Effectors of hemoglobin. Separation of allosteric and affinity factors

The relative contributions of the allosteric and affinity factors toward the change in p50 have been calculated for a series of effectors of hemoglobin (Hb). Shifts in the ligand affinity of deoxy Hb and the values for 50% ligand saturation (p50) were obtained from oxygen equilibrium data. Because the high-affinity parameters (liganded conformation) are poorly determined from the equilibrium curves, they were determined from kinetic measurements of the association and dissociation rates with CO as ligand. The CO on-rates were obtained by flash photolysis measurements. The off-rates were determined from the rate of oxidation of HbCO by ferricyanide, or by replacement of CO with NO. The partition function of fully liganded hemoglobin for oxygen and CO is only slightly changed by the effectors. Measurements were made in the presence of the effectors 2,3-diphosphoglycerate (DPG), inositol hexakisphosphate (IHP), bezafibrate (Bzf), and two recently synthesized derivatives of Bzf (LR16 and L35). Values of p50 change by over a factor of 60; the on-rates decrease by nearly a factor of 8, with little change in the off-rates for the liganded conformation. The data indicate that both allosteric and affinity parameters are changed by the effectors; the changes in ligand affinity represent the larger contribution toward shifts in p50

Efficient Model Learning for Human-Robot Collaborative Tasks

We present a framework for learning human user models from joint-action demonstrations that enables the robot to compute a robust policy for a collaborative task with a human. The learning takes place completely automatically, without any human intervention. First, we describe the clustering of demonstrated action sequences into different human types using an unsupervised learning algorithm. These demonstrated sequences are also used by the robot to learn a reward function that is representative for each type, through the employment of an inverse reinforcement learning algorithm. The learned model is then used as part of a Mixed Observability Markov Decision Process formulation, wherein the human type is a partially observable variable. With this framework, we can infer, either offline or online, the human type of a new user that was not included in the training set, and can compute a policy for the robot that will be aligned to the preference of this new user and will be robust to deviations of the human actions from prior demonstrations. Finally we validate the approach using data collected in human subject experiments, and conduct proof-of-concept demonstrations in which a person performs a collaborative task with a small industrial robot

Composição racial e a avaliação da reação intradérmica de Montenegro em portadores da leishmaniose cutâneo-mucosa

Em um estudo retrospectivo, indivíduos com a forma mucosa da leishmaniose foram pareados (sexo, idade e ocupação) a outros pacientes com a forma cutânea em atividade, não demonstrando-se diferença significante da freqüência nos grupos raciais. Do mesmo modo, o teste intradérmico de Montenegro não se mostrou diferente nos diversos grupos raciais, entre os 96 pares de pacientes estudados. Uma maior enduração foi observada em pacientes com o acometimento mucoso quando comparado aos cutâneos. _______________________________________________________________________________________ ABSTRACTIn a retrospective study patients with mucosal leishmaniasis were paired (as regards age sex and occupation) with patients with active cutaneous disease. No signijicant racial dijference could be detected. In the same way the Montenegro cutaneous reaction was not different in 96pairs ofpatients studied as regards different racial groupings. A larger indurated area was observed in patients with mucosal leishmaniasis compared with the cutaneous form

Two-Stage Priming of Allogeneic Natural Killer Cells for the Treatment of Patients with Acute Myeloid Leukemia: A Phase I Trial

Human Natural Killer (NK) cells require at least two signals to trigger tumor cell lysis. Absence of ligands providing either signal 1 or 2 provides NK resistance. We manufactured a lysate of a tumour cell line which provides signal 1 to resting NK cells without signal 2. The tumor-primed NK cells (TpNK) lyse NK resistant Acute Myeloid Leukemia (AML) blasts expressing signal 2 ligands. We conducted a clinical trial to determine the toxicity of TpNK cell infusions from haploidentical donors. 15 patients with high risk AML were screened, 13 enrolled and 7 patients treated. The remaining 6 either failed to respond to re-induction chemotherapy or the donor refused to undergo peripheral blood apheresis. The conditioning consisted of fludarabine and total body irradiation. This was the first UK trial of a cell therapy regulated as a medicine. The complexity of Good Clinical Practice compliance was underestimated and led to failures requiring retrospective independent data review. The lessons learned are an important aspect of this report. There was no evidence of infusional toxicity. Profound myelosuppression was seen in the majority (median neutrophil recovery day 55). At six months follow-up, three patients treated in Complete Remission (CR) remained in remission, one patient infused in Partial Remission had achieved CR1, two had relapsed and one had died. One year post-treatment one patient remained in CR. Four patients remained in CR after treatment for longer than their most recent previous CR. During the 2 year follow-up six of seven patients died; median overall survival was 400 days post infusion (range 141–910). This is the first clinical trial of an NK therapy in the absence of IL-2 or other cytokine support. The HLA-mismatched NK cells survived and expanded in vivo without on-going host immunosuppression and appeared to exert an anti-leukemia effect in 4/7 patients treated

