gebhart/patrepeval huggingface dataset:
Discussion on the teaching mode of higher vocational nursing specialty based on CDIO model (2013)

基于CDIO模式下高职院校护理专业教学模式的探讨是本文的研究核心。CDIO是国际高等工程教育改革的最新成果，兴起于2000年，国内高校在引入CDIO 模式改革过程中，出现一些问题或疑惑是在所难免的，所以CDIO模式是高等教育院校,尤其是高职院校教师对陈旧教学模式的一次大胆尝试。CDIO模式能够促使教师反思已固有的习惯性教学理念，从而在教学过程中改变教学方法，使教师的教学工作能力得以很大程度的提高，同时鼓励学生的学习行为趋于自主性，培养其自身的专业能力、个人发展能力、人际交往能力和系统创新能力等职业综合能力。
Nicotine intake and dose response when smoking reduced–nicotine content cigarettes (2006)

Our study suggests that reduced-nicotine content cigarettes are reasonable candidates for trying to reduce the level of nicotine addiction in smokers. The flat nicotine dose-cardiovascular response curve is consistent with other studies demonstrating tolerance to the cardiovascular effects of nicotine.
Identification and Functions of Chondroitin Sulfate in the Milieu of Neural Stem Cells (2005)

The behavior of cells is generally considered to be regulated by environmental factors, but the molecules in the milieu of neural stem cells have been little studied. We found by immunohistochemistry that chondroitin sulfate (CS) existed in the surroundings of nestin-positive cells or neural stem/progenitor cells in the rat ventricular zone of the telencephalon at embryonic day 14. Brain-specific chondroitin sulfate proteoglycans (CSPGs), including neurocan, phosphacan/receptor-type protein-tyrosine phosphatase beta, and neuroglycan C, were detected in the ventricular zone. Neurospheres formed by cells from the fetal telencephalon also expressed these CSPGs and NG2 proteoglycan. To examine the structural features and functions of CS polysaccharides in the milieu of neural stem cells, we isolated and purified CS from embryonic day 14 telencephalons. The CS preparation consisted of two fractions differing in size and extent of sulfation: small CS polysaccharides with low sulfation and large CS polysaccharides with high sulfation. Interestingly, both CS polysaccharides and commercial preparations of dermatan sulfate CS-B and an E-type of highly sulfated CS promoted the fibroblast growth factor-2-mediated proliferation of neural stem/progenitor cells. None of these CS preparations promoted the epidermal growth factor-mediated neural stem cell proliferation. These results suggest that these CSPGs are involved in the proliferation of neural stem cells as a group of cell microenvironmental factors.
A study of diode protection for giant magnetoresistive recording heads (2003)

ESD testing of giant magnetoresistive (GMR) heads with diodes is described. While the use of diodes did increase the magnetic and resistance failure voltages of the GMR head, the magnetic failure voltage was increased much less than the resistance failure voltage. This results in an unfortunate side effect, which is to dramatically increase the range over which magnetic damage occurs without a resistance change. This problem was especially clear for the case of two diodes in series. The current flow through the GMR head and diode were measured and agreed with SPICE circuit simulation results. The difference between magnetic and resistance protection is due to the nonlinear clamping behavior of the diode. It is concluded that serious magnetic damage will be the predominant failure signature for GMR heads with ESD protect diodes.
Evidence for the origin of Kaposi's sarcoma from lymphatic endothelium. (1985)

Previous studies utilizing enzyme histochemistry, electron microscopy, and immunohistochemistry have failed to establish the cell of origin in Kaposi's sarcoma. The authors have rigorously tested the prevailing hypothesis that the lesion defined as Kaposi's sarcoma is derived from vascular endothelial cells. They use seven markers to characterize endothelial cells: three antigens (Factor VIII-related antigen, HLA-DR/Ia, macrophage/endothelial antigens), three enzymes (5'-nucleotidase, ATPase, alkaline phosphatase), and lectin binding (Ulex europaeus I). They applied the markers first to normal skin and lymph node, and then to biopsy specimens from 40 patients with Kaposi's sarcoma. Normal blood vessel endothelium was positive for all seven markers, but normal lymphatic endothelium was negative for all of the markers except 5'-nucleotidase and Ulex europaeus lectin. The neoplastic cells in 40 cases of Kaposi's sarcoma closely resembled those of normal lymphatic endothelium but not those of blood vessel endothelium. This suggests that Kaposi's sarcoma may originate in lymphatic endothelium.
Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling (2007)

