induced by membrane‐mimicking detergents (2008)

The amyloid beta peptide (Abeta) with 39-42 residues is the major component of amyloid plaques found in brains of Alzheimer's disease patients, and soluble oligomeric peptide aggregates mediate toxic effects on neurons. The Abeta aggregation involves a conformational change of the peptide structure to beta-sheet. In the present study, we report on the effect of detergents on the structure transitions of Abeta, to mimic the effects that biomembranes may have. In vitro, monomeric Abeta(1-40) in a dilute aqueous solution is weakly structured. By gradually adding small amounts of sodium dodecyl sulfate (SDS) or lithium dodecyl sulfate to a dilute aqueous solution, Abeta(1-40) is converted to beta-sheet, as observed by CD at 3 degrees C and 20 degrees C. The transition is mainly a two-state process, as revealed by approximately isodichroic points in the titrations. Abeta(1-40) loses almost all NMR signals at dodecyl sulfate concentrations giving rise to the optimal beta-sheet content (approximate detergent/peptide ratio = 20). Under these conditions, thioflavin T fluorescence measurements indicate a maximum of aggregated amyloid-like structures. The loss of NMR signals suggests that these are also involved in intermediate chemical exchange. Transverse relaxation optimized spectroscopy NMR spectra indicate that the C-terminal residues are more dynamic than the others. By further addition of SDS or lithium dodecyl sulfate reaching concentrations close to the critical micellar concentration, CD, NMR and FTIR spectra show that the peptide rearranges to form a micelle-bound structure with alpha-helical segments, similar to the secondary structures formed when a high concentration of detergent is added directly to the peptide solution.
A novel addition to the T cell repertory. Cell surface expression of tumor necrosis factor/cachectin by activated normal human T cells. (1990)

Expression of the pluripotent molecule TNF in a focused and antigen-restricted fashion might provide an advantage to the host organism. Given the central role of T cells in antigen-specific immunity, we examined whether activated T cells express TNF on their cell surface. FACS analysis of highly purified normal human T cells labeled with an anti-TNF mAb revealed that T cells express cell surface TNF when signaled with the synergistic combination of a calcium ionophore, ionomycin, and a protein kinase C activator, 12-o-tetradecanoyl phorbol acetate. Cell surface radioiodination studies of stimulated T cells demonstrated the presence of 26-kD transmembrane protein, a size predicted by TNF cDNA and different from that of the 17-kD secreted TNF molecule. The induced cell surface expression of TNF could be blocked with cyclosporine and/or methylprednisolone, and Northern analysis for TNF-specific transcripts revealed that this inhibitory effect occurs pretranslationally. Our demonstration for the first time that stimulated normal human T cells display cell surface TNF provides a mechanistic basis for the realization of effects of TNF in an antigen-specific fashion.
Guidelines for assessment of bone microstructure in rodents using micro–computed tomography (2010)

Use of high-resolution micro-computed tomography (microCT) imaging to assess trabecular and cortical bone morphology has grown immensely. There are several commercially available microCT systems, each with different approaches to image acquisition, evaluation, and reporting of outcomes. This lack of consistency makes it difficult to interpret reported results and to compare findings across different studies. This article addresses this critical need for standardized terminology and consistent reporting of parameters related to image acquisition and analysis, and key outcome assessments, particularly with respect to ex vivo analysis of rodent specimens. Thus the guidelines herein provide recommendations regarding (1) standardized terminology and units, (2) information to be included in describing the methods for a given experiment, and (3) a minimal set of outcome variables that should be reported. Whereas the specific research objective will determine the experimental design, these guidelines are intended to ensure accurate and consistent reporting of microCT-derived bone morphometry and density measurements. In particular, the methods section for papers that present microCT-based outcomes must include details of the following scan aspects: (1) image acquisition, including the scanning medium, X-ray tube potential, and voxel size, as well as clear descriptions of the size and location of the volume of interest and the method used to delineate trabecular and cortical bone regions, and (2) image processing, including the algorithms used for image filtration and the approach used for image segmentation. Morphometric analyses should be based on 3D algorithms that do not rely on assumptions about the underlying structure whenever possible. When reporting microCT results, the minimal set of variables that should be used to describe trabecular bone morphometry includes bone volume fraction and trabecular number, thickness, and separation. The minimal set of variables that should be used to describe cortical bone morphometry includes total cross-sectional area, cortical bone area, cortical bone area fraction, and cortical thickness. Other variables also may be appropriate depending on the research question and technical quality of the scan. Standard nomenclature, outlined in this article, should be followed for reporting of results.
Menstrual pain (dysmenorrhoea) (2014)

