gebhart/patrepeval huggingface dataset:
Reduced Response to Multiple Vaccines Sharing Common Protein Epitopes That Are Administered Simultaneously to Infants (1998)

The plethora of newly discovered vaccines implies that, in the future, many vaccines will have to be administered simultaneously to infants. We examined the potential interference with the immune response of several coadministered vaccines containing the same protein component, namely, tetanus toxoid (TT). Infants simultaneously receiving a tetravalent pneumococcal vaccine conjugated to TT (PncT) and a diphtheria-tetanus-pertussis-poliovirus-Haemophilus influenzae type b-tetanus conjugate vaccine showed significantly lower anti-H. influenzae type b polysaccharide (polyribosylribitol phosphate [PRP]) antibody concentrations than those receiving either a tetravalent pneumococcal vaccine conjugated to diphtheria toxoid or placebo. A dose range study showed that anti-PRP antibody concentrations were inversely related to the TT content of the PncT vaccines administered in infancy. Postimmunization antitetanus antibody concentrations were also affected adversely as the TT content of the coadministered vaccines was increased. This phenomenon, which we believe derives from interference by a common protein carrier, should be taken into account when the introduction of an immunization program including multiple conjugate vaccines is considered.
Production of transmitochondrial cybrids containing naturally occurring pathogenic mtDNA variants (2006)

The human mitochondrial genome (mtDNA) encodes polypeptides that are critical for coupling oxidative phosphorylation. Our detailed understanding of the molecular processes that mediate mitochondrial gene expression and the structure-function relationships of the OXPHOS components could be greatly improved if we were able to transfect mitochondria and manipulate mtDNA in vivo. Increasing our knowledge of this process is not merely of fundamental importance, as mutations of the mitochondrial genome are known to cause a spectrum of clinical disorders and have been implicated in more common neurodegenerative disease and the ageing process. In organellar or in vitro reconstitution studies have identified many factors central to the mechanisms of mitochondrial gene expression, but being able to investigate the molecular aetiology of a limited number of cell lines from patients harbouring mutated mtDNA has been enormously beneficial. In the absence of a mechanism for manipulating mtDNA, a much larger pool of pathogenic mtDNA mutations would increase our knowledge of mitochondrial gene expression. Colonic crypts from ageing individuals harbour mutated mtDNA. Here we show that by generating cytoplasts from colonocytes, standard fusion techniques can be used to transfer mtDNA into rapidly dividing immortalized cells and, thereby, respiratory-deficient transmitochondrial cybrids can be isolated. A simple screen identified clones that carried putative pathogenic mutations in MTRNR1, MTRNR2, MTCOI and MTND2, MTND4 and MTND6. This method can therefore be exploited to produce a library of cell lines carrying pathogenic human mtDNA for further study.
Androgen and glucocorticoid receptors in the stroma and epithelium of prostatic hyperplasia and carcinoma. (1996)

Differences in stromal and epithelial cell staining for androgen and glucocorticoid receptors (ARs and GRs) were investigated in 20 patients with clinically localized prostatic carcinoma treated by radical prostatectomy. Sections of benign prostatic hyperplasia and prostatic carcinoma from each patient were stained with antibodies to AR and GR using an avidin-biotin peroxidase technique. The specificity of the GR immunoreactivity was established in benign prostatic hyperplasia and prostatic carcinoma by immunohistochemistry using the GR antibody absorbed with synthetic peptide and Western blotting. Nuclear staining intensity and percentage of nuclei stained were summed to obtain AR and GR immunostaining scores. AR staining of prostatic carcinoma epithelial [103 +/- 58 (SD)] and stromal (126 +/- 48) nuclei was less than in benign prostatic hyperplasia (142 +/- 47 and 169 +/- 56; paired Student's t tests, P = 0.02 and P = 0.01); however, no difference in staining intensity occurred between stroma and epithelium in either tissue type. GR stained intensely in stromal cells from benign prostatic hyperplasia (189 +/- 50) and prostatic carcinoma (163 +/- 60). However, prostatic carcinoma epithelial cells (34 +/- 57) had low levels of glucocorticoid receptor staining (P < 10(-7)), and benign prostatic hyperplasia epithelium (74 +/- 51) was intermediate. In most patients, GR could not be detected in nuclei of prostatic carcinoma epithelial cells but was undiminished in stromal cell nuclei. There was no relationship by multivariate regression analysis between AR or GR staining and age, serum prostate-specific antigen, Gleason grade, or pathological stage. In comparison with AR, the greater variability of GR staining in epithelium versus stroma of prostatic carcinoma warrants further study of GR, particularly in the area of stromal-epithelial interaction.
Vaccination against self to prevent autoimmune disease: the type 1 diabetes model (2008)