Kinase inhibitors constitute an important new class of cancer drugs, whose selective efficacy is largely determined by underlying tumor cell genetics. We established a high-throughput platform to profile 500 cell lines derived from diverse epithelial cancers for sensitivity to 14 kinase inhibitors. Most inhibitors were ineffective against unselected cell lines but exhibited dramatic cell killing of small nonoverlapping subsets. Cells with exquisite sensitivity to EGFR, HER2, MET, or BRAF kinase inhibitors were marked by activating mutations or amplification of the drug target. Although most cell lines recapitulated known tumor-associated genotypes, the screen revealed low-frequency drug-sensitizing genotypes in tumor types not previously associated with drug susceptibility. Furthermore, comparing drugs thought to target the same kinase revealed striking differences, predictive of clinical efficacy. Genetically defined cancer subsets, irrespective of tissue type, predict response to kinase inhibitors, and provide an important preclinical model to guide early clinical applications of novel targeted inhibitors.
Mimicking Tissue Surfaces by Supported Membrane Coupled Ultrathin Layer of Hyaluronic Acid (2002)

We describe a technique of anchoring ultrathin (50−250 nm) layers of the extracellular matrix polysaccharide hyaluronic acid (HA) on solid supported fluid lipid bilayers through a recombinant HA-binding protein (p32) which is coupled to lipid molecules by reversible histidine−chelator bonds. A novel technique, the dual wavelength reflection interference contrast microscopy (DW-RICM), was applied to measure the local absolute thickness of the soft polymer cushions by measuring the height of the colloidal beads hovering over the surface. By analysis of the mean-square out-of-plane fluctuations of the beads, the surface elasticity and friction of the HA films can be measured as a function of the film thickness. The technique is applied to study the influence of excess salt and the cross-linkers on the film thickness and viscoelastic parameters of membrane coupled HA layer. The mean-square displacement of the lateral diffusion of the colloidal beads over the HA film obeys a non-Brownian power law (〈|x(t) − x(0)|2〉 ∝ tα) with α = 0.70 ± 0.05 attributed to the time-dependent friction of the viscoelastic HA film.
Impact and implications of yeast and human artificial chromosomes (1998)

Artificial chromosomes have been developed in the last 10 years to sustain genome mapping and, more recently, to begin initiating functional studies and some approaches to gene therapy. The use of yeast artificial chromosomes (YACs) in mapping the human X chromosome is reported as an example. The requirements which have postponed the development of human artificial chromosomes have now been relatively met, and some prospects are previewed here.
Fusions of secreted proteins to alkaline phosphatase: an approach for studying protein secretion. (1985)

We have constructed a series of plasmids containing a modified form of the phoA gene of Escherichia coli K-12 that have general utility for studies of protein secretion. In these plasmids, the promoter and signal sequence-encoding region of the phoA gene have been deleted; thus, expression of the gene, giving rise to active alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1], is absolutely dependent upon fusion in the correct reading frame to DNA containing a promoter, a translational start site, and a complete signal sequence-encoding region. Alkaline phosphatase, which is normally located in the periplasm of E. coli, is efficiently secreted to the periplasm when fused either to a signal sequence from another periplasmic protein, beta-lactamase (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6), or to signal sequences from the outer membrane proteins LamB and OmpF. These heterologous signal sequences are processed during secretion. In the absence of a complete signal sequence, phosphatase becomes localized in the cytoplasm and is inactive. Phosphatase fusion proteins lacking up to 13 amino-terminal amino acids beyond the signal sequence show the same specific activity as that of the wild-type enzyme. However, a significant decrease in activity is seen when 39 or more amino-terminal amino acids are deleted. Addition of approximately 150 amino acids from the enzyme beta-lactamase to the amino terminus of alkaline phosphatase has little effect on the specific activity of the enzyme. The ability to change the amino terminus of phosphatase without altering its activity makes the enzyme particularly useful for construction of protein fusions. The fact that phosphatase is designed for transport across the cytoplasmic membrane makes it an ideal tool for study of protein secretion.
Shear properties of a magnetorheological elastomer (2003)

