gebhart/patrepeval huggingface dataset:
Differential expression of HLA-DR antigens in subsets of human CFU-GM (1985)

Expression of HLA-DR surface antigens by granulocyte/monocyte colony- forming cells (CFU-GM) may be important in the regulation of proliferation of these cells. Using immunological techniques to enrich for progenitor cells, we investigated the expression of HLA-DR in subsets of CFU-GM. “Early” (day 14) CFU-GM express higher levels of HLA- DR than do “late” (day 7) CFU-GM. Among late CFU-GM, cells destined to form monocyte (alpha-naphthyl acetate esterase-positive) colonies express higher levels of HLA-DR than do CFU-GM destined to form granulocyte (chloroacetate esterase-positive) colonies. Because high- level expression of DR antigen was a marker for monocyte differentiation, we examined several lymphokines for their effects on both DR expression and in vitro commitment to monocyte differentiation by myeloid precursor cells. DR antigen density could be increased by more than twofold over 48 hours upon exposure to gamma-interferon (gamma-IFN), whereas colony-stimulating factors had no effect. This was associated with a dose-dependent inhibition of total CFU-GM number, and a relative, but not absolute, increase in the ratio of monocyte colonies to granulocyte colonies. Similarly, in day 7 suspension cultures of purified myeloid precursor cells, gamma-IFN inhibited cell proliferation and increased the ratio of monocytes to granulocytes. Thus, despite the induction of high levels of HLA-DR antigen on precursor cells (a marker of monocyte commitment), the dominant in vitro effect of gamma-IFN was inhibition of granulocyte differentiation.
Hybrid integrated silicon optical bench planar lightguide circuits (2002)

As optical system architectures have matured over the past ten years, the use of silicon optical bench (SiOB) technology for cost effective packaging of opto-electronic components has migrated from relatively simple laser and photodetector submounts to sophisticated hybrid integrated optical subsystems. Lucent Technologies Bell Laboratories has been developing SiOB technology for use as an integrated packaging platform for lasers, photodetectors, waveguides and passive optical components. In this paper we describe two integrated optical sub-assemblies using planar lightguide circuits (PLCs) as examples of transceivers and complex laser source modules. The assemblies integrate lasers, photodetectors, passive waveguide splitters, wavelength division multiplex (WDM) filters, etched fiber and ball lens attachment sites, turning mirrors, optical reversing elements, deposited metals, solder dams and solders for mechanical and electrical contacts onto a single silicon optical sub-assembly. The approach allows for low cost batch processing, assembly and testing of complex components using the silicon wafer as a carrier and the use of automated pick-and-place machines for assembly.
Creation of biomolecule arrays by electrostatic immobilization on electron-beam-irradiated polystyrene thin films (1996)

Thin polystyrene films irradiated by an electron beam to create trapped charge are shown to immobilize the positively-charged protein, avidin-fluorescein. Using electron-beam lithography, fluorescent patterns with a minimum feature size of were formed. The electrostatic nature of the immobilization was supported by the spatial and temporal features of the immobilization process. Additional evidence for an electrostatic mechanism was obtained from experiments to screen the trapped charge density with poly-L-lysine.
Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase (2003)

Amyloid precursor protein (APP) is endoproteolytically processed by BACE1 and gamma-secretase to release amyloid peptides (Abeta40 and 42) that aggregate to form senile plaques in the brains of patients with Alzheimer's disease (AD). The C-terminus of Abeta40/42 is generated by gamma-secretase, whose activity is dependent upon presenilin (PS 1 or 2). Missense mutations in PS1 (and PS2) occur in patients with early-onset familial AD (FAD), and previous studies in transgenic mice and cultured cell models demonstrated that FAD-PS1 variants shift the ratio of Abeta40 : 42 to favor Abeta42. One hypothesis to explain this outcome is that mutant PS alters the specificity of gamma-secretase to favor production of Abeta42 at the expense of Abeta40. To test this hypothesis in vivo, we studied Abeta40 and 42 levels in a series of transgenic mice that co-express the Swedish mutation of APP (APPswe) with two FAD-PS1 variants that differentially accelerate amyloid pathology in the brain. We demonstrate a direct correlation between the concentration of Abeta42 and the rate of amyloid deposition. We further show that the shift in Abeta42 : 40 ratios associated with the expression of FAD-PS1 variants is due to a specific elevation in the steady-state levels of Abeta42, while maintaining a constant level of Abeta40. These data suggest that PS1 variants do not simply alter the preferred cleavage site for gamma-secretase, but rather that they have more complex effects on the regulation of gamma-secretase and its access to substrates.
Colony-stimulating factor-1 antisense treatment suppresses growth of human tumor xenografts in mice. (2002)

