Low awareness of the transitivity assumption in complex networks of interventions: a systematic survey from 721 network meta-analyses.

BACKGROUND: The transitivity assumption is the cornerstone of network meta-analysis (NMA). Violating transitivity compromises the credibility of the indirect estimates and, by extent, the estimated treatment effects of the comparisons in the network. The present study offers comprehensive empirical evidence on the completeness of reporting and evaluating transitivity in systematic reviews with multiple interventions. METHODS: We screened the datasets of two previous empirical studies, resulting in 361 systematic reviews with NMA published between January 2011 and April 2015. We updated our evidence base with an additional 360 systematic reviews with NMA published between 2016 and 2021, employing a pragmatic approach. We devised assessment criteria for reporting and evaluating transitivity using relevant methodological literature and compared their reporting frequency before and after the PRISMA-NMA statement. RESULTS: Systematic reviews published after PRISMA-NMA were more likely to provide a protocol (odds ratio (OR): 3.94, 95% CI: 2.79-5.64), pre-plan the transitivity evaluation (OR: 3.01, 95% CI: 1.54-6.23), and report the evaluation and results (OR: 2.10, 95% CI: 1.55-2.86) than those before PRISMA-NMA. However, systematic reviews after PRISMA-NMA were less likely to define transitivity (OR: 0.57, 95% CI: 0.42-0.79) and discuss the implications of transitivity (OR: 0.48, 95% CI: 0.27-0.85) than those published before PRISMA-NMA. Most systematic reviews evaluated transitivity statistically than conceptually (40% versus 12% before PRISMA-NMA, and 54% versus 11% after PRISMA-NMA), with consistency evaluation being the most preferred (34% before versus 47% after PRISMA-NMA). One in five reviews inferred the plausibility of the transitivity (22% before versus 18% after PRISMA-NMA), followed by 11% of reviews that found it difficult to judge transitivity due to insufficient data. In justifying their conclusions, reviews considered mostly the comparability of the trials (24% before versus 30% after PRISMA-NMA), followed by the consistency evaluation (23% before versus 16% after PRISMA-NMA). CONCLUSIONS: Overall, there has been a slight improvement in reporting and evaluating transitivity since releasing PRISMA-NMA, particularly in items related to the systematic review report. Nevertheless, there has been limited attention to pre-planning the transitivity evaluation and low awareness of the conceptual evaluation methods that align with the nature of the assumption.

Transitivity and non-uniform subjecthood in agreement attraction.

Research on human language converges on a view in which a grammatical "subject" is the most saliently encoded entity in mental representation. However, subjecthood is not a syntactically uniform phenomenon. Notably, many languages encode morphological distinctions between subjects of transitive verbs (i.e., verbs that require an object) and subjects of intransitive verbs. We ask how this typological pattern manifests in a language like English (which does not morphologically signal it) by examining the "distinctiveness" of transitive versus intransitive subjects in memory during online sentence processing. We conducted a self-paced reading experiment that tested for "attraction" effects (Dillon et al., Journal of Memory and Language, 69(2), 85-103, 2013; Wagers et al., Journal of Memory and Language, 61, 206-237, 2009) in the processing of subject-verb number agreement. We find that transitive subjects trigger attraction effects, but that these effects are mitigated for intransitive subject attractors (independently of the number of other noun phrases present in the intervening clause). We interpret this as indicating that transitive subjects are less distinctive and therefore less representationally salient than intransitive subjects: This is because a transitive subject must compete with another clause-mate core argument (i.e., a direct object), which draws on resources from the same pool of memory resources. On the other hand, an intransitive subject minimally only competes with a non-core argument (i.e., an oblique noun phrase); this consumes fewer memory resources, leaving the subject to enjoy greater spoils.

Transitivity, coherence, and reliability of network meta-analyses comparing proximal humerus fracture treatments: a meta-epidemiological study.

