gebhart/patrepeval huggingface dataset:
Molecular Characterization of a Putative Antiretroviral Transcriptional Factor, OTK18 (2004)

Elucidation of the factors involved in host defense against human immunodeficiency viral infection remains pivotal if viral control may be achieved. Toward these ends, we investigated the function of a putative antiretroviral factor, OTK18, isolated by differential display of mRNA from HIV type 1-infected primary human monocyte-derived macrophages. Molecular and immunohistochemical analyses showed that the OTK18 nucleotide sequence contains 13 adjacent C(2)H(2)-type zinc finger motifs, a Krüppel-associated box, and is localized to both cytosol and nucleus. Mutational analyses revealed that both the Krüppel-associated box and zinc finger regions of OTK18 are responsible for the transcriptional suppressive activities of this gene. OTK18 was copiously expressed in macrophages following HIV type I infection and diminished progeny virion production. A mechanism for this antiretroviral activity was by suppression of HIV type 1 Tat-induced viral long terminal repeat promoter activity. Our findings suggest that one possible function of OTK18 is as a HIV type 1-inducible transcriptional suppressor.
Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development (2006)

Forkhead winged-helix transcription factor Foxp3 serves as the dedicated mediator of the genetic program governing CD25+CD4+ regulatory T cell (T(R)) development and function in mice. In humans, its role in mediating T(R) development has been controversial. Furthermore, the fate of T(R) precursors in FOXP3 deficiency has yet to be described. Making use of flow cytometric detection of human FOXP3, we have addressed the relationship between FOXP3 expression and human T(R) development. Unlike murine Foxp3- T cells, a small subset of human CD4+ and CD8+ T cells transiently up-regulated FOXP3 upon in vitro stimulation. Induced FOXP3, however, did not alter cell-surface phenotype or suppress T helper 1 cytokine expression. Furthermore, only ex vivo FOXP3+ T(R) cells persisted after prolonged culture, suggesting that induced FOXP3 did not activate a T(r) developmental program in a significant number of cells. FOXP3 flow cytometry was also used to further characterize several patients exhibiting symptoms of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) with or without FOXP3 mutations. Most patients lacked FOXP3-expressing cells, further solidifying the association between FOXP3 deficiency and immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Interestingly, one patient bearing a FOXP3 mutation enabling expression of stable FOXP3(mut) protein exhibited FOXP3(mut)-expressing cells among a subset of highly activated CD4+ T cells. This observation raises the possibility that the severe autoimmunity in FOXP3 deficiency can be attributed, in part, to aggressive T helper cells that have developed from T(R) precursors.
Hollow Silica Spheres of Controlled Size and Porosity by Sol—Gel Processing (1991)

A new technique particularly suitable for fabricating uniform, hollow silica spheres of controlled size and porosity is described. The technique, which combines sol—gel processing with a hollow‐drop generation technique, consists of producing a continuous stream of uniform, hollow drops of a tetraethyl orthosilicate solution and then converting the drops into a rigid form by exposing them to an ammoniated vapor gelation medium. The parameters controlling the properties of the resulting silica spheres are the detailed chemical makeup of the reactant solution and the gelation medium, and the dimensions and relative positions of the nozzles used for drop generation.
Structure and Regulation of the Human Nek2 Centrosomal Kinase (2006)

The dimeric Ser/Thr kinase Nek2 regulates centrosome cohesion and separation through phosphorylation of structural components of the centrosome, and aberrant regulation of Nek2 activity can lead to aneuploid defects characteristic of cancer cells. Mutational analysis of autophosphorylation sites within the kinase domain identified by mass spectrometry shows a complex pattern of positive and negative regulatory effects on kinase activity that are correlated with effects on centrosomal splitting efficiency in vivo. The 2.2-A resolution x-ray structure of the Nek2 kinase domain in complex with a pyrrole-indolinone inhibitor reveals an inhibitory helical motif within the activation loop. This helix presents a steric barrier to formation of the active enzyme and generates a surface that may be exploitable in the design of specific inhibitors that selectively target the inactive state. Comparison of this "auto-inhibitory" conformation with similar arrangements in cyclin-dependent kinase 2 and epidermal growth factor receptor kinase suggests a role for dimerization-dependent allosteric regulation that combines with autophosphorylation and protein phosphatase 1c phosphatase activity to generate the precise spatial and temporal control required for Nek2 function in centrosomal maturation.
Lung injury after deposition of IgA immune complexes. Requirements for CD18 and L-arginine (1992)

