Robustness of DNA Looping Across Multiple Divisions in Individual Bacteria

DNA looping has emerged as a central paradigm of transcriptional regulation as it is shared across many living systems. One core property of DNA looping-based regulation is its ability to greatly enhance repression or activation of genes with only a few copies of transcriptional regulators. However, this property based on small number of proteins raises the question of the robustness of such a mechanism with respect to the large intracellular perturbations taking place during growth and division of the cell. Here we address the issue of sensitivity to variations of intracellular parameters of gene regulation by DNA looping. We use the lac system as a prototype to experimentally identify the key features of the robustness of DNA looping in growing E. coli cells. Surprisingly, we observe time intervals of tight repression spanning across division events, which can sometimes exceed ten generations. Remarkably, the distribution of such long time intervals exhibits memoryless statistics that is mostly insensitive to repressor concentration, cell division events, and the number of distinct loops accessible to the system. By contrast, gene regulation becomes highly sensitive to these perturbations when DNA looping is absent. Using stochastic simulations, we propose that the robustness to division events of memoryless distributions emerges from the competition between fast, multiple re-binding events of repressors and slow initiation rate of the RNA-polymerase. We argue that fast re-binding events are a direct consequence of DNA looping that ensures robust gene repression across a range of intracellular perturbations.

Fuzzy Lexical Representations in Adult Second Language Speakers

We propose the fuzzy lexical representations (FLRs) hypothesis that regards fuzziness as a core property of nonnative (L2) lexical representations (LRs). Fuzziness refers to imprecise encoding at different levels of LRs and interacts with input frequency during lexical processing and learning in adult L2 speakers. The FLR hypothesis primarily focuses on the encoding of spoken L2 words. We discuss the causes of fuzzy encoding of phonological form and meaning as well as fuzzy form-meaning mappings and the consequences of fuzzy encoding for word storage and retrieval. A central factor contributing to the fuzziness of L2 LRs is the fact that the L2 lexicon is acquired when the L1 lexicon is already in place. There are two immediate consequences of such sequential learning. First, L2 phonological categorization difficulties lead to fuzzy phonological form encoding. Second, the acquisition of L2 word forms subsequently to their meanings, which had already been acquired together with the L1 word forms, leads to weak L2 form-meaning mappings. The FLR hypothesis accounts for a range of phenomena observed in L2 lexical processing, including lexical confusions, slow lexical access, retrieval of incorrect lexical entries, weak lexical competition, reliance on sublexical rather than lexical heuristics in word recognition, the precedence of word form over meaning, and the prominence of detailed, even if imprecisely encoded, information about LRs in episodic memory. The main claim of the FLR hypothesis – that the quality of lexical encoding is a product of a complex interplay between fuzziness and input frequency – can contribute to increasing the efficiency of the existing models of LRs and lexical access.

Transforming Growth Factor-β: An Agent of Change in the Tumor Microenvironment

Transforming Growth Factor-β (TGF-β) is a key regulator of embryonic development, adult tissue homeostasis, and lesion repair. In tumors, TGF-β is a potent inhibitor of early stage tumorigenesis and promotes late stage tumor progression and metastasis. Here, we review the roles of TGF-β as well as components of its signaling pathways in tumorigenesis. We will discuss how a core property of TGF-β, namely its ability to change cell differentiation, leads to the transition of epithelial cells, endothelial cells and fibroblasts to a myofibroblastoid phenotype, changes differentiation and polarization of immune cells, and induces metabolic reprogramming of cells, all of which contribute to the progression of epithelial tumors.

Eighteen-month-old infants represent nonlocal syntactic dependencies

The human ability to produce and understand an indefinite number of sentences is driven by syntax, a cognitive system that can combine a finite number of primitive linguistic elements to build arbitrarily complex expressions. The expressive power of syntax comes in part from its ability to encode potentially unbounded dependencies over abstract structural configurations. How does such a system develop in human minds? We show that 18-mo-old infants are capable of representing abstract nonlocal dependencies, suggesting that a core property of syntax emerges early in development. Our test case is English wh-questions, in which a fronted wh-phrase can act as the argument of a verb at a distance (e.g., What did the chef burn?). Whereas prior work has focused on infants’ interpretations of these questions, we introduce a test to probe their underlying syntactic representations, independent of meaning. We ask when infants know that an object wh-phrase and a local object of a verb cannot co-occur because they both express the same argument relation (e.g., *What did the chef burn the pizza). We find that 1) 18 mo olds demonstrate awareness of this complementary distribution pattern and thus represent the nonlocal grammatical dependency between the wh-phrase and the verb, but 2) younger infants do not. These results suggest that the second year of life is a period of active syntactic development, during which the computational capacities for representing nonlocal syntactic dependencies become evident.

