gebhart/patrepeval huggingface dataset:
Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis (2017)

Macrophages play an essential role in the early immune response to Mycobacterium tuberculosis and are the cell type preferentially infected in vivo. Primary macrophages and macrophage-like cell lines are commonly used as infection models, although the physiological relevance of cell lines, particularly for host-pathogen interaction studies, is debatable. Here we use high-throughput RNA-sequencing to analyse transcriptome dynamics of two macrophage models in response to M. tuberculosis infection. Specifically, we study the early response of bone marrow-derived mouse macrophages and cell line J774 to infection with live and γ-irradiated (killed) M. tuberculosis. We show that infection with live bacilli specifically alters the expression of host genes such as Rsad2, Ifit1/2/3 and Rig-I, whose potential roles in resistance to M. tuberculosis infection have not yet been investigated. In addition, the response of primary macrophages is faster and more intense than that of J774 cells in terms of number of differentially expressed genes and magnitude of induction/repression. Our results point to potentially novel processes leading to immune containment early during M. tuberculosis infection, and support the idea that important differences exist between primary macrophages and cell lines, which should be taken into account when choosing a macrophage model to study host-pathogen interactions.
Fluorescent imaging and analysis with Typhoon 8600 (2001)

Current technologies in laser-based imaging systems for life science applications offer highly sensitive and quantitative detection of multiple labels. Typhoon 8600 variable mode imager is capable of fluorescence, storage phosphor, and chemiluminescence detection of gels and blots. The system delivers sensitive fluorescent detection of nucleic acids and proteins in both agarose and polyacrylamide gel formats. Detection and discrimination of multicolor fluorescent signals in fragment analysis, electromobility shift assays, Western blotting and other applications enhance the speed and accuracy of analysis.
Analysis of the Mouse CSF-1 Gene Promoter in a Transgenic Mouse Model1 (2003)

CSF-1 stimulates monocyte and osteoclast populations. However, the molecular mechanisms involved in regulating CSF-1 gene expression are unclear. To identify regulatory regions that control normal CSF-1 gene expression, a -774/+183-bp fragment of the murine CSF-1 promoter was analyzed in vitro and in vivo. Transcriptional activity was high in cultured osteoblasts that express CSF-1 mRNA compared to ARH-77 B cells that lack CSF-1 gene expression. Transient transfection of osteoblasts with promoter deletion constructs showed that the -774-bp fragment conferred the highest transcriptional activity and contained activator and repressor sequences. To assess the ability of the CSF-1 promoter to confer normal tissue expression of CSF-1, transgenic mice containing the -774/+183-bp region driving the E. coli beta-galactosidase (lacZ) reporter gene were generated. beta-Gal analysis of whole tissue extracts showed transgene expression in all tissues tested except liver and kidney. At the cellular level, the pattern of beta-gal expression in the spleen, thymus, bone, lung, and testes of adult transgenic mice mimicked normal endogenous CSF-1 mRNA expression in non-transgenic littermates detected by in situ hybridization. This region also directed appropriate transgene expression to sites in other tissues known to synthesize CSF-1, with the exception of the liver and kidney. These findings indicate that the -774-bp fragment contains cis-acting elements sufficient to direct CSF-1 gene expression in many tissues. CSF-1 promoter/lacZ mice may be useful for studying the transcriptional mechanisms involved in regulating CSF-1 gene expression in tissues throughout development.
Attenuated veterinary virus vaccine for the treatment of cancer. (1993)

