gebhart/patrepeval huggingface dataset:
The rheumatoid factor reactivity of a human IgG monoclonal autoantibody is encoded by a variant V kappa II L chain gene (1991)

To determine the genetic and molecular basis for rheumatoid factor (RF) autoantibody reactivity in patients with destructive, erosive arthritis, we established a human lymphoblastoid cell line (hRF-1) from a patient with polyarthritis that produced an IgG RF mAb, mAb hRF-1. Studies of isolated H and L chains showed that the specificity of RF reactivity is conferred by mAb hRF-1 L chains. The L chain gene was cloned from a cDNA library prepared from hRF-1 cells. The nucleotide sequence was similar to known V kappa II L chains except for a two nucleotide change corresponding to a change of two amino acids in an invariable region of FR3. A germ-line gene with one of the nucleotide changes was identified by polymerase chain reaction in multiple cell lines, including K562 that does not rearrange Ig genes, but the other nucleotide change appeared to be due to mutation. Either or both of these amino acid changes may contribute to the RF reactivity, because an antibody with the same V kappa II L chain except for these two amino acid changes in FR3 did not have RF reactivity. The RF reactivity of isolated L chains from mAb hRF-1 was confirmed by transfecting COS cells with an expression vector encoding the hRF-1 kappa-chain and showing that the secreted k-chains had RF reactivity. Expression of this variant V kappa II L chain gene may form the basis for RF autoantibody reactivity in some patients.
Al-Induced Crystallization of an Amorphous Si Thin Film in a Polycrystalline Al/Native SiO2/Amorphous Si Structure (1996)

Al-induced crystallization of an amorphous Si (a-Si) thin film in a polycrystalline Al/native SiO 2 /a-Si structure has been investigated on an atomic level using cross-sectional high-resolution transmission electron microscopy. A 7-nm polycrystalline Al layer was thermally deposited onto a 50-nm a-Si thin film, deposited by low-pressure chemical vapor deposition and covered with a 2.2-nm layer of native SiO 2 . The a-Si thin film in this structure was partially crystallized at 250°Cand completely crystallized at 500°C after 30 min. Lattice fringes of Si(111) were observed in the original Al layer and interfacial native SiO 2 layer after the annealing process. From the above results, it was concluded that Al-induced crystallization of the a-Si thin film occurred by interdiffusion of Al and Si atoms through the native oxide layer even though the 2.2-nm native SiO 2 layer was not removed completely at the Al/a-Si interface. A possible model, that can be used to explain the Al-induced crystallization phenomena by taking into account the changes that take place within or near the native SiO 2 layer during the annealing process, was proposed.
Plasmonics-Based Nanostructures for Surface-Enhanced Raman Scattering Bioanalysis (2005)

Surface-enhanced Raman scattering (SERS) spectroscopy is a plasmonics-based spectroscopic technique that combines modern laser spectroscopy with unique optical properties of metallic nanostructures, resulting in strongly increased Raman signals when molecules are adsorbed on or near nanometer-size structures of special metals such as gold, silver, and transition metals. This chapter provides a synopsis of the development and application of SERS-active metallic nanostructures, especially for the analysis of biologically relevant compounds. Some highlights of this chapter include reports of SERS as an immunoassay readout method, SERS gene nanoprobes, near-field scanning optical microscopy SERS probes, SERS as a tool for single-molecule detection, and SERS nanoprobes for cellular studies.
SRR: An O(1) time complexity packet scheduler for flows in multi-service packet networks (2001)

In this paper, we present a novel fair queueing scheme, which we call Smoothed Round Robin (SRR). Ordinary round robin schedulers are well known for their burstiness in the scheduling output. In order to overcome this problem, SRR codes the weights of the flows into binary vectors to form a Weight Matrix, then uses a Weight Spread Sequence (WSS), which is specially designed to distribute the output more evenly, to schedule packets by scanning the Weight Matrix. By using the WSS and the Weight Matrix, SRR can emulate the Generalized Processor Sharing (GPS) well. It possesses better short-term fairness and schedule delay properties in comparison with various round robin schedulers. At the same time, it preserves O(1) time complexity by avoiding the time-stamp maintenance employed in various Fair Queueing schedulers. Simulation and implementation experiments show that SRR can provide good average end-to-end delay for soft real-time services. SRR can also be implemented in high-speed networks to provide QoS for its simplicity and low time complexity.
Effect of osteogenic differentiation medium on proliferation and differentiation of human mesenchymal stem cells in three-dimensional culture with radial flow bioreactor (2015)

