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.

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)

We describe a categorial system (PPTS) based on partial proof trees(PPTs) as the building blocks of the system. The PPTs are obtained byunfolding the arguments of the type that would be associated with a lexicalitem in a simple categorial grammar. The PPTs are the basic types in thesystem and a derivation proceeds by combining PPTs together. We describe theconstruction of the finite set of basic PPTs and the operations forcombining them. PPTS can be viewed as a categorial system incorporating someof (...) the key insights of lexicalized tree adjoining grammar, namely the notionof an extended domain of locality and the consequent factoring of recursionfrom the domain of dependencies. PPTS therefore inherits the linguistic andcomputational properties of that system, and so can be viewed as a middleground between a categorial grammar and a phrase structure grammar. We alsodiscuss the relationship between PPTS, natural deduction, and linear logicproof-nets, and argue that natural deduction rather than a proof-net systemis more appropriate for the construction of the PPTs. We also discuss howthe use of PPTs allows us to localize the management of resources, therebyfreeing us from this management as the PPTs are combined. (shrink)

We describe a categorial system (PPTS) based on partial proof trees(PPTs) as the building blocks of the system. The PPTs are obtained byunfolding the arguments of the type that would be associated with a lexicalitem in a simple categorial grammar. The PPTs are the basic types in thesystem and a derivation proceeds by combining PPTs together. We describe theconstruction of the finite set of basic PPTs and the operations forcombining them. PPTS can be viewed as a categorial system incorporating someof (...) the key insights of lexicalized tree adjoining grammar, namely the notionof an extended domain of locality and the consequent factoring of recursionfrom the domain of dependencies. PPTS therefore inherits the linguistic andcomputational properties of that system, and so can be viewed as a ’middleground‘ between a categorial grammar and a phrase structure grammar. We alsodiscuss the relationship between PPTS, natural deduction, and linear logicproof-nets, and argue that natural deduction rather than a proof-net systemis more appropriate for the construction of the PPTs. We also discuss howthe use of PPTs allows us to ’localize‘ the management of resources, therebyfreeing us from this management as the PPTs are combined. (shrink)

This chapter argues that governments have a duty to take reasonably effective and humane steps to minimize the occurrence of unauthorized migration and stay. While the effects of unauthorized migration on a country’s citizens and institutions have been vigorously debated, the literature has largely ignored duties of fairness to would-be immigrants. It is argued here that failing to take reasonable steps to prevent unauthorized migration and stay is deeply unfair to would-be immigrants who are not in a position to bypass (...) visa regulations. Importantly, the argument here is orthogonal to the debate as to how much and what kinds of immigration ought to be allowed. (shrink)

P¯an.ini’s grammar includes several types of metarules which determine how its operational rules apply. Among them are “traffic rules” which constrain how rules interact with each other in grammatical derivations. These are typically formulated as designating a rule or class of rules asiddha “not effected” (or asiddhavat “as if not effected”) with respect to another rule or class of rules. For economy, the rules so designated are grouped into several sections, whose headings collectively declare them to be asiddha(vat). The biggest (...) such section, under the famous heading 8.2.1 p ¯urvatr¯asiddham, extends from 8.2.1 through the end of the grammar (8.4.68), and is hence called the Trip¯ad¯ı ‘Three Sections’. (shrink)

This paper explores some key commitments of the idea that it can be rational to do what you believe you ought not to do. I suggest that there is a prima facie tension between this idea and certain plausible coherence constraints on rational agency. I propose a way to resolve this tension. While akratic agents are always irrational, they are not always practically irrational, as many authors assume. Rather, “inverse” akratics like Huck Finn fail in a distinctively theoretical way. What (...) explains why akratic agents are always either theoretically or practically irrational? I suggest that this is true because an agent’s total evidence determines both the beliefs and the intentions it is rational for her to have. Moreover, an agent’s evidence does so in a way such that it is never rational for the agent to at once believe that she ought to Φ and lack the intention to Φ. (shrink)

In evolutionary psychology predictions, women’s mate preferences shift between fertile and nonfertile times of the month to reflect ancestral fitness benefits. Our meta-analytic test involving 58 independent reports (13 unpublished, 45 published) was largely nonsupportive. Specifically, fertile women did not especially desire sex in short-term relationships with men purported to be of high genetic quality (i.e., high testosterone, masculinity, dominance, symmetry). The few significant preference shifts appeared to be research artifacts. The effects declined over time in published work, were limited (...) to studies that used broader, less precise definitions of the fertile phase, and were found only in published research. (shrink)

The word “privilege” has become a part of our everyday conversations. However, it is not evident whether the various interlocutors in discussions on privilege are using it in the same sense. While different instances of privilege like white, male, or caste privilege have been discussed in contemporary academic discourses, we believe there is a lack of clarity regarding the notion of privilege. We critically analyse existing accounts of privilege to show that they leave some room for improvement. We offer an (...) alternative account of privilege as “entitlements that fail to track deserts” that circumvents prevalent definitional ambiguities and emphasises the inherent undeserving nature of privilege. The hitherto underexplored links between privileges, deserts, entitlements, and rights can help us formulate a more accurate grasp of privilege. (shrink)

Kireet Joshi, b. 1931, Indian philosopher and educationist; contributed articles.