Matrix metalloproteinases (MMPs) foster cellular invasion by disrupting extracellular matrix barriers and thereby facilitate tumor development. MMPs are synthesized by both cancer cells and adjacent stromal cells, primarily macrophages. The production of macrophages is regulated by colony-stimulating factor-1 (CSF-1). Tissue CSF-1 expression increased significantly in embryonic and colon cancer xenografts. We, therefore, hypothesized that blocking CSF-1 may suppress tumor growth by decelerating macrophage-mediated extracellular matrix breakdown. Cells expressing CSF-1 and mice xenografted with CSF-1 receptor (c-fms)- and CSF-1-negative malignant human embryonic or colon cancer cells were treated with mouse CSF-1 antisense oligonucleotides. Two weeks of CSF-1 antisense treatment selectively down-regulated CSF-1 mRNA and protein tissue expression in tumor lysates. CSF-1 blockade suppressed the growth of embryonic tumors to dormant levels and the growth of the colon carcinoma by 50%. In addition, tumor vascularity and the expression of MMP-2 and angiogenic factors were reduced. Six-month survival was observed in colon carcinoma mice only after CSF-1 blockade, whereas controls were all dead at day 65. These results suggest that human embryonic and colon cancer cells up-regulate host CSF-1 and MMP-2 expression. Because the cancer cells used were CSF-1 negative, CSF-1 antisense targeted tumor stromal cell CSF-1 production. CSF-1 blockade could be a novel strategy in treatment of solid tumors.
In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles (2011)

Recent studies have demonstrated a simple, potentially universal strategy to enhance vaccine potency, via intralymph node (i.LN) injection. To date, intranodal immunization studies have focused on the delivery of unadjuvanted vaccines (e.g., naked DNA, peptide, or protein). We hypothesized that combining i.LN vaccination with controlled release biomaterials permitting sustained dosing of molecular adjuvants to the local tissue microenvironment would further enhance this promising vaccination strategy. To test this idea, we encapsulated the Toll-like receptor-3 ligand poly(inosinic:cytidylic acid) (polyIC) in biodegradable poly(lactide-co-glycolide) microparticles (MPs) designed to remain extracellular and release polyIC in the LN over several days. Intranodal injection of MPs increased persistence of polyIC in LNs compared to the same dose of soluble polyIC or polyIC formulated in nanoparticles, leading to increased accumulation of Toll-like receptor agonist in LN-resident antigen presenting cells and more enduring dendritic cell activation. Intralymph node injection of ovalbumin mixed with polyIC-releasing MPs enhanced the humoral response and expanded ovalbumin-specific T cells to frequencies as high as 18% among all CD8(+) cells following a single injection (8.2-fold greater than the same vaccine given i.m.), a response that could not be matched by antigen mixed with polyIC-loaded nanoparticles or a 10-fold greater dose of soluble polyIC. Thus, i.LN immunization with slow release-formulated adjuvants may be a broadly applicable strategy to enhance therapeutic or prophylactic vaccines.
Broadband Seismic Background Noise at Temporary Seismic Stations Observed on a Regional Scale in the Southwestern United States (2002)