Attenuated (nonpathogenic) avian viruses have been used as a form of nonspecific immunological treatment for advanced human cancer. For this study, we used Newcastle disease virus (NDV) vaccine MTH-68/N in an open phase II/B, placebo-controlled (26 patients), multicenter clinical trial for the treatment of 33 patients with advanced cancers. NDV (4000 U/day) or placebo was administered by inhalation twice weekly. During the 6-month trial, the size and presence of primary tumors and metastases were objectively monitored at five institutions by radiologists unaware of the type of treatment that was given. Regression of tumor(s) and/or metastases were observed in eight cases treated with virus (vs. none in the placebo group; p < 0.01). Ten additional patients treated with NDV had no further progression of their tumor sizes, whereas tumor stabilization was noted in only two control patients. Objective, favorable responses (regressions plus stabilization) to virus therapy thus occurred in a total of 18 patients (55%) compared to 2 patients in the placebo group (8%; p < 0.01). Two cases of complete remission were noted in the group treated with NDV. Patients receiving virus therapy had a higher rate of survival at 1 to 2 years. Of 33 patients receiving virus vaccine, 22 survived 1 year, compared to only 4 of 26 patients in the control group (p < 0.02). After 2 years, all seven survivors in the study were in the virus therapy group. There were no 2-year survivors in the control group (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Carbohydrate influences the immunogenic and antigenic characteristics of the ZP3 macromolecule ( M r 55 000) of the pig zona pellucida (1986)

The glycoprotein molecule ZP3 of the pig zona pellucida (Mr 55 000) was deglycosylated by trifluoromethane-sulphonic acid. While gas chromatography established that deglycosylation resulted in greater than 91% carbohydrate removal, deglycosylated ZP3 (DG-ZP3) still retained significant immunogenic potential as shown by its ability to elicit antibody production in the rabbit. Several lines of evidence, however, demonstrated that deglycosylation produced significant modifications in the ZP3 macromolecule which profoundly altered its antigenicity: 125I-radiolabelling procedures using chloramine-T consistently resulted in 125I-labelled ZP3 with a higher specific activity than 125I-labelled DG-ZP3; in competitive binding radioimmunoassays (RIAs) using an 125I-labelled-ZP3 vs anti-ZP3 system, unlabelled DG-ZP3 successfully displaced ZP3 in a dose-related manner; in direct binding RIAs comparing the reaction of labelled ZP3 and DG-ZP3 versus 5 different zona antisera, higher titres were consistently achieved with 125I-labelled ZP3; as compared to ZP3, 2-dimensional immunoelectrophoresis using DG-ZP3 as antigen yielded significantly modified precipitin arc patterns; with electrophoretic blotting procedures, antisera to ZP3 or DG-ZP3 cross-reacted with the heterologous antigen; treatment of pig zonae with anti-DG-ZP3 serum produced a dense precipitation layer on the zona surface. When evaluated collectively, these results provide grounds for an important role for protein and carbohydrate in establishing the immunological characteristics of the Mr 55 000 macromolecule of the pig zona pellucida.
Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study (2002)

This study investigated the efficacy, safety, and clinical benefit of alemtuzumab (Campath-1H) for patients with relapsed or refractory B-cell chronic lymphocytic leukemia exposed to alkylating agents and having failed fludarabine therapy. Ninety-three patients received alemtuzumab in 21 centers worldwide, with the aim to obtain an overall response rate of at least 20%. Dosage was increased gradually (target 30 mg, 3 times weekly, for a maximum of 12 weeks). Infection prophylaxis was mandatory, beginning on day 8, and continuing for a minimum of 2 months after treatment. Responses were assessed at weeks 4, 8, and 12, and patients were followed for 34 months. Overall objective response in the intent-to-treat population (n = 93) was 33% (CR 2%, PR 31%). Median time to response was 1.5 months (range, 0.4-3.7 months). Median time to progression was 4.7 months overall, 9.5 months for responders. At data cut-off, 27 patients (29%) were alive; overall median survival was 16 months (95% CI: 11.8-21.9) and 32 months for responders. Nineteen responders survived more than 21 months. Clinical benefit was observed both in responders and in patients with stable disease. The most common adverse events were related to infusion, generally grade 1 or 2 in severity, occurring mainly in the first week. Grade 3 or 4 infections were reported in 25 patients (26.9%). However, only 3 (9.7%) of 31 patients who responded to alemtuzumab treatment developed grade 3 or 4 infections on the study. Alemtuzumab induced significant responses in these patients with clinical benefit in the majority and with acceptable toxicity in a high-risk group.
The response of cancellous and cortical canine bone to hydroxylapatite‐coated and uncoated titanium rods (1995)