Acute lung injury produced by deposition of IgA immune complexes is complement-dependent, neutrophil-independent, oxygen radical-mediated, and may be a result of the formation of the hydroxyl radical (HO) generated directly or indirectly from activated lung macrophages. The current studies were designed to evaluate further the pathophysiologic events that occur after intrapulmonary deposition of IgA immune complexes. Pretreatment of rats with the human recombinant soluble complement receptor-1 resulted in marked attenuation of IgA immune complex-induced lung injury. Intravenous administration of antibody to CD18, but not antibody to CD11b, was highly protective against lung injury. Treatment of animals with either anti-endothelial leukocyte-adhesion molecule-1 or anti-TNF-alpha, both of which were highly protective against IgG immune complex-induced lung injury, had no protective effects in the model of IgA immune complex-induced lung injury. Immunohistochemical analysis revealed up-regulation of the endothelial leukocyte adhesion molecule-1 in the pulmonary vasculature after deposition of IgA immune complexes. This up-regulation was TNF-alpha-dependent. The arginine analog, NG-monomethyl-L-arginine, was highly protective against IgA immune complex-induced lung injury. This protective effect was reversed by the co-presence of L-arginine (but not D-arginine). Protective interventions against IgA immune complex-induced lung injury were inversely correlated with the numbers of macrophages that could be retrieved by lung lavage. These data suggest fundamental differences in the pathogenesis of lung injury after intrapulmonary deposition of IgA immune complexes, as compared with injury caused by deposition of IgG immune complexes. In the latter, neutrophils, intrapulmonary generation of TNF-alpha, and up-regulation of pulmonary vascular endothelial leukocyte-adhesion molecule-1 are required for the full development of lung injury, whereas no such requirements appear in the case of IgA immune complex-induced lung injury. Full expression of IgA immune complex-induced lung injury also appears to require L-arginine, suggesting a possible role for nitric oxide or its derivatives in events ultimately leading to injury.
Cellular binding site and membrane binding proteins for triglyceride-rich lipoproteins in human monocyte-macrophages and THP-1 monocytic cells. (1994)

Triglyceride- and cholesterol-rich foam cells derived from monocyte-macrophages are commonly associated with some forms of hypertriglyceridemia. In this report, direct binding studies at 4 degrees C demonstrate that human monocyte-macrophages (HMM) 1-6 days after isolation from blood and human THP-1 monocytic cells, before and up to 7 days after differentiation with phorbol ester, exhibit a high affinity (Kd 3-6 nM), saturable, specific, and apolipoprotein (apo) E-independent binding site for the uptake and degradation of certain triglyceride-rich lipoproteins (TGRLP). Ligand blotting analysis identified two membrane binding proteins (MBP) of apparent molecular weights of 200 and 235 kDa (MBP 200 and MBP 235) in both cell types that share the same ligand specificity as the cellular site and bind hypertriglyceridemic (HTG) VLDL, trypsinized VLDL devoid of apoE (tryp-VLDL), and dietary plasma chylomicrons from normal subjects but not LDL, acetyl LDL, or normal VLDL with high affinity. Neither lipoprotein lipase nor apoE are required for TGRLP binding to the cells or the isolated MBPs. The cellular binding site and the MBPs are expressed at similar levels at all stages of differentiation, unlike the LDL or the acetyl LDL receptor. TGRLP that bind to the MBPs induce rapid, saturable, cellular triglyceride accumulation in monocytes as well as macrophages; normal VLDL does not. In addition, the cellular high affinity binding site and MBP 200 and 235 are not affected by the media sterol content, unlike the LDL receptor. Taken together, these data indicate that human monocyte-macrophages exhibit a high affinity, saturable, specific, apoE- and lipoprotein lipase-independent binding site and membrane binding proteins for TGRLP that differ in expression, specificity, and molecular size from receptors of the LDL receptor gene family or the acetyl LDL receptor. The shared characteristics of the cellular binding site with MBP 200 and MBP 235 suggest that they are candidates for the receptor-mediated, apoE-independent uptake of HTG-VLDL and chylomicrons by monocytes and macrophages and therefore may be involved in foam cell formation.
Compressed data cubes for OLAP aggregate query approximation on continuous dimensions (1999)

of pre-computation are to be realized.
Combining time-delayed decorrelation and ICA: towards solving the cocktail party problem (2002)