Background noise power spectral density (PSD) estimates for 54 PASS- CAL Colorado Plateau/Rio Grande Rift/Great Plains Seismic Transect (LA RISTRA) stations were computed using data from 1999 to 2000. At long periods (0.01-0.1 Hz), typical vertical noise levels are approximately 12 dB higher than the nearby Global Seismic Network (GSN) borehole station ANMO, but horizontal power spec- tral density (PSD) noise levels are approximately 30 dB higher. Long-period noise levels exhibit essentially no spatial correlation along the LA RISTRA transect, indi- cating that local thermal or atmosphere-driven local slab tilt is the dominant source of noise in this band. Between 0.1 and 0.3 Hz, typical noise levels are dominated by naturally occurring microseismic noise and are essentially identical to those observed at ANMO. At short periods, 0.3-8 Hz, typical noise levels along the network exceed ANMO levels by approximately 15 dB, with the highest levels corresponding to proximity to cultural noise sources. No significant day/night variations were observed in the microseismic band; however, both low- and high-frequency noise levels show an increase of up to 8 dB in median midday versus midnight noise levels. We find that the major shortcomings of these shallow PASSCAL-style temporary vaults rela- tive to a GSN-style borehole installation are increased susceptibility to long-period horizontal (20 sec) noise and to surface noise sources above approximately 2 Hz. Although the high-frequency near-surface noise field is unavoidable in shallow vaults, we suggest that increased understanding and mitigation of local tilt effects in shallow vaults offers the possibility of significantly improving the long-period noise environment.
Effect of Alloying Elements on the Electronic Structure of NiAl (2005)

The change of the electronic structure in NiAl is investigated through DVM-the first principle method when Al in NiAl is substituted by Sc,Ti,V, Cr, Mn, Fe, Co, Ni, Cu, Zn. The results including Mulliken population, the charge distribution and cohesion energies are presented. The calculation of the electronic structure indicates that the substitution atoms take effect on the electronic structure of Ni and Al atoms surrounding the substitution atoms, and the ductility of NiAl. Among the substitution atoms that we studied, Fe, Co and Ni with more d electrons may be good for the ductility of NiAl.
The role of lymphoid organs in the immunopathogenesis of HIV infection (1993)

Conclusions Although HIV infection is characterized by a long period of clinical latency, HIV actively replicates in the lymphoid organs during this period, despite the fact that virus replication is barely detectable or absent in peripheral blood. Histopathologic alterations (i.e., follicular hyperplasia and expansion of the FDC network) may partly explain the dichotomy between the levels of viral burden in the lymphoid organs versus peripheral blood. These findings demonstrate that lymphoid organs function as reservoirs and potentially as major sites of virus replication. However, they also indicate that the peripheral blood does not accurately reflect the actual state of HIV disease, particularly in early-stage infection. In fact, HIV disease is active and progressive even when there is little evidence of disease activity in peripheral blood. Therefore, a state of true microbiological latency is non-existent during the course of HIV infection.
Bovine papilloma virus contains an activator of gene expression at the distal end of the early transcription unit. (1983)

Bovine papilloma virus (BPV) contains a cis-acting DNA element which can enhance transcription of distal promoters. Utilizing both direct and indirect transient transfection assays, we showed that a 59-base-pair DNA sequence from the BPV genome could activate the simian virus 40 promoter from distances exceeding 2.5 kilobases and in an orientation-independent manner. In contrast to the promoter 5'-proximal localization of other known viral activators, this element was located immediately 3' to the early polyadenylation signal in the BPV genome. Deletion of these sequences from the BPV genome inactivated the transforming ability of BPV recombinant plasmids. Orientation-independent reinsertion of this 59-base-pair sequence, or alternatively of activator DNA sequences from simian virus 40 or polyoma virus, restored the transforming activity of the BPV recombinant plasmids. Furthermore, the stable transformation frequency of the herpes simplex virus type 1 thymidine kinase gene was enhanced when linked to restriction fragments of BPV DNA which included the defined activator element. This enhancement was orientation independent with respect to the thymidine kinase promoter. The enhancement also appeared to be unrelated to the establishment of the recombinant plasmids as episomes, since in transformed cells these sequences are found linked to high-molecular-weight DNA. We propose that the enhancement of stable transformation frequencies and the activation of transcription units are in this case alternate manifestations of the same biochemical events.
Construction, arraying, and high-density screening of large insert libraries of human chromosomes X and 21: their potential use as reference libraries. (1991)

