gebhart/patrepeval huggingface dataset:
Duration and Specificity of Humoral Immune Responses in Mice Vaccinated with the Alzheimer's Disease-Associated β -Amyloid 1-42 Peptide (2001)

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by overproduction of beta-amyloid (Abeta), which is formed from amyloid precursor protein (APP), with the subsequent pathologic deposition of Abeta in regions of the brain important for memory and cognition. Recently, vaccination of murine models of AD that exhibit Abeta deposition has halted or delayed the usual progression of the pathology of AD. Our group has demonstrated that vaccination of a doubly transgenic mouse model (expressing mutant APP and presenilin-1) with the Abeta 1-42 peptide protects these mice from the memory deficits they would ordinarily develop. This report further characterizes the Abeta 1-42 peptide vaccine in mice. Anti-Abeta response time course analysis indicated that at least three vaccinations (each 100 microg) were necessary to elicit a significant anti-Abeta titer. Subsequent vaccinations resulted in half-maximal antibody titers of at least 10,000, and these titers were maintained for at least 5 months after the final boost. Peptide binding competition studies indicated that the highest humoral responses are generated against the N terminus of the Abeta peptide. Also, measurement of specific murine Ig isotypes in Abeta-vaccinated mice demonstrated a predominant IgG(1) and IgG(2b) response, suggesting a type 2 (Th2) T-helper cell immune response, which drives humoral immunity. Finally, lymphocyte proliferation assay experiments using Abeta peptides and splenocytes from vaccinated mice demonstrated that the vaccine specifically stimulates T-cell epitopes present within the Abeta peptide.
Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing human myocardium. (1994)

Expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase was shown to be reduced in failing human myocardium. The functional relevance of this finding, however, is not known. We investigated the relation between myocardial function and protein levels of SR Ca(2+)-ATPase in nonfailing human myocardium (8 muscle strips from 4 hearts) and in myocardium from end-stage failing hearts with dilated (10 muscle strips from 9 hearts) or ischemic (7 muscle strips from 5 hearts) cardiomyopathy. Myocardial function was evaluated by the force-frequency relation in isometrically contracting muscle strip preparations (37 degrees C, 30 to 180 min-1). In nonfailing myocardium, twitch tension rose with increasing rates of stimulation and was 76% higher at 120 min-1 compared with 30 min-1 (P < .02). In failing myocardium, there was no significant increase in average tension at stimulation rates above 30 min-1. At 120 min-1, twitch tension was decreased by 59% (P < .05) in dilated cardiomyopathy and 76% (P < .05) in ischemic cardiomyopathy compared with nonfailing myocardium. Protein levels of SR Ca(2+)-ATPase, normalized per total protein or per myosin, were reduced by 36% (P < .02) or 32% (P < .05), respectively, in failing compared with nonfailing myocardium. SR Ca(2+)-ATPase protein levels were closely related to SR Ca2+ uptake, measured in homogenates from the same hearts (r = .70, n = 16, and P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)
First Identification of Caldesmon Transcripts in Bovine Oviduct Epithelial Cells in vitro by means of an RNA Differential Display Technique Examining Culture‐induced Expression Changes (2001)

Innovative molecular biology techniques enable the quick evaluation of distinct gene expression pattern of cells or tissues. Hitherto, a cell-type-specific behaviour has been difficult to evaluate. In addition to standard morphological and immunological criteria in this study the expression of in vitro-cultured bovine oviduct epithelial cells (BOECs) was compared with fresh cells by RNA arbitrarily primed polymerase chain reaction (RAP-PCR). The cultured cells showed mitotic activity during the whole culture period (6 days) until they had reached about 80% confluency. Remarkable results of a random transcript screening using fresh versus cultured BOECs were reported, in which a single PCR product appeared during culture, but was absent in fresh cells. Sequence analysis of the culture-induced 522 bp fragment revealed a high homology (87%) to caldesmon (CaD) of various species and a 92% homology to a short cDNA fragment of a bovine non-muscle CaD. Specific, cross-species PCR primers were used to elongate this partial sequence (1,036 bp). This resulting cDNA showed an open reading frame and was identified as a bovine non-muscle CaD isoform. When compared with human non-muscle CaDs (89% homology) a deletion of 2 codons was observed. According to sequential culture experiments, CaD expression was not found in fresh BOECs but specific transcripts appeared within 48-113 h under specific culture conditions. It is likely that augmented CaD expression in cultured BOECs may reflect the cell effort adapting to specific culture conditions. The hypothesis that increased CaD levels could be important to facilitate adherence and spreading by formation of new stress fibres can be favoured. This first identification of caldesmon expression being specifically induced during in vitro culture demonstrates the potential of RAP-PCR for the analysis and validation of cell culture techniques.
The role of adhesion molecules and chemokine receptor CXCR4 (CD184) in small cell lung cancer. (2005)