We present methods to separate blindly mixed signals recorded in a room. The learning algorithm is based on the information maximization in a single layer neural network. We focus on the implementation of the learning algorithm and on issues that arise when separating speakers in room recordings. We used an infomax approach in a feedforward neural network implemented in the frequency domain using the polynomial filter matrix algebra technique. A fast convergence speed was achieved by using a time-delayed decorrelation method as a preprocessing step. Under minimum-phase mixing conditions this preprocessing step was sufficient for the separation of signals. These methods successfully separated a recorded voice with music in the background (cocktail party problem). Finally, we discuss problems that arise in real world recordings and their potential solutions.
Pharmacokinetics of recombinant human interleukin‐2 in advanced renal cell carcinoma patients following subcutaneous application (1998)

In patients with metastatic renal cell cancer administration of 20 x 10(6) IU m(-2) of rhIL-2 s.c. in two daily doses (10 x 10(6) IU m(-2) every 12 h) provides better bioavailability and is preferable to the single dose administration.
Interplay between LXR and Wnt/ -Catenin Signaling in the Negative Regulation of Peripheral Myelin Genes by Oxysterols (2011)

Oxysterols are reactive molecules generated from the oxidation of cholesterol. Their implication in cholesterol homeostasis and in the progression of neurodegenerative disorders is well known, but few data are available for their functions in the peripheral nervous system. Our aim was to study the influence of oxysterols on myelin gene expression and myelin sheath formation in peripheral nerves. We show by gas chromatography/mass spectrometry that Schwann cells and sciatic nerves contain 24(S)-hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol and that they express their biosynthetic enzymes and receptors (liver X receptors LXRα and LXRβ). We demonstrate that oxysterols inhibit peripheral myelin gene expression [myelin protein zero (MPZ) and peripheral myelin protein-22 (PMP22)] in a Schwann cell line. This downregulation is mediated by either LXRα or LXRβ, depending on the promoter context, as suggested by siRNA strategy and chromatin immunoprecipitation assays in Schwann cells and in the sciatic nerve of LXR knock-out mice. Importantly, the knock-out of LXR in mice results in thinner myelin sheaths surrounding the axons. Oxysterols repress myelin genes via two mechanisms: by binding of LXRs to myelin gene promoters and by inhibiting the Wnt/β-catenin pathway that is crucial for the expression of myelin genes. The Wnt signaling components (Disheveled, TCF/LEF, β-catenin) are strongly repressed by oxysterols. Furthermore, the recruitment of β-catenin at the levels of the MPZ and PMP22 promoters is decreased. Our data reveal new endogenous mechanisms for the negative regulation of myelin gene expression, highlight the importance of oxysterols and LXR in peripheral nerve myelination, and open new perspectives of treating demyelinating diseases with LXR agonists.
SMTP Service Extension for Secure SMTP over TLS (1999)

This document describes an extension to the SMTP service that allows an SMTP server and client to use transport-layer security to provide private, authenticated communication over the Internet. This gives SMTP agents the ability to protect some or all of their communications from eavesdroppers and attackers.
Both Subunits of the Dimeric Plant Photoreceptor Phytochrome Require Chromophore for Stability of the Far-red Light-absorbing Form (2001)

