gebhart/patrepeval huggingface dataset:
Cardiomyocyte Enrichment from Human Embryonic Stem Cell Cultures by Selection of Alcam Surface Expression (2009)

We demonstrate that cardiomyocytes derived from hESC cultures express ALCAM and that this surface antigen can be used to select a population of differentiated cells that are enriched for cardiomyocytes. Expression of contractile proteins and ion channels, and DNA methylation patterns, suggest that ALCAM-enriched cardiomyocytes have an embryonic phenotype. Selected cardiomyocyte populations survive sorting, adhere to collagen-coated tissue culture plastic and proliferate in short-term culture. Long-term in vitro survival of cardiomyocytes was achieved by culturing cells in 3D aggregates.
Increased CD69 and Human Leukocyte Antigen-DR Expression on T Lymphocytes in Insulin-Dependent Diabetes Mellitus of Long Standing (1998)

To better define prevailing activation of circulating T cell subsets in insulin-dependent diabetes mellitus (IDDM) of recent onset (DM; n = 31; median age +/- SD, 28 +/- 6.9 yr) and of long standing (DML; n = 27; age, 33 +/- 10.4 yr; median duration of disease, 105 months), CD4+ and CD8+ T cells were analyzed to determine their naive and memory subsets as well as their expression of human leukocyte antigen (HLA)-DR, interleukin-2 receptor alpha-chain (CD25), and CD69 by three-color flow cytometry. Twenty-six healthy subjects (HS; age, 32.0 +/- 8.2 yr) served as controls. No deviation was seen in either IDDM group compared to HS in CD25 expression on CD4+ or CD8+ cells or in their CD45RA+ or CD45RA- subsets. HLA-DR expression, however, was increased (P < 0.05) in total CD8+ cells and CD45RA+ cells, with CD45RA- CD8+ cells joining the prevailing pattern only in DML. Among CD4+ cells, increased expression of HLA-DR molecules was restricted to total and CD45RA- cells in DML. CD69 expression did not differ between IDDM and HS, but differed between DML (CD4+, CD8+, and CD45RA- CD4+) and DM only. In conclusion, our data demonstrate that HLA-DR expression in IDDM is restricted to memory cells (CD45RA-) among CD4+ cells in DML and is more markedly confined to naive (CD45RA+) than to memory CD8+ cells, whereas the early activation antigen CD69 is more readily expressed in DML than in DM. The observed activation of circulating T cells suggests an ongoing immune process in IDDM both at clinical manifestation and after long duration.
C-SRC tyrosine kinase activity is associated with tumor colonization in bone and lung in an animal model of human breast cancer metastasis. (2003)

The proto-oncogene, c-src, has been implicated in the tumorigenesis in breast cancer. However, the relationship of c-src with distant metastasis is unclear. Moreover, the role of c-src in organ-preferential metastasis of breast cancer is unknown. Because breast cancer has a strong predilection for metastasizing to bone, we examined the role of c-src in bone metastases using an animal model in which inoculation of the MDA-231 human breast cancer cells into the left cardiac ventricle preferentially developed osteolytic bone metastases in female nude mice. A clone of the MDA-231 with the increased capacity of bone metastasis exhibited elevated c-src tyrosine kinase (TK) activity compared with parental cells. MDAsrc527 cells caused significantly increased size of the osteolytic bone metastases with increased number of osteoclasts and mitotic cancer cells compared with MDA-231EV or MDAsrcWT. In contrast, MDAsrc295 cells caused impaired metastases to bone. Of note, mice inoculated with MDAsrc295 cells via tail vein developed reduced lung metastases and prolonged survival compared with mice with MDA-231EV cells, suggesting that c-src TK is unlikely to play a specific role in bone metastases. The growth in vitro and in vivo and production of parathyroid hormone-related protein, a key cytokine in the pathogenesis of osteolytic bone metastases in breast cancer, were promoted in MDAsrc527 and diminished in MDAsrc295. These results suggest that c-src TK is associated with the capacity of breast cancer to metastasize to bone through regulating cell growth and parathyroid hormone-related protein production. Our results together with the fact that c-src is an essential molecule for bone resorption by osteoclasts, which are central players in osteolytic bone metastases, support the notion that c-src TK is a potential target molecule for designing novel therapeutic interventions, especially for bone metastases in breast cancer.
Here Comes Everybody (2005)