Human mesenchymal stem cells (hMSCs) are multipotent cells, and have been expanded and differentiated into several kinds of mesodermal tissue in vitro. In order to promote bone repair, enhancement of the proliferation and differentiation of hMSCs into osteoblasts in vitro is recommended prior to therapeutic delivery. However, for clinical applications, it is still unclear which method is more advanced for tissue engineering: to transplant undifferentiated cells or partially differentiated stem cells. Therefore, the present study aimed to investigate how osteogenic differentiation medium (ODM) affects hMSCs cultured in a 3D scaffold using a radial-flow bioreactor (RFB) besides cell growth medium (GM). To produce precultured sheets, the hMSCs were first seeded onto type 1 collagen sheets and incubated for 12 h, after which they were placed in the RFB for scaffold fabrication. The culture medium was circulated at 3 mL/min and the cells dynamically cultured for 1 week at 37 °C. Static cultivation in a culture dish was also carried out. Cell proliferations were evaluated by histological analysis and DNA-based cell count. Alkaline phosphatase (ALP) activity, immunocytochemical analysis with BMP-2, and osteopontin on the hMSCs in the collagen scaffold were performed. After 14 days of ODM culture, a significant increase in cell number and a higher density of cell distribution in the scaffold were observed after both static and dynamic cultivation compared to GM culture. A significant increase in ALP activity after 14 days of ODM was recognized in dynamic cultivation compared with that of static cultivation. Cells that BMP-2 expressed were frequently observed after 14 days in dynamic culture compared with other conditions, and the expression of osteopontin was confirmed in dynamic cultivation after both 7 days and 14 days. The results of this study revealed that both the proliferation and bone differentiation of hMSCs in 3D culture by RFB were accelerated by culture in osteogenic differentiation medium, suggesting an advantageous future clinical applications for RFB cell culture and cell transplantation for tissue engineering.
Expression of cell-cycle-regulated proteins pRb2/p130, p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) in prostatic gland adenocarcinoma. (2002)

This study showed that all of the proteins but mdm-2 were expressed at a different rate in normal and pathological prostate specimens. Multivariate analysis showed that pRb2/p130 and p107 may be involved in the pathogenesis and progression of prostate cancers, and that the expression of the retinoblastoma-related protein pRb2/p130 along with Ki-67 (MIB-1), expressed as differences between cytoplasmic and nuclear concentrations, could be considered new parameters to be evaluated in discriminating patients at a higher risk for prostate cancer.
Identification of perivascular mesenchymal stromal/stem cells by flow cytometry (2013)

Mesenchymal stem/stromal cells (MSCs) are adult multipotent progenitors of great promise for cell therapy. MSCs can mediate tissue regeneration, immunomodulation, and hematopoiesis support. Despite the unique properties of MSCs and their broad range of potential clinical applications, the very nature of these cells has been uncertain. Furthermore, MSCs are heterogeneous and only defined subpopulations of these are endowed with the particular abilities to sustain hematopoietic stem cells, regulate immune responses, or differentiate into mesodermal cell lineages. It is becoming evident that current criteria used to define cultured polyclonal MSCs (expression of nonspecific markers and in vitro mesodermal differentiation) are not sufficient to fully understand and exploit the potential of these cells. Here, we describe how flow cytometry has been used to reveal a perivascular origin of MSCs. As a result, the prospective purification of MSCs and specialized subsets thereof is now possible, and the clinical use of purified autologous MSCs is now within reach.
Temporal secretion of a multicellulolytic system in Myxobacter sp. AL‐1 (2000)

