gebhart/patrepeval huggingface dataset:
S and Z alpha1-antitrypsin alleles are risk factors for bronchial hyperresponsiveness in young farmers: an example of gene/environment interaction (2000)

Several studies have found an association between the rare Pi-alleles and asthma or bronchial hyperresponsiveness (BHR). This study deals with the effect of Pi-type on BHR among 2,308 young Danish people living in rural areas with a mean +/- SD age of 19.7+/-2.4 yrs. Interviews, pulmonary function testing, bronchial histamine provocation and skin-prick tests were performed. Serum alpha1-antitrypsin levels were determined and phenotyping was performed by means of isoelectric focusing and the subjects categorized into four groups: 1) MM and MX; 2) MS; 3) MZ; and 4) rare, i.e. SZ, SS and ZZ. Among the farmers, a significant positive trend for sensitization towards house dust mites was found, ranging from 12% in the MM group to 22% in the rare Pi-group. A positive test for trend was found within the Pi-groups in a one-sided test for doctor-diagnosed asthma with a peak prevalence of 40% for these symptoms among smokers in the rare Pi-group. On multiple logistic regression analysis, an increased odds ratio (OR) for BHR was found among farming school attendants with the rare Pi-alleles. The OR (95% confidence interval) was 1.71 (0.84-3.49) for MS, 1.93 (1.10-3.39) for MZ and 4.34 (1.19-15.8) for the rare Pi-group. Such a relationship was not found among the conscripts. These results show that a gene/environment interaction may exist between the farming occupation and the rare Pi-alleles, leading to a higher proportion of bronchial hyperresponsiveness related to the rare Pi-alleles in farming school attendants, in contrast to what is found among other young people living in rural areas.
Synthesis and Characterization of Monodisperse Nanocrystals and Close-Packed Nanocrystal Assemblies (2000)

▪ Abstract Solution phase syntheses and size-selective separation methods to prepare semiconductor and metal nanocrystals, tunable in size from ∼1 to 20 nm and monodisperse to ≤5%, are presented. Preparation of monodisperse samples enables systematic characterization of the structural, electronic, and optical properties of materials as they evolve from molecular to bulk in the nanometer size range. Sample uniformity makes it possible to manipulate nanocrystals into close-packed, glassy, and ordered nanocrystal assemblies (superlattices, colloidal crystals, supercrystals). Rigorous structural characterization is critical to understanding the electronic and optical properties of both nanocrystals and their assemblies. At inter-particle separations 5–100 Å, dipole-dipole interactions lead to energy transfer between neighboring nanocrystals, and electronic tunneling between proximal nanocrystals gives rise to dark and photoconductivity. At separations &lt;5 Å, exchange interactions cause otherwise insulating assemblies to become semiconducting, metallic, or superconducting depending on nanocrystal composition. Tailoring the size and composition of the nanocrystals and the length and electronic structure of the matrix may tune the properties of nanocrystal solid-state materials.
Essential role of Rac1/NADPH oxidase in nerve growth factor induction of TRPV1 expression (2005)

Nerve growth factor (NGF) regulates the nociceptive properties of a subset of small diameter sensory neurons by increasing the expression of the heat-sensing transient receptor potential (TRP) channel, TRPV1. This action involves activation of the tyrosine kinase receptor (Trk) A/p38 MAPK pathway. Recent studies indicate that activation of TrkA promotes superoxide generation via NADPH oxidase. In this study, we determined whether the NADPH oxidase pathway is involved in NGF-stimulated TRPV1 expression using a rat pheochromocytoma 12 line and rat dorsal root ganglion neurons. Treatment of these cells with NGF (100 ng/mL) increased TRPV1 protein expression (approx. twofold) but not mRNA. This increase was mimicked by H(2)O(2) and attenuated by catalase and inhibitors of NADPH oxidase. NGF stimulated NADPH oxidase activity, while 24 h exposure further increased expression of the Rac1 and gp91(phox) subunits of the holoenzyme. Inhibition of NADPH oxidase by transient transfection of a dominant negative Rac1 mutant (RacN17) plasmid blocked NGF-stimulated TRPV1 protein expression, while expression of a constitutively active Rac1 increased basal and NGF-stimulated TRPV1 levels. Inhibition of NADPH oxidase activity also attenuated NGF-dependent p38 MAPK activation. We conclude that the Rac1/NADPH oxidase pathway regulates p38 activation and TRPV1 expression which aids in the maintenance of peripheral neuron integrity and pain perception.
Effects of Time Variant Channel on a Time Reversal UWB System (2009)