The possible causes of these rarely reported opacities are discussed.
Elevated Fusiform Cell Activity in the Dorsal Cochlear Nucleus of Chinchillas with Psychophysical Evidence of Tinnitus (2002)

Chinchillas with psychophysical evidence of chronic tinnitus were shown to have significantly elevated spontaneous activity and stimulus-evoked responses in putative fusiform cells of the dorsal cochlear nuclei (DCN). Chinchillas were psychophysically trained and tested before and after exposure to a traumatic unilateral 80 dB (sound pressure level) 4 kHz tone. Before exposure, two groups were matched in terms of auditory discrimination performance (noise, and 1, 4, 6, and 10 kHz tones). After exposure, a single psychophysical difference emerged between groups. The exposed group displayed enhanced discrimination of 1 kHz tones (p = 0.00027). Postexposure discrimination of other stimuli was unaffected. It was hypothesized that exposed animals experienced a chronic subjective tone (i.e., tinnitus), resulting from their trauma, and that features of this subjective tone were similar enough to 1 kHz to affect discrimination of 1 kHz objective signals. After psychophysical testing, single-unit recordings were obtained from each animal's DCN fusiform cell layer. Putative fusiform cells of exposed animals showed significantly (p = 0.0136) elevated spontaneous activity, compared with cells of unexposed animals. Putative fusiform cells of exposed animals showed a greater stimulus-evoked response to tones at 1 kHz (p = 0.0000006) and at characteristic-frequency (p = 0.0000009). This increased activity was more pronounced on the exposed side. No increase in stimulus-evoked responses was observed to other frequencies or noise. These parallel psychophysical and electrophysiological results are consistent with the hypothesis that chronic tonal tinnitus is associated with, and may result from, trauma-induced elevation of activity of DCN fusiform cells.
An Improved Oxidative Cleavage Method for Large Scale Preparation of Some Acid‐Labile Aglycones from Glycosides (2002)

Abstract A practical method for large‐scale preparation of acid‐labile aglycones including protopanaxadiol, protopanaxatriol, cycloastragenol, and jujubogenin from the corresponding glycoside containing fraction was developed. The key point of this improved method is to generate and maintain the critical reaction conditions, anhydrous and strongly basic, in situ . This effort over comes the weakness of the reported method for oxidative cleavage of glycones and scales up the preparation of these acid‐labile aglycones for further studies.
Oral Antiplatelet Therapy in Cerebrovascular Disease, Coronary Artery Disease, and Peripheral Arterial Disease (2004)

Aspirin, ticlopidine, clopidogrel, aspirin combined with clopidogrel, and aspirin combined with dipyridamole are effective in preventing recurrent vascular events among various subgroups of patients with vascular disease. Current clinical trial evidence favors the use of aspirin or clopidogrel as first-line agents for the majority of patients with vascular disease. Clinical trials evaluating combination antiplatelet therapies will direct future practice.
Long-Circulating Immunoliposomal Amphotericin B against Invasive Pulmonary Aspergillosis in Mice (1998)

We investigated the efficacy of long-circulating immunoliposomal amphotericin B (AmB) against invasive pulmonary aspergillosis in mice using three types of liposomal AmB: conventional liposomal AmB (AmBisome), a long-circulating liposomal AmB and prepared by coating the liposome surface with polyethylene glycol (PEG; PEG-L-AmB), long-circulating immunoliposomal AmB (34A-PEG-L-AmB). The survival rates for mice with invasive pulmonary aspergillosis treated with an intravenous dose of 2 mg of AmBisome, PEG-L-AmB, or 34A-PEG-L-AmB per kg of body weight were 16.7, 83.3, and 100%, respectively. Treatment with 34A-PEG-L-AmB produced a marked reduction in the number of Aspergillus fumigatus organisms in the lungs. Pharmacokinetic studies showed the presence of high AmB concentrations in the plasma of mice treated with PEG-L-AmB (40.8 microg/ml) and in the lungs of mice treated with 34A-PEG-L-AmB (42.3 microg/g). We conclude that 34A-PEG-L-AmB, a long-circulating immunoliposomal AmB, is a promising form of AmB against invasive pulmonary aspergillosis.
Prediction Model for Prevalence and Incidence of Advanced Age-Related Macular Degeneration Based on Genetic, Demographic, and Environmental Variables (2009)

Factors reflective of nature and nurture are independently related to prevalence and incidence of advanced AMD, with excellent predictive power.
Using GPS to Determine Vehicle Attitude (1988)