BACKGROUND: Network meta-analyses can be valuable for decision-makers in guiding clinical practice. However, for network meta-analysis results to be reliable, the assumptions of both transitivity and coherence must be met, and the methodology should adhere to current best practices. We aimed to assess whether network meta-analyses of randomized controlled trials (RCTs) comparing interventions for proximal humerus fractures provide reliable estimates of intervention effects. METHODS: We searched PubMed, EMBASE, The Cochrane Library, and Web of Science for network meta-analyses comparing interventions for proximal humerus fractures. We critically assessed the methodology regarding the development of a protocol, search strategy, trial inclusion, outcome extraction, and the methods used to conduct the network meta-analyses. We assessed the transitivity and coherence of the network graphs for the Constant score (CS), Disabilities of the Arm, Shoulder, and Hand score (DASH), and additional surgery. Transitivity was assessed by comparing probable effect modifiers (age, gender, fracture morphology, and comorbidities) across intervention comparisons. Coherence was assessed using Separating Indirect from Direct Evidence (SIDE) (Separating Indirect from Direct Evidence) and the design-by-treatment interaction test. We used CINeMA (Confidence in Network Meta-analyses) to assess the confidence in the results. RESULTS: None of the three included network meta-analyses had a publicly available protocol or data-analysis plan, and they all had methodological flaws that could threaten the validity of their results. Although we did not detect incoherence for most comparisons, the transitivity assumption was violated for CS, DASH, and additional surgery in all three network meta-analyses. Additionally, the confidence in the results was 'very low' primarily due to within-study bias, reporting bias, intransitivity, imprecision, and heterogeneity. CONCLUSIONS: Current network meta-analyses of RCTs comparing interventions for proximal humerus fractures do not provide reliable estimates of intervention effects. We advise caution in using these network meta-analyses to guide clinical practice. To improve the utility of network meta-analyses to guide clinical practice, journal editors should require that network meta-analyses are done according to a predefined analysis plan in a publicly available protocol and that both coherence and transitivity have been adequately assessed and reported.

Perceptions of the Agency and Responsibility of the NHS COVID-19 App on Twitter: Critical Discourse Analysis.

BACKGROUND: Since September 2020, the National Health Service (NHS) COVID-19 contact-tracing app has been used to mitigate the spread of COVID-19 in the United Kingdom. Since its launch, this app has been a part of the discussion regarding the perceived social agency of decision-making algorithms. On the social media website Twitter, a plethora of views about the app have been found but only analyzed for sentiment and topic trajectories thus far, leaving the perceived social agency of the app underexplored. OBJECTIVE: We aimed to examine the discussion of social agency in social media public discourse regarding algorithm-operated decisions, particularly when the artificial intelligence agency responsible for specific information systems is not openly disclosed in an example such as the COVID-19 contact-tracing app. To do this, we analyzed the presentation of the NHS COVID-19 App on Twitter, focusing on the portrayal of social agency and the impact of its deployment on society. We also aimed to discover what the presentation of social agents communicates about the perceived responsibility of the app. METHODS: Using corpus linguistics and critical discourse analysis, underpinned by social actor representation, we used the link between grammatical and social agency and analyzed a corpus of 118,316 tweets from September 2020 to July 2021 to see whether the app was portrayed as a social actor. RESULTS: We found that active presentations of the app-seen mainly through personalization and agency metaphor-dominated the discourse. The app was presented as a social actor in 96% of the cases considered and grew in proportion to passive presentations over time. These active presentations showed the app to be a social actor in 5 main ways: informing, instructing, providing permission, disrupting, and functioning. We found a small number of occasions on which the app was presented passively through backgrounding and exclusion. CONCLUSIONS: Twitter users presented the NHS COVID-19 App as an active social actor with a clear sense of social agency. The study also revealed that Twitter users perceived the app as responsible for their welfare, particularly when it provided instructions or permission, and this perception remained consistent throughout the discourse, particularly during significant events. Overall, this study contributes to understanding how social agency is discussed in social media discourse related to algorithmic-operated decisions This research offers valuable insights into public perceptions of decision-making digital contact-tracing health care technologies and their perceptions on the web, which, even in a postpandemic world, may shed light on how the public might respond to forthcoming interventions.

High-pressure sprayed siRNAs influence the efficiency but not the profile of transitive silencing.