Visual predictions, neural oscillations and naïve physics

Prediction is a core function of the human visual system. Contemporary research suggests the brain builds predictive internal models of the world to facilitate interactions with our dynamic environment. Here, we wanted to examine the behavioural and neurological consequences of disrupting a core property of peoples’ internal models, using naturalistic stimuli. We had people view videos of basketball and asked them to track the moving ball and predict jump shot outcomes, all while we recorded eye movements and brain activity. To disrupt people’s predictive internal models, we inverted footage on half the trials, so dynamics were inconsistent with how movements should be shaped by gravity. When viewing upright videos people were better at predicting shot outcomes, at tracking the ball position, and they had enhanced alpha-band oscillatory activity in occipital brain regions. The advantage for predicting upright shot outcomes scaled with improvements in ball tracking and occipital alpha-band activity. Occipital alpha-band activity has been linked to selective attention and spatially-mapped inhibitions of visual brain activity. We propose that when people have a more accurate predictive model of the environment, they can more easily parse what is relevant, allowing them to better target irrelevant positions for suppression—resulting in both better predictive performance and in neural markers of inhibited information processing.

Holistic face recognition is an emergent phenomenon of spatial processing in face-selective regions

Spatial processing by receptive fields is a core property of the visual system. However, it is unknown how spatial processing in high-level regions contributes to recognition behavior. As face inversion is thought to disrupt typical holistic processing of information in faces, we mapped population receptive fields (pRFs) with upright and inverted faces in the human visual system. Here we show that in face-selective regions, but not primary visual cortex, pRFs and overall visual field coverage are smaller and shifted downward in response to face inversion. From these measurements, we successfully predict the relative behavioral detriment of face inversion at different positions in the visual field. This correspondence between neural measurements and behavior demonstrates how spatial processing in face-selective regions may enable holistic perception. These results not only show that spatial processing in high-level visual regions is dynamically used towards recognition, but also suggest a powerful approach for bridging neural computations by receptive fields to behavior.

Multiple Event Readings with Dependent Indefinites

This chapter surveys empirical and theoretical issues raised by dependent indefinites in three unrelated languages, Hungarian, Telugu, and Kaqchikel. Dependent indefinites are specially marked noun phrases that can only occur when interpreted within a predication that distributes over events or individuals. Their determiner can either be a simple indefinite or a cardinal numeral. The chapter lays out the theoretical challenges the data raise and discusses how these challenges are met in three approaches that differ with respect to what they take as the core property of these indefinites.

EVALUATE THE INFLUENCE OF STEEL FIBERS ON THE STRENGTH OF CONCRETE USING PLASTIC WASTE AS FINE AGGREGATES

The plastic existence in abundance and its low biodegradability affect the environment. In recent years, researchers have tested numerous recycling techniques. However, each has its demerits. One such technique is recycling plastic as aggregates in concrete. It improves the concrete thermal insulation but depreciates its compressive and tensile strength, which is its core property in the construction industry. The objective of this research work is to efficiently utilize the plastic aggregate in concrete without deteriorating its strength with the use of steel fibers. In total eight concrete mix configurations were studied in this research. The result discussion includes compressive strength, split tensile test, and toughness index. The steel fiber used in the concrete mix with recycled plastic as fine aggregates improved the concrete strength. Its effects increase with an increase in % vol replacement of plastic aggregates with fine aggregates from 5 to 20.

Ingredients for robustness

A core property of robust systems is given by the invariance of their function against the removal of some of their structural components. This intuition has been formalised in the context of input–output maps, thereby introducing the notion of exclusion independence. We review work on how this formalisation allows us to derive characterisation theorems that provide a basis for the design of robust systems.