939 research outputs found
IRX-2, a Novel Immunotherapeutic, Enhances Functions of Human Dendritic Cells
Background: In a recent phase II clinical trial for HNSCC patients, IRX-2, a cell-derived biologic, promoted T-cell infiltration into the tumor and prolonged overall survival. Mechanisms responsible for these IRX-2-mediated effects are unknown. We hypothesized that IRX-2 enhanced tumor antigen-(TA)-specific immunity by up-regulating functions of dendritic cells (DC). Methodology/Principal Findings: Monocyte-derived DC obtained from 18 HNSCC patients and 12 healthy donors were matured using IRX-2 or a mix of TNF-α, IL-1β and IL-6 ("conv. mix"). Multicolor flow cytometry was used to study the DC phenotype and antigen processing machinery (APM) component expression. ELISPOT and cytotoxicity assays were used to evaluate tumor-reactive cytotoxic T lymphocytes (CTL). IL-12p70 and IL-10 production by DC was measured by Luminex® and DC migration toward CCL21 was tested in transwell migration assays. IRX-2-matured DC functions were compared with those of conv. mix-matured DC. IRX-2-matured DC expressed higher levels (p<0.05) of CD11c, CD40, CCR7 as well as LMP2, TAP1, TAP2 and tapasin than conv. mix-matured DC. IRX-2-matured DC migrated significantly better towards CCL21, produced more IL-12p70 and had a higher IL12p70/IL-10 ratio than conv. mix-matured DC (p<0.05 for all). IRX-2-matured DC carried a higher density of tumor antigen-derived peptides, and CTL primed with these DC mediated higher cytotoxicity against tumor targets (p<0.05) compared to the conv. mix-matured DC. Conclusion: Excellent ability of IRX-2 to induce ex vivo DC maturation in HNSCC patients explains, in part, its clinical benefits and emphasizes its utility in ex vivo maturation of DC generated for therapy. © 2013 Schilling et al
Use of models for the environmental risk assessment of veterinary medicines in European aquaculture: current situation and future perspectives
Veterinary Medicinal Products (VMPs) are used in intensive aquaculture production to treat a wide range of bacterial and parasitic infestations. Their release into the environment poses concerns regarding their potential ecotoxicological risks to aquatic ecosystems, which need to be evaluated making use of appropriate Environmental Risk Assessment (ERA) schemes and models. This study presents an overview of the major aquaculture production systems in Europe, the VMPs most commonly used, and the environmental quality standards and regulatory procedures available for their ERA. Furthermore, it describes the state-of-the-art on the development of environmental models capable of assessing the fate, exposure, ecotoxicological effects and risks of VMPs in aquaculture production systems, and discusses their level of development and implementation within European aquaculture. This study shows that the use of environmental models in regulatory ERA is somewhat limited in many European countries. Major efforts have been dedicated to assess the fate and exposure of antiparasitic compounds in salmonid cage systems, particularly in Scotland, while models and scenarios for assessing dispersal of antimicrobials, in general, and antiparasitic compounds in the Mediterranean as well as in Scandinavian regions are less available. On the other hand, the use of ecological models for assessing the effects and risks of VMPs is almost absent. Recommendations are provided to improve the chemical exposure and effect assessments and the ecological realism of the modelling outcomes, paying special attention to the protection goals set for the regulatory ERA of VMPs in Europ
Topological Surface States Protected From Backscattering by Chiral Spin Texture
Topological insulators are a new class of insulators in which a bulk gap for
electronic excitations is generated by strong spin orbit coupling. These novel
materials are distinguished from ordinary insulators by the presence of gapless
metallic boundary states, akin to the chiral edge modes in quantum Hall
systems, but with unconventional spin textures. Recently, experiments and
theoretical efforts have provided strong evidence for both two- and
three-dimensional topological insulators and their novel edge and surface
states in semiconductor quantum well structures and several Bi-based compounds.
