gebhart/patrepeval huggingface dataset:
IL-15 as a mediator of CD4 + help for CD8 + T cell longevity and avoidance of TRAIL-mediated apoptosis (2008)

CD4+ helper T cells contribute to the induction and maintenance of antigen-specific CD8+ T cells. Their absence results in short-lived antigen-specific CD8+ T cells and defective secondary CD8+ T cell responses because of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Here, we show that IL-15 codelivered with vaccines can overcome CD4+ T cell deficiency for promoting longevity of antigen-specific CD8+ T cells and avoidance of TRAIL-mediated apoptosis. In both priming and secondary responses, IL-15 down-regulates proapoptotic Bax, an intermediate in TRAIL-mediated apoptosis, and increases anti-apoptotic Bcl-X(L) in CD8+ T cells. Thus, IL-15 is sufficient to mimic CD4+ T cell help. Antigen-specific CD4+ T cells induce dendritic cells (DCs) to produce IL-15. IL-15 is also necessary for optimal help, because helper cells do not deliver effective help through IL-15-/- DCs. Therefore, IL-15 codelivered with vaccines can overcome CD4+ helper T cell deficiency for induction of functionally efficient CD8+ T cells and maintenance of CD8+ cytotoxic T lymphocytes (CTLs), and IL-15 is probably one of the natural mediators of help. These findings suggest new vaccine strategies against infections and cancers, especially in individuals with CD4-deficiency.
Microcell design principles (1993)

The ways in which microcell systems can help cellular operators face a number of challenges to achieve continued growth, including the need for increased system capacity, enhanced coverage, lower network cost per subscriber, improved performance, delivery of innovative value-added services, and well-planned equipment and service migration strategies, are discussed. It is argued that microcells must work with conventional cellular systems with lower equipment costs per subscriber, and should require only minimal preinstallation RF design and engineering. Keys to cost-effective microcell deployment are high-performance RF component and digital signal processing technology, efficient radio resource management, optimized distributed network design, and effective switch and network integration.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cannabinoids Enhance NMDA-Elicited Ca2+Signals in Cerebellar Granule Neurons in Culture (1999)

A physiological role for cannabinoids in the CNS is indicated by the presence of endogenous cannabinoids and cannabinoid receptors. However, the cellular mechanisms of cannabinoid actions in the CNS have yet to be fully defined. In the current study, we identified a novel action of cannabinoids to enhance intracellular Ca2+ responses in CNS neurons. Acute application of the cannabinoid receptor agonists R(+)-methanandamide, R(+)-WIN, and HU-210 (1-50 nM) dose-dependently enhanced the peak amplitude of the Ca2+ response elicited by stimulation of the NMDA subtype of glutamate receptors (NMDARs) in cerebellar granule neurons. The cannabinoid effect was blocked by the cannabinoid receptor antagonist SR141716A and the Gi/Go protein inhibitor pertussis toxin but was not mimicked by the inactive cannabinoid analog S(-)-WIN, indicating the involvement of cannabinoid receptors. In current-clamp studies neither R(+)-WIN nor R(+)-methanandamide altered the membrane response to NMDA or passive membrane properties of granule neurons, suggesting that NMDARs are not the primary sites of cannabinoid action. Additional Ca2+ imaging studies showed that cannabinoid enhancement of the Ca2+ signal to NMDA did not involve N-, P-, or L-type Ca2+ channels but was dependent on Ca2+ release from intracellular stores. Moreover, the phospholipase C inhibitor U-73122 and the inositol 1,4,5-trisphosphate (IP3) receptor antagonist xestospongin C blocked the cannabinoid effect, suggesting that the cannabinoid enhancement of NMDA-evoked Ca2+ signals results from enhanced release from IP3-sensitive Ca2+ stores. These data suggest that the CNS cannabinoid system could serve a critical modulatory role in CNS neurons through the regulation of intracellular Ca2+ signaling.
Cyclic shifting and time inversion of partial transmit sequences to reduce the peak-to-average power ratio in OFDM (2002)

An adaptation of the work by Huber and Muller (see Electronic Letters, vol.33, no.5, p.368-69, 1997) on partial transmit sequences (PTS) for the reduction of the peak-to-average power ratio (PAPR) in orthogonal frequency division multiplexing (OFDM) is described.
Quantitative analysis of relative protein contents by Western blotting: Comparison of three members of the dystrophin-glycoprotein complex in slow and fast rat skeletal muscle (2000)