Immune tolerance to self-antigens is physiological. Given a repertoire of self-reactive, potentially pathogenic lymphocytes, therapeutic options to diminish autoimmune disease risk include deletion, reduced activation or increased regulation of self-reactive lymphocytes by means that mimic or promote physiological mechanisms of immunity. Vaccination with self-antigen to promote self-antigen-specific tolerance, 'negative vaccination', may represent the most specific and potentially safest means of averting autoimmune disease. This strategy is therapeutically effective in inbred rodent models but its translation in humans has failed to meet expectations. This failure can be attributed to the use of suboptimal dosage regimens in end-stage disease, as well as other factors. This review focuses on vaccination against self-antigen in type 1 diabetes, an autoimmune disease unique in that individuals at risk can be identified years before clinical presentation. Moreover, the spontaneously diabetic non-obese diabetic mouse, which mimics human type 1 diabetes in many ways, has provided 'proof-of-concept' for negative vaccination. Recent trials of a nasal insulin vaccine in humans at risk of type 1 diabetes provide evidence of tolerance induction as a basis for clinical efficacy.
Cholinergic Modulation of the Action Potential in Rat Hippocampal Neurons (1996)

The cholinergic input to the hippocampus from the medial septum is important for modulating hippocampal activity and functions, including theta rhythm and spatial learning. Neuromodulation by transmitters in central nervous system neurons usually affects cell excitability by modifying the membrane potential, discharge pattern and spike frequency. Here we describe another type of neuromodulation: changing the action potential waveform. During intracellular recordings from CA1 pyramidal cells in hippocampal slices from rats, the cholinergic agonist carbachol caused several reversible changes in the action potential: low doses (2 microM) caused an increase in spike duration; high doses (10-40 microM) or long-lasting applications also reduced the spike amplitude and rate of rise, and raised the spike threshold. These effects are similar to those of metabotropic glutamate receptor agonists or phorbol esters, both of which activate protein kinase C. The effects were blocked by the muscarinic antagonist atropine, and were prevented by Ca(2+)-free medium and by Ca(2+)-channel blockers. However, the cholinergic spike modulation was not occluded or mimicked by blocking the Ca(2+)-dependent K+ currents IC or IAHP, suggesting that these K+ currents are not involved in the modulation. We conclude that muscarinic receptor activation modulates the action potential in CA1 pyramidal cells via a Ca(2+)-dependent mechanism, possibly involving protein kinase C. This modulation and the similar effects mediated by metabotropic glutamate receptors to our knowledge provide the only examples of neuromodulation of the action potential in the vertebrate central nervous system-a form of modulation known to regulate Ca2+ influx and transmitter release, and to mediate synaptic plasticity and learning in invertebrates.
The role of cell‐cell contact in “contact” inhibition of cell division: A review and new evidence (1972)

Abstract The term “contact inhibition of cell division” was borrowed from “contact inhibition of cell movement.” We prefer the term “postconfluence inhibition of cell division” as being more operational and less mechanistically biased; it is operationally defined as a pronounced depression of the mitotic rate in a postconfluent culture which displays a stationary density despite periodic nutrient renewal, the inhibition being locally reversibly by removal of the adjacent cells. The mechanism of postconfluence inhibition is of considerable interest because of the inverse correlation between postconfluence inhibition and the tumorigenicity of a number of cell lines. Several hypotheses, involving direct cell‐to‐cell contacts or locally restricted diffusion gradiens, could explain postconfluence inhibition. With the goal of discriminating among these hypotheses, time‐lapse films were taken of carefully regulated, perfused cultures of 3T3 mouse cells, in which the transition from rapid growth to the stationary phase was recorded. Measurements of cell‐to‐cell contact, local cell density, and generation times were made on an individual cell level and analyzed with the aid of a computer. We observed that all‐around cell‐cell contact or a high local cell density present throughout G1 often did not produce immediate inhibition of cell division. We conclude that either (i) simple visible cell‐cell contacts or a high local cell density are not the direct cause of postconfluence inhibition of cell division, or (ii) their effects often do not inhibit cell division until after a delay of about one cell generation time. Such a delay may be partly responsible for the 50% overshoot past the stationary density that we observed in 3T3 cultures.
Learning data augmentation policies using augmented random search (2018)