On average, women have a menstrual period every 28 days with bleeding (menstruation) lasting approximately four to seven days. During this time, the muscles of the uterus contract in response to hormone-like substances called prostaglandins, produced by the lining of the uterus. The levels of the prostaglandins increase prior to menstruation, and peak at the start of the menses. The levels decline again as a woman menstruates, resulting in less uterine discomfort or cramps after the first few days of the menstrual period.
Frequency Regulation Basics and Trends (2005)

The electric power system must address two unique requirements: the need to maintain a near real-time balance between generation and load, and the need to adjust generation (or load) to manage power flows through individual transmission facilities. These requirements are not new: vertically integrated utilities have been meeting them for a century as a normal part of conducting business. With restructuring, however, the services needed to meet these requirements, now called ''ancillary services'', are being more clearly defined. Ancillary services are those functions performed by the equipment and people that generate, control, and transmit electricity in support of the basic services of generating capacity, energy supply, and power delivery. The Federal Energy Regulatory Commission (FERC) has defined such services as those ''necessary to support the transmission of electric power from seller to purchaser given the obligations of control areas and transmitting utilities within those control areas to maintain reliable operations of the interconnected transmission system''. This statement recognizes the importance of ancillary services for both bulk-power reliability and support of commercial transactions. Balancing generation and load instantaneously and continuously is difficult because loads and generators are constantly fluctuating. Minute-to-minute load variability results from the random turning on and off of millions of individual loads. Longer-term variability results from predictable factors such as the daily and seasonal load patterns as well as more random events like shifting weather patterns. Generators also introduce unexpected fluctuations because they do not follow their generation schedules exactly and they trip unexpectedly due to a range of equipment failures. The output from wind generators varies with the wind. Storage technologies should be ideal suppliers of several ancillary services, including regulation, contingency reserves (spinning reserve, supplemental reserve, replacement reserve), and voltage support. These services are not free; in regions with energy markets, generators are paid to supply these services. In vertically integrated utilities (without energy markets) the utility incurs significant costs to supply these services. Supplying these services may be a significant business opportunity for emerging storage technologies. This report briefly explores the various ancillary services that may be of interest to storage. It then focuses on regulation, the most expensive ancillary service. It also examines the impact that increasing amounts of wind generation may have on regulation requirements, decreasing conventional regulation supplies, and the implications for energy storage.
Utilization of non‐AUG initiation codons in a flow cytometric method for efficient selection of recombinant cell lines (2011)

Here we describe a method that couples flow cytometric detection with the attenuated translation of a reporter protein to enable efficient selection of CHO clones producing high levels of recombinant proteins. In this system, a small cell surface reporter protein is expressed from an upstream open reading frame utilizing a non-AUG initiation (alternate start) codon. Due to the low translation initiation efficiency of this alternate start codon, the majority of translation initiation events occur at the first AUG of the downstream open reading frame encoding the recombinant protein of interest. While translation of the reporter is significantly reduced, the levels are sufficient for detection using flow cytometric methods and, in turn, predictive of protein expression from the gene of interest since both ORFs are translated from the same mRNA. Using this system, CHO cells have been sorted to obtain enriched pools producing significantly higher levels of recombinant proteins than the starting cell population and clones with significantly better productivity than those generated from limiting dilution cloning. This method also serves as an effective screening tool during clone expansion to enable resources to be focused solely on clones with both high and stable expression.
Multiple transformation of Saccharomyces cerevisiae by protoplast fusion (1992)

A technique for the multiple transformation of yeast by protoplast fusion is described. This involved the PEG-induced fusion of protoplasts from cells which had been treated with chromosome-fragmenting agents (in this case cupferron and hydroxylamine) with protoplasts of triply auxotrophic cells. The recovery of transformants was increased significantly if one of the amino acid requirements of the recipient strain was included in the selection medium. Transformants isolated on supplemented media remained auxotrophic for that requirement. Prototrophic, uninucleate transformants had a DNA content and cellular volume similar to that of the parental strains. Possible mechanisms of gene transfer are discussed. This technique offers the possibility of transferring desirable characteristics from one yeast strain to another without altering the ploidy level of the recipient strain.
The new World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas: a practical marriage of two giants (2005)