Because of the recent trend in total hip arthroplasty to achieve direct contact of the endoprosthesis with cortical bone, comparison of bone apposition from cortical bone and cancellous bone was performed. The response of cortical and cancellous bone to hydroxylapatite was also compared. Implants in cortical bone demonstrated a higher interface shear strength and more bone apposition than those in cancellous bone over all time periods tested. Hydroxylapatite coating increased the interfacial shear and bone apposition in cortical bone at all time periods and in both the 3- and 6-week cancellous bone models. The potential effect of stress shielding (and subsequent bone resorption) by femoral stems ingrown with cortical bone is discussed.
T Cell Development in Mice Lacking All T Cell Receptor ζ Family Members (ζ, η, and FcεRIγ) (1998)

The zeta family includes zeta, eta, and FcepsilonRIgamma (Fcgamma). Dimers of the zeta family proteins function as signal transducing subunits of the T cell antigen receptor (TCR), the pre-TCR, and a subset of Fc receptors. In mice lacking zeta/eta chains, T cell development is impaired, yet low numbers of CD4+ and CD8+ T cells develop. This finding suggests either that pre-TCR and TCR complexes lacking a zeta family dimer can promote T cell maturation, or that in the absence of zeta/eta, Fcgamma serves as a subunit in TCR complexes. To elucidate the role of zeta family dimers in T cell development, we generated mice lacking expression of all of these proteins and compared their phenotype to mice lacking only zeta/eta or Fcgamma. The data reveal that surface complexes that are expressed in the absence of zeta family dimers are capable of transducing signals required for alpha/beta-T cell development. Strikingly, T cells generated in both zeta/eta-/- and zeta/eta-/--Fcgamma-/- mice exhibit a memory phenotype and elaborate interferon gamma. Finally, examination of different T cell populations reveals that zeta/eta and Fcgamma have distinct expression patterns that correlate with their thymus dependency. A possible function for the differential expression of zeta family proteins may be to impart distinctive signaling properties to TCR complexes expressed on specific T cell populations.
Renewed activity from GX 399-4 (2009)

Further to the alert by Markwardt et al. (ATel #1945), the Swift-BAT scaled map transient analysis and the RXTE Galactic bulge scans indicate that GX 339-4 is entering another epoch of activity. Within the RXTE-PCA energy band the source has attained its brightest state since the 2007 major outburst. Monitoring over the coming weeks will reveal whether this source continues to brighten towards a major outburst or undergoes one of its more common minor high state episodes.
Alginate plasma expander maintains perfusion and plasma viscosity during extreme hemodilution (2004)

Extreme hemodilution was performed in the hamster chamber window model using 6% Dextran 70, lowering systemic hematocrit by 60%. Animals were subsequently divided into three groups and hemodiluted to a hematocrit of 11% using 6% Dextran 70, 6% Dextran 500, and a 4% Dextran 70 + 0.7% alginate solution (n = 6 each group). Final plasma viscosities were 1.4 +/- 0.2, 2.2 +/- 0.1, and 2.7 +/- 0.2 cp, respectively, (P < 0.05, high viscosity vs. low viscosity). Blood viscosities were 2.1 +/- 0.2, 2.9 +/- 0.4, and 3.9 +/- 0.3 cp, respectively. The lowest blood and plasma viscosity group had a significantly lower functional capillary density, 37 +/- 16%, whereas the two high-viscosity solutions were 71 +/- 15% and 76 +/- 12% (P < 0.05, high viscosity vs. low viscosity), respectively. Arteriolar and venular flow in the Dextran 500 and alginate groups was higher than baseline (i.e., normal nontreated animals), whereas the low-viscosity group showed a reduction in flow. These microvascular changes were paralleled by changes in base excess, which was negative for the Dextran 70 group and positive for the other groups. However, tissue Po(2) was uniformly low for all groups (average of 1.4 mmHg). Calculation of tissue oxygen consumption in the window chamber based on the microvascular data, flow, and intravascular Po(2) showed that only the alginate + Dextran 70 solution-exchanged animals returned to baseline oxygen consumption, whereas the other groups were lower than baseline (P < 0.05). These results show that hemodilution performed with high-viscosity plasma expanders yields systemic arterial pressures and functional capillary densities that are significantly higher (P < 0.05) than those obtained with 6% Dextran 70, a fluid whose viscosity is similar to that of plasma. A condition for obtaining these results is that the oncotic pressure of the plasma expander be titrated to near normal, so that autotransfusion of fluid from the tissue into the vascular compartment does not reduce the effects of increasing plasma viscosity and increased shear stress on the microvascular wall.
Abciximab (ReoPro, Chimeric 7E3 Fab) Demonstrates Equivalent Affinity and Functional Blockade of Glycoprotein IIb/IIIa and α v β 3 Integrins (1998)

