5,413 research outputs found
Armed and accurate: engineering cytotoxic T cells for eradication of leukemia
Translational medicine depends on a rapid and efficient exchange of results between the bench and the bedside. A recent example from the field of cancer immunotherapy highlights the essential nature of this exchange. Methods have been developed to convert a patient's cytotoxic T cells into efficient and specific killers of cancer cells in patients with leukemia. By using recombinant DNA techniques, a lentiviral vector was constructed to express chimeric antigen receptors in cytotoxic T cells from patients with advanced chronic lymphocytic leukemia. The purpose of the chimeric receptors was to direct the cytotoxic T cell activity against cells causing the cancer. The effect of infusing the engineered T cells back into the cancer patients was tested in a Phase I trial at the University of Pennsylvania, and the initial results were described in two articles from the research team of Dr. Carl June. The remarkable success of this trial should energize further applications of biotechnology in the development of new cancer immunotherapies
First-principles kinetic Monte Carlo simulations for heterogeneous catalysis, applied to the CO oxidation at RuO2(110)
We describe a first-principles statistical mechanics approach enabling us to
simulate the steady-state situation of heterogeneous catalysis. In a first step
density-functional theory together with transition-state theory is employed to
obtain the energetics of all relevant elementary processes. Subsequently the
statistical mechanics problem is solved by the kinetic Monte Carlo method,
which fully accounts for the correlations, fluctuations, and spatial
distributions of the chemicals at the surface of the catalyst under
steady-state conditions. Applying this approach to the catalytic oxidation of
CO at RuO2(110), we determine the surface atomic structure and composition in
reactive environments ranging from ultra-high vacuum (UHV) to technologically
relevant conditions, i.e. up to pressures of several atmospheres and elevated
temperatures. We also compute the CO2 formation rates (turnover frequencies).
The results are in quantitative agreement with all existing experimental data.
We find that the high catalytic activity of this system is intimately connected
with a disordered, dynamic surface ``phase'' with significant compositional
fluctuations. In this active state the catalytic function results from a
self-regulating interplay of several elementary processes.Comment: 18 pages including 9 figures; related publications can be found at
http://www.fhi-berlin.mpg.de/th/th.htm
Bounds for State Degeneracies in 2D Conformal Field Theory
In this note we explore the application of modular invariance in
2-dimensional CFT to derive universal bounds for quantities describing certain
state degeneracies, such as the thermodynamic entropy, or the number of
marginal operators. We show that the entropy at inverse temperature 2 pi
satisfies a universal lower bound, and we enumerate the principal obstacles to
deriving upper bounds on entropies or quantum mechanical degeneracies for fully
general CFTs. We then restrict our attention to infrared stable CFT with
moderately low central charge, in addition to the usual assumptions of modular
invariance, unitarity and discrete operator spectrum. For CFT in the range
c_left + c_right < 48 with no relevant operators, we are able to prove an upper
bound on the thermodynamic entropy at inverse temperature 2 pi. Under the same
conditions we also prove that a CFT can have a number of marginal deformations
no greater than ((c_left + c_right) / (48 - c_left - c_right)) e^(4 Pi) - 2.Comment: 23 pages, LaTeX, minor change
Duration of red blood cell storage is associated with increased incidence of deep vein thrombosis and in hospital mortality in patients with traumatic injuries
Three geographically separate domestications of Asian rice
Domesticated rice (Oryza sativa L.) accompanied the dawn of Asian civilization(1) and has become one of world's staple crops. From archaeological and genetic evidence various contradictory scenarios for the origin of different varieties of cultivated rice have been proposed, the most recent based on a single domestication(2,3). By examining the footprints of selection in the genomes of different cultivated rice types, we show that there were three independent domestications in different parts of Asia. We identify wild populations in southern China and the Yangtze valley as the source of the japonica gene pool, and populations in Indochina and the Brahmaputra valley as the source of the indica gene pool. We reveal a hitherto unrecognized origin for the aus variety in central India or Bangladesh. We also conclude that aromatic rice is a result of a hybridization between japonica and aus, and that the tropical and temperate versions of japonica are later adaptations of one crop. Our conclusions are in accord with archaeological evidence that suggests widespread origins of rice cultivation(1,4). We therefore anticipate that our results will stimulate a more productive collaboration between genetic and archaeological studies of rice domestication, and guide utilization of genetic resources in breeding programmes aimed at crop improvement.European Research Council [339941]info:eu-repo/semantics/publishedVersio
Comparison of total ankle replacement and ankle arthrodesis in patients with haemophilia using gait analysis : two case reports
BACKGROUND: Severe hemophilia is an inherited, lifelong bleeding disorder characterized by spontaneous bleeding, which results in painful joint deformities. Currently two surgical treatments are available to treat haemophilia-related ankle joint destruction: ankle arthrodesis and total ankle replacement. The aim of the present study was to compare these two surgical procedures in haemophiliac subjects. CASE PRESENTATION: Kinematic and dynamic parameters were quantified using a three-dimensional gait-analysis system in two similar clinical cases. In Caucasian case 1, ankle arthrodesis was chosen because of a kinematic ankle flexion defect and lack of dynamic power regeneration. The defect in energy absorption was compensated for by the contralateral side. Total ankle replacement in Caucasian case 2 allowed sparing the ipsilateral knee (maximum 0.27 preoperatively vs. 0.71 W/kg postoperatively) and hip joints powers (maximum 0.43 preoperatively vs. 1.25 W/kg postoperatively) because of the small ankle dorsiflexion motion. CONCLUSIONS: Total ankle replacement is recommended for haemophiliac patients who present with a preserved ankle range of motion