Following consensus meetings of the two parent organizations, a new World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification for primary cutaneous lymphomas has recently been published. This important development will now end the ongoing debate as to which of these was the preferred classification. The new classification will facilitate more uniformity in diagnosis, management and treatment of cutaneous lymphomas. In particular, it provides a useful distinction between indolent and more aggressive types of primary cutaneous lymphoma and provides practical advice on preferred management and treatment regimens. This will thereby prevent patients receiving high-grade treatment for low-grade biological disease. This review focuses on those diseases which have found new consensus agreement compared with the original WHO and EORTC classifications. In cutaneous T-cell lymphomas, these include folliculotropic mycosis fungoides, defining features of Sézary syndrome, primary cutaneous CD30+ lymphoproliferative disorders (primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis and borderline lesions) and subcutaneous panniculitis-like T-cell lymphoma. Primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma, primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma and cutaneous gamma/delta T-cell lymphoma are allocated provisional entry status and thereby afford better definitions for some cases of currently unspecified primary cutaneous peripheral T-cell lymphoma. In cutaneous B-cell lymphomas, diseases which have found new consensus agreement include primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicular centre lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type and primary cutaneous diffuse large B-cell lymphoma, other. CD4+/CD56+ haematodermic neoplasm (early plasmacytoid dendritic cell leukaemia/lymphoma) now appears as a precursor haematological neoplasm and replaces the previous terminology of blastic NK-cell lymphoma. Other haematopoietic and lymphoid tumours involving the skin, as part of systemic disease, will appear in the forthcoming WHO publication Tumours of the Skin. The new classification raises interesting new problems and questions about primary cutaneous lymphoma and some of these are discussed in this article. It is, however, a splendid signpost indicating the direction in which research in cutaneous lymphoma needs to go. In the interim, we have an international consensus classification which is clinically meaningful.
Closure of skin incisions in rabbits by laser soldering: I: Wound healing pattern (2004)

Temperature-controlled laser soldering offers an accelerated wound reparative process with numerous advantages over the conventional methods. Further investigations may reveal additional benefits in the spectrum of advantages that this innovative surgical technology has to offer. This can introduce new scientific insight that will pave the way for clinical use.
Activation, Inhibition, and Destabilization of Thermomyces lanuginosus Lipase by Detergents (2005)

Lipases catalyze the hydrolysis of triglycerides and are activated at the water-lipid interface. Thus, their interaction with amphiphiles such as detergents is relevant for an understanding of their enzymatic mechanism. In this study, we have characterized the effect of nonionic, anionic, cationic, and zwitterionic detergents on the enzymatic activity and thermal stability of Thermomyces lanuginosus lipase (TlL). For all detergents, low concentrations enhance the activity of TlL toward p-nitrophenyl butyrate by more than an order of magnitude; at higher detergent concentrations, the activity declines, leveling off close to the value measured in the absence of detergent. Surprisingly, these phenomena mainly involve monomeric detergent, as activation and inhibition occur well below the cmc for the nonionic and zwitterionic detergents. For anionic and cationic detergents, activation straddles the monomer-micelle transition. The data can be fitted to a three state interaction model, comprising free TlL in the absence of detergent, an activated complex with TlL at low detergent concentrations, and an enzyme-inhibiting complex at higher concentrations. For detergents with the same headgroup, there is an excellent correspondence between carbon chain length and ability to activate and inhibit TlL. However, the headgroup and number of chains also modulate these effects, dividing the detergents overall into three broad groups with rising activation and inhibition ability, namely, anionic and cationic detergents, nonionic and single-chain zwitterionic detergents, and double-chain zwitterionic detergents. As expected, only anionic and cationic detergents lead to a significant decrease in lipase thermal stability. Since nonionic detergents activate TlL without destabilizing the protein, activation/inhibition and destabilization must be independent processes. We conclude that lipase-detergent interactions occur at many independent levels and are governed by a combination of general and structurally specific interactions. Furthermore, activation of TlL by detergents apparently does not involve the classical interfacial activation phenomenon as monomeric detergent molecules are in most cases responsible for the observed increase in activity.
A highly porous 3-dimensional polyphosphazene polymer matrix for skeletal tissue regeneration (1996)

