A forward-backward splitting algorithm for the minimization of non-smooth convex functionals in Banach space

We consider the task of computing an approximate minimizer of the sum of a smooth and non-smooth convex functional, respectively, in Banach space. Motivated by the classical forward-backward splitting method for the subgradients in Hilbert space, we propose a generalization which involves the iterative solution of simpler subproblems. Descent and convergence properties of this new algorithm are studied. Furthermore, the results are applied to the minimization of Tikhonov-functionals associated with linear inverse problems and semi-norm penalization in Banach spaces. With the help of Bregman-Taylor-distance estimates, rates of convergence for the forward-backward splitting procedure are obtained. Examples which demonstrate the applicability are given, in particular, a generalization of the iterative soft-thresholding method by Daubechies, Defrise and De Mol to Banach spaces as well as total-variation based image restoration in higher dimensions are presented

Pulsed Feedback Defers Cellular Differentiation

Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable “polyphasic” positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a “timer” that operates over timescales much longer than a cell cycle

Harnessing the Creative Potential of Consumers: Money, Participation and Creativity in Idea Crowdsourcing

Given the growing importance of innovation and consumer engagement, many firms are strongly interested in finding ways to encourage their consumers to generate creative new product ideas for them in their crowdsourcing initiatives. To that end, managers often use monetary rewards – one of the most commonly used managerial tools to stimulate desired behaviors. A critical question in this respect is whether the use of monetary rewards is effective in stimulating creativity and, if so, how large those rewards should be. This study aims to answer these questions. The results of an experiment suggest that introducing monetary rewards does not contribute to the number of new product ideas generated by a single consumer or the novelty of his/her ideas, and when the reward is relatively small it can even be harmful. Monetary rewards, however, are effective in encouraging widespread participation in crowdsourcing initiatives and improving the appropriateness of the new product ideas. As a whole, these findings take us a step further toward better understanding the motivational mechanisms of consumer creativity in new product ideation

Key Rotation for Authenticated Encryption

A common requirement in practice is to periodically rotate the keys used to encrypt stored data. Systems used by Amazon and Google do so using a hybrid encryption technique which is eminently practical but has questionable security in the face of key compromises and does not provide full key rotation. Meanwhile, symmetric updatable encryption schemes (introduced by Boneh et al. CRYPTO 2013) support full key rotation without performing decryption: ciphertexts created under one key can be rotated to ciphertexts created under a different key with the help of a re-encryption token. By design, the tokens do not leak information about keys or plaintexts and so can be given to storage providers without compromising security. But the prior work of Boneh et al. addresses relatively weak confidentiality goals and does not consider integrity at all. Moreover, as we show, a subtle issue with their concrete scheme obviates a security proof even for confidentiality against passive attacks. This paper presents a systematic study of updatable Authenticated Encryption (AE). We provide a set of security notions that strengthen those in prior work. These notions enable us to tease out real-world security requirements of different strengths and build schemes that satisfy them efficiently. We show that the hybrid approach currently used in industry achieves relatively weak forms of confidentiality and integrity, but can be modified at low cost to meet our stronger confidentiality and integrity goals. This leads to a practical scheme that has negligible overhead beyond conventional AE. We then introduce re-encryption indistinguishability, a security notion that formally captures the idea of fully refreshing keys upon rotation. We show how to repair the scheme of Boneh et al., attaining our stronger confidentiality notion. We also show how to extend the scheme to provide integrity, and we prove that it meets our re- encryption indistinguishability notion. Finally, we discuss how to instantiate our scheme efficiently using off-the-shelf cryptographic components (AE, hashing, elliptic curves). We report on the performance of a prototype implementation, showing that fully secure key rotations can be performed at a throughput of approximately 116 kB/s

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Evaluation of the Effects of Different Natural Dietary Feed Additives on Performance and Intestinal Histomorphology in Quails

The aim of the present study was to investigate the influence of a commercial probiotic and a commercial essential oil blend and their mixture, as a natural feed additive, on growth parameters live weight (LW), live weight gain (LWG), feed intake (FI), feed conversion ratio (FCR), carcass yield (CY) and small intestinal histomorphology of quails. A total of 200 1-day-old Japanese (Coturnix coturnix japonica) quails, including both males and females, were divided into four groups containing 50 quails and treated as follows: (1) a control treatment without medication (2) 18 g ton-1 probiotic;  (3) 300 g ton-1  essential oil blend  and (4) 18 g ton-1  probiotic plus 300 g ton-1 essential oil blend. The results of the research show that the additives added to quail diets do not have a significant effect (P > 0.05) on the performance parameters of LW, LWG, FI and FCR. However, significant differences (P < 0.05) were found in the CY, which is one of the performance parameters. A probiotic addition of 18 g ton -1 (treatment 1) to the quail diet resulted in a significant increase (P < 0.05) in carcass yield. Moreover, the addition of natural feed additives such as probiotics, essential oil blends and mixture to quail diets caused significant (P < 0.001) increases in villus heights and crypt depth in the duodenum and ileum segments. In addition, significant (P < 0.05) enlargements were found in the villus surface area in the experimental groups compared to the control group. In conclusion, in this study, it was determined that the addition of feed additives, which are developed as an alternative to antibiotics to the quail diet did not have a negative effect on performance and caused significant differences in the effective parameters in the evaluation of intestinal health

Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank

Background: Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. Methods: In the present analysis, three cohort studies (ntotal = 48,002) were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS), the English Longitudinal Study of Ageing (ELSA), and the UK Biobank. A genome-wide haplotype-based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions. Results: None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P-value overlapped with the D-amino acid oxidase activator (DAOA) gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimer’s disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10-7), was the butyrylcholinesterase (BCHE) gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimer’s disease and its role in cognitive ability merits further investigation. Conclusions: Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect

Breaking into the blackbox: Trend following, stop losses and the frequency of trading - The case of the S&P500

In this article, we compare a variety of technical trading rules in the context of investing in the S&P500 index. These rules are increasingly popular, both among retail investors and CTAs and similar investment funds. We find that a range of fairly simple rules, including the popular 200-day moving average (MA) trading rule, dominate the long-only, passive investment in the index. In particular, using the latter rule we find that popular stop-loss rules do not add value and that monthly end-of-month investment decision rules are superior to those which trade more frequently: this adds to the growing view that trading can damage your wealth. Finally, we compare the MA rule with a variety of simple fundamental metrics and find the latter far inferior to the technical rules over the last 60 years of investing

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.