Implications of laws of software evolution on continuing successful use of COTS software

However completely specified, integration of COTS software into real world systems makes it of type E even though, were it to be fully and absolutely specified, it would satisfy the definition of an S-type system. Thus, the laws of software evolution that apply to E-type systems are also relevant in the COTS context. This paper examines the wider implications of this fact and, in particular, that such systems must undergo continuing evolution. Managerial implications of the laws of software evolution in the context of COTS are also briefly highlighted

Continuous-mode 448 kHz capacitive resistive monopolar radiofrequency induces greater deep blood flow changes compared to pulsed mode shortwave: a crossover study in healthy adults

This document is the Accepted Manuscript version of the following article: Binoy Kumaran, Anthony Herbland and Tim Watson, ‘Continuous-mode 448 kHz capacitive resistive monopolar radiofrequency induces greater deep blood flow changes compared to pulsed mode shortwave: a crossover study in healthy adults’, European Journal of Physiotheraphy, first published online 20 April 2017. The version of record is available online at doi: http://dx.doi.org/10.1080/21679169.2017.1316310. © 2017 Informa UK Limited, trading as Taylor & Francis Group.Aims: Radiofrequency-based electrophysical agents (EPAs) have been used in therapy practice over several decades (e.g. shortwave therapies). Currently, there is insufficient evidence supporting such EPAs operating below shortwave frequencies. This laboratory-based study investigated the deep physiological effects of 448 kHz capacitive resistive monopolar radiofrequency (CRMRF) and compared them to pulsed shortwave therapy (PSWT). Methods: In a randomized crossover study, 17 healthy volunteers initially received four treatment conditions: high, low and placebo dose conditions receiving 15-min CRMRF treatment and a control condition receiving no intervention. Fifteen participants additionally received high-dose PSWT as fifth condition, for comparison. Pre- and post-treatment measurements of deep blood flow and tissue extensibility were obtained using Doppler ultrasound and sonoelastography. Group data were compared using analysis of variance model. Statistical significance was set at p ≤ .05, 0.8 power, and 95% confidence interval. Results: Significant increases in volume and intensity of deep blood flow were obtained with CRMRF over placebo, control (p = .003) and PSWT (p < .001). No significant changes in blood flow velocity or tissue extensibility were noted for any condition. Conclusions: Deep blood flow changes with CRMRF were more pronounced than that with PSWT, placebo or control. Potential greater therapeutic benefits need to be confirmed with comparative clinical studies.Peer reviewe

Spin qubits with electrically gated polyoxometalate molecules

Spin qubits offer one of the most promising routes to the implementation of quantum computers. Very recent results in semiconductor quantum dots show that electrically-controlled gating schemes are particularly well-suited for the realization of a universal set of quantum logical gates. Scalability to a larger number of qubits, however, remains an issue for such semiconductor quantum dots. In contrast, a chemical bottom-up approach allows one to produce identical units in which localized spins represent the qubits. Molecular magnetism has produced a wide range of systems with tailored properties, but molecules permitting electrical gating have been lacking. Here we propose to use the polyoxometalate [PMo12O40(VO)2]q-, where two localized spins-1/2 can be coupled through the electrons of the central core. Via electrical manipulation of the molecular redox potential, the charge of the core can be changed. With this setup, two-qubit gates and qubit readout can be implemented.Comment: 9 pages, 6 figures, to appear in Nature Nanotechnolog

Altruism can proliferate through group/kin selection despite high random gene flow

The ways in which natural selection can allow the proliferation of cooperative behavior have long been seen as a central problem in evolutionary biology. Most of the literature has focused on interactions between pairs of individuals and on linear public goods games. This emphasis led to the conclusion that even modest levels of migration would pose a serious problem to the spread of altruism in group structured populations. Here we challenge this conclusion, by analyzing evolution in a framework which allows for complex group interactions and random migration among groups. We conclude that contingent forms of strong altruism can spread when rare under realistic group sizes and levels of migration. Our analysis combines group-centric and gene-centric perspectives, allows for arbitrary strength of selection, and leads to extensions of Hamilton's rule for the spread of altruistic alleles, applicable under broad conditions.Comment: 5 pages, 2 figures. Supplementary material with 50 pages and 26 figure