Time reversal (TR) is gaining more and more attention due to its potential to simplify the receiver for an ultra-wideband communication system. The temporal and spatial focusing properties of a TR communication system allow the detection of the received signal with simple receivers. However, the transmitter system becomes complicated as perfect channel estimation is required on regular basis. However, if the TR system is robust and can resist the changes in the channel, frequency of the estimation cycles will be less resulting in an increased transmission throughput. In this paper, we study the robustness of a TR system in a time varying channel environment. Different TR characteristics are compared and the ability of a TR system to resist the varying channel is shown.
Application of probe electrospray to direct ambient analysis of biological samples (2008)

Recently, we have developed probe electrospray ionization (PESI) that uses a solid needle. In this system, the probe needle moves up and down along the vertical axis by a motor-driven system. At the highest position of the probe needle, electrospray is generated by applying a high voltage. In this study, we applied PESI directly to biological samples such as urine, mouse brain, mouse liver, salmon egg, and fruits (orange, banana, etc.). Strong ion signals for almost all the samples were obtained. The amount of liquid sample picked up by the needle is as small as pL or less, making PESI a promising non-invasive technique for detecting biomolecules in living systems such as cells. Therefore, PESI may be useful as a versatile and ready-to-use semi-online analytical tool in the fields of medicine, pharmaceuticals, agriculture, food science, etc.
Five tumor necrosis factor-inducible cell adhesion mechanisms on the surface of mouse endothelioma cells mediate the binding of leukocytes. (1993)

We have distinguished five TNF-alpha-inducible cell adhesion mechanisms on microvasculature-derived endothelioma cells of the mouse which mediate the binding of different types of leukocytes. Three of these mechanisms could be identified as the mouse homologs of ICAM-1, VCAM-1, and E-selectin, of which the latter was defined by the novel mAb 21KC10. The fourth TNF-alpha-inducible cell adhesion mechanism was blocked by antibodies specific for mouse P-selectin. We have recently shown that TNF-alpha stimulates the synthesis of P-selectin in mouse endothelioma cells (A. Weller, S. Isenmann, D. Vestweber. 1992. J. Biol. Chem. 267:15176-15183). Here we show that this stimulation leads to maximal cell surface expression levels within 4 h after stimulation while the same endothelioma cells are also able to upregulate P-selectin at the cell surface within minutes after stimulation with PMA. Both effects are additive. The fifth TNF-induced cell adhesion mechanism is defined by mediating the binding to the mouse monocyte/macrophage cell line J774. This adhesion mechanism is not inhibited by antibodies against any of the other four CAMs; it functions well at 7 degrees C (in contrast to ICAM-1 and VCAM-1) and it is as active after 16 h of TNF induction as after 4 h (in contrast to E- and P-selectin). Furthermore, this new adhesion mechanism only functions on two of three endothelioma cell lines and is undetectable on the third, although ICAM-1, VCAM-1, E-selectin, and P-selectin could be demonstrated to function well on this cell line. Thus, in addition to the three known TNF-inducible CAMs, ICAM-1, VCAM-1, and E-selectin, also P-selectin and a fifth, as yet molecularly undefined cell adhesion mechanism, are TNF inducible at the cell surface of mouse endothelioma cells.
Positive regulation of motility and flhDC expression by the RNA‐binding protein CsrA of Escherichia coli (2001)

Many species of bacteria devote considerable metabolic resources and genetic information to the ability to sense the environment and move towards or away from specific stimuli using flagella. In Escherichia coli and related species, motility is regulated by several global regulatory circuits, which converge to modulate the overall expression of the master operon for flagellum biosynthesis, flhDC. We now show that the global regulator CsrA of E. coli K-12 is necessary for motility under a variety of growth conditions, as a result of its role as an activator of flhDC expression. A chromosomally encoded flhDC'-'lacZ translational fusion was expressed at three- to fourfold higher levels in csrA wild-type strains than in isogenic csrA mutants. Purified recombinant CsrA protein stimulated the coupled transcription-translation of flhDC'-' lacZ in S-30 extracts and bound to the 5' segment of flhDC mRNA in RNA mobility shift assays. The steady-state level of flhDC mRNA was higher and its half-life was approximately threefold greater in a csrA wild-type versus a csrA mutant strain. Thus, CsrA stimulates flhDC gene expression by a post-transcriptional mechanism reminiscent of its function in the repression of glycogen biosynthesis.
The α2D/A‐adrenergic receptor‐linked membrane guanylate cyclase: a new signal transduction system in the pineal gland (1998)