The dimeric plant photoreceptor phytochrome is converted from its inactive red light-absorbing form (Pr) into the active far-red light-absorbing form (Pfr) upon light absorption. Dynamics of Pfr generation and of thermal Pfr-to-Pr conversion are of fundamental importance for inducing adequate responses to light signals. Here, we analyzed the role of subunit interactions on spectroscopic properties of dimeric phytochrome A. Using a coexpression system and affinity chromatography, we prepared mixed phytochrome dimers that can incorporate the essential chromophore only in one subunit. We demonstrate that such mixed dimers have unaltered difference spectra. In contrast, dark reversion differed greatly between Pfr-Pfr homodimers and Pfr-Pr heterodimers, the former being about 100-fold more stable. Temperature dependence of reaction rates revealed an additional stabilization of about 4 kcal/mol in homodimers. Consequences of these findings are discussed in relation to the biological function of, and functional diversification between, phytochrome family members.
Messenger RNA release from ribosomes during 5′‐translational blockage by consecutive low‐usage arginine but not leucine codons in Escherichia coli (1997)

In '5'-translational blockage', significantly reduced yields of proteins are synthesized in Escherichia coli when consecutive low-usage codons are inserted near translation starts of messages (with reduced or no effect when these same codons are inserted downstream). We tested the hypothesis that ribosomes encountering these low-usage codons near the translation start prematurely release the mRNA. RNA from polysome gradients was fractionated into pools of polysomes and monosomes and a ribosome-free pool. New hybridization probes, called 'molecular beacons', and standard slot blots were used to detect test messages containing either consecutive low-usage AGG (arginine) or synonymous high-usage CGU insertions near the 5' end. The results show an approximately twofold increase in the ratio of free to bound mRNA when the low-usage codons were present in the message compared with when high-usage codons were present. In contrast, there was no difference in the ratio of free to bound mRNA when consecutive low-usage CUA or high-usage CUG (leucine) codons were inserted or when the arginine codons were inserted near the 3' end. These data indicate that at least some mRNA is released from ribosomes during 5'-translational blockage by arginine but not leucine codons, and they support proposals that premature termination of translation can occur in some conditions in vivo in the absence of a stop codon.
Synergism between Analgesics (1995)

The concept and value of 'multimodal' or 'balanced' analgesia in the treatment of postoperative pain is reviewed. Based upon the relatively few multimodal studies compared to unimodal studies, it is concluded that a combination of analgesics will improve pain relief including movement-associated pain. Since analgesic combination therapy is rational, further studies are needed to evaluate the optimal combination for each surgical procedure, as well as to assess the risk of side effects and need for surveillance in large-scale studies.
Aberrant Overexpression of the Wilms Tumor Gene (WT1) in Human Leukemia (1997)

To clarify whether the expression of the WT1 gene in leukemic cells is aberrant or merely reflects that in normal counterparts, the expression levels of the WT1 gene were quantitated for normal hematopoietic progenitor cells. Bone marrow (BM) and umbilical cord blood (CB) cells were fluorescence-activated cell sorting (FACS)-sorted into CD34+ and CD34- cell populations, and the CD34+ cells into nine subsets (CD34+ CD33-, CD34+ CD33+, CD34+ CD38-, CD34+ CD38+, CD34+ HLA-DR-, CD34+ HLA-DR+, CD34+ c-kit(high), CD34+ c-kit(low), and CD34+ c-kit-) according to the expression levels of CD34, CD33, CD38, HLA-DR, and c-kit. Moreover, acute myeloid leukemic cells were also FACS-sorted into four populations (CD34+ CD33-, CD34+ CD33+, CD34- CD33+, and CD34- CD33-). FACS-sorted normal hematopoietic progenitor and leukemic cells and FACS-unsorted leukemic cells were examined for the WT1 expression by quantitative reverse transcriptase-polymerase chain reaction. The WT1 expression in the CD34+ and CD34- cell populations and in the nine CD34+ subsets of BM and CB was at either very low (1.0 to 2.4 x 10(-2)) or undetectable (< 10(-2)) levels (the WT1 expression level of K562 cells was defined as 1.0), whereas the average levels of WT1 expression in FACS-sorted and -unsorted leukemic cells were 2.4 to 9.3 x 10(-1). Thus, the WT1 expression levels in normal hematopoietic progenitor cells were at least 10 times less than those in leukemic cells. Therefore, we could not find any normal counterparts of BM or CB that expressed the WT1 at levels comparable with those in leukemic cells. These results indicate an aberrant overexpression of the WT1 gene in leukemic cells and imply the involvement of this gene in human leukemogenesis.
A phase 1 study evaluating the pharmacokinetics, safety and tolerability of repeat dosing with a human IL-13 antibody (CAT-354) in subjects with asthma (2010)