The Gram-negative soil micro-organism Myxobacter sp. AL-1 possesses at least five extracellular cellulases, the production of which is regulated by the growth cycle. We cloned the complete gene for one of these cellulases, termed cel9, which encoded a 67-kDa modular family 9 endoglycohydrolase, which was produced during the stationary phase of growth and was strongly enhanced by avicel. The predicted product of cel9 matches the structural architecture of family 9 cellulases such as Thermonospora fusca endo/exocellulase E4. Cel9 protein was synthesized in Escherichia coli from a multicopy plasmid and in Bacillus subtilis from the isopropyl thiogalactoside-inducible Pspac promoter and was purified from the culture medium. Thermal stability, optimum pH and temperature dependence of Cel9 were similar when expressed from either source, and were indistinguishable from related cellulases produced by thermophilic bacteria. Downstream from cel9 was found a partial ORF, designated cel48, the deduced product of which was highly similar to bacterial exocellobiohydrolases and processive endoglucanases belonging to family 48 of the glycosyl hydrolases. The cel9 and cel48 genes appear to be arranged as part of an operon.
A 0.1-to-1.2GHz tunable 6th-order N-path channel-select filter with 0.6dB passband ripple and +7dBm blocker tolerance (2013)

Radio receivers should be robust to large out-of-band blockers with small degradation in their sensitivity. N-path mixers can be used as mixer-first receivers [1] with good linearity and RF filtering [2]. However, 1/f noise calls for large active device sizes for IF circuits and high power consumption. The 1/f noise issue can be relaxed by having RF gain. However, to avoid desensitization by large out-of-band blockers, a bandpass filter (BPF) with sharp cut-off frequency is required in front of the RF amplifiers. g <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> -C BPFs suffer from tight tradeoffs among DR, power consumption, Q and f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">c</sub> . Also, on-chip Q-enhanced LC BPFs [3] are not suitable due to low DR, large area and non-tunability. Therefore, bulky and non-tunable SAW filters are used. N-path BPFs offer high Q while their center frequency is tuned by the clock frequency [2]. Compared to g <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sub> -C filters, this technique decouples the required Q from the DR. The 4-path filter in [4] has only 2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">nd</sup> -order filtering and limited rejection. The order and rejection of N-path BPFs can be increased by cascading [5], but this renders a “round” passband shape. The 4 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sup> -order 4-path BPF in [6] has a “flat” passband shape and high rejection but a high NF. This work solves the noise issue of [6] while achieving the same out-of-band linearity and adding 25dB of voltage gain to relax the noise requirement of the subsequent stages.
TNF-α induces leukemic clonal evolution ex vivo in Fanconi anemia group C murine stem cells (2007)

The molecular pathogenesis of the myeloid leukemias that frequently occur in patients with Fanconi anemia (FA) is not well defined. Hematopoietic stem cells bearing inactivating mutations of FA complementation group C (FANCC) are genetically unstable and hypersensitive to apoptotic cytokine cues including IFN-gamma and TNF-alpha, but neoplastic stem cell clones that arise frequently in vivo are resistant to these cytokines. Reasoning that the combination of genetic instability and cytokine hypersensitivity might create an environment supporting the emergence of leukemic stem cells, we tested the leukemia-promoting effects of TNF-alpha in murine stem cells. TNF-alpha exposure initially profoundly inhibited the growth of Fancc-/- stem cells. However, longer-term exposure of these cells promoted the outgrowth of cytogenetically abnormal clones that, upon transplantation into congenic WT mice, led to acute myelogenous leukemia. TNF-alpha induced ROS-dependent genetic instability in Fancc-/- but not in WT cells. The leukemic clones were TNF-alpha resistant but retained their characteristic hypersensitivity to mitomycin C and exhibited high levels of chromosomal instability. Expression of FANCC cDNA in Fancc-/- stem cells protected them from TNF-alpha-induced clonal evolution. We conclude that TNF-alpha exposure creates an environment in which somatically mutated preleukemic stem cell clones are selected and from which unaltered TNF-alpha-hypersensitive Fancc-/- stem cells are purged.
Genetic ablation in transgenic mice. (1989)