Analytical study of the concept of creation and perception in Vedāntasiddhāntamuktāvalī, treatise on Hindu Advaita (non-dualistic) Vedanta philosophy by Prakāśānanda, 16th cent.

The Papers In This Volume, Presented At A Seminar Organised By The Gurukula Kangri Viswavidyalaya, Offer A Kaleidoscopic View Of Myriad Aspects Of Himalayan Eco-System Like Causes Of Its Degradation, Impact Of Hydroelectric To Deforestation And Role Of Wild Life. The Deliberations Also Highlight The Relevance Of Vedic Philosophy In Conserving The Fragile Himalayan Eco-System.

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)

There has recently been a growth in research that examines how corporations respond to allegations of unethical actions. Although scholars have gained much insight about the range of responses available to and used by organizations, there has been almost no study of why firms choose one response over another. In this article, the authors present a framework of likely organizational response choices to allegations of wrongdoing; we propose that response choices are based on the degree of reputational risk from stakeholder (...) withdrawal of support and on perceived threats to the firm’s primary or secondary identity. (shrink)

Political protests, debates on college campuses, and social media tirades make it seem like everyone is speaking their minds today. Surveys, however, reveal that many people increasingly feel like they're walking on eggshells when communicating in public. Speaking your mind can risk relationships and professional opportunities. It can alienate friends and anger colleagues. Isn't it smarter to just put your head down and keep quiet about controversial topics? In this book, Hrishikesh Joshi offers a novel defense of speaking your (...) mind. He explains that because we are social creatures, we never truly think alone. What we know depends on what our community knows. And by bringing our unique perspectives to bear upon public discourse, we enhance our collective ability to reach the truth on a variety of important matters. Speaking your mind is also important for your own sake. It is essential for developing your own thinking. And it's a core aspect of being intellectually courageous and independent. Joshi argues that such independence is a crucial part of a well-lived life. The book draws from Aristotle, John Stuart Mill, Friedrich Nietzsche, Bertrand Russell, and a range of contemporary thinkers to argue that it's OK to speak your mind. Key Features Shows that we have not just a right but a moral duty to publicly share what we know. Argues that discussing your unique ideas with others is essential for developing as a critical thinker. Explores the value of intellectual honesty and independence in the writings of John Stuart Mill and Friedrich Nietzsche and connects their thinking to contemporary problems. Argues that avoiding cultural blind spots today is important for the fate of future generations. (shrink)

Although representations of female scientists in the media have increased over time, stereotypical portrayals of science persist. In-depth, contemporary profiles of scientists’ roles have an opportunity to reflect or to challenge stereotypes of science and of gender. We employed content and linguistic analyses to examine whether publicly available profiles of scientists from New York Times and The Scientist Magazine support or challenge pervasive beliefs about science. Consistent with broader stereotypes of STEM fields, these portrayals focused more on agency than communality. (...) However, profiles also challenged stereotypes through integrating communality, purpose, and growth. This analysis also found similar presence of communal and agentic constructs for both female and male scientists. The current findings highlight the importance of considering counterstereotypic representations of science in the media: Communicating messages to the public that challenge existing beliefs about the culture of science may be one path toward disrupting stereotypes that dissuade talented individuals from choosing science pathways. (shrink)

Inventory prediction and management is a key issue in a retail store. There are a number of inventory prediction techniques. However, it is difficult to identify a time series prediction model for inventory forecasting that provides uniformly good results for all the products in a store. This paper uses data from a small retail store to demonstrate the variability of results for different modeling techniques and different products. We demonstrate inadequacy of a generic inventory model. Stability and seasonality analysis of (...) the time series is used to identify groups of products exhibiting similar sales patterns. Different clustering techniques are applied to determine reasonable local groups. With the help of Mean absolute percentage error, the effectiveness of dataset partitioning for better inventory management is demonstrated. Appropriate inventory management strategies are proposed based on the stability and seasonality analysis. (shrink)

Smell perception plays an important role in eating behavior and might be involved in body weight gain. Since a body of literature implies that olfactory perception and function is hampered in obesity, we here investigate neuroanatomical correlates of this phenomenon. We assessed olfactory bulb volume with magnetic resonance imaging in 67 healthy participants with a body mass index from 18.9 to 45.4 kg/m2. Moreover, we obtained psychophysiological data on olfactory ability and self-report measurements on eating behavior. Additionally, we collected parameters (...) associated with metabolic health in obesity to investigate recently proposed mechanistic explanatory models of why olfaction may be altered in obesity. We showed that OB volume was significantly lower in participants with obesity when compared to those of normal weight. Moreover, we found weak to moderate negative correlations between OB volume and BMI and related measures of metabolic health, especially leptin, body fat percentage, waist-height ratio and insulin resistance. However, neither OB volume nor BMI were related to olfactory function in our young and healthy sample. Nevertheless, our results provide first indications that obesity is associated with brain anatomical changes in the OBs. (shrink)

Papers presented at the Seminar on Indian Philosophical Thought on Pramāṇa and Dharmakīrti organized by Tibet House, New Delhi from 10-13 Nov. 2003.