We have developed a method for accurate quantitative analysis and statistical comparison of the relative contents of the dystrophin-glycoprotein complex (DGC) in skeletal muscle. This method was applied to compare DGC contents in slow (soleus) and in fast (extensor digitorum longus, EDL) rat skeletal muscles. The quantitative analysis combines a modified bicinchoninic acid (BCA) assay with Western blotting and enhanced chemiluminescence (ECL). This combination allows the use of high levels of detergents and reducing reagents essential for extracting DGC. In addition, the evaluation of the total amount of proteins in each sample makes it possible to have a reference and to accurately compare relative protein levels without using a specific standard. With a large gradient gel, we could concomitantly compare two groups (n = 9) and quantify all protein contents differing highly in their molecular masses (from 35 kDa to 427 kDa). Each experiment was triplicated and normalized; the two muscles were compared using the Mann-Whitney test (P<0.001) to establish their protein content. The DGC relative levels for the slow muscle soleus and the fast muscle EDL differed significantly: dystrophin, beta-dystroglycan, and gamma-sarcoglycan levels were 130%, 110% and 120% higher in the soleus, respectively. The differences observed in the expression level of cytoskeletal associated protein (dystrophin) and transmembranous anchorage components may correspond to a physiological response of the muscle fibers to duration, magnitude, and frequency of the imposed mechanical loading.
Cutting Edge: Role of B Lymphocytes in Protective Immunity Against Salmonella typhimurium Infection (2000)

Infection of mice with Salmonella typhimurium gives rise to a disease similar to human typhoid fever caused by S. typhi. Since S. typhimurium is a facultative intracellular bacterium, the requirement of B cells in the immune response against S. typhimurium is a longstanding matter of debate. By infecting mice on a susceptible background and deficient in B cells (Igmu-/- mice) with different strains of S. typhimurium, we could for the first time formally clarify the role of B cells in the response against S. typhimurium. Compared with Igmu+/+ mice, LD50 values in Igmu-/- mice were reduced during primary, and particularly secondary, oral infection with virulent S. typhimurium. After systemic infection, Igmu-/- mice cleared attenuated aroA- S. typhimurium, but vaccine-induced protection against systemic infection with virulent S. typhimurium involved both B cell-dependent and -independent effector mechanisms. Thus, B cell-mediated immunity plays a distinct role in control of S. typhimurium in susceptible mice.
Synthesis and properties of zinc complexes of meso-hexadecyloxy-substituted tetrabenzoporphyrin and tetrabenzoazaporphyrins (2008)

The hexadecyloxyacetic acid was prepared by alkylation of glycolic acid. Proceeding from the acid obtained zinc complexes were synthesized of meso-trans-di(hexadecyloxy)tetra-benzoporphyrin, meso-tetra(hexadecyloxy)tetrabenzoporphyrin, and also of meso-hexadecyloxytetrabenzoazaporphyrins. The spectral properties of compounds synthesized were investigated.
Variant tricarboxylic acid cycle in Mycobacterium tuberculosis : Identification of α-ketoglutarate decarboxylase (2005)

Mycobacterium tuberculosis (Mtb) has adapted its metabolism for persistence in the human macrophage. The adaptations are likely to involve Mtb's core intermediary metabolism, whose enzymes have been little studied. The tricarboxylic acid cycle is expected to yield precursors for energy, lipids, amino acids, and heme. The genome sequence of Mtb H37Rv predicts the presence of a complete tricarboxylic acid cycle, but we recently found that alpha-ketoglutarate dehydrogenase (KDH) activity is lacking in Mtb lysates. Here we showed that citrate synthase, aconitase, isocitrate dehydrogenase, fumarase, malate dehydrogenase, and succinate dehydrogenase, but not KDH, are present, raising the possibility of separate oxidative and reductive half-cycles. As a potential link between the half-cycles, we found that Rv1248c, annotated as encoding SucA, the putative E1 component of KDH, instead encodes alpha-ketoglutarate decarboxylase (Kgd) and produces succinic semialdehyde. Succinic semialdehyde dehydrogenase activity was detected in Mtb lysates and recapitulated with recombinant proteins GabD1 (encoded by Rv0234c) and GabD2 (encoded by Rv1731). Kgd and GabD1 or GabD2 form an alternative pathway from alpha-ketoglutarate to succinate. Rv1248c, which is essential or required for normal growth of Mtb [Sassetti, C., Boyd, D. H. & Rubin, E. J. (2003) Mol. Microbiol 48, 77-84] is the first gene shown to encode a Kgd. Kgd is lacking in humans and may represent a potential target for chemotherapy of tuberculosis.
Abrogation of species specificity for activation of tumoricidal properties in macrophages by recombinant mouse or human interferon-gamma encapsulated in liposomes. (1985)