In plants, small interfering RNAs (siRNAs) are a quintessential class of RNA interference (RNAi)-inducing molecules produced by the endonucleolytic cleavage of double-stranded RNAs (dsRNAs). In order to ensure robust RNAi, siRNAs are amplified through a positive feedback mechanism called transitivity. Transitivity relies on RNA-DIRECTED RNA POLYMERASE 6 (RDR6)-mediated dsRNA synthesis using siRNA-targeted RNA. The newly synthesized dsRNA is subsequently cleaved into secondary siRNAs by DICER-LIKE (DCL) endonucleases. Just like primary siRNAs, secondary siRNAs are also loaded into ARGONAUTE proteins (AGOs) to form an RNA-induced silencing complex reinforcing the cleavage of the target RNA. Although the molecular players underlying transitivity are well established, the mode of action of transitivity remains elusive. In this study, we investigated the influence of primary target sites on transgene silencing and transitivity using the green fluorescent protein (GFP)-expressing Nicotiana benthamiana 16C line, high-pressure spraying protocol, and synthetic 22-nucleotide (nt) long siRNAs. We found that the 22-nt siRNA targeting the 3' of the GFP transgene was less efficient in inducing silencing when compared with the siRNAs targeting the 5' and middle region of the GFP. Moreover, sRNA sequencing of locally silenced leaves showed that the amount but not the profile of secondary RNAs is shaped by the occupancy of the primary siRNA triggers on the target RNA. Our findings suggest that RDR6-mediated dsRNA synthesis is not primed by primary siRNAs and that dsRNA synthesis appears to be generally initiated at the 3'-end of the target RNA.

Systemic silencing of an endogenous plant gene by two classes of mobile 21-nucleotide artificial small RNAs.

Artificial small RNAs (art-sRNAs) are 21-nucleotide small RNAs (sRNAs) computationally designed to silence plant genes or pathogenic RNAs with high efficacy and specificity. They are typically produced in transgenic plants to induce silencing at the whole-organism level, although their expression in selected tissues for inactivating genes in distal tissues has not been reported. Here, art-sRNAs designed against the magnesium chelatase subunit CHLI-encoding SULFUR gene (NbSu) were agroinfiltrated in Nicotiana benthamiana leaves, and the induction of local and systemic silencing was analyzed phenotypically by monitoring the appearance of the characteristic bleached phenotype, as well as molecularly by analyzing art-sRNA processing, accumulation and targeting activity and efficacy. We found that the two classes of art-sRNAs, artificial microRNAs (amiRNAs) and synthetic trans-acting small interfering RNAs (syn-tasiRNAs), are able to induce systemic silencing of NbSu, which requires high art-sRNA expression in the vicinity of the leaf petiole but is independent on the production of secondary sRNAs from NbSu mRNAs. Moreover, we revealed that 21-nucleotide amiRNA and syn-tasiRNA duplexes, and not their precursors, are the molecules moving between cells and through the phloem to systemically silence NbSu in upper leaves. In sum, our results indicate that 21-nucleotide art-sRNAs can move throughout the plant to silence plant genes in tissues different from where they are produced. This highlights the biotechnological potential of art-sRNAs, which might be applied locally for triggering whole-plant and highly specific silencing to regulate gene expression or induce resistance against pathogenic RNAs in next-generation crops. The present study demonstrates that artificial small RNAs, such as artificial microRNAs and synthetic trans-acting small interfering RNAs, can move long distances in plants as 21-nucleotide duplexes, specifically silencing endogenous genes in tissues different from where they are applied. This highlights the biotechnological potential of artificial small RNAs, which might be applied locally for triggering whole-plant, highly specific silencing to regulate gene expression or induce resistance against pathogenic RNAs in next-generation crops.

Inconsistency identification in network meta-analysis via stochastic search variable selection.

The reliability of the results of network meta-analysis (NMA) lies in the plausibility of the key assumption of transitivity. This assumption implies that the effect modifiers' distribution is similar across treatment comparisons. Transitivity is statistically manifested through the consistency assumption which suggests that direct and indirect evidence are in agreement. Several methods have been suggested to evaluate consistency. A popular approach suggests adding inconsistency factors to the NMA model. We follow a different direction by describing each inconsistency factor with a candidate covariate whose choice relies on variable selection techniques. Our proposed method, stochastic search inconsistency factor selection (SSIFS), evaluates the consistency assumption both locally and globally, by applying the stochastic search variable selection method to determine whether the inconsistency factors should be included in the model. The posterior inclusion probability of each inconsistency factor quantifies how likely is a specific comparison to be inconsistent. We use posterior model odds or the median probability model to decide on the importance of inconsistency factors. Differences between direct and indirect evidence can be incorporated into the inconsistency detection process. A key point of our proposed approach is the construction of a reasonable "informative" prior concerning network consistency. The prior is based on the elicitation of information derived historical data from 201 published network meta-analyses. The performance of our proposed method is evaluated in two published network meta-analyses. The proposed methodology is publicly available in an R package called ssifs, published on CRAN and developed and maintained by the authors of this work.