In the pineal gland, the membrane guanylate cyclase activity was specifically stimulated by alpha(2D/A)-adrenergic receptor (alpha(2D/A)-AR) agonists. The agonists, however, did not stimulate the cyclase activity in the cell-free membranes. It was possible to stimulate the cyclase in cell-free membranes by the addition of the pineal soluble fraction, but this stimulation was Ca2+-dependent and alpha(2D/A)-agonist-independent. It was also possible to achieve Ca2+-dependent stimulation of the cyclase by the direct addition of CD-GCAP to the isolated pineal membranes. CD-GCAP is a Ca2+-binding protein and is a specific activator of one of the two members of the ROS-GC subfamily of membrane guanylate cyclases, ROS-GC1. The soluble fraction of the pineal gland stimulated recombinant ROS-GC1 in a Ca2+-dependent fashion. The direct presence of both ROS-GC1 and CD-GCAP in the pineal was established by molecular cloning/PCR studies. The findings demonstrate the existence of a novel signal transduction mechanism--the linkage of the alpha(2D/A)-AR signaling system with ROS-GC1 transduction system, occurring through intracellular Ca2+ via CD-GCAP.
Spatiotemporal measurements based on spatial spectral interferometry for ultrashort optical pulses shaped by a Fourier pulse shaper (2002)

We measured the space–time profile of ultrashort optical pulses shaped with a Fourier pulse shaper. Spatial chirp, which originated in the space–time coupling at the pulse shaper, was observed directly with two-dimensional spatial spectral interferometry. By analyzing the two-dimensional fringe pattern, we successfully obtained a spatial and a temporal distribution in both amplitude and phase for shaped pulses. Numerically predicted spatiotemporal patterns were compared with experimental results.
Three-dimensional reconstruction of coronal mass ejections (1994)

Computer assisted tomography (CAT) techniques are used to reconstruct the three dimensional shape of coronal mass ejections in the interplanetary medium. Both the Helios 2 spacecraft zodiacal-light photometers and the Solwind coronograph measure changes in Thomson scattering of sunlight from electrons. The technique from near-perpendicular Solwind and Helios views are applied to determine the density of a mass ejection which left the solar surface on 24 May 1979. The coronograph and the Helios perspective views are not simultaneous; the Solwind observations extend outward to sky plane distances of only 10 of the solar radius, whereas the Helios 16 photometer observes to as close as 17 of the solar radius from the sun. The solution is obtained by assuming outward radial expansion and that the coronal mass ejections (CME's) have the same speed everywhere at the same height. The analyses show that CME's are extensive three dimensional structures (the CME of 24 May appears approximately shell) like in three dimensions.
Wireless Network Coding: Opportunities &#x00026; Challenges (2007)

Wireless networks suffer from a variety of unique problems such as low throughput, dead spots, and inadequate support for mobility. However, their characteristics such as the broadcast nature of the medium, spatial diversity, and significant data redundancy, provide opportunities for new design principles to address these problems. There has been recent interest in employing network coding in wireless networks. This paper explores the case for network coding as a unifying design paradigm for wireless networks, by describing how it addresses issues of throughput, reliability, mobility, and management. We also discuss the practical challenges facing the integration of such a design into the network stack.
Farnesoid X Receptor Responds to Bile Acids and Represses Cholesterol 7α-Hydroxylase Gene (CYP7A1) Transcription (2000)

