Minichromosome maintenance (Mcm) proteins are well‐known for their functions in DNA replication. However, their roles in chromosome segregation are yet to be reviewed in detail. Following the discovery in 1984, a group of Mcm proteins, known as the ARS‐nonspecific group consisting of Mcm13, Mcm16‐19, and Mcm21‐22, were characterized as bonafide kinetochore proteins and were shown to play significant roles in the kinetochore assembly and high‐fidelity chromosome segregation. This review focuses on the structure, function, and evolution of this group of Mcm (...) proteins. Our in silico analysis of the physical interactors of these proteins reveals that they share non‐overlapping functions despite being copurified in biochemically stable complexes. We have discussed the contrasting results reported in the literature and experimental strategies to address them. Taken together, this review focuses on the structure‐function of the ARS‐nonspecific Mcm proteins and their evolutionary flexibility to maintain genome stability in various organisms. (shrink)

Increased amyloid beta (Aβ) production by sequential cleavage of the amyloid precursor protein (APP) by the β‐ and γ‐secretases contributes to the etiological basis of Alzheimer's disease (AD). This process requires APP and the secretases to be in the same subcellular compartments, such as the endosomes. Since all membrane organelles in the endomembrane system are kinetically and functionally linked, any defects in the trafficking and sorting machinery would be expected to change the functional properties of the whole system. The Golgi (...) is a primary organelle for protein trafficking, sorting and modifications, and Golgi defects have been reported in AD. Here we hypothesize that Golgi fragmentation in AD accelerates APP trafficking and Aβ production. Furthermore, Golgi defects may perturb the proper trafficking and processing of many essential neuronal proteins, resulting in compromised neuronal function. Therefore, molecular tools that can restore Golgi structure and function could prove useful as potential drugs for AD treatment. (shrink)

Sitting on the fine line between pathogen ‘transmissibility’ and ‘severity’, the Behavioural Immune System (BIS) is responsible for activating behaviours that minimise infection risks and maximise fitness. To achieve self-preservation, the BIS also fuels social and political attitudes. We aim to explain societal changes that may be sparked by COVID-19 by highlighting links between human evolutionary history and our psychological faculties mediated by the BIS.

It can seem incoherent to fully characterize fundamentality in terms of grounding, given that the fundamental is precisely that which cannot be fully characterized independently. I argue that there is no such incoherence.

The enduring appeal of liberalism lies in its commitment to the idea that human beings have a "natural" potential to live as free and equal individuals. The realization of this potential, however, is not a matter of nature, but requires that people be molded by a complex constellation of political and educational institutions. In this eloquent and provocative book, Uday Singh Mehta investigates in the major writings of John Locke the implications of this tension between individuals and the institutions (...) that mold them. The process of molding, he demonstrates, involves an external conformity and an internal self-restraint that severely limit the scope of individuality. Mehta explores the centrality of the human imagination in Locke's thought, focusing on his obsession with the potential dangers of the cognitive realm. Underlying Locke's fears regarding the excesses of the imagination is a political anxiety concerning how to limit their potential effects. In light of Locke's views on education, Mehta concludes that the promise of liberation at the heart of liberalism is vitiated by its constraints on cognitive and political freedom. (shrink)

From Kabir to Krishnamurti is a far cry. For, they are separated one from the other by over five centuries. But quantitative measurement of this distance has a qualitative aspect which cannot be measured in any time-scale. Two great seers lived in two completely different worlds-with no comparison between the two. And yet they expressed their thoughts and experience not only in a similar language but almost in identical terms. In these two streams of thought represented by Kabir and Krishnaji, (...) the authors note a fascinating parallelism. These streams run parallel to each other-and yet they meet from time to time-at the intersections between the two approaches to life. J. Krishnamurti and Sant Kabir focuses on these meeting points between the two approaches to life. The book also presents the intersections between the writings and sayings of Kabir and Krishnaji. (shrink)

Most contemporary theories of perception, including leading forms of representationalism and naive realism, are monistic: they assume that to consciously perceive is to deploy only one kind of sensory awareness. Here I instead argue for rich pluralism, which says that to consciously perceive is to deploy two very different kinds of sensory awareness in concert: representational awareness of particulars, and non-representational, partly essence-revealing awareness of sensory qualities.