Algorithm for the treatment of type 2 diabetes: a position statement of Brazilian Diabetes Society
The Brazilian Diabetes Society is starting an innovative project of quantitative assessment of medical arguments of and implementing a new way of elaborating SBD Position Statements. The final aim of this particular project is to propose a new Brazilian algorithm for the treatment of type 2 diabetes, based on the opinions of endocrinologists surveyed from a poll conducted on the Brazilian Diabetes Society website regarding the latest algorithm proposed by American Diabetes Association /European Association for the Study of Diabetes, published in January 2009
Nonlinear modeling of venous leg ulcer healing rates
<p>Abstract</p> <p>Background</p> <p>The purpose of this manuscript was to determine whether the change in wound surface area over time could be described through nonlinear mathematics.</p> <p>Methods</p> <p>We studied 3,588 serial wound tracings of 338 venous leg ulcers (VLUs) that had been followed during a controlled, prospective, randomized trial of two topical wound treatments.</p> <p>Results</p> <p>A majority (72%) of VLUs exhibited surface area reduction via an exponential decay model, particularly during the early stages of healing. These results were consistent with the mechanics of wound contraction and epithelial cell proliferation, supported by the higher frequency at which exponential surface area reduction associated with full wound closure (35% of wounds that fit the exponential model healed vs. 21% of wounds that did not fit the exponential model completely healed during the study period, p = 0.018). Goodness-of-fit statistics suggested that much of the individual variation in healing could be described as nonlinear variation from the exponential model.</p> <p>Conclusion</p> <p>We believe that parameter estimates from a mathematical model may provide a more accurate quantification of wound healing rates, and that similar models may someday reach routine use in comparing the efficacy of various treatments in routine practice and in product registration trials.</p
Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection
Abstract: Bcl-2 family proteins including the pro-apoptotic BH3-only proteins are central regulators of apoptotic cell death. Here we show by a focused siRNA miniscreen that the synergistic action of the BH3-only proteins Bim and Bmf is required for apoptosis induced by infection with Neisseria gonorrhoeae (Ngo). While Bim and Bmf were associated with the cytoskeleton of healthy cells, they both were released upon Ngo infection. Loss of Bim and Bmf from the cytoskeleton fraction required the activation of Jun-N-terminal kinase-1 (JNK-1), which in turn depended on Rac-1. Depletion and inhibition of Rac-1, JNK-1, Bim, or Bmf prevented the activation of Bak and Bax and the subsequent activation of caspases. Apoptosis could be reconstituted in Bim-depleted and Bmf-depleted cells by additional silencing of antiapoptotic Mcl-1 and Bcl-XL, respectively. Our data indicate a synergistic role for both cytoskeletal-associated BH3-only proteins, Bim, and Bmf, in an apoptotic pathway leading to the clearance of Ngo-infected cells. Author Summary: A variety of physiological death signals, as well as pathological insults, trigger apoptosis, a genetically programmed form of cell death. Pathogens often induce host cell apoptosis to establish a successful infection. Neisseria gonorrhoeae (Ngo), the etiological agent of the sexually transmitted disease gonorrhoea, is a highly adapted obligate human-specific pathogen and has been shown to induce apoptosis in infected cells. Here we unveil the molecular mechanisms leading to apoptosis of infected cells. We show that Ngo-mediated apoptosis requires a special subset of proapoptotic proteins from the group of BH3-only proteins. BH3-only proteins act as stress sensors to translate toxic environmental signals to the initiation of apoptosis. In a siRNA-based miniscreen, we found Bim and Bmf, BH3-only proteins associated with the cytoskeleton, necessary to induce host cell apoptosis upon infection. Bim and Bmf inactivated different inhibitors of apoptosis and thereby induced cell death in response to infection. Our data unveil a novel pathway of infection-induced apoptosis that enhances our understanding of the mechanism by which BH3-only proteins control apoptotic cell death
The effective action of D6-branes in N=1 type IIA orientifolds
We use a Kaluza-Klein reduction to compute the low-energy effective action
for the massless modes of a spacetime-filling D6-brane wrapped on a special
Lagrangian 3-cycle of a type IIA Calabi-Yau orientifold. The modifications to
the characteristic data of the N=1 bulk orientifold theory in the presence of a
D6-brane are analysed by studying the underlying Type IIA supergravity coupled
to the brane worldvolume in the democratic formulation and performing a
detailed dualisation procedure. The N=1 chiral coordinates are found to be in
agreement with expectations from mirror symmetry. We work out the Kahler
potential for the chiral superfields as well as the gauge kinetic functions for
the bulk and the brane gauge multiplets including the kinetic mixing between
the two. The scalar potential resulting from the dualisation procedure can be
formally interpreted in terms of a superpotential. Finally, the gauging of the
Peccei-Quinn shift symmetries of the complex structure multiplets reproduces
the D-term potential enforcing the calibration condition for special Lagrangian
3-cycles.Comment: 48 pages, v2: typos corrected, references adde
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