Previous attempts for data augmentation are designed manually, and the augmentation policies are dataset-specific. Recently, an automatic data augmentation approach, named AutoAugment, is proposed using reinforcement learning. AutoAugment searches for the augmentation polices in the discrete search space, which may lead to a sub-optimal solution. In this paper, we employ the Augmented Random Search method (ARS) to improve the performance of AutoAugment. Our key contribution is to change the discrete search space to continuous space, which will improve the searching performance and maintain the diversities between sub-policies. With the proposed method, state-of-the-art accuracies are achieved on CIFAR-10, CIFAR-100, and ImageNet (without additional data). Our code is available at https://github.com/gmy2013/ARS-Aug.
Triggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum (2013)

Invasion of erythrocytes by Plasmodium falciparum merozoites is a complex multi-step process mediated by specific interactions between host receptors and parasite ligands. Reticulocyte-binding protein homologues (RHs) and erythrocyte-binding-like (EBL) proteins are discharged from specialized organelles and used in early steps of invasion. Here we show that monoclonal antibodies against PfRH1 (an RH) block merozoite invasion by specifically inhibiting calcium signalling in the parasite, whereas invasion-inhibiting monoclonal antibodies targeting EBA175 (an EBL protein) have no effect on signalling. We further show that inhibition of this calcium signalling prevents EBA175 discharge and thereby formation of the junction between parasite and host cell. Our results indicate that PfRH1 has an initial sensing as well as signal transduction role that leads to the subsequent release of EBA175. They also provide new insights on how RH-host cell interactions lead to essential downstream signalling events in the parasite, suggesting new targets for malaria intervention.
Therapy of human pancreatic carcinoma implants by irinotecan and the oral immunomodulator JBT 3002 is associated with enhanced expression of inducible nitric oxide synthase in tumor-infiltrating macrophages. (2000)

We determined the therapeutic effect of irinotecan (CPT-11) combined with the immunomodulator JBT 3002, a synthetic bacterial lipopeptide (N-acylated derivative of psi-amino-C1-C3-alkane-sulfonic acid), against highly metastatic human pancreatic carcinoma cells injected into the pancreas of athymic nude mice. Mice received four courses consisting of three daily oral doses of JBT 3002, followed by once weekly i.p. injection of CPT-11. Control mice were treated with CPT-11 alone, JBT 3002 alone, or saline. Tumor growth and metastasis were assessed by gross pathology and confirmed by histological examination. Treatment with CPT-11 alone significantly decreased the median volume of pancreatic tumors and the incidence of metastasis, whereas treatment with only JBT 3002 did not. The combination therapy of CPT-11 plus JBT 3002 decreased tumor volume and incidence of metastasis significantly more than CPT-11 alone. The number of apoptotic cells (terminal deoxynucleotidyl transferase-mediated nick end labeling assay), the number of scavenger-receptor-positive macrophages, and expression level of inducible nitric oxide synthase (iNOS) within lesions directly correlated with therapeutic effects. Indeed, the in vitro incubation of tumor cells with macrophages activated by JBT 3002 plus IFN-gamma produced a significant lysis of tumor cells that could be blocked by a specific inhibitor of iNOS. Collectively, these data demonstrate that the oral administration of the immunomodulator JBT 3002 combined with i.p. injection of CPT-11 can decrease the growth of human pancreatic carcinoma and the incidence of metastasis in nude mice by both a direct antitumor effect and the activation of iNOS in infiltrating macrophages.
Topological dynamics of holins in programmed bacterial lysis (2006)