A key characteristic of these spin-textured boundary states is their
insensitivity to spin-independent scattering, which protects them from
backscattering and localization. These chiral states are potentially useful for
spin-based electronics, in which long spin coherence is critical, and also for
quantum computing applications, where topological protection can enable
fault-tolerant information processing. Here we use a scanning tunneling
microscope (STM) to visualize the gapless surface states of the
three-dimensional topological insulator BiSb and to examine their scattering
behavior from disorder caused by random alloying in this compound. Combining
STM and angle-resolved photoemission spectroscopy, we show that despite strong
atomic scale disorder, backscattering between states of opposite momentum and
opposite spin is absent. Our observation of spin-selective scattering
demonstrates that the chiral nature of these states protects the spin of the
carriers; they therefore have the potential to be used for coherent spin
transport in spintronic devices.Comment: to be appear in Nature on August 9, 200
Real-Time decision support using data mining to predict blood pressure critical events in intensive medicine patients
Patient blood pressure is an important vital signal to the physicians take a decision and to better understand the patient condition. In Intensive Care Units is possible monitoring the blood pressure due the fact of the patient being in continuous monitoring through bedside monitors and the use of sensors. The intensivist only have access to vital signs values when they look to the monitor or consult the values hourly collected. Most important is the sequence of the values collected, i.e., a set of highest or lowest values can signify a critical event and bring future complications to a patient as is Hypotension or Hypertension. This complications can leverage a set of dangerous diseases and side-effects. The main goal of this work is to predict the probability of a patient has a blood pressure critical event in the next hours by combining a set of patient data collected in real-time and using Data Mining classification techniques. As output the models indicate the probability (%) of a patient has a Blood Pressure Critical Event in the next hour. The achieved results showed to be very promising, presenting sensitivity around of 95%
Modulation of the <i>Neisseria gonorrhoeae </i>drug efflux conduit MtrE
We acknowledge funding through the Wellcome Trust Interdisciplinary Research Funds (grant WT097818MF), the Scottish Universities’ Physics Alliance (SUPA), Tenovus Tayside (grant T16/30) and the Tayside Charitable Trust. O.N.V. has been funded through a BBSRC CASE award (BB/J013072/1).Widespread antibiotic resistance, especially of Gram-negative bacteria, has become a severe concern for human health. Tripartite efflux pumps are one of the major contributors to resistance in Gram-negative pathogens, by efficiently expelling a broad spectrum of antibiotics from the organism. In Neisseria gonorrhoeae, one of the first bacteria for which pan-resistance has been reported, the most expressed efflux complex is MtrCDE. Here we present the electrophysiological characterisation of the outer membrane component MtrE and the membrane fusion protein MtrC, obtained by a combination of planar lipid bilayer recordings and in silico techniques. Our in vitro results show that MtrE can be regulated by periplasmic binding events and that the interaction between MtrE and MtrC is sufficient to stabilize this complex in an open state. In contrast to other efflux conduits, the open complex only displays a slight preference for cations. The maximum conductance we obtain in the in vitro recordings is comparable to that seen in our computational electrophysiology simulations conducted on the MtrE crystal structure, indicating that this state may reflect a physiologically relevant open conformation of MtrE. Our results suggest that the MtrC/E binding interface is an important modulator of MtrE function, which could potentially be targeted by new efflux inhibitors.Publisher PDFPeer reviewe
Hadronic Mass Moments in Inclusive Semileptonic B Meson Decays
We have measured the first and second moments of the hadronic mass-squared
distribution in B -> X_c l nu, for P(lepton) > 1.5 GeV/c. We find <M_X^2 -
M_D[Bar]^2> = 0.251 +- 0.066 GeV^2, )^2 > = 0.576 +- 0.170
GeV^4, where M_D[Bar] is the spin-averaged D meson mass.
From that first moment and the first moment of the photon energy spectrum in
b -> s gamma, we find the HQET parameter lambda_1 (MS[Bar], to order 1/M^3 and
beta_0 alpha_s^2) to be -0.24 +- 0.11 GeV^2. Using these first moments and the
B semileptonic width, and assuming parton-hadron duality, we obtain |V_cb| =
0.0404 +- 0.0013.Comment: 11 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLNS, submitted to PR
Observation of the Charmed Baryon at CLEO
The CLEO experiment at the CESR collider has used 13.7 fb of data to
search for the production of the (css-ground state) in
collisions at {\rm GeV}. The modes used to
study the are ,
, , , and
. We observe a signal of 40.49.0(stat) events
at a mass of 2694.62.6(stat)1.9(syst) {\rm MeV/}, for all modes
combined.Comment: 10 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLN
Observation of and
We have studied two-body charmless hadronic decays of mesons into the
final states phi K and phi K^*. Using 9.7 million pairs collected
with the CLEO II detector, we observe the decays B- -> phi K- and B0 -> phi K*0
with the following branching fractions: BR(B- -> phi K-)=(5.5 +2.1-1.8 +- 0.6)
x 10^{-6} and BR(B0 -> phi K*0)=(11.5 +4.5-3.7 +1.8-1.7) x 10^{-6}. We also see
evidence for the decays B0 -> phi K0 and B- -> phi K*-. However, since the
statistical significance is not overwhelming for these modes we determine upper
limits of <12.3 x 10^{-6} and <22.5 x 10^{-6} (90% C.L.) respectively.Comment: 9 pages postscript, also available through
http://w4.lns.cornell.edu/public/CLN
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