The study of mammalian development has very quickly moved from a largely descriptive endeavour to one in which very precise mechanistic questions can now be formulated and answered. Undoubtedly, advances in this area have been the result of a strong foundation in experimental embryology, the application of molecular genetic techniques to the isolation and analysis of genes of developmental interest, and the ability to manipulate genetically the embryo through transgenic mouse technology. Perhaps the most dramatic illustration of the power of these new technologies is the potential ability to generate mice either that carry mutations in virtually any gene in the germ line through gene targeting in totipotent embryonic stem (ES) cells or that lack specific cell types through the genetic ablation technology reviewed here. Together, these two approaches have made it possible to knock out either a specific gene or a specific cell type in an intact animal and thus offer almost unlimited possibilities for addressing questions concerning the molecular and cellular biology of development. As well, animal models for various human diseases such as dwarfism, immunodeficiencies and demyelination can now be generated. It is clear that further refinements in both gene targeting and genetic ablation technologies are necessary before the full potential of either approach will be realized. Further development of conditional or inducible ablation strategies, coupled with a more precise definition of the cis-acting sequences, responsible for directing gene expression in fully differentiated and more primitive cells, will greatly broaden the range of questions that can be addressed by this approach.(ABSTRACT TRUNCATED AT 250 WORDS)
A remote center of motion robotic arm for computer assisted surgery (1996)

Summary We have designed a robotic arm based on a double parallel four bar linkage to act as an assistant in minimally invasive surgical procedures. The remote center of motion (RCM) geometry of the robot arm kinematically constraints the robot motion such that minimal translation of an instrument held by the robot takes place at the entry portal into the patientApos;s body. In addition to the two rotational degrees of freedom comprising the RCM arm, distal translation and rotation are provided to manoeuver the instrument within the patient's body about an axis coincident with the RCM. An XYZ translation stage located proximal to the RCM arm provides positioning capability to establish the RCM location relative to the patients anatomy. An electronics set capable of controlling the system, as well as performing a series of safety checks to verify correct system operation, has also been designed and constructed. The robot is capable of precise positional motion. Repeatability in the ±10 micron range is demonstrated. The complete robotic system consists of the robot hardware and an IBM PC-AT based servo controller connected via a custom shared memory link to a host IBM PS/2. For laparoscopic applications, the PS/2 includes an image capture board to capture and process video camera images. A camera rotation stage has also been designed for this application. We have successfully demonstrated this system as an assistant in a laparoscopic cholecystectomy. Further applications for this system involving active tissue manipulation are under development.
Transgenic cell lines for detection of animal viruses (1996)

Rapid diagnostic assays based on direct detection of viral antigen or nucleic acid are being used with increasing frequency in clinical virology laboratories. Virus culture, however, remains the only way to detect infectious virus and to analyze clinically relevant viral phenotypes, such as drug resistance. Growth of viruses in cell culture is labor intensive and time-consuming and requires the use of many different cell lines. Transgenic technology, together with increasing knowledge of the molecular pathways of virus replication, offers the possibility of using genetically modified cell lines to improve virus growth in cell culture and to facilitate detection of virus-infected cells. Genetically modifying cells so that they express a reporter gene only after infection with a specific virus can allow the detection of infectious virus by rapid and simple enzyme assays such as beta-galactosidase assays without the need for antibodies. Although transgenic cells have recently been successfully used for herpes simplex virus detection, much more work needs to be done to adapt this technology to other human viral pathogens such as cytomegalovirus and respiratory viruses. This review offers some strategies for applying this technology to a wide spectrum of animal viruses.
Influence of insulin antibodies on pharmacokinetics and bioavailability of recombinant human and highly purified beef insulins in insulin dependent diabetics. (1985)