Highly purified human blood monocytes, isolated by continuous Percoll density gradients under endotoxin-free conditions, and mouse peritoneal exudate macrophages (PEM) were activated in vitro by the combination of muramyl dipeptide (MDP) and recombinant interferon-gamma (r-IFN-gamma) to become tumoricidal against their respective tumorigenic target cells. The activation of human monocytes or mouse PEM by free unencapsulated r-IFN-gamma and MDP was species specific: human r-IFN-gamma activated human blood monocytes to lyse allogeneic melanoma cells, but did not activate mouse PEM. Mouse r-IFN-gamma activated mouse PEM to lyse syngeneic melanoma cells, but did not activate cytotoxic properties in human monocytes. The encapsulation of either mouse or human r-IFN-gamma with MDP within the same liposome preparation produced synergistic activation of cytotoxic properties in both PEM and monocytes without apparent species specificity. The activation of tumoricidal properties in macrophages by r-IFN-gamma and MDP occurred as a consequence of intracellular interaction. We base this conclusion on the data showing that whereas free r-IFN-gamma and MDP did not activate macrophages pretreated with pronase, liposome-encapsulated r-IFN-gamma and MDP did. Moreover, the i.v. injection of liposomes containing human or mouse r-IFN-gamma and MDP produced in vivo activation of mouse alveolar macrophages. These data suggest that in contrast to activation with free r-IFN-gamma, which requires binding to macrophage surface receptors, the intracellular interaction of r-IFN-gamma, which produces tumoricidal activity in macrophages, is not species specific.
Advances in indolo[2,3-a]carbazole chemistry: design and synthesis of protein kinase C and topoisomerase I inhibitors. (1999)

Indolo[2,3-a]carbazoles, their pyrrolo[3,4-c]anellated variants and structurally closely related bisindolylmaleimides represent a biologically highly interesting class of natural compounds which are potential anticancer agents. According to the ongoing literature new and efficient synthetic methods yield a great variety of these compounds which have been reported in detail. The biological activities and the inhibitory activities against the target enzymes protein kinase C and topoisomerase I are also discussed including structure activity relationships. A molecular binding model of the protein kinase C inhibitors with the target enzyme at the atomic level is presented and supported by X-ray crystallographic structures and by molecular modelling studies.
Know Before You Do: Anticipating Maneuvers via Learning Temporal Driving Models (2015)

Abstract : Advanced Driver Assistance Systems (ADAS) have made driving safer over the last decade. They prepare vehicles for unsafe road conditions and alert drivers if they perform a dangerous maneuver. However, many accidents are unavoidable because by the time drivers are alerted, it is already too late. Anticipating maneuvers a few seconds beforehand can alert drivers before they perform the maneuver and also give ADAS more time to avoid or prepare for the danger. Anticipation requires modeling the driver's action space, events inside the vehicle such as their head movements, and also the outside environment. Performing this joint modeling makes anticipation a challenging problem. In this work we anticipate driving maneuvers a few seconds before they occur. For this purpose we equip a car with cameras and a computing device to capture the context from both inside and outside of the car. We represent the context with expressive features and propose an Autoregressive Input-Output HMM to model the contextual information. We evaluate our approach on a diverse data set with 1180 miles of natural freeway and city driving and show that we can anticipate maneuvers 3.5 seconds before they occur with over 80% F1-score. Our computation time during inference is under 3.6 milliseconds.
Growth of Triple-Negative Breast Cancer Cells Relies upon Coordinate Autocrine Expression of the Proinflammatory Cytokines IL-6 and IL-8 (2013)