This paper presents an experiment testing the damped free vibration of a system composed of a magnetorheological elastomer and a mass. The goal of this experiment was to obtain the dependence of the natural frequency and the damping ratio of the structure on the applied magnetic field. The shear properties, including the shear storage modulus and the damping factor, were therefore determined. The experimental results revealed that the shear storage modulus could reach a value of 60% of the zero-field modulus and was dominated by the magnetic field, but the change in the damping factor could be neglected. Furthermore, when the field was moderate and saturation did not occur, the shear storage modulus increased proportionally with the applied field. This interesting phenomenon was analysed, and it is suggested that the subquadratic field dependence, which arises from the saturation of the magnetization near the poles of closely spaced pairs of spheres, must be taken into consideration.
Dengue virus envelope glycoprotein structure: New insight into its interactions during viral entry (2003)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
A Potential Role for Shed Soluble Major Histocompatibility Class I Molecules as Modulators of Neurite Outgrowth (2011)

The neurobiological activities of classical major histocompatibility class I (MHCI) molecules are just beginning to be explored. To further examine MHCI's actions during the formation of neuronal connections, we cultured embryonic mouse retina explants a short distance from wildtype thalamic explants, or thalami from transgenic mice (termed "NSE-Db") whose neurons express higher levels of MHCI. While retina neurites extended to form connections with wildtype thalami, we were surprised to find that retina neurite outgrowth was very stunted in regions proximal to NSE-Db thalamic explants, suggesting that a diffusible factor from these thalami inhibited retina neurite outgrowth. It has been long known that MHCI-expressing cells release soluble forms of MHCI (sMHCI) due to the shedding of intact MHCI molecules, as well as the alternative exon splicing of its heavy chain or the action proteases which cleave off it's transmembrane anchor. We show that the diffusible inhibitory factor from the NSE-Db thalami is sMHCI. We also show that COS cells programmed to express murine MHCI release sMHCI that inhibits neurite outgrowth from nearby neurons in vitro. The neuroinhibitory effect of sMHCI could be blocked by lowering cAMP levels, suggesting that the neuronal MHCI receptor's signaling mechanism involves a cyclic nucleotide-dependent pathway. Our results suggest that MHCI may not only have neurobiological activity in its membrane-bound form, it may also influence local neurons as a soluble molecule. We discuss the involvement of complement proteins in generating sMHCI and new theoretical models of MHCI's biological activities in the nervous system.
Suicide Gene Therapy Mediated by the Herpes Simplex Virus Thymidine Kinase Gene / Ganciclovir System: Fifteen Years of Application (2003)

Gene-directed enzyme prodrug therapy (GDEPT) is a two step therapeutic approach for cancer gene therapy. In the first step, the transgene is delivered into the tumor and expressed. In the second step a prodrug is administered and is selectively activated by the expressed enzyme. The first GDEPT system described was the thymidine kinase gene of the Herpes Simplex virus (HSVtk) in combination with the prodrug Ganciclovir (GCV). A large number of experiments have been performed with this system, in different types of tumors and initial studies in animal models were very promising. This encouraged investigators to move into clinical trials although poor results have been obtained so far. A large effort has been made with numerous different strategies to enhance HSVtk/GCV efficacy in cellular and in vivo models and very strong cytotoxic effects have been obtained. The present review describes the current state of preclinical research and summarizes the results of the clinical trials undertaken.
Molecular Characterization of the Human β 3 -Adrenergic Receptor (1989)

Since the classification of beta-adrenergic receptors (beta-ARs) into beta 1 and beta 2 subtypes, additional beta-ARs have been implicated in the control of various metabolic processes by catecholamines. A human gene has been isolated that encodes a third beta-AR, here referred to as the "beta 3-adrenergic receptor." Exposure of eukaryotic cells transfected with this gene to adrenaline or noradrenaline promotes the accumulation of adenosine 3',5'-monophosphate; only 2 of 11 classical beta-AR blockers efficiently inhibited this effect, whereas two others behaved as beta 3-AR agonists. The potency order of beta-AR agonists for the beta 3-AR correlates with their rank order for stimulating various metabolic processes in tissues where atypical adrenergic sites are thought to exist. In particular, novel beta-AR agonists having high thermogenic, antiobesity, and antidiabetic activities in animal models are among the most potent stimulators of the beta 3-AR.
Cancer stem cells: a metastasizing menace! (2016)