Cholesterol 7alpha-hydroxylase gene (CYP7A1) transcription is repressed by bile acids. The goal of this study is to elucidate the mechanism of CYP7A1 transcription by bile acid-activated farnesoid X receptor (FXR) in its native promoter and cellular context and to identify FXR response elements in the gene. In Chinese hamster ovary cells transfected with retinoid X receptor alpha (RXRalpha)/FXR, only chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) were able to stimulate a heterologous promoter/reporter containing an ecdysone response element. In HepG2 cells, all bile acids (25 microM) were able to repress CYP7A1/luciferase reporter activity, and only CDCA and DCA further repressed reporter activity when cotransfected with RXRalpha/FXR. The concentration of CDCA required to inhibit 50% of reporter activity (IC(50)) was determined to be approximately 25 microM without FXR and 10 microM with FXR. Deletion analysis revealed that the bile acid response element located between nucleotides -148 and -128 was the FXR response element, but RXRalpha/FXR did not bind to this sequence. These results suggest that bile acid-activated FXR exerts its inhibitory effect on CYP7A1 transcription by an indirect mechanism, in contrast to the stimulation and binding of FXR to intestinal bile acid-binding protein gene promoter. Results also reveal that bile acid receptors other than FXR are present in HepG2 cells.
POLY I:C, AN INDUCER OF INTERFERON AND INTERFERENCE AGAINST VIRUS INFECTIONS (1972)

FIELD, A KIRK; TYTELL, ALFRED A.; PIPERNO, ELLIOT; LAMPSON, GEORGE P.; NEMES, MARJORIE M.; HILLEMAN, MAURICE R.1 Author Information
Real-Time Anomaly Detection for Streaming Analytics (2016)

Much of the worlds data is streaming, time-series data, where anomalies give significant information in critical situations. Yet detecting anomalies in streaming data is a difficult task, requiring detectors to process data in real-time, and learn while simultaneously making predictions. We present a novel anomaly detection technique based on an on-line sequence memory algorithm called Hierarchical Temporal Memory (HTM). We show results from a live application that detects anomalies in financial metrics in real-time. We also test the algorithm on NAB, a published benchmark for real-time anomaly detection, where our algorithm achieves best-in-class results.
Immunology of Tumor Infiltrating Lymphocytes (1985)

Frequently peripheral blood lymphocytes (PBL) do not reflect the tumor host relationship and cell mediated immunity in the PBL does not often correlate with prognosis. The tumor infiltrating lymphocytes (TIL) interact most closely with the tumor cells and are likely to more accurately reflect tumor host interactions. These studies indicate that TIL from pulmonary tumors are similar to PBL so far as their cell surface markers are concerned. The percentage of T-cells, B-cells, helper cells, suppressor cells, and NK cells are similar in the two compartments. However, the TIL are markedly suppressed in their functional capacity as measured by their proliferative and cytotoxic activity. In addition, natural killer (NK) cell activity is markedly diminished in TIL as opposed to the PBL. In addition, the direct injection of BCG into these tumors reverses this phenomenon by significantly increasing T-cell and NK cell functional activity. Thus, the microenvironment of the tumor profoundly affects the immunologic relationship between the tumor and the host.
A CRITICAL ANALYSIS OF SERUM AND URINE INTERLEUKIN-2 RECEPTOR ASSAYS IN RENAL ALLOGRAFT RECIPIENTS1,2 (1989)

A component of the interleukin 2 receptor (IL-2R) is released in soluble form during T cell activation and can be detected in the blood during acute renal allograft rejection. This study evaluates the diagnostic utility of a sandwich enzyme immunoassay test for serum and urine IL-2R in renal allograft recipients. A rise in serum IL-2R during the week prior to the clinical diagnosis of rejection correlated better with rejection than did isolated serum IL-2R levels or urine values. For the diagnosis of acute rejection, a rise in serum IL-2R (sensitivity 73%, specificity 87%) was comparable in overall test performance to a rise in serum creatinine (sensitivity 70%, specificity 84%). Overall, the two tests had equivalent receiver operating characteristic curves. Because the etiology of false positives in creatinine and IL-2R assays differed (primarily cyclosporine toxicity and infection, respectively), the predictive value of the combined tests was superior to either alone.
Activation of Rac and Cdc42 Video Imaged by Fluorescent Resonance Energy Transfer-Based Single-Molecule Probes in the Membrane of Living Cells (2002)