Triple-negative breast cancers (TNBC) are aggressive with no effective targeted therapies. A combined database analysis identified 32 inflammation-related genes differentially expressed in TNBCs and 10 proved critical for anchorage-independent growth. In TNBC cells, an LPA-LPAR2-EZH2 NF-κB signaling cascade was essential for expression of interleukin (IL)-6, IL-8, and CXCL1. Concurrent inhibition of IL-6 and IL-8 expression dramatically inhibited colony formation and cell survival in vitro and stanched tumor engraftment and growth in vivo. A Cox multivariable analysis of patient specimens revealed that IL-6 and IL-8 expression predicted patient survival times. Together these findings offer a rationale for dual inhibition of IL-6/IL-8 signaling as a therapeutic strategy to improve outcomes for patients with TNBCs.
Tumor cell and connective tissue cell interactions in human colorectal adenocarcinoma. Transfer of platelet-derived growth factor-AB/BB to stromal cells. (1997)

Mechanisms underlying stimulation of platelet-derived growth factor (PDGF) beta-receptors expressed on connective tissue cells in human colorectal adenocarcinoma were investigated in this study. PDGF-AB/BB, but not PDGF receptors, was expressed by tumor cells in situ, as well as in tumor cell isolates of low passage from human colorectal adenocarcinoma. In an experimental co-culture system, conditioned medium from tumor cells only marginally activated PDGF beta-receptors expressed on fibroblasts. In contrast, co-culturing of the two cell types led to a marked PDGF beta-receptor activation. Functional PDGF-AB/BB was found to be associated with heparinase-I-sensitive components on the tumor cell surface. PDGF-AB/BB, isolated from heparinase-I-sensitive cell surface components, induced a marked activation of PDGF beta-receptors. Furthermore, co-culturing tumor cells together with fibroblasts led to a sustained activation of PDGF beta-receptors expressed on fibroblasts. Double immunofluorescence staining of tissue sections from human colorectal adenocarcinoma, combined with computer-aided image analysis, revealed that nonproliferating tumor cells were the predominant cellular source of PDGF-AB/BB in the tumor stroma. In addition, PDGF-AB/BB-expressing tumor cells were found juxtapositioned to microvascular cells expressing activated PDGF beta-receptors. Confocal microscopy revealed a cytoplasmic and cell-membrane-associated expression of PDGF-AB/BB in tumor cells situated in the stroma. In contrast, epithelial cells situated in normal or tumorous acinar structures revealed only a cell-membrane-associated PDGF-AB/BB expression. The is vitro and in situ results demonstrate that tumor cells not only facilitate but also have the ability to modulate connective tissue cell responsiveness to PDGF-AB/BB in a paracrine fashion, through direct cell-cell interactions in human colorectal adenocarcinoma.
On the Distribution Function and Moments of Power Sums With Log-Normal Components (1982)

An approximate technique is presented for the evaluation of the mean and variance of the power sums with log-normal components. Exact expressions for the moments with two components are developed and then used in a nested fashion to obtain the moments of the desired sum. The results indicate more accurate estimates of these quantities over a wider range of individual component variances than any previously reported procedure. Coupling our estimates with the Gaussian assumption for the power sum provides a characterization of the cumulative distribution function which agrees remarkably well with a Monte Carlo simulation in the 1 to 99 percent range of the variate. Simple polynomial expressions obtained for the moments lead to an effective analytical tool for various system performance studies. They allow quick and accurate calculation of quantities such as cochannel interference caused by shadowing in mobile telephony.
Activation of NF-κB1 by OX40 Contributes to Antigen-Driven T Cell Expansion and Survival (2008)

The costimulatory molecule OX40 (CD134) is required in many instances for effective T cell-mediated immunity, controlling proliferation, and survival of T cells after encountering specific Ag. We previously found that the functional targets of OX40 are survivin and aurora B that regulate proliferation and Bcl-2 antiapoptotic family members that regulate survival. However, the intracellular pathways from OX40 that mediate these effects are unclear. In this study, we show that OX40 signaling can target the canonical NF-kappaB (NF-kappaB1) pathway in peripheral Ag-responding CD4 T cells. Phosphorylation of IkappaBalpha, nuclear translocation of NF-kappaB1/p50 and RelA, and NF-kappaB1 activity, are impaired in OX40-deficient T cells. Retroviral transduction of active IkappaB kinase that constitutively activates NF-kappaB1 rescues the poor expansion and survival of OX40-deficient T cells, directly correlating with increased expression and activity of survivin, aurora B, and Bcl-2 family members. Moreover, active IkappaB kinase expression alone is sufficient to restore the defective expansion and survival of OX40-deficient T cells in vivo when responding to Ag. Thus, OX40 signals regulate T cell number and viability through the NF-kappaB1 pathway that controls expression and activity of intracellular targets for proliferation and survival.
The reproducibility of subjective appetite scores (1995)