The influence of age and verb transitivity on written sentence production.

In this paper we explore the influences of normal ageing and verb transitivity on sentence production. The underlying aim is to provide a foundation for further research on sentence production in Alzheimer's disease (AD). We used a computer-based written sentence production task, designed to elicit intransitive, monotransitive and ditransitive sentences. Data was collected using keystroke logging, a technique to capture the entire typing process. Data of ninety healthy elderly was analysed focusing on the following writing process variables: time on task, production time and pause times. Results show that age influences time on task, pause time before sentences and within words. Verb transitivity influences time on task, production time and pause time between words. For pause time before sentences and between words, an interaction effect between age and verb transitivity was found as well. These results indicate that a follow-up study with AD patients should not attribute a slowdown in one of these variables to the disease in its entirety but should instead be compared with the slowdown in age-matched healthy peers.

Observations on the Lovász θ-Function, Graph Capacity, Eigenvalues, and Strong Products †.

This paper provides new observations on the Lovász θ-function of graphs. These include a simple closed-form expression of that function for all strongly regular graphs, together with upper and lower bounds on that function for all regular graphs. These bounds are expressed in terms of the second-largest and smallest eigenvalues of the adjacency matrix of the regular graph, together with sufficient conditions for equalities (the upper bound is due to Lovász, followed by a new sufficient condition for its tightness). These results are shown to be useful in many ways, leading to the determination of the exact value of the Shannon capacity of various graphs, eigenvalue inequalities, and bounds on the clique and chromatic numbers of graphs. Since the Lovász θ-function factorizes for the strong product of graphs, the results are also particularly useful for parameters of strong products or strong powers of graphs. Bounds on the smallest and second-largest eigenvalues of strong products of regular graphs are consequently derived, expressed as functions of the Lovász θ-function (or the smallest eigenvalue) of each factor. The resulting lower bound on the second-largest eigenvalue of a k-fold strong power of a regular graph is compared to the Alon-Boppana bound; under a certain condition, the new bound is superior in its exponential growth rate (in k). Lower bounds on the chromatic number of strong products of graphs are expressed in terms of the order and the Lovász θ-function of each factor. The utility of these bounds is exemplified, leading in some cases to an exact determination of the chromatic numbers of strong products or strong powers of graphs. The present research paper is aimed to have tutorial value as well.

Infants' selective imitation of a transitive agent and an intransitive agent.

This study examined how the reliability (i.e., transitivity) of an agent's object choices affects 16-month-old infants' (N = 48) imitation of her unconventional way of turning on a touch light box with her head when her hands were available. When the agent made transitive choices (i.e., she chose Object A over Object B, Object B over Object C, and then A over C), infants imitated her head touch actions. When the agent made intransitive choices (i.e., after choosing A over B and B over C, she chose C over A), infants were more likely to use only their hands to touch the light box. In addition, when it was presumably difficult for infants to judge the transitivity of the agent's choices (i.e., she chose B over C, A over B, and then A over C), they used their hands more. These results demonstrate that infants' understanding informs their decisions to selectively imitate others' specific ways to act on novel artifacts, consistent with young children's selective trust in information provided by other people based on their epistemic reliability.

Network Meta-Analysis Techniques for Synthesizing Prevention Science Evidence.