Cancer is one of the leading causes of death worldwide, and is estimated to be a reason of death of more than 18 billion people in the coming 5 years. Progress has been made in diagnosis and treatment of cancer; however, a sound understanding of the underlying cell biology still remains an unsolved mystery. Current treatments include a combination of radiation, surgery, and/or chemotherapy. However, these treatments are not a complete cure, aimed simply at shrinking the tumor and in majority of cases, there is a relapse of tumor. Several evidences suggest the presence of cancer stem cells (CSCs) or tumor-initiating stem-like cells, a small population of cells present in the tumor, capable of self-renewal and generation of differentiated progeny. The presence of these CSCs can be attributed to the failure of cancer treatments as these cells are believed to exhibit therapy resistance. As a result, increasing attention has been given to CSC research to resolve the therapeutic problems related to cancer. Progress in this field of research has led to the development of novel strategies to treat several malignancies and has become a hot topic of discussion. In this review, we will briefly focus on the main characteristics, therapeutic implications, and perspectives of CSCs in cancer therapy.
Steroid‐induced diabetes: a clinical and molecular approach to understanding and treatment (2013)

Since the advent of glucocorticoid therapy for autoimmune disease in the 1940s, their widespread application has led to the concurrent therapy-limiting discovery of many adverse metabolic side effects. Unanticipated hyperglycemia associated with the initiation of glucocorticoids often leads to preventable hospital admissions, prolonged hospital stays, increased risks for infection and reduced graft function in solid organ transplant recipients. Challenges in managing steroid-induced diabetes stem from wide fluctuations in post-prandial hyperglycemia and the lack of clearly defined treatment protocols. The mainstay of treatment is insulin therapy coincident with meals. This article aims to review the pathogenesis, risk factors, diagnosis and treatment principles unique to steroid-induced diabetes.
Overcoming glucose repression in mixed sugar fermentation by co-expressing a cellobiosetransporter and a β-glucosidase in Saccharomyces cerevisiae (2010)

Glucose repression is one of the main limitations in mixed lignocellulosic sugar fermentation for cost-effective production of fuels and chemicals. Here we report a novel strategy to overcome glucose repression by co-expressing a cellobiose transporter and a β-glucosidase in an engineered d-xylose-utilizing Saccharomyces cerevisiae strain. The resulting strain can simultaneously utilize cellobiose and d-xylose for ethanol production.
Novel patterns of genome rearrangement and their association with survival in breast cancer (2006)

Representational Oligonucleotide Microarray Analysis (ROMA) detects genomic amplifications and deletions with boundaries defined at a resolution of approximately 50 kb. We have used this technique to examine 243 breast tumors from two separate studies for which detailed clinical data were available. The very high resolution of this technology has enabled us to identify three characteristic patterns of genomic copy number variation in diploid tumors and to measure correlations with patient survival. One of these patterns is characterized by multiple closely spaced amplicons, or "firestorms," limited to single chromosome arms. These multiple amplifications are highly correlated with aggressive disease and poor survival even when the rest of the genome is relatively quiet. Analysis of a selected subset of clinical material suggests that a simple genomic calculation, based on the number and proximity of genomic alterations, correlates with life-table estimates of the probability of overall survival in patients with primary breast cancer. Based on this sample, we generate the working hypothesis that copy number profiling might provide information useful in making clinical decisions, especially regarding the use or not of systemic therapies (hormonal therapy, chemotherapy), in the management of operable primary breast cancer with ostensibly good prognosis, for example, small, node-negative, hormone-receptor-positive diploid cases.
Taxol produces a predominantly sensory neuropathy (1989)

Taxol, a plant alkaloid with promise as an antineoplastic agent, produced a predominantly sensory neuropathy in 16 of 60 patients treated in two phase I trials. This neuropathy occurred only at taxol doses greater than 200 mg/m2. Symptoms typically started 1 to 3 days following treatment, beginning in the hands and feet simultaneously in most patients. Electrophysiologic data suggests both axonal degeneration and demyelination. This previously undefined neurotoxic neuropathy most likely results from taxol's unique ability to produce microtubule aggregation in dorsal root ganglion cells, axons, and Schwann cells.
Prevention of interleukin-8-induced mobilization of hematopoietic progenitor cells in rhesus monkeys by inhibitory antibodies against the Metalloproteinase gelatinase B (MMP-9) (1999)