Chaotic maps and flows: Exact Riemann-Siegel lookalike for spectral fluctuations

To treat the spectral statistics of quantum maps and flows that are fully chaotic classically, we use the rigorous Riemann-Siegel lookalike available for the spectral determinant of unitary time evolution operators $F$. Concentrating on dynamics without time reversal invariance we get the exact two-point correlator of the spectral density for finite dimension $N$ of the matrix representative of $F$, as phenomenologically given by random matrix theory. In the limit $N\to\infty$ the correlator of the Gaussian unitary ensemble is recovered. Previously conjectured cancellations of contributions of pseudo-orbits with periods beyond half the Heisenberg time are shown to be implied by the Riemann-Siegel lookalike

Insights into the Development and Evolution of Exaggerated Traits Using \u3ci\u3e De Novo \u3c/i\u3e Transcriptomes of Two Species of Horned Scarab Beetles

Scarab beetles exhibit an astonishing variety of rigid exo-skeletal outgrowths, known as ‘‘horns’’. These traits are often sexually dimorphic and vary dramatically across species in size, shape, location, and allometry with body size. In many species, the horn exhibits disproportionate growth resulting in an exaggerated allometric relationship with body size, as compared to other traits, such as wings, that grow proportionately with body size. Depending on the species, the smallest males either do not produce a horn at all, or they produce a disproportionately small horn for their body size. While the diversity of horn shapes and their behavioural ecology have been reasonably well studied, we know far less about the proximate mechanisms that regulate horn growth. Thus, using 454 pyrosequencing, we generated transcriptome profiles, during horn growth and development, in two different scarab beetle species: the Asian rhinoceros beetle, Trypoxylus dichotomus, and the dung beetle, Onthophagus nigriventris. We obtained over half a million reads for each species that were assembled into over 6,000 and 16,000 contigs respectively. We combined these data with previously published studies to look for signatures of molecular evolution. We found a small subset of genes with horn-biased expression showing evidence for recent positive selection, as is expected with sexual selection on horn size. We also found evidence of relaxed selection present in genes that demonstrated biased expression between horned and horn-less morphs, consistent with the theory of developmental decoupling of phenotypically plastic traits

Tunneling and the Band Structure of Chaotic Systems

We compute the dispersion laws of chaotic periodic systems using the semiclassical periodic orbit theory to approximate the trace of the powers of the evolution operator. Aside from the usual real trajectories, we also include complex orbits. These turn out to be fundamental for a proper description of the band structure since they incorporate conduction processes through tunneling mechanisms. The results obtained, illustrated with the kicked-Harper model, are in excellent agreement with numerical simulations, even in the extreme quantum regime.Comment: 11 pages, Latex, figures on request to the author (to be sent by fax

A Lovelock black hole bestiary

We revisit the study of (A)dS black holes in Lovelock theories. We present a new tool that allows to attack this problem in full generality. In analyzing maximally symmetric Lovelock black holes with non-planar horizon topologies many distinctive and interesting features are observed. Among them, the existence of maximally symmetric vacua do not supporting black holes in vast regions of the space of gravitational couplings, multi-horizon black holes, and branches of solutions that suggest the existence of a rich diagram of phase transitions. The appearance of naked singularities seems unavoidable in some cases, raising the question about the fate of the cosmic censorship conjecture in these theories. There is a preferred branch of solutions for planar black holes, as well as non-planar black holes with high enough mass or temperature. Our study clarifies the role of all branches of solutions, including asymptotically dS black holes, and whether they should be considered when studying these theories in the context of AdS/CFT.Comment: 40 pages, 16 figures; v2: references added and minor amendments; v3: title changed to improve its accuracy and general reorganization of the results to ameliorate their presentatio

Quantum Chaotic Dynamics and Random Polynomials

We investigate the distribution of roots of polynomials of high degree with random coefficients which, among others, appear naturally in the context of "quantum chaotic dynamics". It is shown that under quite general conditions their roots tend to concentrate near the unit circle in the complex plane. In order to further increase this tendency, we study in detail the particular case of self-inversive random polynomials and show that for them a finite portion of all roots lies exactly on the unit circle. Correlation functions of these roots are also computed analytically, and compared to the correlations of eigenvalues of random matrices. The problem of ergodicity of chaotic wave-functions is also considered. For that purpose we introduce a family of random polynomials whose roots spread uniformly over phase space. While these results are consistent with random matrix theory predictions, they provide a new and different insight into the problem of quantum ergodicity. Special attention is devoted all over the paper to the role of symmetries in the distribution of roots of random polynomials.Comment: 33 pages, Latex, 6 Figures not included (a copy of them can be requested at [email protected]); to appear in Journal of Statistical Physic

the effect of different selenium sources during the finishing phase on beef quality

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