Tumor tissue includes cancer cells and their associated stromal cells, such as adipocytes, myocytes, and immune cells. Obesity modulates tumor microenvironment through the secretion of several inflammatory mediators by inducing adipogenesis and myogenesis. Previously, we indicated that tumor growth is promoted by a transcription factor nuclear factor erythroid 2-related factor 3 (NRF3) in human cancer cells. However, the impact of obesity on NRF3-mediated tumorigenesis remains unknown. Here we show that obesity reprograms the tumorigenic to the antitumorigenic function of Nrf3 using a diet-induced obese mouse model. Nrf3 knockdown decreased tumor growth in mice fed a normal diet (ND), whereas it reversely increased tumor growth in mice fed a high-fat diet (HFD). Then, the tumor tissues derived from Nrf3 knockdown or control cancer cells in ND- or HFD-fed mice were subjected to a DNA microarray-based analysis. Similar to the tumor formation results, the expressions of genes related to adipogenesis, myogenesis, and interferon-alpha response were reversed by obesity, implying an increase or recruitment (or both combined) of adipocytes, myocytes, and immune cells. Among these gene sets, we focused on adipocytes. We showed that Nrf3 knockdown reduced cancer cell growth in the preadipocyte culture medium, while the growth inhibitory effect of Nrf3 knockdown on cancer cells was abolished in the adipocyte culture medium. These results suggest the possibility that cancer-associated adipocytes secrete the potential reprogramming factor from the tumorigenic to the antitumorigenic function of Nrf3 in cancer cells.
IQGAP1 Mediates VE-Cadherin–Based Cell–Cell Contacts and VEGF Signaling at Adherence Junctions Linked to Angiogenesis (2006)

IQGAP1 is required for establishment of cell-cell contacts in quiescent ECs. To induce angiogenesis, it may function to link VEGFR2 to the VE-cadherin containing adherens junctions, thereby promoting VEGF-stimulated, ROS-dependent tyrosine phosphorylation of VE-cadherin and loss of cell-cell contacts.
Aspartyl β-Hydroxylase (Asph) and an Evolutionarily Conserved Isoform of Asph Missing the Catalytic Domain Share Exons with Junctin (2000)

The mouse aspartyl beta-hydroxylase gene (Asph, BAH) has been cloned and characterized. The mouse BAH gene spans 200 kilobase pairs of genomic DNA and contains 24 exons. Of three major BAH-related transcripts, the two largest (6,629 and 4,419 base pairs) encode full-length protein and differ only in the use of alternative polyadenylation signals. The smallest BAH-related transcript (2,789 base pairs) uses an alternative 3' terminal exon, resulting in a protein lacking a catalytic domain. Evolutionary conservation of this noncatalytic isoform of BAH (humbug) is demonstrated in mouse, man, and Drosophila. Monoclonal antibody reagents were generated, epitope-mapped, and used to definitively correlate RNA bands on Northern blots with protein species on Western blots. The gene for mouse junctin, a calsequestrin-binding protein, was cloned and characterized and shown to be encoded from the same locus. When expressed in heart tissue, BAH/humbug preferably use the first exon and often the fourth exon of junctin while preserving the reading frame. Thus, three individual genes share common exons and open reading frames and use separate promoters to achieve differential expression, splicing, and function in a variety of tissues. This unusual form of exon sharing suggests that the functions of junctin, BAH, and humbug may be linked.
An in vitro model of differentiation of memory B cells into plasmablasts and plasma cells including detailed phenotypic and molecular characterization (2009)

Human plasma cells (PCs) and their precursors play an essential role in humoral immune response but are rare and difficult to harvest. We report the generation of human syndecan-1(+) and immunoglobulin secreting PCs starting from memory B cells in a 3-step and 10-day (D) culture, including a 6-fold cell amplification. We report the detailed phenotypic and Affymetrix gene expression profiles of these in vitro PCs as well as of intermediate cells (activated B cells and plasmablasts) compared with memory B cells and bone marrow PCs, which is accessible through an open web ATLAS (http://amazonia.transcriptome.eu/). We show this B cell-to-PC differentiation to involve IRF4 and AICDA expressions in D4 activated B cells, decrease of PAX5 and BCL6 expressions, and increase in PRDM1 and XBP1 expressions in D7 plasmablasts and D10 PCs. It involves down-regulation of genes controlled by Pax5 and induction of genes controlled by Blimp-1 and XBP1 (unfold protein response). The detailed phenotype of D10 PCs resembles that of peripheral blood PCs detected after immunization of healthy donors. This in vitro model will facilitate further studies in PC biology. It will likewise be helpful to study PC dyscrasias, including multiple myeloma.
The Staphylococcus aureus and Staphylococcus epidermidis transferrin-binding proteins are expressed in vivo during infection (1998)