We have constructed cosmid libraries from flow-sorted human chromosomes X and 21, each of which contains greater than 30 genome equivalents, and have developed systems allowing permanent storage of primary clones, easy screening of libraries in high-density filter formats, and the simultaneous generation of fingerprinting and mapping data on the same set of cosmid clones. Clones are picked into microtiter plate wells and stored at -70 degrees C. A semiautomatic robot system allows the generation of filter replicas containing up to 10,000 clones per membrane. Sets of membranes containing 15-20 chromosome equivalents of both chromosomes will be used for the construction of ordered clone libraries by hybridization fingerprinting protocols. In addition, multiple sets of two membranes containing 4 chromosome equivalents of the human X chromosome, and one membrane containing 3 chromosome equivalents of chromosome 21, have been distributed to other interested laboratories as part of a system of reference libraries. This system allows other groups easy access to the clones and offers an efficient protocol to combine results generated in different laboratories using these libraries. Here we describe the construction of the libraries and demonstrate the use of high-density screening filters in oligonucleotide probe hybridizations and the isolation of cosmids by hybridization with probes from the X chromosome.
Resistance to Degradation by Nucleases of (2′S)-2′-Deoxy-2′-C-methyloligonucleotides, Novel Potential Antisense Probes (1994)

An oligonucleotide must fulfill two main requirements to become a potential antisense probe: effective hybridization properties with the complementary sequence and stability toward nucleases. In this article the degradation pattern of a new class of potential antisense fragment, (2'S)-2'-deoxy-2'-C-methyloligonucleotides, is analyzed. The results described here show that the modification introduced in these oligonucleotides confers an enhanced stability toward purified nucleases, human sera, and HeLa cell extracts.
Evaluation of the BYG Carba Test, a New Electrochemical Assay for Rapid Laboratory Detection of Carbapenemase-Producing Enterobacteriaceae (2015)

Accurate detection of carbapenemase-producing Enterobacteriaceae (CPE) constitutes a major laboratory diagnostic challenge. We evaluated an electrochemical technique (the BYG Carba test) which allows detection of CPE in less than 35 min. The BYG Carba test was first validated in triplicate against 57 collection isolates with previously characterized β-lactam resistance mechanisms (OXA-48, n = 12; KPC, n = 8; NDM, n = 8; VIM, n = 8; IMP, n = 3; GIM, n = 1; GES-6, n = 1; no carbapenemase, n = 16) and against a panel of 10 isolates obtained from the United Kingdom National External Quality Assessment Service (NEQAS). The test was then evaluated prospectively against 324 isolates referred to the national reference center for suspicion of CPE. The BYG Carba test results were compared with those obtained with the Carba NP test using multiplex PCR sequencing as the gold standard. Of the 57 collection and the 10 NEQAS isolates, all but one GES-6-producing isolate were correctly identified by the Carba BYG test. Among the 324 consecutive Enterobacteriaceae isolates tested prospectively, 146 were confirmed as noncarbapenemase producers by PCR while 178 harbored a carbapenemase gene (OXA-48, n = 117; KPC, n = 25; NDM, n = 23; and VIM, n = 13). Prospectively, in comparison with PCR results, the BYG Carba test displayed 95% sensitivity and 100% specificity versus 89% and 100%, respectively, for the Carba NP test. The BYG Carba test is a novel, rapid, and efficient assay based on an electro-active polymer biosensing technology discriminating between CPE and non-CPE. The precise electrochemical signal (electrochemical impedance variations) allows the establishment of real-time objective measurement and interpretation criteria which should facilitate the accreditation process of this technology.
Identification and characterization of specific receptors for monocyte-derived neutrophil chemotactic factor (MDNCF) on human neutrophils. (1989)

Specific receptors for a recently purified and cloned monocyte-derived neutrophil chemotactic factor (MDNCF) have been identified on the surface of normal human peripheral blood neutrophils using 125I-labeled recombinant human MDNCF (125I-MDNCF). Competitive binding of 125I-MDNCF to human neutrophils reached a maximal level at 1-3 h at 4 degrees C. The Scatchard analysis showed that there are approximately 20,000 receptors per cell with a single type of high affinity binding (Kd, 8 x 10(-10) M). The receptors for MDNCF are clearly distinct from the receptors for other cytokines and chemotactic agents, e.g., IL-1 alpha, TNF-alpha, and FMLP, C5a, leukotriene B4, and platelet activating factor. Based on the SDS-PAGE analysis of chemically crosslinked 125I-MDNCF receptor complex, there are two polypeptides that bind MDNCF; the molecular weight of these two MDNCF receptors were estimated to be 67,000 and 59,000. Treatment of a promyelocytic cell line, HL60, with 1.25% DMSO for 5 d in vitro increased the number of receptors up to 7,000 receptors/cell with a Kd of 1.2 x 10(-9) M.
Hemolytic and antigenic measurements of complement. A comparison of serum and plasma samples in normal individuals and patients. (1982)