As an antagonist of not only GP IIb/IIIa but also alpha(v)beta3, abciximab may provide additional clinical benefit in preventing alpha(v)beta3-mediated effects such as thrombin generation, clot retraction, or smooth muscle cell migration and proliferation. Abciximab binds with equivalent affinity to both GP IIb/IIIa and alphavss3 and redistributes between the 2 integrin receptors in vitro. Abciximab has been previously shown to circulate on platelets for up to 2 weeks. Taken together, these findings suggest that abciximab may have the ability to inhibit both GP IIb/IIIa and alpha(v)beta3 for extended periods.
Advanced siRNA Designs Further Improve In Vivo Performance of GalNAc-siRNA Conjugates (2018)

Significant progress has been made in the advancement of RNAi therapeutics by combining a synthetic triantennary N-acetylgalactosamine ligand targeting the asialoglycoprotein receptor with chemically modified small interfering RNA (siRNA) designs, including the recently described Enhanced Stabilization Chemistry. This strategy has demonstrated robust RNAi-mediated gene silencing in liver after subcutaneous administration across species, including human. Here we demonstrate that substantial efficacy improvements can be achieved through further refinement of siRNA chemistry, optimizing the positioning of 2'-deoxy-2'-fluoro and 2'-O-methyl ribosugar modifications across both strands of the double-stranded siRNA duplex to enhance stability without compromising intrinsic RNAi activity. To achieve this, we employed an iterative screening approach across multiple siRNAs to arrive at advanced designs with low 2'-deoxy-2'-fluoro content that yield significantly improved potency and duration in preclinical species, including non-human primate. Liver exposure data indicate that the improvement in potency is predominantly due to increased metabolic stability of the siRNA conjugates.
Distance of Hydroxyl Functionality from the Quaternized Center Influence DNA Binding and in Vitro Gene Delivery Efficacies of Cationic Lipids with Hydroxyalkyl Headgroups (2004)

In vitro gene delivery efficacies of cationic amphiphiles 1-7 (Scheme 1) were measured by both the reporter gene expression assays in CHO, COS-1, HepG2, and MCF7 cells and by the whole cell histochemical X-gal staining of representative Chinese hamster ovary cells. Our results demonstrated that in vitro gene delivery efficiencies of cationic lipids with hydroxyalkyl headgroups are adversely affected by increased covalent distances between the hydroxyl functionality and the cationic centers. Findings in the DNase I protection experiments and transmission electron microscopic study support the notion that such compromised gene delivery efficacies may originate from poor lipid-DNA binding interactions and significantly increased lipoplex nanosizes.
Cactus protein degradation mediates Drosophila dorsal-ventral signaling. (1995)