Rho family G proteins, including Rac and Cdc42, regulate a variety of cellular functions such as morphology, motility, and gene expression. We developed fluorescent resonance energy transfer-based probes which monitored the local balance between the activities of guanine nucleotide exchange factors and GTPase-activating proteins for Rac1 and Cdc42 at the membrane. These probes, named Raichu-Rac and Raichu-Cdc42, consisted of a Cdc42- and Rac-binding domain of Pak, Rac1 or Cdc42, a pair of green fluorescent protein mutants, and a CAAX box of Ki-Ras. With these probes, we video imaged the Rac and Cdc42 activities. In motile HT1080 cells, activities of both Rac and Cdc42 gradually increased toward the leading edge and decreased rapidly when cells changed direction. Under a higher magnification, we observed that Rac activity was highest immediately behind the leading edge, whereas Cdc42 activity was most prominent at the tip of the leading edge. Raichu-Rac and Raichu-Cdc42 were also applied to a rapid and simple assay for the analysis of putative guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) in living cells. Among six putative GEFs and GAPs, we identified KIAA0362/DBS as a GEF for Rac and Cdc42, KIAA1256 as a GEF for Cdc42, KIAA0053 as a GAP for Rac and Cdc42, and KIAA1204 as a GAP for Cdc42. In conclusion, use of these single-molecule probes to determine Rac and Cdc42 activity will accelerate the analysis of the spatiotemporal regulation of Rac and Cdc42 in a living cell.
The mTOR inhibitor CCI-779 induces apoptosis and inhibits growth in preclinical models of primary adult human ALL (2005)

Acute lymphoblastic leukemia (ALL) in adult patients is often resistant to current therapy, making the development of novel therapeutic agents paramount. We investigated whether mTOR inhibitors (MTIs), a class of signal transduction inhibitors, would be effective in primary human ALL. Lymphoblasts from adult patients with precursor B ALL were cultured on bone marrow stroma and were treated with CCI-779, a second generation MTI. Treated cells showed a dramatic decrease in cell proliferation and an increase in apoptotic cells, compared to untreated cells. We also assessed the effect of CCI-779 in a NOD/SCID xenograft model. We treated a total of 68 mice generated from the same patient samples with CCI-779 after establishment of disease. Animals treated with CCI-779 showed a decrease in peripheral-blood blasts and in splenomegaly. In dramatic contrast, untreated animals continued to show expansion of human ALL. We performed immunoblots to validate the inhibition of the mTOR signaling intermediate phospho-S6 in human ALL, finding down-regulation of this target in xenografted human ALL exposed to CCI-779. We conclude that MTIs can inhibit the growth of adult human ALL and deserve close examination as therapeutic agents against a disease that is often not curable with current therapy.
IL-17–Secreting γδ T Cells Are Completely Dependent upon CCR6 for Homing to Inflamed Skin (2017)

mAbs that neutralize IL-17 or its receptor have proven efficacious in treating moderate-to-severe psoriasis, confirming IL-17 as an important driver of this disease. In mice, a rare population of T cells, γδT17 cells, appears to be a dominant source of IL-17 in experimental psoriasis. These cells traffic between lymph nodes and the skin, and are identified by their coexpression of the TCR variable regions γ4 and δ4. These cells are homologous to the Vγ9Vδ2 T cell population identified in human psoriatic plaques. In this study we report that a potent and specific small molecule antagonist of the CCR6 chemokine receptor, CCX2553, was efficacious in reducing multiple aspects of psoriasis in two different murine models of the disease. Administration of CCX2553 ameliorated skin inflammation in both the IL-23-induced ear swelling model and the topical imiquimod model, and significantly reduced the number of γδT17 cells in inflamed skin. γδT17 cells were greatly reduced in imiquimod-treated skin of CCR6<sup>-/-</sup> mice, but adoptively transferred wild-type (CCR6<sup>+/+</sup>) γδT17 cells homed normally to the skin of imiquimod-treated CCR6<sup>-/-</sup> mice. Our data suggest that γδT17 cells are completely dependent on CCR6 for homing to psoriasiform skin. Thus, CCR6 may constitute a novel target for a mechanistically distinct therapeutic approach to treating psoriasis.
Dynamic modeling of gene expression data (2001)

We describe the time evolution of gene expression levels by using a time translational matrix to predict future expression levels of genes based on their expression levels at some initial time. We deduce the time translational matrix for previously published DNA microarray gene expression data sets by modeling them within a linear framework by using the characteristic modes obtained by singular value decomposition. The resulting time translation matrix provides a measure of the relationships among the modes and governs their time evolution. We show that a truncated matrix linking just a few modes is a good approximation of the full time translation matrix. This finding suggests that the number of essential connections among the genes is small.