Small-cell lung cancer (SCLC) is a particularly aggressive form of lung cancer. Responsible for this highly malignant phenotype is an early and widespread metastasis with a high propensity of SCLC cells for bone marrow involvement and the ability to develop resistance against chemotherapeutic agents. Tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and adhesion molecules. There is growing evidence that the chemokine stromal derived factor-1 (SDF-1/CXCL12) and its receptor CXCR4 (CD184) regulate migration and metastasis of a variety of cancers including SCLC. SCLC cells express high levels of functional CXCR4 receptors. Engagement of CXCR4 by CXCL12 leads to an upregulation of integrin-mediated adhesion in SCLC and other tumor cells. Activation of CXCR4 chemokine receptors and integrins on SCLC cells promotes adhesion to accessory cells (such as stromal cells) and extracellular matrix molecules within the tumor microenvironment. These adhesive interactions result in an increased resistance of SCLC cells to chemotherapy. As such, inhibitors of the CXCR4/CXCL12 axis and/or integrin activation may increase the chemosensitivity of SCLC cells and lead to new therapeutic avenues for patients with SCLC.
Requirement of Circadian Genes for Cocaine Sensitization in Drosophila (1999)

The circadian clock consists of a feedback loop in which clock genes are rhythmically expressed, giving rise to cycling levels of RNA and proteins. Four of the five circadian genes identified to date influence responsiveness to freebase cocaine in the fruit fly, Drosophila melanogaster. Sensitization to repeated cocaine exposures, a phenomenon also seen in humans and animal models and associated with enhanced drug craving, is eliminated in flies mutant for period, clock, cycle, and doubletime, but not in flies lacking the gene timeless. Flies that do not sensitize owing to lack of these genes do not show the induction of tyrosine decarboxylase normally seen after cocaine exposure. These findings indicate unexpected roles for these genes in regulating cocaine sensitization and indicate that they function as regulators of tyrosine decarboxylase.
Current Status of Biosimilar Growth Hormone (2009)

&lt;p/&gt; &lt;p&gt;As the first wave of biopharmaceuticals is set to expire, biosimilars or follow-on protein products (FOPPs) have emerged. The regulatory foundation for these products is more advanced and better codified in Europe than in the US. Recent approval of biosimilar Somatropin (growth hormone) in Europe and the US prompted this paper. The scientific viability of biosimilar growth hormone is reviewed. Efficacy and safety data (growth rates, IGF-1 generation) for up to 7 years for pediatric indications measure up favorably to previously approved growth hormones as reference comparators. While the approval in the US is currently only for treatment of growth hormone deficiency (GHD) in children and adults, the commercial use of approved biosimilar growth hormones will allow in the future for in-depth estimation of their efficacy and safety in non-GH deficient states as well.&lt;/p&gt;
Multipurpose vectors for peptide expression on the M13 viral surface. (1992)

We have developed a set of three cloning vectors for the expression of polypeptides on the surface of the M13 viral coat. The M13mp8 genome has been engineered for expression of foreign protein sequences near the NH2-terminus of the mature pIII protein, which is present in five copies on the outside of each M13 viral particle. All three of the vectors carry the same two useful restriction sites for directed cloning of inserts in the pIII coding region; in addition, one vector carries the bacterial gene conferring resistance to the antibiotic tetracycline, and another expresses the lacZ' polypeptide that allows functional complementation of beta-galactosidase activity within the host bacterial cell. All of these vectors propagate well in E. coli DH5 alpha F' cells and do not require helper phage. We demonstrate that a bacteriophage, expressing an eleven amino acid epitope (from human c-myc) at the NH2-terminus of pIII in one of our vectors, can be purified from a vast mixture of other M13 phage through panning techniques. In particular, we find that the c-myc-expressing viral particles can be easily recovered from phage mixtures with the biotinylated form of the monoclonal antibody, 9E10, and streptavidin-coated MagneSphere beads.
Instrumentation design for hydrodynamic sample injection in microchip electrophoresis: A review (2012)

Reproducible and representative sample injection in microchip electrophoresis has been a bottleneck for quantitative analytical applications. Electrokinetic sample injection is the most used because it is easy to perform. However, this injection method is usually affected by sample composition and the bias effect. On the other hand, these drawbacks are overcome by the hydrodynamic (HD) sample injection, although this injection mode requires HD flow control. This review gives an overview of the basic principles, the instrumentation designs, and the performance of HD sample injection systems for microchip electrophoresis.
Unified temporal and spatial calibration for multi-sensor systems (2013)