Previously, we demonstrated that IL-8 induces rapid mobilization of hematopoietic progenitor cells (HPC) from the bone marrow of rhesus monkeys. Because activation of neutrophils by IL-8 induces the release of gelatinase B (MMP-9), which is involved in the degradation of extracellular matrix molecules, we hypothesized that MMP-9 release might induce stem cell mobilization by cleaving matrix molecules to which stem cells are attached. Rhesus monkeys were treated with a single i.v. injection of 0.1 mg/kg human IL-8, which resulted in a 10- to 100-fold increase in HPC within 30 min after injection. Zymographic analysis revealed a dramatic instantaneous increase in the plasma levels of MMP-9, followed by the increase in circulating HPC. Enzyme levels decreased at 2 h after injection of IL-8, simultaneously with the decrease in the numbers of circulating HPC. To test the hypothesis that MMP-9 induction was involved in HPC mobilization, rhesus monkeys were treated with a highly specific inhibitory monoclonal anti-gelatinase B antibody. Anti-gelatinase B at a dose of 1-2 mg/kg completely prevented the IL-8-induced mobilization of HPC, whereas a dose of 0.1 mg/kg had only a limited effect. Preinjection of inhibitory antibodies did not preclude the IL-8-induced production and secretion of MMP-9. Pretreatment with an irrelevant control antibody did not affect IL-8-induced mobilization, showing that the inhibition by the anti-gelatinase B antibody was specific. In summary, IL-8 induces the rapid systemic release of MMP-9 with concurrent mobilization of HPC that is prevented by pretreatment with an inhibitory anti-gelatinase B antibody, indicating that MMP-9 is involved as a mediator of the IL-8-induced mobilization of HPC.
Bacillus subtilis Requires a "Stringent" Shine-Dalgarno Region for Gene Expression (1984)

A series of plasmids was constructed differing only in the sequence of the Shine-Dalgarno region preceding the leukocyte interferon-A gene. This series of plasmids was used to test the efficiency of interferon expression in both Bacillus subtilis and Escherichia coli. In B. subtilis, interferon expression was much more sensitive to changes in the sequence of the Shine-Dalgarno region than in E. coli and it appeared to require more homology to the 3' end of 16S ribosomal RNA.
Controlling the diameter, monodispersity, and solubility of ApoA1 nanolipoprotein particles using telodendrimer chemistry (2013)

Nanolipoprotein particles (NLPs) are nanometer-scale discoidal particles that feature a phospholipid bilayer confined within an apolipoprotein "scaffold," which are useful for solubilizing hydrophobic molecules such as drugs and membrane proteins. NLPs are synthesized either by mixing the purified apolipoprotein with phospholipids and other cofactors or by cell-free protein synthesis followed by self-assembly of the nanoparticles in the reaction mixture. Either method can be problematic regarding the production of homogeneous and monodispersed populations of NLPs, which also currently requires multiple synthesis and purification steps. Telodendrimers (TD) are branched polymers made up of a dendritic oligo-lysine core that is conjugated to linear polyethylene glycol (PEG) on one end, and the lysine "branches" are terminated with cholic acid moieties that enable the formation of nanomicelles in aqueous solution. We report herein that the addition of TD during cell-free synthesis of NLPs produces unique hybrid nanoparticles that have drastically reduced polydispersity as compared to NLPs made in the absence of TD. This finding was supported by dynamic light scattering, fluorescence correlation spectroscopy, and cryo transmission electron microscopy (Cryo-EM). These techniques demonstrate the ability of TDs to modulate both the NLP size (6-30 nm) and polydispersity. The telodendrimer NLPs (TD-NLPs) also showed 80% less aggregation as compared to NLPs alone. Furthermore, the versatility of these novel nanoparticles was shown through direct conjugation of small molecules such as fluorescent dyes directly to the TD as well as the insertion of a functional membrane protein.