Our sense of self includes awareness of our thoughts and movements, and our control over them. This feeling can be altered or lost in neuropsychiatric disorders as well as in phenomena such as “automatic writing” whereby writing is attributed to an external source. Here, we employed suggestion in highly hypnotically suggestible participants to model various experiences of automatic writing during a sentence completion task. Results showed that the induction of hypnosis, without additional suggestion, was associated with a small but significant (...) reduction of control, ownership, and awareness for writing. Targeted suggestions produced a double dissociation between thought and movement components of writing, for both feelings of control and ownership, and additionally, reduced awareness of writing. Overall, suggestion produced selective alterations in the control, ownership, and awareness of thought and motor components of writing, thus enabling key aspects of automatic writing, observed across different clinical and cultural settings, to be modelled. (shrink)

The common law system is a legal system that values precedent, or previous court decisions, in the resolution of current cases. As the availability of legal documents in digital form has increased, it has become more difficult for legal professionals to manually identify relevant past cases due to the vast amount of data. Researchers have developed automated systems for determining the similarity between legal documents to address this issue. Our research explores various representations of a legal document and discusses a (...) novel paragraph filtering process to identify key paragraphs using legal citation information to remove unnecessary text paragraphs without disturbing the concept of the legal document. State-of-the-art techniques like TF-IDF, BERT, Legal Bert, Doc2Vec, and Legal-longformer are used for the performance analysis of the proposed approach with document comparison. It has been shown that a model trained on the proposed filtered paragraphs can achieve better results than a model trained on the complete text and can also shorten the document by over 40%. The proposed filtering strategy could be helpful for models like BERT, where the maximum token length is fixed. (shrink)

When used in conjunction with the current floorplan and the optimization technique in circuit design engineering, this research allows for the evaluation of design parameters that can be used to reduce congestion during integrated circuit fabrication. Testing the multiple alternative consequences of IC design will be extremely beneficial in this situation, as will be demonstrated further below. If the importance of placement and routing congestion concerns is underappreciated, the IC implementation may experience significant nonlinear problems throughout the process as a (...) result of the underappreciation of placement and routing congestion concerns. The use of standard optimization techniques in integrated circuit design is not the most effective strategy when it comes to precisely estimating nonlinear aspects in the design of integrated circuits. To this end, advanced tools such as Xilinx VIVADO and the ICC2 have been developed, in addition to the ICC1 and VIRTUOSO, to explore for computations and recover the actual parameters that are required to design optimal placement and routing for well-organized and ordered physical design. Furthermore, this work employs the perimeter degree technique to measure routing congestion in both horizontal and vertical directions for a silicon chip region and then applies the technique to lower the density of superfluous routing. Recently, a metaheuristic approach to computation has increased in favor, particularly in the last two decades. It is a classic graph theory problem, and it is also a common topic in the field of optimization. However, it does not provide correct information about where and how nodes should be put, despite its popularity. Consequently, in conjunction with the optimized floorplan data, the optimized model created by the Improved Harmonic Search Optimization algorithm undergoes testing and investigation in order to estimate the amount of congestion that occurs during the routing process in VLSI circuit design and to minimize the amount of congestion that occurs. (shrink)

In the past few decades, increased awareness of environmental pollution has led to the exploitation of microbial metabolic potential in the construction of several genetically engineered microorganisms (GEMs) for bioremediation purposes. At the same time, environmental concerns and regulatory constraints have limited the in situ application of GEMs, the ultimate objective behind their development. In order to address the anticipated risks due to the uncontrolled survival/dispersal of GEMs or recombinant plasmids into the environment, some attempts have been made to construct (...) systems that would contain the released organisms. This article discusses the designing of safer genetically engineered organisms for environmental release with specific emphasis on the use of bacterial plasmid addiction systems to limit their survival thus minimizing the anticipated risk. We also conceptualize a novel strategy to construct “Suicidal Genetically Engineered Microorganisms (SGEMs)” by exploring/combining the knowledge of different plasmid addiction systems (such as antisense RNA‐regulated plasmid addiction, proteic plasmid addiction etc.) and inducible degradative operons of bacteria. BioEssays 27:563–573, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Our actions and decisions are regularly influenced by the social environment around us. Can social cues be leveraged to induce curiosity and affect subsequent behavior? Across two experiments, we show that curiosity is contagious: The social environment can influence people's curiosity about the answers to scientific questions. Participants were presented with everyday questions about science from a popular on‐line forum, and these were shown with a high or low number of up‐votes as a social cue to popularity. Participants indicated their (...) curiosity about the answers, and they were given an opportunity to reveal a subset of those answers. Participants reported greater curiosity about the answers to questions when the questions were presented with a high (vs. low) number of up‐votes, and they were also more likely to choose to reveal the answers to questions with a high (vs. low) number of up‐votes. These effects were partially mediated by surprise and by the inferred usefulness of knowledge, with a more dramatic effect of low up‐votes in reducing curiosity than of high up‐votes in boosting curiosity. Taken together, these results highlight the important role social information plays in shaping our curiosity. (shrink)