In order to increase accuracy and robustness in state estimation for robotics, a growing number of applications rely on data from multiple complementary sensors. For the best performance in sensor fusion, these different sensors must be spatially and temporally registered with respect to each other. To this end, a number of approaches have been developed to estimate these system parameters in a two stage process, first estimating the time offset and subsequently solving for the spatial transformation between sensors. In this work, we present on a novel framework for jointly estimating the temporal offset between measurements of different sensors and their spatial displacements with respect to each other. The approach is enabled by continuous-time batch estimation and extends previous work by seamlessly incorporating time offsets within the rigorous theoretical framework of maximum likelihood estimation. Experimental results for a camera to inertial measurement unit (IMU) calibration prove the ability of this framework to accurately estimate time offsets up to a fraction of the smallest measurement period.
A Comparison of Standard Cardiopulmonary Resuscitation and Active Compression–Decompression Resuscitation for Out-of-Hospital Cardiac Arrest (1999)

Active compression-decompression CPR performed during advanced life support significantly improved long-term survival rates among patients who had cardiac arrest outside the hospital.
Trill: Engineering a Library for Diverse Analytics. (2015)

Trill is a streaming query processor that fulfills three requirements to serve the diverse big data analytics space: (1) Query Model: Trill is based on the tempo-relational model that enables it to handle streaming and relational queries with early results, across the latency spectrum from real-time to offline; (2) Fabric and Language Integration: Trill is architected as a high-level language library that supports rich data-types and user libraries, and integrates well with existing distribution fabrics and applications; and (3) Performance: Trill’s throughput is high across the latency spectrum. For streaming data, Trill’s throughput is 2-4 orders of magnitude higher than comparable traditional streaming engines. For offline relational queries, Trill’s throughput is comparable to modern columnar database systems. Trill uses a streaming batched-columnar data representation with a new dynamic compilation-based system architecture that addresses all these requirements. Trill’s ability to support diverse analytics has resulted in its adoption across many usage scenarios at Microsoft. In this article, we provide an overview of Trill: how we engineered it as a library that achieves seamless language integration with a rich query language at high performance, while executing in the context of a high-level programming language.
Effect of Duration of Osmotherapy on Blood–Brain Barrier Disruption and Regional Cerebral Edema after Experimental Stroke (2005)

Osmotherapy is the cornerstone of medical management for cerebral edema associated with large ischemic strokes. We determined the effect of duration of graded increases in serum osmolality with mannitol and hypertonic saline (HS) on blood-brain barrier (BBB) disruption and regional cerebral edema in a well-characterized rat model of large ischemic stroke. Halothane-anesthetized adult male Wistar rats were subjected to transient (2-h) middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. Beginning at 6 h after MCAO, rats were treated with either no intravenous fluids or a continuous intravenous infusion (0.3 mL/h) of 0.9% saline, 20% mannitol, 3% HS, or 7.5% HS for 24, 48, 72, and 96 h. In the first series of experiments, BBB permeability was quantified by the Evans blue (EB) extravasation method. In the second series of experiments, water content was assessed by comparing wet-to-dry weight ratios in six predetermined brain regions. Blood-brain barrier disruption was maximal in rats treated with 0.9% saline for 48 h, but did not correlate with increases in serum osmolality or treatment duration with osmotic agents. Treatment with 7.5% HS attenuated water content in the periinfarct regions and all subregions of the contralateral nonischemic hemisphere to a greater extent than mannitol did with no adverse effect on survival rates. These data show that (1) BBB integrity is not affected by the duration and degree of serum osmolality with osmotic agents, and (2) attenuation of increases in brain water content with HS to target levels >350 mOsm/L may have therapeutic implications in the treatment of cerebral edema associated with ischemic stroke.
Endothelial cell injury in vitro is associated with increased secretion of an Mr 43,000 glycoprotein ligand (1986)

A novel, serum albumin-binding glycoprotein of molecular weight (mw) 43,000 (43K protein) was initially purified from the culture medium of bovine aortic endothelial (BAE) cells (Sage, H., Johnson, C., and Bornstein, P., J. Biol. Chem. 259:3993-4007, 1984). Its secretion by normal mesenchymal cells and by transformed cells of both ectodermal and endodermal origin suggested a general role in cellular function. To examine the effect of sublethal injury in vitro on the biosynthesis of 43K protein, BAE cells were exposed to endotoxin. At concentrations which produced minimal cell detachment and lysis, the cells secreted 70-100% more protein compared to control cultures, and the relative increase in 43K protein over total protein was approximately three-fold. A second type of cellular injury, manifested by rapid cellular proliferation and migration in response to sparse plating density (a condition that we have termed 'culture shock'), was also accompanied by a significant increase in the secretion of 43K protein. Pulse-chase studies revealed that the initial product secreted within 1.5 h was of Mr 38,000, and that between 6 and 21 h this molecule was converted to the final form of Mr 43,000. The 43K protein was not associated with RNA or glycosaminoglycan, but appeared to be linked to complex oligosaccharides containing peripheral sialosyl residues. Treatment with tunicamycin produced lower mw forms that displayed reduced affinity for albumin. By immunologic criteria, peptide mapping, and amino acid analysis, the 43K protein was shown to be structurally distinct from several proteins of Mr 40,000-50,000 associated with endothelium or with serum, including tissue factor, a plasminogen anti-activator, and several apolipoproteins. In addition, the 43K protein was not present in the extracellular matrices of endothelial, fibroblastic, or smooth muscle cells, nor was it found in plasma, serum, platelet releasate, or alveolar lavage fluids. These studies identify a unique Mr 43,000 glycoprotein that is associated with cellular stress or injury in vitro. As a secreted but nonmatrix macromolecule, this protein may be part of a 'survival kit' used by the endothelium to cope with cellular injury.
Nurses’ views on ease of patient care in postoperative pain management (2007)