Estimating magnetic filling factors from Zeeman-Doppler magnetograms

This is the author accepted manuscript. The final version is available from American Astronomical Society via the DOI in this record.Low-mass stars are known to have magnetic fields that are believed to be of dynamo origin. Two complementary techniques are principally used to characterise them. Zeeman-Doppler imaging (ZDI) can determine the geometry of the large-scale magnetic field while Zeeman broadening can assess the total unsigned flux including that associated with small-scale structures such as spots. In this work, we study a sample of stars that have been previously mapped with ZDI. We show that the average unsigned magnetic flux follows an activity-rotation relation separating into saturated and unsaturated regimes. We also compare the average photospheric magnetic flux recovered by ZDI, hBV i, with that recovered by Zeeman broadening studies, hBI i. In line with previous studies, hBV i ranges from a few % to ∼20% of hBI i. We show that a power law relationship between hBV i and hBI i exists and that ZDI recovers a larger fraction of the magnetic flux in more active stars. Using this relation, we improve on previous attempts to estimate filling factors, i.e. the fraction of the stellar surface covered with magnetic field, for stars mapped only with ZDI. Our estimated filling factors follow the well-known activity-rotation relation which is in agreement with filling factors obtained directly from Zeeman broadening studies. We discuss the possible implications of these results for flux tube expansion above the stellar surface and stellar wind models.European CommissionAustrian Space Application Programm

Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.

Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed

A differential equation for a class of discrete lifetime distributions with an application in reliability: A demonstration of the utility of computer algebra

YesIt is shown that the probability generating function of a lifetime random variable T on a finite lattice with polynomial failure rate satisfies a certain differential equation. The interrelationship with Markov chain theory is highlighted. The differential equation gives rise to a system of differential equations which, when inverted, can be used in the limit to express the polynomial coefficients in terms of the factorial moments of T. This then can be used to estimate the polynomial coefficients. Some special cases are worked through symbolically using Computer Algebra. A simulation study is used to validate the approach and to explore its potential in the reliability context

Profiles of Human Serum Antibody Responses Elicited by Three Leading HIV Vaccines Focusing on the Induction of Env-Specific Antibodies

In the current report, we compared the specificities of antibody responses in sera from volunteers enrolled in three US NIH-supported HIV vaccine trials using different immunization regimens. HIV-1 Env-specific binding antibody, neutralizing antibody, antibody-dependent cell-mediated cytotoxicity (ADCC), and profiles of antibody specificity were analyzed for human immune sera collected from vaccinees enrolled in the NIH HIV Vaccine Trial Network (HVTN) Study #041 (recombinant protein alone), HVTN Study #203 (poxviral vector prime-protein boost), and the DP6-001 study (DNA prime-protein boost). Vaccinees from HVTN Study #041 had the highest neutralizing antibody activities against the sensitive virus along with the highest binding antibody responses, particularly those directed toward the V3 loop. DP6-001 sera showed a higher frequency of positive neutralizing antibody activities against more resistant viral isolate with a significantly higher CD4 binding site (CD4bs) antibody response compared to both HVTN studies #041 and #203. No differences were found in CD4-induced (CD4i) antibody responses, ADCC activity, or complement activation by Env-specific antibody among these sera. Given recent renewed interest in realizing the importance of antibody responses for next generation HIV vaccine development, different antibody profiles shown in the current report, based on the analysis of a wide range of antibody parameters, provide critical biomarker information for the selection of HIV vaccines for more advanced human studies and, in particular, those that can elicit antibodies targeting conformational-sensitive and functionally conserved epitopes

An insight into the suspected HbA2' cases detected by high performance liquid chromatography in Pakistan

Background:Hemoglobin A2\u27 (delta 16 Gly Arg) is globally the commonest delta chain variant of HbA2. It is clinically and hematologically silent but its sole importance lies in the underestimation of HbA2 quantity during the workup of beta-thalassaemia trait. High performance liquid chromatography (HPLC) identifies it as a small S-window peak with a mean retention time of 4.59 0.03 minutes. This study aims at describing the frequency of detection of HbA2\u27 by HPLC in Pakistan and its confirmation at a molecular level. Potential HbA2\u27 cases were identified by a retrospective review of 10186 HPLC chromatograms in year 2006. Prospective samples were collected for polymerase chain reaction (PCR) amplification, restriction digestion and nucleotide sequencing. Findings: One hundred and ninety two potential cases (1.89%) of HbA2\u27 were detected on HPLC, having mean retention time of 4.59 0.05 minutes. Sixty four (0.6%) new cases were suspected of having co-existing beta-thalassaemia trait when the quantity of S-window peaks was taken into account. Thirteen samples with presumed HbA2\u27 on HPLC were subjected to molecular analysis and the said mutation (delta 16 GGC CGC) was not detected in any sample. Conclusion: It is concluded that diagnosis of HbA2\u27 on HPLC alone is not justified, as evidence of the presence of this delta chain variant in Pakistani population is yet to be proven. Such small S-window peaks should be either disregarded or confirmed at molecular level, and only then should influence the diagnosis of beta-thalassaemia trait. Further studies are required to determine the true nature of these peaks