Dorsal-ventral patterning in the Drosophila embryo relies on a signal transduction pathway that is similar to a signaling pathway leading to the activation of the mammalian transcription factor NF-kappa B. Stimulation of this Drosophila pathway on the ventral side of the embryo causes the nuclear translocation of Dorsal, the Drosophila NF-kappa B homolog. Cactus, like its mammalian homolog I kappa B, inhibits nuclear translocation by binding Dorsal and retaining it in the cytoplasm. We show that Cactus, like I kappa B, is rapidly degraded in response to signaling. More importantly, signal-dependent degradation of Cactus does not require the presence of Dorsal, indicating that Cactus degradation is a direct response to signaling, and that disruption of the Dorsal/Cactus complex is a secondary result of Cactus degradation. Mutant alleles of cactus that encode more stable forms of the protein block signaling, showing that efficient degradation is necessary for signaling. We find that Cactus protein stability is regulated by two independent processes that rely on different regions within the protein: signal-dependent degradation requires sequences in the amino terminus or ankyrin repeats, whereas signal-independent degradation of free Cactus requires the carboxy-terminal region of the protein that includes a PEST sequence.
<title>Novel surface plasmon resonance sensor based on single-mode optical fiber</title> (1997)

Surface plasmon resonance sensor based on resonant interaction between a guided mode of a single-mode optical fiber and a surface plasmon wave supported by a thin metal overlayer is presented. Two modes of operation of the sensor based on the measurement of changes in the fiber mode attenuation and on the measurement of changes in the wavelength at which the resonance occurs are described. Theoretical analysis of the proposed sensing structure based on the equivalent planar waveguide approach and the mode expansion and propagation method is carried out. It is shown that the operation range of the sensor may be tuned by a thin dielectric overlayer. Experimental results have shown that in both the modes of operation the sensor is capable of detecting changes in the refractive index of the sensed medium below 2 multiplied by 10<SUP>-5</SUP>.
Absolute light output of scintillators (1997)

The absolute light outputs of BGO, CsI(Tl) and some new Ce-doped crystals have been measured to an accuracy of about /spl plusmn/5% using calibrated XP2020Q photomultipliers and standard S3590.03 and S2740.03 photodiodes. The use of small crystals, 9 mm in diameter and 1 mm thick, reduces the corrections for imperfections in the light collection process and in the photoelectron collection by the photomultipliers. The measured light-output of 8500/spl plusmn/350 ph/MeV (photons/MeV) for the BGO crystals agree well with the earlier measurement done by Holl et al. (1988). The carried out study highlighted the importances of the spread in the published emission spectra of the crystals which seems to limit measurement accuracy. Finally, a simple comparative method of measuring light output to an accuracy of /spl plusmn/10%, is proposed using an uncalibrated XP2020 photomultiplier and a 1 mm thick BGO crystal as a standard.
Exposure of human osteosarcoma and bone marrow cells to tumour-targeted α-particles and γ-irradiation: analysis of cell survival and microdosimetry (2000)

High-LET targeted alpha-particle exposure killed osteosarcoma cells more effectively than bone marrow cells, although heterogeneous antigen expression among these tumour cells limited the magnitude of this effect.
Nomatic: Location by, for, and of crowds (2006)

In this paper we present a social and technical architecture which will enable the study of localization from the perspective of crowds. Our research agenda is to leverage new computing opportunities that arise when many people are simultaneously localizing themselves. By aggregating this and other types of context information we intend to develop a statistically powerful data set that can be used by urban planners, users and their software. This paper presents an end-to-end strategy, motivated with preliminary user studies, for lowering the social and technical barriers to sharing context information. The primary technology through which we motivate participation is an intelligent contextaware instant messaging client called Nomatic*Gaim. We investigate social barriers to participation with a small informal user study evaluating automatic privacy mechanisms which give people control over their context disclosure. We then analyze some preliminary data from an early deployment. Finally we show how leveraging these mass-collaborations could help to improve Nomatic*Gaim by allowing it to infer position to place mappings.
CAD-compatible high-speed CMOS/SIMOX technology using field-shield isolation for 1 M gate array (2002)

A specific 0.5 /spl mu/m CMOS/SIMOX technology was developed for a 1 M gate array/SOG (Sea Of Gates) using field-shield (FS) isolation to overcome a pending problem of source-to-drain breakdown voltage (BV ds) lowering. The ring oscillator fabricated on the FS isolated SOG gate array exhibited 1.7 times higher speed operation than that on a bulk-Si counterpart keeping the lower power consumption feature even at a relatively high drain voltage of 3 V.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>