The fentanyl HCl iontophoretic transdermal system (ITS) is a compact, needle-free, pre-programmed patient-controlled analgesic system that was developed to address limitations to existing therapies for postoperative pain management. A randomized, controlled trial was conducted in 11 European countries to evaluate the efficacy and safety of postoperative pain control using fentanyl ITS compared with a standard regimen of morphine provided by an intravenous patient-controlled analgesia (IV PCA) pump. This article summarizes results from Nurse Ease-of-Care Questionnaires which were completed to assess the convenience and ease of use of each pain management modality from the perspective of the nurse. Nurses' ratings of patient-care tasks associated with each pain management system were significantly more favourable for fentanyl ITS than for morphine IV PCA. These findings suggest that nurses consider fentanyl ITS to be easier to use than morphine IV PCA.
Optimal prefetching via data compression (2002)

A form of the competitive philosophy is applied to the problem of prefetching to develop an optimal universal prefetcher in terms of fault ratio, with particular applications to large-scale databases and hypertext systems. The algorithms are novel in that they are based on data compression techniques that are both theoretically optimal and good in practice. Intuitively, in order to compress data effectively, one has to be able to predict feature data well, and thus good data compressors should be able to predict well for purposes of prefetching. It is shown for powerful models such as Markov sources and mth order Markov sources that the page fault rates incurred by the prefetching algorithms presented are optimal in the limit for almost all sequences of page accesses.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Data strip mining for the virtual design of pharmaceuticals with neural networks (2000)

A novel neural network based technique, called "data strip mining" extracts predictive models from data sets which have a large number of potential inputs and comparatively few data points. This methodology uses neural network sensitivity analysis to determine which predictors are most significant in the problem. Neural network sensitivity analysis holds all but one input to a trained neural network constant while varying each input over its entire range to determine its effect on the output. The least sensitive variables are iteratively removed from the input set. For each iteration, model cross-validation uses multiple splits of training and validation data to determine an estimate of the model's ability to predict the output for data points not used during training. Elimination of variables through neural network sensitivity analysis and predicting performance through model cross-validation allows the analyst to reduce the number of inputs and improve the model's predictive ability at the same time. This paper illustrates this technique using a cartoon problem from classical physics. It then demonstrates its effectiveness on a pair of challenging problems from combinatorial chemistry with over 400 potential inputs each. For these data sets, model selection by neural sensitivity analysis outperformed other variable selection methods including forward selection and a genetic algorithm.
Detection of Cyclins in Individual Cells by Flow and Laser Scanning Cytometry (2003)

Progression of cells through successive phases and checkpoints of the cell cycle is maintained by sequential phosphorylation of different sets of nuclear and cytoplasmic proteins by cyclin-dependent kinases (CDKs) (1–12). By activating their partner CDKs and targeting them to the respective protein substrates cyclins play a key regulatory role in this process. Cyclins Bl, A, E, and D are expressed discontinuously during the cycle. The synthesis and degradation of these cyclins occurs at well-defined time points of the cell cycle (Table 1).
Neurotrophins, NMDA receptors, and nitric oxide in development and protection of the auditory system. (1999)

Neurotrophic factors are secreted peptides that when interacting with specific classes of membrane receptors activate intracellular signaling cascades that prevents neuronal death during embryonic development. The establishment of gene-targeted null mutant mice for the neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) has led to the discovery that they are crucial trophic factors for the survival of auditory and vestibular neurons during development. BDNF is the major survival factor for vestibular ganglion neurons, while NT-3 only support a small number of these neurons. In the cochlea, auditory type I neurons require NT3 for their survival, whereas type II neurons depend on BDNF. With this information at hand recent progress has been made regarding the prevention of aminoglycoside-induced hearing loss in the adult guinea pig. These results and the mechanisms leading to hair cell damage are discussed in this paper.