Current methods for the replacement of skeletal tissue in general involve the use of autografts or allografts. There are considerable drawbacks in the use of either of these tissues. In an effort to provide an alternative to traditional graft materials, a degradable 3-dimensional (3-D) osteoblast cell-polymer matrix was designed as a construct for skeletal tissue regeneration. A degradable amino acid containing polymer, poly[(methylphenoxy)(ethyl glycinato) phosphazene], was synthesized and a 3-D matrix system was prepared using a salt leaching technique. This 3-D polyphosphazene polymer matrix system, 3-D-PHOS, was then seeded with osteoblast cells for the creation of a cell-polymer matrix material. The 3-D-PHOS matrix possessed an average pore diameter of 165 microns. Environmental scanning electron microscopy revealed a reconnecting porous network throughout the polymer with an even distribution of pores over the surface of the matrix. Osteoblast cells were found attached and grew on the 3-D-PHOS at a steady rate throughout the 21-day period studied in vitro, in contrast to osteoblast growth kinetics on similar, but 2-D polyphosphazene matrices, that showed a decline in cell growth after 7 days. Characterization of 3-D-PHOS osteoblastpolymer matrices by light microscopy revealed cells growing within the pores as well as on surface of the polymer as early as day 1. This novel porous 3-D-PHOS matrix may be suitable for use as a bioerodible scaffold for regeneration of skeletal tissue.
An Optimized System for Interventional Magnetic Resonance Imaging-Guided Stereotactic Surgery (2011)

This novel system provides the submillimetric accuracy required for stereotactic interventions, including deep brain stimulation placement. It also overcomes technical limitations inherent in the first-generation interventional MRI system.
Recent Advances in Our Understanding of Receptor Binding, Viral Fusion and Cell Entry of Hepatitis C Virus: New Targets for the Design of Antiviral Agents (2007)

Improvements to antiviral therapies for the treatment of hepatitis C virus (HCV) infections will require the use of multiple drugs that target viral proteins essential for replication. The discovery of anti-HCV compounds has been severely hampered by the lack of cell culture replication systems. Since the late 1990s, the advent of sub-genomic replicons that model the intracellular events leading to HCV genome replication have enabled the discovery of HCV protease and polymerase inhibitors, but did not allow the study of HCV entry or entry inhibitors. More recently, retroviral pseudotyping of the viral glycoproteins and the development of a cell culture-based system that recapitulates the entire HCV replication cycle were achieved. These new experimental systems have enabled a rapid advance in our knowledge of how HCV glycoproteins, E1 and E2, mediate receptor binding and viral entry. These systems have facilitated the discovery of a range of viral receptors. Evidence is emerging that CD81, scavenger receptor class B type I, claudin-1 and the low-density lipoprotein receptor are involved in viral entry. In addition, DC-SIGN and L-SIGN may function to internalize virus into dendritic or endothelial cells, facilitating the transport of virions to sites of infection such as the liver. This review focuses on the interaction between the HCV glycoproteins and cellular receptors, and our current understanding of the viral entry pathway. In addition, key questions on the role that these receptors play in viral entry are raised and potential avenues for the discovery of new antiviral agents are highlighted.
Inhibition of TRIP1/S8/hSug1, a component of the human 19S proteasome, enhances mitotic apoptosis induced by spindle poisons (2006)

Mitotic spindle poisons (e.g., Taxol and vinblastine), used as chemotherapy drugs, inhibit mitotic spindle function, activate the mitotic spindle checkpoint, arrest cells in mitosis, and then cause cell death by mechanisms that are poorly understood. By expression cloning, we identified a truncated version of human TRIP1 (also known as S8, hSug1), an AAA (ATPases associated with diverse cellular activities) family ATPase subunit of the 19S proteasome regulatory complex, as an enhancer of spindle poison-mediated apoptosis. Stable expression of the truncated TRIP1/S8/hSug1 in HeLa cells [OP-TRIP1(88-406)] resulted in a decrease of measurable cellular proteasome activity, indicating that OP-TRIP1(88-406) had a dominant-negative effect on proteasome function. OP-TRIP1(88-406) revealed an increased apoptotic response after treatment with spindle poisons or with proteasome inhibitors. The increased apoptosis coincided with a significant decrease in expression of BubR1, a kinase required for activation and maintenance of the mitotic spindle checkpoint in response to treatment with spindle poisons. Small interfering RNA (siRNA)-mediated knockdown of TRIP1/S8/hSug1 resulted in a reduction of general proteasome activity and an increase in mitotic index. The siRNA treatment also caused increased cell death after spindle poison treatment. These results indicate that inhibition of TRIP1/S8/hSug1 function by expression of a truncated version of the protein or by siRNA-mediated suppression enhances cell death in response to spindle poison treatment. Current proteasome inhibitor drugs in trial as anticancer agents target elements of the 20S catalytic subcomplex. Our results suggest that targeting the ATPase subunits in 19S regulatory complex in the proteasome may enhance the antitumor effects of spindle poisons.