Network meta-analysis is a popular statistical technique for synthesizing evidence from studies comparing multiple interventions. Benefits of network meta-analysis, over more traditional pairwise meta-analysis approaches, include evaluating efficacy/safety of interventions within a single framework, increased precision, comparing pairs of interventions that have never been directly compared in a trial, and providing a hierarchy of interventions in terms of their effectiveness. Network meta-analysis is relatively underutilized in prevention science. This paper therefore presents a primer of network meta-analysis for prevention scientists who wish to apply this method or to critically appraise evidence from publications using the method. We introduce the key concepts and assumptions of network meta-analysis, namely, transitivity and consistency, and demonstrate their applicability to the field of prevention science. We then illustrate the method using a network meta-analysis examining the comparative effectiveness of brief alcohol interventions for preventing hazardous drinking among college students. We provide data and code for all examples. Finally, we discuss considerations that are particularly relevant in network meta-analyses in the field of prevention, such as including non-randomized evidence.

Implications and Consequences of SL(2R) as Invariance Group in the Description of Complex Systems Dynamics from a Multifractal Perspective of Motion.

Possible implications and consequences of using SL(2R) as invariance groups in the description at any scale resolution of the dynamics of any complex system are analyzed. From this perspective and based on Jaynes' remark (any circumstance left unspecified in the description of any complex system dynamics has the concrete expression in the existence of an invariance group), in the present paper one specifies such unspecified circumstances that result directly from the consideration of the canonical formalism induced by the SL(2R) as invariance group. It follows that both the Hamiltonian function and the Guassian distribution acquire the status of invariant group functions, the parameters that define the Hamiltonian acquire statistical significances based on a principle of maximizing informational energy, the class of statistical hypotheses specific to Gaussians of the same average acts as transitivity manifolds of the group (transitivity manifolds which can be correlated with the multifractal-non-multifractal scale transitions), joint invariant functions induced through SL(2R) groups isomorphism (the SL(2R) variables group, and the SL(2R) parameters group, etc.). For an ensemble of oscillators of the same frequency, the unspecified circumstances return to the ignorance of the amplitude and phase of each of the oscillators, which forces the recourse to a statistical ensemble traversed by the transformations of the Barbilian-type group. Finally, the model is validated based on numerical simulations and experimental results that refer to transient phenomena in ablation plasmas. The novelty of our model resides in the fact that fractalization through stochasticization is imposed through group invariance, situation in which the group's transitivity manifolds can be correlated with the scale resolution.

The key role of terminators on the expression and post-transcriptional gene silencing of transgenes.

Transgenes have become essential to modern biology, being an important tool in functional genomic studies and also in the development of biotechnological products. One of the major challenges in the generation of transgenic lines concerns the expression of transgenes, which, compared to endogenes, are particularly susceptible to silencing mediated by small RNAs (sRNAs). Several reasons have been put forward to explain why transgenes often trigger the production of sRNAs, such as the high level of expression induced by commonly used strong constitutive promoters, the lack of introns, and features resembling viral and other exogenous sequences. However, the relative contributions of the different genomic elements with respect to protecting genes from the silencing machinery and their molecular mechanisms remain unclear. Here, we present the results of a mutagenesis screen conceived to identify features involved in the protection of endogenes against becoming a template for the production of sRNAs. Interestingly, all of the recovered mutants had alterations in genes with proposed function in transcription termination, suggesting a central role of terminators in this process. Indeed, using a GFP reporter system, we show that, among different genetic elements tested, the terminator sequence had the greatest effect on transgene-derived sRNA accumulation and that a well-defined poly(A) site might be especially important. Finally, we describe an unexpected mechanism, where transgenes containing certain intron/terminator combinations lead to an increase in the production of sRNAs, which appears to interfere with splicing.

Network meta-analyses in reproductive medicine: challenges and opportunities.

Network meta-analysis allows researchers to synthesise both direct and indirect evidence, thus enabling simultaneous comparisons of multiple treatments. A relatively recent addition to evidence synthesis in reproductive medicine, this approach has become increasingly popular. Yet, the underlying assumptions of network meta-analyses, which drive the validity of their findings, have been frequently ignored. In this article, we discuss the strengths and limitations of network meta-analyses. In addition, we present an overview of published network meta-analyses in reproductive medicine, summarize their challenges and provide insights into future research opportunities.

Monkeys choose as if maximizing utility compatible with basic principles of revealed preference theory.