Staphylococci express a 42 kDa cell-wall-associated protein which functions as a receptor for the mammalian iron-binding glycoprotein transferrin. To determine whether this transferrin-binding protein (TBP) is expressed during infection, Staphylococcus aureus and Staphylococcus epidermidis were grown in vivo in chambers implanted intraperitoneally in rats. SDS-PAGE and Western blotting of cell wall proteins prepared from staphylococci recovered directly from the chambers revealed the presence of both the TBP and bacterial-surface-associated rat transferrin. To obtain evidence for the in vivo expression of the staphylococcal TBPs in humans, sera and human peritoneal dialysate (HPD) from non-infected patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and sera from healthy human volunteers were screened for anti-TBP antibodies. Western immunoblots revealed that three out of ten samples from the latter group, seven out of ten HPD samples and ten of ten CAPD patient serum samples contained antibodies to the TBP of both S. aureus and S. epidermidis. To gain further insights into the appearance of TBP antibodies, HPD samples were collected over time from CAPD patients whose HPD samples taken immediately after catheter insertion lacked anti-TBP antibodies. In two of these patients, each of whom experienced an episode of peritonitis due to S. epidermidis or Staphylococcus hominis, antibodies to the TBP appeared in the HPD collected immediately post-infection. To determine whether such TBP antibodies were capable of blocking interactions between transferrin and its staphylococcal receptor, HPD immunoglobulin fractions were purified using protein A-Sepharose beads. In competition assays, these immunoglobulins blocked the binding of 125I-labelled transferrin both to whole bacteria and to the isolated 42 kDa TBPs of S. aureus and S. epidermidis. These provide evidence to show that staphylococcal TBPs are expressed in vivo during infection.
Composite Photonic Crystals from Semiconductor Nanocrystal/Polyelectrolyte-Coated Colloidal Spheres (2003)

Submicrometer-sized polystyrene colloidal spheres were coated with hybrid films consisting of HgTe semiconductor nanocrystal (HgTe NC) and polyelectrolyte (PE) multilayers by the layer-by-layer (LbL) technique. The prepared coated spheres were crystallized, forming composite colloidal crystals. Increasing the number of the HgTe NC layers deposited on the colloidal spheres leads to an increase in both the diameter and the effective refractive index of the spheres, which causes a systematic red shift of the stop bands of the composite colloidal crystals. The photoluminescence properties of the HgTe NCs assembled around the spheres in the composite colloidal crystals are impacted by the stop band of the colloidal crystals, giving rise to modifications of their emission properties. A titanium(IV) isopropoxide (TIP)/isopropyl alcohol solution was infiltrated into the voids of the colloidal crystals, and after solidification of TIP and removal of the colloidal crystal template by calcination, composite TiO2/HgTe inverse opals with HgTe embedded in the interior surface of the macroporous TiO2 were obtained. The strategy presented demonstrates the feasibility of fabricating composite photonic crystals (both colloidal crystals and inverse opals) from nanoscale-coated colloidal spheres. Such composite opaline photonic crystals provide a means of combining electronic confinement, originating from the NCs, with photon confinement, due to the ordered dielectric structures, hence opening new avenues in the design and construction of novel electrooptical devices based on photonic crystals.
The communication of emotion via touch. (2009)

The study of emotional communication has focused predominantly on the facial and vocal channels but has ignored the tactile channel. Participants in the current study were allowed to touch an unacquainted partner on the whole body to communicate distinct emotions. Of interest was how accurately the person being touched decoded the intended emotions without seeing the tactile stimulation. The data indicated that anger, fear, disgust, love, gratitude, and sympathy were decoded at greater than chance levels, as well as happiness and sadness, 2 emotions that have not been shown to be communicated by touch to date. Moreover, fine-grained coding documented specific touch behaviors associated with different emotions. The findings are discussed in terms of their contribution to the study of emotion-related communication.
Regulation of EGFR Protein Stability by the HECT-type Ubiquitin Ligase SMURF2 (2011)

Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial tumors and is considered to be an important therapeutic target. Although gene amplification is responsible for EGFR overexpression in certain human malignancies including lung and head and neck cancers, additional molecular mechanisms are likely. Here, we report a novel interaction of EGFR with an HECT-type ubiquitin ligase SMURF2, which can ubiquitinate, but stabilize EGFR by protecting it from c-Cbl-mediated degradation. Conversely, small interfering RNA (siRNA)-mediated knockdown of SMURF2 destabilized EGFR, induced an autophagic response and reduced the clonogenic survival of EGFR-expressing cancer cell lines, with minimal effects on EGFR-negative cancer cells, normal fibroblasts, and normal epithelial cells. UMSCC74B head and neck squamous cancer cells, which form aggressive tumors in nude mice, significantly lost in vivo tumor-forming ability on siRNA-mediated SMURF2 knockdown. Gene expression microarray data from 443 lung adenocarcinoma patients, and tissue microarray data from 67 such patients, showed a strong correlation of expression between EGFR and SMURF2 at the messenger RNA and protein levels, respectively. Our findings suggest that SMURF2-mediated protective ubiquitination of EGFR may be responsible for EGFR overexpression in certain tumors and support targeting SMURF2-EGFR interaction as a novel therapeutic approach in treating EGFR-addicted tumors.
Protein tolerance to random amino acid change (2004)

Mutagenesis of protein-encoding sequences occurs ubiquitously; it enables evolution, accumulates during aging, and is associated with disease. Many biotechnological methods exploit random mutations to evolve novel proteins. To quantitate protein tolerance to random change, it is vital to understand the probability that a random amino acid replacement will lead to a protein's functional inactivation. We define this probability as the "x factor." Here, we develop a broadly applicable approach to calculate x factors and demonstrate this method using the human DNA repair enzyme 3-methyladenine DNA glycosylase (AAG). Three gene-wide mutagenesis libraries were created, each with 10(5) diversity and averaging 2.2, 4.6, and 6.2 random amino acid changes per mutant. After determining the percentage of functional mutants in each library using high-stringency selection (>19,000-fold), the x factor was found to be 34% +/- 6%. Remarkably, reanalysis of data from studies of diverse proteins reveals similar inactivation probabilities. To delineate the nature of tolerated amino acid substitutions, we sequenced 244 surviving AAG mutants. The 920 tolerated substitutions were characterized by substitutability index and mapped onto the AAG primary, secondary, and known tertiary structures. Evolutionarily conserved residues show low substitutability indices. In AAG, beta strands are on average less substitutable than alpha helices; and surface loops that are not involved in DNA binding are the most substitutable. Our results are relevant to such diverse topics as applied molecular evolution, the rate of introduction of deleterious alleles into genomes in evolutionary history, and organisms' tolerance of mutational burden.
Clinical Disorders of Potassium Homeostasis (1998)

Potassium plays an important role in cell metabolism and membrane excitability. Disorders of potassium balance can have profound clinical effects, particularly on the cardiovascular and neuromuscular systems. Chronic hyperkalemia invariably results from impaired renal potassium excretion. Hyperkalemia can be a potentially life-threatening disturbance requiring emergency intervention. Treatment is usually directed at correcting the defect in potassium excretion. Hypokalemia has become closely linked with in cats. Clinical signs include muscle weakness and renal dysfunction, which usually respond well to oral potassium supplementation.
Requirements for an Internet Standard Point-to-Point Protocol (1993)

This document discusses the evaluation criteria for an Internet Standard Data Link Layer protocol to be used with point-to-point links. Although many industry standard protocols and ad hoc protocols already exist for the data link layer, none are both complete and sufficiently versatile to be accepted as an Internet Standard. In preparation to designing such a protocol, the features necessary to qualify a point-to-point protocol as an Internet Standard are discussed in detail. An analysis of the strengths and weaknesses of several existing protocols on the basis of these requirements demonstrates the failure of each to address key issues.
Large-Scale Machine Learning with Stochastic Gradient Descent (2010)

During the last decade, the data sizes have grown faster than the speed of processors. In this context, the capabilities of statistical machine learning methods is limited by the computing time rather than the sample size. A more precise analysis uncovers qualitatively different tradeoffs for the case of small-scale and large-scale learning problems. The large-scale case involves the computational complexity of the underlying optimization algorithm in non-trivial ways. Unlikely optimization algorithms such as stochastic gradient descent show amazing performance for large-scale problems. In particular, second order stochastic gradient and averaged stochastic gradient are asymptotically efficient after a single pass on the training set.