NCT00974675.
Multicast support for mobile IP using a modified IGMP (2003)

To handle connectivity of mobile hosts to the Internet, the mobile Internet Protocol (IP) has been proposed. Mobile IP functions by assigning a home agent and a foreign agent and creating a tunnel between the two. While this protocol works satisfactorily for point-to-point IP communication between mobile hosts, it results in avoidable overheads for multicast communication. We propose modifications to the Internet Group Management Protocol (IGMP) for enhancing support to multicast communication in a mobile environment. Because of the large overhead involved in IP tunneling for the multicast communication, we propose eliminating tunneling. Instead, we enhance the IGMP to manage the memberships of various multicast groups for mobile hosts more effectively. As currently implemented, the IGMP handles multicast groups one at a time. When a mobile host moves to a new point of IP attachment, it needs to leave and rejoin many groups. We propose a modified IGMP that allows a host to leave or join many multicast groups simultaneously.
A Motion-Adaptive Deinterlacer via Hybrid Motion Detection and Edge-Pattern Recognition (2008)

A novel motion-adaptive deinterlacing algorithm with edge-pattern recognition and hybrid motion detection is introduced. The great variety of video contents makes the processing of assorted motion, edges, textures, and the combination of them very difficult with a single algorithm. The edge-pattern recognition algorithm introduced in this paper exhibits the flexibility in processing both textures and edges which need to be separately accomplished by line average and edge-based line average before. Moreover, predicting the neighboring pixels for pattern analysis and interpolation further enhances the adaptability of the edge-pattern recognition unit when motion detection is incorporated. Our hybrid motion detection features accurate detection of fast and slow motion in interlaced video and also the motion with edges. Using only three fields for detection also renders higher temporal correlation for interpolation. The better performance of our deinterlacing algorithm with higher content-adaptability and less memory cost than the state-of-the-art 4-field motion detection algorithms can be seen from the subjective and objective experimental results of the CIF and PAL video sequences.
Automated Selection of the Active Device in Interactive Multi-Device Smart Spaces (2002)

Pervasive computing offers the vision of seamless interaction by users with pervasive smart spaces filled with many wireless and wired devices, including monitors, speakers, printers, kiosks, soda machines, appliances, toys, sensors, and networked software services. To achieve seamless interaction, we must first address what we term as the active device resolution problem: when a user enters a smart room filled with N devices, which of the N devices is the &amp;quot;active device&amp;quot; that the user intends to interact with immediately? This paper focuses on the particular interaction mode introduced by remote control PDA&amp;apos;s and cell phones. Manual selection of the intended device, either by pointing-and-clicking, gesturing or selecting a device from a software menu, is either imprecise or decidedly intrusive. Automated selection of the active device, using context clues and user history, is a step towards the vision of more seamless interaction. In this paper, we study the historical behavior of a small sample of users and apply various prediction algorithms to user history to automatically select the next active device that a user intends to interact with. We show that the accuracy of prediction can vary depending upon the algorithm, e.g. up to 90% using 3 order Markov prediction, and upon the length of training.
Self‐Reported Headache Frequency and Features Associated With Frequent Headaches in Canadian Young Adolescents (2004)

The NLSCY reveals a remarkable insight into headache frequency and the life experience of Canada's young adolescents with frequent headaches.
The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights (2010)

Since the discovery of glucocorticoids in the 1940s and the recognition of their anti-inflammatory effects, they have been amongst the most widely used and effective treatments to control inflammatory and autoimmune diseases. However, their clinical efficacy is compromised by the metabolic effects of long-term treatment, which include osteoporosis, hypertension, dyslipidaemia and insulin resistance/type 2 diabetes mellitus. In recent years, a great deal of effort has been invested in identifying compounds that separate the beneficial anti-inflammatory effects from the adverse metabolic effects of glucocorticoids, with limited effect. It is clear that for these efforts to be effective, a greater understanding is required of the mechanisms by which glucocorticoids exert their anti-inflammatory and immunosuppressive actions. Recent research is shedding new light on some of these mechanisms and has produced some surprising new findings. Some of these recent developments are reviewed here.