Revealed preference theory provides axiomatic tools for assessing whether individuals make observable choices "as if" they are maximizing an underlying utility function. The theory evokes a tradeoff between goods whereby individuals improve themselves by trading one good for another good to obtain the best combination. Preferences revealed in these choices are modeled as curves of equal choice (indifference curves) and reflect an underlying process of optimization. These notions have far-reaching applications in consumer choice theory and impact the welfare of human and animal populations. However, they lack the empirical implementation in animals that would be required to establish a common biological basis. In a design using basic features of revealed preference theory, we measured in rhesus monkeys the frequency of repeated choices between bundles of two liquids. For various liquids, the animals' choices were compatible with the notion of giving up a quantity of one good to gain one unit of another good while maintaining choice indifference, thereby implementing the concept of marginal rate of substitution. The indifference maps consisted of nonoverlapping, linear, convex, and occasionally concave curves with typically negative, but also sometimes positive, slopes depending on bundle composition. Out-of-sample predictions using homothetic polynomials validated the indifference curves. The animals' preferences were internally consistent in satisfying transitivity. Change of option set size demonstrated choice optimality and satisfied the Weak Axiom of Revealed Preference (WARP). These data are consistent with a version of revealed preference theory in which preferences are stochastic; the monkeys behaved "as if" they had well-structured preferences and maximized utility.

Quality transitivity of Danhong Huayu Koufuye: A study on chemical profiles of medicinal herbs, compound preparation and dosed rat plasma using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

Danhong Huayu Koufuye (DHK), an effective Chinese medicine preparation, is mainly used for the treatment of blurred vision and sudden blindness caused by qi stagnation and blood stasis, as well as the absorption period of central retinal vein occlusion. However, the current quality standard is relatively low, only stipulating the content of protocatechualdehyde. Chemical transitivity is the basis for discovering quality markers and is used in quality process control of Chinese medicines. Herein, the chemical profiles of seven medicinal herbs, DHK and dosed rat plasma were comprehensively analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. As a result, 134 chemical constituents were identified in seven medicinal herbs, including salvianolic acids, diterpene quinones, phenolic acids, phthalides, cyanogenic glycosides, flavonoids and triterpenoid saponins. Among them, 55 chemical constituents were transferred to DHK along with extraction and preparation, and 26 were further absorbed into blood and metabolized to produce 11 metabolites after oral administration. The transitivity of DHK from medicinal herbs to compound preparation and into blood was analyzed for the first time. This article will be valuable to ascertain the quality markers for quality process control and further pharmacokinetic studies.

From the Kinetic Theory of Gases to the Kinetics of Rate Processes: On the Verge of the Thermodynamic and Kinetic Limits.

A variety of current experiments and molecular dynamics computations are expanding our understanding of rate processes occurring in extreme environments, especially at low temperatures, where deviations from linearity of Arrhenius plots are revealed. The thermodynamic behavior of molecular systems is determined at a specific temperature within conditions on large volume and number of particles at a given density (the thermodynamic limit): on the other side, kinetic features are intuitively perceived as defined in a range between the extreme temperatures, which limit the existence of each specific phase. In this paper, extending the statistical mechanics approach due to Fowler and collaborators, ensembles and partition functions are defined to evaluate initial state averages and activation energies involved in the kinetics of rate processes. A key step is delayed access to the thermodynamic limit when conditions on a large volume and number of particles are not fulfilled: the involved mathematical analysis requires consideration of the role of the succession for the exponential function due to Euler, precursor to the Poisson and Boltzmann classical distributions, recently discussed. Arguments are presented to demonstrate that a universal feature emerges: Convex Arrhenius plots (super-Arrhenius behavior) as temperature decreases are amply documented in progressively wider contexts, such as viscosity and glass transitions, biological processes, enzymatic catalysis, plasma catalysis, geochemical fluidity, and chemical reactions involving collective phenomena. The treatment expands the classical Tolman's theorem formulated quantally by Fowler and Guggenheim: the activation energy of processes is related to the averages of microscopic energies. We previously introduced the concept of "transitivity", a function that compactly accounts for the development of heuristic formulas and suggests the search for universal behavior. The velocity distribution function far from the thermodynamic limit is illustrated; the fraction of molecules with energy in excess of a certain threshold for the description of the kinetics of low-temperature transitions and of non-equilibrium reaction rates is derived. Uniform extension beyond the classical case to include quantum tunneling (leading to the concavity of plots, sub-Arrhenius behavior) and to Fermi and Bose statistics has been considered elsewhere. A companion paper presents a computational code permitting applications to a variety of phenomena and provides further examples.