Small unmanned aerial systems (sUAS) are used more regularly and widely in disaster response. Like other personnel involved in disaster response, the sUAS pilots work for long periods, experience extreme stress and fatigue. They often arrive at the disaster fatigued (due to long drives to get there). However, unlike other personnel in this domain, there is little research on the effects of fatigue on sUAS pilots. Our experiences with a series of three real-world deployments highlight the challenges of conducting human (...) factors research during disaster response and recovery. We specifically present lessons learned from having participant researchers embedded in three disasters with the sUAS pilot teams. These lessons result in a set of feasible and non-interruptive methods and metrics for conducting human factors research during field events. Preliminary results and recommended next steps are presented. (shrink)

Nature contact has associations with emotional ill-being and well-being. However, the mechanisms underlying these associations are not fully understood. We hypothesised that increased adaptive and decreased maladaptive emotion regulation strategies would be a pathway linking nature contact to ill-being and well-being. Using data from a survey of 600 U.S.-based adults administered online in 2022, we conducted structural equation modelling to test our hypotheses. We found that (1) frequency of nature contact was significantly associated with lesser emotional ill-being and greater emotional (...) well-being, (2) effective emotion regulation was significantly associated with lesser emotional ill-being and greater emotional well-being, and (3) the associations of higher frequency of nature contact with these benefits were partly explained via emotion regulation. Moreover, we found a nonlinear relationship for the associations of duration of nature contact with some outcomes, with a rise in benefits up to certain amounts of time, and a levelling off after these points. These findings support and extend previous work that demonstrates that the associations of nature contact with emotional ill-being and well-being may be partly explained by changes in emotion regulation. (shrink)

Meditation refers to a family of self-regulation practices that focuses on training attention and awareness to foster psycho-emotional well-being and to develop specific capacities such as calmness, clarity, and concentration. We report a prospective convenience-controlled study in which we analyzed the effect of two components of Preksha Dhyāna – buzzing bee sound meditation and color meditation on healthy college students. Mahapran and leśya dhyāna are two Preksha Dhyāna practices that are based on sound and green color, respectively. The study population (...) represents a suitable target as college students experience different stress factors during the school year. This study measures the individual and combined effects of two techniques, on short-term memory, attention, and affect, in novice meditators. We used a battery of cognitive, performance, and compared results with baseline and control values. We found improved cognition, especially attention, short-term memory, and affect in terms of positivity and reduced negativity. Overall, the two techniques produced variable benefits and subjects showed improved scores over baseline for short-term memory, cognitive function, and overall wellbeing. Further studies are required to understand underlying mechanisms for the observed differences between the two techniques and to elucidate mechanisms underlying the more pronounced and global benefits observed with the combined techniques. These results underscore a need to examine individual components of meditation practices in order to individualize treatment approaches for attention disorders in young adults.Clinical Trail Registration:ClinicalTrials.gov Identifier: NCT03779269. (shrink)

This essay is a study on national self-determination and justice from the differing perspectives of John Rawls and Rabindranath Tagore. Both thinkers have addressed the problem of conflict caused by national loyalties. Influenced by Immanuel Kant’s philosophy of cosmopolitanism, John Rawls articulates the “Law of People” that suggests that mutual consent consists in economic interdependence among nations and tolerance for cultural diversity under monitored conditions of the international relations. Such an arrangement is not inclusive as it excludes the subaltern perspectives (...) and reinforces the hierarchies between East and West. Tagore offers post-colonial versions of nationalism and cosmopolitanism that call for a creative and spiritual unity of nations through cultural exchange where each is equal in dialogue. The essay makes a case for Tagore’s cosmopolitanism being more inclusive than Rawls, yet, limited in its accommodation of the “other” as Tagore’s creative unity domesticates this “other” on the basis of spiritual familiarity. The essay also critiques Martha Nussbaum’s cosmopolitanism that suggests reconciliation of both. It makes a case for a paradoxical understanding of hospitality, friendship and otherness theorized by Jacques Derrida as the basis of self-determination and global justice. (shrink)

Criminal juries in the United States typically deliver their decisions through a “general verdict,” expressing only their ultimate conclusion of “guilty” or “not guilty,” rather than through a “special verdict” that identifies whether each element of the charged crime has been proven beyond a reasonable doubt. American courts have broadly favored the use of general verdicts in criminal cases due to concerns that the special verdict will curtail the jury’s decision-making autonomy, including its power to nullify the law in favor (...) of the defense, potentially undermining the criminal defendant’s constitutional right to trial by jury. This Article confronts the legal status quo on verdict format and its underlying, untested assumptions. Drawing upon prior psychology findings and legal professionals’ anecdotal observations, it questions whether the general verdict poses its own under-acknowledged threats to the rights of criminal defendants and the decision-making agency of jurors. While the more guided special verdict format is presumed to threaten nullifying acquittals, the unguided general verdict format might be enabling convictions that violate constitutional norms of due process, impartial adjudication, and equal protection. Given the high-stakes values potentially implicated in the choice of verdict format in criminal cases, it is time to put the conventional wisdom in favor of general verdicts to an empirical test. This Article therefore proposes a methodological framework for investigating whether the legal status quo accurately reflects (1) current stakeholders’ preferences and predictions, and (2) experimentally testable legal and cognitive effects of general versus special verdicts in lay determinations of criminal liability. A data-informed understanding is needed to assess whether the general verdict is optimizing the integrity, fairness, and constitutionality of criminal jury decision making. (shrink)

Shedding light on a fundamental tension in liberal theory, Liberalism and Empire reaches beyond post-colonial studies to revise our conception of the grand liberal tradition and the conception of experience with which it is associated.