The fate of phage-infected bacteria is determined by the holin, a small membrane protein that triggers to disrupt the membrane at a programmed time, allowing a lysozyme to attack the cell wall. S(21)68, the holin of phage 21, has two transmembrane domains (TMDs) with a predicted N-in, C-in topology. Surprisingly, TMD1 of S(21)68 was found to be dispensable for function, to behave as a SAR ("signal-anchor-release") domain in exiting the membrane to the periplasm, and to engage in homotypic interactions in the soluble phase. The departure of TMD1 from the bilayer coincides with the lethal triggering of the holin and is accelerated by membrane depolarization. Basic residues added at the N terminus of S(21)68 prevent the escape of TMD1 to the periplasm and block hole formation by TMD2. Lysis thus depends on dynamic topology, in that removal of the inhibitory TMD1 from the bilayer frees TMD2 for programmed formation of lethal membrane lesions.
Waferscale assembly of Field‐Aligned nanotube Networks (FANs) (2006)

Abstract We demonstrate the integration of nanotube networks on 512 individual devices on a full 4‐inch wafer in less than 60 seconds with a roughly 80% yield using dielectrophoresis. We present here investigations of the morphology and electrical resistance of such field aligned networks for different frequencies of the electrical field used to attract the nanotubes to the electrodes. Preliminary data of response to visible light irradiation as well as changes in the humidity indicate that the field aligned networks could be used as sensor components that may well integrate with CMOS due to mild assembly conditions. (© 2006 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Hashed samples (2008)

We study selectivity estimation techniques for set similarity queries. A wide variety of similarity measures for sets have been proposed in the past. In this work we concentrate on the class of weighted similarity measures (e.g., TF/IDF and BM25 cosine similarity and variants) and design selectivity estimators based on a priori constructed samples. First, we study the pitfalls associated with straightforward applications of random sampling, and argue that care needs to be taken in how the samples are constructed; uniform random sampling yields very low accuracy, while query sensitive realtime sampling is more expensive than exact solutions (both in CPU and I/O cost). We show how to build robust samples a priori, based on existing synopses for distinct value estimation. We prove the accuracy of our technique theoretically, and verify its performance experimentally. Our algorithm is orders of magnitude faster than exact solutions and has very small space overhead.
Hybrid Optical RF Airborne Communications (2009)

The use of hybrid free-space optical (FSO)/radio-frequency (RF) links to provide robust, high-throughput communications, fixed infrastructure links, and their associated networks have been thoroughly investigated for both commercial and military applications. The extension of this paradigm to mobile, long-range networks has long been a desire by the military communications community for multigigabit mobile backbone networks. The FSO communications subsystem has historically been the primary limitation. The challenge has been addressing the compensation of propagation effects and dynamic range of the received optical signal. This paper will address the various technologies required to compensate for the effects referenced above. We will outline the effects FSO and RF links experience and how we overcome these degradations. Results from field experiments conducted, including those from the Air Force Research Laboratory Integrated RF/Optical Networked Tactical Targeting Networking Technologies (IRON-T2) program, will be presented.
A role for the thiol isomerase protein ERP5 in platelet function (2004)

Formation and rearrangement of disulfide bonds during the correct folding of nascent proteins is modulated by a family of enzymes known as thiol isomerases, which include protein disulfide isomerase (PDI), endoplasmic reticulum protein 5 (ERP5), and ERP57. Recent evidence supports an alternative role for this family of proteins on the surface of cells, where they are involved in receptor remodeling and recognition. In platelets, blocking PDI with inhibitory antibodies inhibits a number of platelet activation pathways, including aggregation, secretion, and fibrinogen binding. Analysis of human platelet membrane fractions identified the presence of the thiol isomerase protein ERP5. Further study showed that ERP5 is resident mainly on platelet intracellular membranes, although it is rapidly recruited to the cell surface in response to a range of platelet agonists. Blocking cell-surface ERP5 using inhibitory antibodies leads to a decrease in platelet aggregation in response to agonists, and a decrease in fibrinogen binding and P-selectin exposure. It is possible that this is based on the disruption of integrin function, as we observed that ERP5 becomes physically associated with the integrin beta(3) subunit during platelet stimulation. These results provide new insights into the involvement of thiol isomerases and regulation of platelet activation.
High Activity of Serum Response Factor in the Mesenchymal Transition of Epithelial Tumor Cells Is Regulated by RhoA Signaling (2002)