Molecular basis of transitivity in plant RNA silencing.

The discovery of small RNAs has offered exciting opportunities in manipulating gene expression. The non-coding RNAs cause target gene inactivation at the transcriptional, post-transcriptional or translational level. In addition to the default silencing approach, they provide another mode of gene regulation by transitivity. Here, gradual amplification in effector RNAs number allows regulation of genes other than the original target and causes the outspread of silencing from its origin to aid a robust response. Unlike the short-range cell-to-cell movement of silencing signal (through plasmodesmata), little is known of the mediators of systemic silencing (usually through phloem). Through the present review, we combine the reports available so far to better understand the characteristics of secondary silencing, factors involved, and summarize the instances where it has been employed in plants. Understanding the molecular mechanism behind transitivity has led to the designing of efficient transgenes for targeted gene inactivation, utilized in silencing of a multigene family, and in the field of functional genomics. Studies uncovering the origin of distinct secondary silencing pathways in plants have been exploited for developing artificial RNA silencing methods such as hairpin RNA, artificial microRNA, intrinsic direct repeat, inverted repeat, artificial trans-acting siRNA, phased siRNA, and virus-induced gene silencing. The techniques have facilitated the spread of traits such as pathogenic resistance or alter plant growth and development features. The mechanism of reprogramming in the silencing machinery and the consequent genetic manipulation through transitive RNA is still not completely understood and its exploitation in crop improvement programmes is still in a developing phase.

"Transitivity": A Code for Computing Kinetic and Related Parameters in Chemical Transformations and Transport Phenomena.

The Transitivity function, defined in terms of the reciprocal of the apparent activation energy, measures the propensity for a reaction to proceed and can provide a tool for implementing phenomenological kinetic models. Applications to systems which deviate from the Arrhenius law at low temperature encouraged the development of a user-friendly graphical interface for estimating the kinetic and thermodynamic parameters of physical and chemical processes. Here, we document the Transitivity code, written in Python, a free open-source code compatible with Windows, Linux and macOS platforms. Procedures are made available to evaluate the phenomenology of the temperature dependence of rate constants for processes from the Arrhenius and Transitivity plots. Reaction rate constants can be calculated by the traditional Transition-State Theory using a set of one-dimensional tunneling corrections (Bell (1935), Bell (1958), Skodje and Truhlar and, in particular, the deformed ( d -TST) approach). To account for the solvent effect on reaction rate constant, implementation is given of the Kramers and of Collins-Kimball formulations. An input file generator is provided to run various molecular dynamics approaches in CPMD code. Examples are worked out and made available for testing. The novelty of this code is its general scope and particular exploit of d -formulations to cope with non-Arrhenius behavior at low temperatures, a topic which is the focus of recent intense investigations. We expect that this code serves as a quick and practical tool for data documentation from electronic structure calculations: It presents a very intuitive graphical interface which we believe to provide an excellent working tool for researchers and as courseware to teach statistical thermodynamics, thermochemistry, kinetics, and related areas.

From Octahedral to Icosahedral Metal-Organic Polyhedra Assembled from Two Types of Polyoxovanadate Clusters.

Design and synthesis of metal-organic polyhedra (MOPs) with targeted geometries from predetermined secondary building units (SBUs) is a long-standing challenge in chemistry and material science. Theoretical prediction shows that there are 6 possible polyhedra from the 3-coordinated, 4-coordinated octahedron ((3,4)-c octahedron) to (3,5)-c icosahedron with minimal transitivity (simplest possible). Except for one missing polyhedron (mtr) due to the unfavorable angles, we report five MOPs based on these structures, including an octahedral (3,4)-c VMOP-21 (rdo), an icosahedral (3,5)-c VMOP-25 (trc), and three intermediate derived trinodal (3,4,5)-c VMOP-22-24 (ghm, hmg, xum). Remarkably, all these MOPs obey the minimal transitivity principle and are consistent with geometrical predictions.