The American political landscape exhibits significant polarization. People’s political beliefs cluster around two main camps. However, many of the issues with respect to which these two camps disagree seem to be rationally orthogonal. This feature raises an epistemic challenge for the political partisan. If she is justified in consistently adopting the party line, it must be true that her side is reliable on the issues that are the subject of disagreements. It would then follow that the other side is anti-reliable (...) with respect to a host of orthogonal political issues. Yet, it is difficult to find a psychologically plausible explanation for why one side would get things reliably wrong with respect to a wide range of orthogonal issues. While this project’s empirical discussion focuses on the US context, the argument generalizes to any situation where political polarization exists on a sufficiently large number of orthogonal claims. (shrink)

This paper argues for the existence of a certain type of defeater for one’s belief that P—the presence of social incentives not to share evidence against P. Such pressure makes it relatively likely that there is unpossessed evidence that would provide defeaters for P because it makes it likely that the evidence we have is a lopsided subset. This offers, I suggest, a rational reconstruction of a core strand of argument in Mill’s On Liberty. A consequence of the argument is (...) that on morally and politically laden issues in particular, a high degree of doxastic openness might be appropriate. (shrink)

According to the World Health Organisation, three to five million individuals are infected by influenza, and around 250,000 to 500,000 people die of this infectious disease worldwide. Influenza epidemics pose a serious public health threat. Moreover, graver dangers are encountered with influenza subtypes against which there is little or no preexisting human immunity. Such subtypes of influenza have the potential to cause devastating epidemics. Thus, enhancing surveillance systems for the purpose of detecting influenza epidemics in an early stage can quicken (...) response times and save millions of lives. This paper presents three adapting intelligence models: support vector machine regression, artificial neural network using particle swarm optimisation, and our intelligent time series to predict influenza epidemics. The novelty of the current study is that it proposes a new intelligent model to predict influenza outbreaks. The INTS model combines clustering with a time series model to enhance the prediction of influenza outbreaks. The innovation of our proposed model integrates the results obtained from the existing weighted exponential smoothing model with centroids obtained from clustering. We developed a surveillance system for influenza epidemics using Google search queries. The current research is based on a weighted version of the Center for Disease Control and Prevention influenza-like illness activity level obtained from the Center for Disease Control and Prevention data, as well as query data obtained from the Goggle search engine in the USA. The influenza-like illness data was collected from January 4, 2009, to December 27, 2015, stretching across a total time span of 312 weeks. Google Correlate was used to select search queries related to influenza epidemics. In total, 100 search queries were obtained from Google Correlate, 10 of which were better and more relevant search queries selected in this study. The model was evaluated using online Google search queries collected from Google Correlate. Standard measure performance MSE, RMSE, and MAE were employed to estimate the results of the proposed model. The empirical results of the INTS model showed MSE = 0.003, RMSE = 0.036, and MAE = 0.0185, indicating that the errors of the proposed model are very limited. A comparative model of predicting results between the INTS model, alternative Google Flu Trend, and autoregression with Google search data is also presented. The proposed model outperformed the existing models. (shrink)

Introduction: Electroconvulsive therapy is a commonly used brain stimulation treatment for treatment-resistant or severe depression. This study was planned to find the effects of ECT on brain connectivity by conducting a systematic review and coordinate-based meta-analysis of the studies performing resting state fMRI in patients with depression receiving ECT.Methods: We systematically searched the databases published up to July 31, 2020, for studies in patients having depression that compared resting-state functional connectivity before and after a course of pulse wave ECT. Meta-analysis (...) was performed using the activation likelihood estimation method after extracting details about coordinates, voxel size, and method for correction of multiple comparisons corresponding to the significant clusters and the respective rsFC analysis measure with its method of extraction.Results: Among 41 articles selected for full-text review, 31 articles were included in the systematic review. Among them, 13 articles were included in the meta-analysis, and a total of 73 foci of 21 experiments were examined using activation likelihood estimation in 10 sets. Using the cluster-level interference method, one voxel-wise analysis with the measure of amplitude of low frequency fluctuations and one seed-voxel analysis with the right hippocampus showed a significant reduction in the left cingulate gyrus and a significant increase in the right hippocampus with the right parahippocampal gyrus, respectively. Another analysis with the studies implementing network-wise resting state functional connectivity showed a significant increase in bilateral posterior cingulate cortex. There was considerable variability as well as a few key deficits in the preprocessing and analysis of the neuroimages and the reporting of results in the included studies. Due to lesser studies, we could not do further analysis to address the neuroimaging variability and subject-related differences.Conclusion: The brain regions noted in this meta-analysis are reasonably specific and distinguished, and they had significant changes in resting state functional connectivity after a course of ECT for depression. More studies with better neuroimaging standards should be conducted in the future to confirm these results in different subgroups of depression and with varied aspects of ECT. (shrink)