Randomly Evolving Idiotypic Networks: Structural Properties and Architecture

We consider a minimalistic dynamic model of the idiotypic network of B-lymphocytes. A network node represents a population of B-lymphocytes of the same specificity (idiotype), which is encoded by a bitstring. The links of the network connect nodes with complementary and nearly complementary bitstrings, allowing for a few mismatches. A node is occupied if a lymphocyte clone of the corresponding idiotype exists, otherwise it is empty. There is a continuous influx of new B-lymphocytes of random idiotype from the bone marrow. B-lymphocytes are stimulated by cross-linking their receptors with complementary structures. If there are too many complementary structures, steric hindrance prevents cross-linking. Stimulated cells proliferate and secrete antibodies of the same idiotype as their receptors, unstimulated lymphocytes die. Depending on few parameters, the autonomous system evolves randomly towards patterns of highly organized architecture, where the nodes can be classified into groups according to their statistical properties. We observe and describe analytically the building principles of these patterns, which allow to calculate number and size of the node groups and the number of links between them. The architecture of all patterns observed so far in simulations can be explained this way. A tool for real-time pattern identification is proposed.Comment: 19 pages, 15 figures, 4 table

A Two-Player Game of Life

We present a new extension of Conway's game of life for two players, which we call p2life. P2life allows one of two types of token, black or white, to inhabit a cell, and adds competitive elements into the birth and survival rules of the original game. We solve the mean-field equation for p2life and determine by simulation that the asymptotic density of p2life approaches 0.0362.Comment: 7 pages, 3 figure

Efficacy and Safety of Alirocumab as Add-on Therapy in High–Cardiovascular-Risk Patients With Hypercholesterolemia Not Adequately Controlled With Atorvastatin (20 or 40 mg) or Rosuvastatin (10 or 20 mg)::Design and Rationale of the ODYSSEY OPTIONS Studies

The phase 3 ODYSSEY OPTIONS studies (OPTIONS I, NCT01730040; OPTIONS II, NCT01730053) are multicenter, multinational, randomized, double-blind, active-comparator, 24-week studies evaluating the efficacy and safety of alirocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, as add-on therapy in ∼ 650 high-cardiovascular (CV)-risk patients whose low-density lipoprotein cholesterol (LDL-C) levels are ≥100 mg/dL or ≥70 mg/dL according to the CV-risk category, high and very high CV risk, respectively, with atorvastatin (20–40 mg/d) or rosuvastatin (10–20 mg/d). Patients are randomized to receive alirocumab 75 mg via a single, subcutaneous, 1-mL injection by prefilled pen every 2 weeks (Q2W) as add-on therapy to atorvastatin (20–40 mg) or rosuvastatin (10–20 mg); or to receive ezetimibe 10 mg/d as add-on therapy to statin; or to receive statin up-titration; or to switch from atorvastatin to rosuvastatin (OPTIONS I only). At week 12, based on week 8 LDL-C levels, the alirocumab dose may be increased from 75 mg to 150 mg Q2W if LDL-C levels remain ≥100 mg/dL or ≥70 mg/dL in patients with high or very high CV risk, respectively. The primary efficacy endpoint in both studies is difference in percent change in calculated LDL-C from baseline to week 24 in the alirocumab vs control arms. The studies may provide guidance to inform clinical decision-making when patients with CV risk require additional lipid-lowering therapy to further reduce LDL-C levels. The flexibility of the alirocumab dosing regimen allows for individualized therapy based on the degree of LDL-C reduction required to achieve the desired LDL-C level

Predictive feedback control and Fitts' law

Fitts’ law is a well established empirical formula, known for encapsulating the “speed-accuracy trade-off”. For discrete, manual movements from a starting location to a target, Fitts’ law relates movement duration to the distance moved and target size. The widespread empirical success of the formula is suggestive of underlying principles of human movement control. There have been previous attempts to relate Fitts’ law to engineering-type control hypotheses and it has been shown that the law is exactly consistent with the closed-loop step-response of a time-delayed, first-order system. Assuming only the operation of closed-loop feedback, either continuous or intermittent, this paper asks whether such feedback should be predictive or not predictive to be consistent with Fitts law. Since Fitts’ law is equivalent to a time delay separated from a first-order system, known control theory implies that the controller must be predictive. A predictive controller moves the time-delay outside the feedback loop such that the closed-loop response can be separated into a time delay and rational function whereas a non- predictive controller retains a state delay within feedback loop which is not consistent with Fitts’ law. Using sufficient parameters, a high-order non-predictive controller could approximately reproduce Fitts’ law. However, such high-order, “non-parametric” controllers are essentially empirical in nature, without physical meaning, and therefore are conceptually inferior to the predictive controller. It is a new insight that using closed-loop feedback, prediction is required to physically explain Fitts’ law. The implication is that prediction is an inherent part of the “speed-accuracy trade-off”

Study of Non-Standard Neutrino Interactions with Atmospheric Neutrino Data in Super-Kamiokande I and II