Over a 2-year period we evaluated 10 patients with a discrepancy between functional and antigenic assays in the routinely employed clinical assays for measuring serum complement concentrations. These differences were shown to be secondary to cold-dependent activation of the classical complement pathway in vitro, in some cases by cryoglobulins and in others by unknown means. Plasma samples were procured with commonly used anticoagulants (EDTA, citrate, or heparin) that prevent in vitro complement activation. To assess whether plasma samples were suitable for complement determination, a comparison of serum vs. plasma samples for THC, C4, C2, C3, factor B, and C6 levels in normals and patient populations was undertaken. Only modest differences were found between serum and plasma samples for these functional and antigenic assays except for heparinized samples in which determinations by rate nephelometry produced falsely elevated C4, C3, and factor B antigenic levels. Thus plasma samples, especially EDTA or citrate, are suitable for complement determinations and could be used either routinely or, more selectively, in patients in whom there is a discrepancy between functional and antigenic determinations.
Effects of dietary nitrate on oxygen cost during exercise (2007)

We conclude that dietary nitrate supplementation, in an amount achievable through a diet rich in vegetables, results in a lower oxygen demand during submaximal work. This highly surprising effect occurred without an accompanying increase in lactate concentration, indicating that the energy production had become more efficient. The mechanism of action needs to be clarified but a likely first step is the in vivo reduction of dietary nitrate into bioactive nitrogen oxides including nitrite and NO.
Bicuspid aortic valve. (2002)

The bicuspid aortic valve is a common congenital cardiac anomaly, having an incidence in the general population of 0.9% to 2.0% and a frequency of 54% in all patients aged >15 years with valvular aortic stenosis. In most cases it remains undetected until infective endocarditis or calcification supervenes. The bicuspid aortic valve may function normally throughout life, may develop progressive calcification and stenosis or may develop regurgitation with or without infection. The association of the bicuspid aortic valve with dissection of the aorta is also common. The recognition of the bicuspid valve in patients with aortic valve disease remains an important challenge to the clinician, whereas preoperative knowledge of valve morphology would be helpful in planning the surgery. Antibiotic prophylaxis is also recommended in such patients, since these valves are likely to become the most important intrinsic cardiac predisposition for infective endocarditis with the virtual disappearance of rheumatic fever in developed countries.
Chemostimulatory Protein: A New Type of Taste Stimulus (1973)

Three taste-active proteins have recently been discovered. It is proposed that two of these (monellin and thaumatin) should be classified as chemostimulatory proteins because of their sensory effect; these two proteins taste intensely sweet. The third protein (miraculin), a taste-modifier protein, changes the normal sour taste of acids to sweet. The taste-modifier protein, miraculin, occurs in the fruit of the tropical plant Synsepalum dulcificum. Though itself not sweet, it is able to change the taste of acids from sour to sweet after the tongue has been treated with the protein. Miraculin is a basic glycoprotein with a molecular weight of 44,000. Monellin, a chemostimulatory protein, is found in the fruit of a different tropical plant, Dioscoreophyllum cumminsii. It has been characterized as a basic protein with a molecular weight of 10,700 that contains no carbohydrate. Thaumatin, another chemostimulatory protein, occurs in the fruit of a third tropical plant, Thaumatococcus daniellii. Like monellin, it is a basic protein that contains no carbohydrate. Its molecular weight is around 21,000. Certain gross similarities among the three proteins have been noted. Their basic ionic character and some features of the amino acid compositions are similar. Little is known of the structural features of the chemostimulatory proteins that are required for eliciting their intense sweetness; they are of the order of 10(5) times more effective than sucrose. The precise role of the tertiary structure in their biological activity is not known but appears to be an important area for further study. The relatively large size (11,000 to 21,000 molecular weight) of the chemostimulatory proteins provides indirect evidence that the initial interaction of these stimuli with taste receptor cells occurs at the plasma membrane.