Although subjective appetite scores are widely used, studies on the reproducibility of this method are scarce. In the present study nine healthy, normal weight, young men recorded their subjective appetite sensations before and during 5 h after two different test meals A and B. The subjects tested each meal twice and in randomized order. Visual analogue scale (VAS) scores, 10 cm in length, were used to assess hunger, satiety, fullness, prospective food consumption and palatability of the meals. Plasma glucose and lactate concentrations were determined concomitantly. The repeatability was investigated for fasting values, delta-mean 5 h and mean 5 h values, delta-peak/nadir and peak/nadir values. Although the profiles of the postprandial responses were similar, the coefficients of repeatability (CR = 2SD) on the mean differences were large, ranging from 2.86 to 5.24 cm for fasting scores, 1.36 to 1.88 cm for mean scores, 2.98 to 5.42 cm for delta-mean scores, and 3.16 to 6.44 cm for peak and delta-peak scores. For palatability ratings the CR values varied more, ranging from 2.38 (taste) to 8.70 cm (aftertaste). Part of the difference in satiety ratings could be explained by the differences in palatability ratings. However, the low reproducibility may also be caused by a conditioned satiation or hunger due to the subjects' prior experience of the meals and therefore not just be a reflection of random noise. It is likely, however, that the variation in appetite ratings is due both to methodological day-to-day variation and to biological day-to-day variation in subjective appetite sensations.
Long-term effectiveness of danazol corticosteroids and cytotoxic drugs in the treatment of hematologic manifestations of systemic lupus erythematosus (2003)

The purpose of this study was to compare the long-term effectiveness among danazol, corticosteroids, cytotoxics, and dapsone in the treatment of hematological manifestations of systemic lupus erythematosus (SLE). Medical charts of all patients seen at the Rheumatic Disease Unit from January to December of 1998 were reviewed. Patient characteristics, disease and treatment information were collected. The main outcome measures were the cause of and time to discontinuation of drugs used to treat hematological manifestations of SLE resulting from all causes, mainly toxicity and inefficacy or both. Bivariate analysis including one-way ANOVA and chi2 tests were used to compare differences between means and proportions, respectively. Survival curves among the different drugs were evaluated using the Kaplan-Meier method. Multivariate analysis (Cox-regression) was used to adjust for potential confounders. After all medical records were reviewed 41 cases were eligible. Two cases had hemolytic anemia, 34 had thrombocytopenia, and five had both. These cases had received a total of 121 cycles of treatment at different times and they represent the study population (corticosteroids n = 37, danazol n = 51, citotoxic drugs n = 29, and dapsone n = 4). Crude rates of discontinuations due to any cause, toxicity and inefficacy werenot statistically significant among the drugs. However, the Kaplan-Meier curves showed statistically significant difference for discontinuations due to all causes as well as inefficacy. Prednisone and cytotoxic drugs had the lowest probability of continuation. In contrast, there were not statistically significant differences among the drugs with respect to first relapse. This is the first study examining the long-term termination rates of several drugs used to treat hematological manifestations of SLE. Using rates of discontinuation adjusted for time there were statistically significant differences among the drugs. Danazol had the highest probability of continuation.
Differential localization of nuclear-encoded tRNAs between the cytosol and mitochondrion in Leishmania tarentolae (2002)

All mitochondrial tRNAs of the kinetoplastid protozoan Leishmania tarentolae are encoded in the nucleus and are imported from the cytosol into the mitochondrion. We previously reported the partitioning of five tRNAs and found that all were shared between the two compartments to different extents. To increase our knowledge of the tRNAs of this organism, and to attempt to understand the signals involved in their subcellular localization, a method to RT-PCR amplify new tRNAs was developed. Various tRNAs were 3' polyadenylated and reverse transcribed with a sequence-tagged primer. The cDNA was tagged by ligation to an anchor oligonucleotide, and the resulting double-tagged cDNA was amplified by PCR. Four new tRNAs were obtained, bringing to 20 the total number of L. tarentolae tRNAs identified to date. The subcellular localization of 17 tRNAs was quantitatively analyzed by two-dimensional gel electrophoresis and northern hybridization. In general, the previously suggested operational classification of tRNAs into three groups (mainly cytosolic, mainly mitochondrial, and shared between the two compartments) is still valid, but the relative abundance of each tRNA in the cytosol or mitochondrion varied greatly as did the level of expression.