Sixteen insulin dependent diabetics of long standing, with undetectable fasting plasma C peptide concentrations, and eight non-diabetic controls were each infused intravenously with biosynthetic human and highly purified beef insulin (1 mU/kg/min) while euglycaemia was maintained by a Biostator. No difference was observed between the two insulins in respect of insulin pharmacokinetics or biological action. The diabetics showed appreciable insulin resistance, manifested by a 40% reduction in the rate of insulin mediated glucose disposal, which was unrelated to the presence of insulin antibodies. Insulin binding antibodies, however, increased insulin's clearance rate and distribution space and prolonged its pharmacological and biological half lives. The rate at which insulin action was lost, after an intravenous infusion, was more rapid in diabetics without insulin antibody binding than in controls. In respect of their influence on insulin pharmacokinetics, moderate concentrations of insulin antibodies may be of positive advantage to all diabetics without endogenous insulin secretion and are not responsible for the insulin resistance of type 1 diabetes.
Endothelin-1 contributes to antigen-induced airway hyperresponsiveness (1995)

Endothelin A (ETA)-receptors mediate ET-1 contractions of ovine airway smooth muscle. Therefore, the ETA-receptor antagonist, BQ-123, was used to test the hypothesis that ET-1 contributes to antigen-induced airway responses in sheep allergic to Ascaris suum. We first established the protective effect of BQ-123 by demonstrating that BQ-123 given as an aerosol (0.3 or 1.0 mg/kg in 3 ml buffer) or by continuous intravenous infusion (100 micrograms.kg-1.min-1) significantly blocked the bronchoconstriction to aerosolized ET-1 (0.2-200 micrograms/ml). To determine whether ET-1 contributed to antigen-induced airway responses, BQ-123 was given either as an intravenous infusion (100 micrograms.kg-1.min-1) beginning 30 min before and continuing for 8 h after antigen challenge or as an aerosol (1 mg/kg in 3 ml buffer) 30 min before and 4, 8, and 24 h after antigen challenge. Neither treatment with intravenous infusion nor aerosolized BQ-123 blocked the immediate antigen-induced bronchoconstriction, but both treatments significantly reduced the late response (approximately 50%). The treatments with aerosolized BQ-123 also blocked the antigen-induced airway hyperresponsiveness to inhaled carbachol seen 24 h after challenge. Subsequently, we found that sheep developed airway hyperresponsiveness to inhaled carbachol at 4 and 24 h after ET-1 challenge, an effect that was blocked by aerosolized BQ-123. We conclude that in allergic sheep 1) aerosolized ET-1 causes bronchoconstriction, in part, by stimulation of ETA-receptors, 2) ET-1 is released in the airways after antigen challenge, and 3) this peptide contributes to the severity of the allergic responses, probably by increasing airway smooth muscle responsiveness.
Strategies for achieving high-level expression of genes in Escherichia coli. (1996)

Progress in our understanding of several biological processes promises to broaden the usefulness of Escherichia coli as a tool for gene expression. There is an expanding choice of tightly regulated prokaryotic promoters suitable for achieving high-level gene expression. New host strains facilitate the formation of disulfide bonds in the reducing environment of the cytoplasm and offer higher protein yields by minimizing proteolytic degradation. Insights into the process of protein translocation across the bacterial membranes may eventually make it possible to achieve robust secretion of specific proteins into the culture medium. Studies involving molecular chaperones have shown that in specific cases, chaperones can be very effective for improved protein folding, solubility, and membrane transport. Negative results derived from such studies are also instructive in formulating different strategies. The remarkable increase in the availability of fusion partners offers a wide range of tools for improved protein folding, solubility, protection from proteases, yield, and secretion into the culture medium, as well as for detection and purification of recombinant proteins. Codon usage is known to present a potential impediment to high-level gene expression in E. coli. Although we still do not understand all the rules governing this phenomenon, it is apparent that "rare" codons, depending on their frequency and context, can have an adverse effect on protein levels. Usually, this problem can be alleviated by modification of the relevant codons or by coexpression of the cognate tRNA genes. Finally, the elucidation of specific determinants of protein degradation, a plethora of protease-deficient host strains, and methods to stabilize proteins afford new strategies to minimize proteolytic susceptibility of recombinant proteins in E. coli.