The serum response factor (SRF) regulates the transcription of target genes by binding to serum response elements in dimeric form and by interacting with ternary complex factors. In this study, we have analyzed the role of the serum response factor and mechanisms that regulate its activity in tumor progression utilizing a multistage model of mouse skin carcinogenesis. We demonstrate elevated SRF DNA binding activity only in the cell lines that have undergone an epithelial to mesenchymal transition and have increased actin stress fiber formation. Transient transfection experiments of activated or dominant negative forms of RhoA showed that the high activity of SRF and the induced formation of actin stress fibers in cells with spindle morphology were mediated by RhoA signaling. A dominant negative form of SRF inhibited RhoA-induced actin polymerization and stress fiber formation. The DNA binding activity of SRF in mesenchymal tumor cells was also correlated with elevated expression of SRF target genes, similar to SRF itself, actin, and vinculin. These observations suggest for the first time that SRF may play an important role in tumor progression, specifically at the transition to an invasive metastatic stage of carcinogenesis.
Matrix sialoprotein of developing bone. (1983)

Using nondegradative isolation procedures, we purified and characterized a glycoprotein from fetal calf bone that is rich in sialic acid. This bone sialoprotein (BSP) has an apparent Mr = 70,000-80,000 and stains with Alcian blue and Stains All on sodium dodecyl sulfate gels but does not stain with Coomassie blue without prior treatment with neuraminidase. This glycoprotein contains 50% protein, 12% sialic acid, 7% glucosamine, and 6% galactosamine. Fetal calf BSP is rich in glutamate (19%), aspartate (15.4%), and glycine (11.8%) but, in contrast to osteonectin and the bone proteoglycan, has relatively low amounts of leucine (4.3%). Antisera raised against fetal calf BSP localized the glycoprotein by indirect immunofluorescence to developing bone trabeculae with an overall tissue distribution identical with that of osteonectin. On competition enzyme-linked immunosorbent assay analysis, BSP was 11.5% (+/-2.4%, S.E.) of mineral-bound (guanidine-EDTA-soluble) calf bone protein. Immunoreplicas (Western blots) of calf bone extracts suggest that more than 95% of the antigenicity resided in the Mr = 70,000-80,000 region with the remaining cross-reactivity in Alcian blue positive, Mr = approximately 20,000 and approximately 30,000 bands. Brief treatment of the Mr = 70,000-80,000 species with trypsin produced lower molecular weight, Alcian blue-staining products of similar size. No BSP was detected in guanidine extracts of various soft or unmineralized connective tissues, but dentin contained small amounts (0.4%) of the protein. Rat and fetal human bone were also observed to contain a sialoprotein with similar properties and a certain degree of cross-reactivity with the bovine BSP.
Predictive Accuracy of MCI Subtypes for Alzheimer’s Disease and Vascular Dementia in Subjects with Mild Cognitive Impairment: A 2-Year Follow-Up Study (2004)

The subtype 'multiple domain MCI' has high sensitivity in identifying people at risk for developing AD or VaD. The predictive accuracy of the MCI subtypes was similar for both AD and VaD.
A high precision method for measuring very small capacitance changes (1999)

A novel method for measuring very small capacitance changes based on capacitance-to-phase angle conversion is introduced in this article. This new method is the improved or linearized version of the nonlinear capacitance-to-phase angle conversion method. The main features of this scheme are the very good linearity, extremely high stray immunity and a very high resolution. The experimental results of the prototype version of this scheme have also been reported. By using this prototype and a simple capacitive transducer, a minimum detectable distance of about 16 nm can be achieved. This means that a capacitance change of about 0.7 fF (0.7×10−15 F) in a capacitance of 22 pF can be resolved, so the minimum resolvable relative capacitance is about 32 ppm. By the theory it can be seen that the minimum resolvable relative capacitance of 2 ppm could be achieved by this method.