Consider two deeply appealing thoughts: first, that we experience external particulars, and second, that what it’s like to have an experience – the phenomenal character of an experience – is somehow independent of external particulars. The first thought is readily captured by phenomenal particularism, the view that external particulars are sometimes part of the phenomenal character of experience. The second thought is readily captured by phenomenal generalism, the view that external particulars are never part of phenomenal character. -/- Here I (...) show that a novel version of phenomenal generalism can capture both thoughts in a satisfying fashion. Along the way, I reveal severe problems facing phenomenal particularism and also shed light on the mental kinds under which experiences fall. (shrink)

Philosophy and Phenomenological Research, Volume 104, Issue 1, Page 209-231, January 2022.

Here I advance a unified account of the structure of the epistemic normativity of assertion, action, and belief. According to my Teleological Account, all of these are epistemically successful just in case they fulfill the primary aim of knowledgeability, an aim which in turn generates a host of secondary epistemic norms. The central features of the Teleological Account are these: it is compact in its reliance on a single central explanatory posit, knowledge-centered in its insistence that knowledge sets the fundamental (...) epistemic norm, and yet fiercely pluralistic in its acknowledgment of the legitimacy and value of a rich range of epistemic norms distinct from knowledge. Largely in virtue of this pluralist character, I argue, the Teleological Account is far superior to extant knowledge-centered accounts. (shrink)

What grounds facts of the form? One promising answer is: facts of the form. A different promising answer is: x itself. Isaac Wilhelm has recently argued that the second answer is superior to the first. In this paper, I rebut his argument.

The impetus of this study is to gauge the nexus between economic policy uncertainty and financial innovation in Brazil, Russia, India, China, and South Africa nations for the period from 2004M1 to 2018M12. This study utilizes both the linear and non-linear autoregressive distributed lag models to evaluate the long-run and the short-run association between EPU and financial innovation; furthermore, the causal effects are investigated by following the non-Granger casualty framework. The results of long-run cointegration, i.e., the test statistics of modified (...) F-test, standard Wald test, and tBDM, reject the null hypothesis and establish the presence of the long-run association between EPU and financial innovation. Conversely, long-run asymmetry cointegration revealed the test statistics of FPSS, WPSS, and tBDM in non-linear estimation. Furthermore, both in the long run and short run, the Wald test results disclose asymmetric effects running from EPU to financial innovation. In regards to the asymmetric impact of EPU on financial innovation, this study documents that the positive and negative shocks in EPU are negatively linked with financial innovation in the long run but are insignificant for short-run effects. Besides, financial innovation measured by R&D investment exhibits a positive linkage with shocks in EPU, implying that uncertainty induces innovation in the economy. Referring to causality effects, this study divulges the feedback hypothesis, i.e., bidirectional causality prevails between EPU and financial innovation in all sample countries. (shrink)

The bioethics literature has paid little attention to matters of informed reproductive decision-making among women of childbearing age who have chronic kidney disease (CKD), including women who are on dialysis or women who have had a kidney transplant. Women with CKD receive inconsistent and, sometimes, inadequate reproductive counseling, particularly with respect to information about pursuing pregnancy. We identify four factors that might contribute to inadequate and inconsistent reproductive counseling. We argue that women with CKD should receive comprehensive reproductive counseling, including (...) information about the possibility of pursuing pregnancy, and that more rigorous research on pregnancy in women with CKD, including women on dialysis or who have received a kidney transplant, is warranted to improve informed reproductive decision making in this population. (shrink)

I assume that there exists a general phenomenon, the phenomenon of the explanatory gap, surrounding consciousness, normativity, intentionality, and more. Explanatory gaps are often thought to foreclose reductive possibilities wherever they appear. In response, reductivists who grant the existence of these gaps have offered countless local solutions. But typically such reductivist responses have had a serious shortcoming: because they appeal to essentially domain-specific features, they cannot be fully generalized, and in this sense these responses have been not just local but (...) parochial. Here I do better. Taking for granted that the explanatory gap is a genuine phenomenon, I offer a fully general diagnosis that unifies these previously fragmented reductivist responses. (shrink)