In this paper we study non-standard neutrino interactions as an example of physics beyond the standard model using atmospheric neutrino data collected during the Super-Kamiokande I(1996-2001) and II(2003-2005) periods. We focus on flavor-changing-neutral-currents (FCNC), which allow neutrino flavor transitions via neutral current interactions, and effects which violate lepton non-universality (NU) and give rise to different neutral-current interaction-amplitudes for different neutrino flavors. We obtain a limit on the FCNC coupling parameter, varepsilon_{mu tau}, |varepsilon_{mu tau}|<1.1 x 10^{-2} at 90%C.L. and various constraints on other FCNC parameters as a function of the NU coupling, varepsilon_{e e}. We find no evidence of non-standard neutrino interactions in the Super-Kamiokande atmospheric data.Comment: 12 Pages, 14 figures. To be submitted to Phys. Rev.

Solar neutrino results in Super-Kamiokande-III

The results of the third phase of the Super-Kamiokande solar neutrino measurement are presented and compared to the first and second phase results. With improved detector calibrations, a full detector simulation, and improved analysis methods, the systematic uncertainty on the total neutrino flux is estimated to be ?2.1%, which is about two thirds of the systematic uncertainty for the first phase of Super-Kamiokande. The observed 8B solar flux in the 5.0 to 20 MeV total electron energy region is 2.32+/-0.04 (stat.)+/-0.05 (sys.) *10^6 cm^-2sec^-1, in agreement with previous measurements. A combined oscillation analysis is carried out using SK-I, II, and III data, and the results are also combined with the results of other solar neutrino experiments. The best-fit oscillation parameters are obtained to be sin^2 {\theta}12 = 0.30+0.02-0.01(tan^2 {\theta}12 = 0.42+0.04 -0.02) and {\Delta}m2_21 = 6.2+1.1-1.9 *10^-5eV^2. Combined with KamLAND results, the best-fit oscillation parameters are found to be sin^2 {\theta}12 = 0.31+/-0.01(tan^2 {\theta}12 = 0.44+/-0.03) and {\Delta}m2_21 = 7.6?0.2*10^-5eV^2 . The 8B neutrino flux obtained from global solar neutrino experiments is 5.3+/-0.2(stat.+sys.)*10^6cm^-2s^-1, while the 8B flux becomes 5.1+/-0.1(stat.+sys.)*10^6cm^-2s^-1 by adding KamLAND result. In a three-flavor analysis combining all solar neutrino experiments, the upper limit of sin^2 {\theta}13 is 0.060 at 95% C.L.. After combination with KamLAND results, the upper limit of sin^2 {\theta}13 is found to be 0.059 at 95% C.L..Comment: 19 pages, 33 figures in the main text. The appendix section on errata is added in v

Atmospheric neutrino oscillation analysis with sub-leading effects in Super-Kamiokande I, II, and III

We present a search for non-zero theta_{13} and deviations of sin^2 theta_{23} from 0.5 in the oscillations of atmospheric neutrino data from Super-Kamiokande -I, -II, and -III. No distortions of the neutrino flux consistent with non-zero theta_{13} are found and both neutrino mass hierarchy hypotheses are in agreement with the data. The data are best fit at Delta m^2 = 2.1 x 10^-3 eV^2, sin^2 theta_{13} = 0.0, and sin^2 theta_{23} =0.5. In the normal (inverted) hierarchy theta_{13} and Delta m^2 are constrained at the one-dimensional 90% C.L. to sin^2 theta_{13} < 0.04 (0.09) and 1.9 (1.7) x 10^-3 < Delta m^2 < 2.6 (2.7) x 10^-3 eV^2. The atmospheric mixing angle is within 0.407 <= sin^2 theta_{23} <= 0.583 at 90% C.L.Comment: 17 Pages, 14 figures. To be submitted to Phys. Rev. D Minor update to text after referee comments. Figures modified for better grayscale printing

Search for Nucleon Decay into Charged Anti-lepton plus Meson in Super-Kamiokande I and II

Searches for a nucleon decay into a charged anti-lepton (e^+ or {\mu}^+) plus a light meson ({\pi}^0, {\pi}^-, {\eta}, {\rho}^0, {\rho}^-, {\omega}) were performed using the Super-Kamiokande I and II data. Twelve nucleon decay modes were searched for. The total exposure is 140.9 kiloton \cdot years, which includes a 91.7 kiloton \cdot year exposure (1489.2 live days) of Super-Kamiokande-I and a 49.2 kiloton \cdot year exposure (798.6 live days) of Super-Kamiokande-II. The number of candidate events in the data was consistent with the atmospheric neutrino background expectation. No significant evidence for a nucleon decay was observed in the data. Thus, lower limits on the nucleon partial lifetime at 90% confidence level were obtained. The limits range from 3.6 \times 10^31 to 8.2 \times 10^33 years, depending on the decay modes.Comment: 25 pages, 18 figure