Emerging roles of MCPH1: Expedition from primary microcephaly to cancer

Genetic mutations in microcephalinl (MCPH1) cause primary autosomal recessive microcephaly which is characterized by a marked reduction in brain size. MCPH1 encodes a centrosomal protein with three BRCT (BRCA1 C-terminal) domains. Also, it is a key regulator of DNA repair pathway and cell cycle checkpoints. Interestingly, in the past few years, many research studies have explored the role of MCPH1, a neurodevelopmental gene in several cancers and its tumor suppressor functions have been elucidated. Given the diverse new emerging roles, it becomes critical to review and summarize the multiple roles of MCPH1 that is currently lacking in the literature. In this review after systematic analysis of literature, we summarise the multiple functional roles of MCPH1 in centrosomal, DNA repair and apoptotic pathways. Additionally, we discuss the considerable efforts taken to understand the implications of MCPH1 in diseases such as primary microcephaly and its other emerging association with cancer and otitis media. The promising view is that MCPH1 has distinct roles and its clinical associations in various diseases makes it an attractive therapeutic target. (C) 2014 Elsevier GmbH. All rights reserved.

Statistical significance of episodes with general partial orders

Frequent episode discovery is one of the methods used for temporal pattern discovery in sequential data. An episode is a partially ordered set of nodes with each node associated with an event type. For more than a decade, algorithms existed for episode discovery only when the associated partial order is total (serial episode) or trivial (parallel episode). Recently, the literature has seen algorithms for discovering episodes with general partial orders. In frequent pattern mining, the threshold beyond which a pattern is inferred to be interesting is typically user-defined and arbitrary. One way of addressing this issue in the pattern mining literature has been based on the framework of statistical hypothesis testing. This paper presents a method of assessing statistical significance of episode patterns with general partial orders. A method is proposed to calculate thresholds, on the non-overlapped frequency, beyond which an episode pattern would be inferred to be statistically significant. The method is first explained for the case of injective episodes with general partial orders. An injective episode is one where event-types are not allowed to repeat. Later it is pointed out how the method can be extended to the class of all episodes. The significance threshold calculations for general partial order episodes proposed here also generalize the existing significance results for serial episodes. Through simulations studies, the usefulness of these statistical thresholds in pruning uninteresting patterns is illustrated. (C) 2014 Elsevier Inc. All rights reserved.

How Does Effectual Logic Impact Survival of High-tech Startups in an Emerging Economy? - Evidence from 99tests.com Case Study

During the early stages of operation, high-tech startups need to overcome the liability of newness and manage high degree of uncertainty. Several high-tech startups fail due to inability to deal with skeptical customers, underdeveloped markets and limited resources in selling an offering that has no precedent. This paper leverages the principles of effectuation (a logic of entrepreneurial decision making under uncertainty) to explain the journey from creation to survival of high-tech startups in an emerging economy. Based on the 99tests.com case study, this paper suggests that early stage high-tech startups in emerging economies can increase their probability of survival by adopting the principles of effectuation.

Multifarious facets of sugar-derived molecular gels: molecular features, mechanisms of self-assembly and emerging applications

The remarkable capability of nature to design and create excellent self-assembled nano-structures, especially in the biological world, has motivated chemists to mimic such systems with synthetic molecular and supramolecular systems. The hierarchically organized self-assembly of low molecular weight gelators (LMWGs) based on non-covalent interactions has been proven to be a useful tool in the development of well-defined nanostructures. Among these, the self-assembly of sugar-derived LMWGs has received immense attention because of their propensity to furnish biocompatible, hierarchical, supramolecular architectures that are macroscopically expressed in gel formation. This review sheds light on various aspects of sugar-derived LMWGs, uncovering their mechanisms of gelation, structural analysis, and tailorable properties, and their diverse applications such as stimuli-responsiveness, sensing, self-healing, environmental problems, and nano and biomaterials synthesis.

Phytomedicinal importance of Saraca asoca (Ashoka): an exciting past, an emerging present and a promising future

Since the dawn of civilization, natural resources have remained the mainstay of various remedial approaches of humans vis-a-vis a large number of illnesses. Saraca asoca (Roxb.) de Wilde (Saraca indica L.) belonging to the family Caesalpiniaceae has been regarded as a universal panacea in old Indian Ayurvedic texts and has especially been used to manage gynaecological complications and infections besides treating haemmorhagic dysentery, uterine pain, bacterial infections, skin problems, tumours, worm infestations, cardiac and circulatory problems. Almost all parts of the plant are considered pharmacologically valuable. Extensive folkloric practices and ethnobotanical applications of this plant have even lead to the availability of several commercial S. asoca formulations recommended for different indications though adulteration of these remains a pressing concern. Though a wealth of knowledge on this plant is available in both the classical and modern literature, extensive research on its phytomedicinal worth using state-of-the-art tools and methodologies is lacking. Recent reports on bioprospecting of S. asoca endophytic fungi for industrial bioproducts and useful pharmacologically relevant metabolites provide a silver lining to uncover single molecular bio-effectors from its endophytes. Here, we describe socio-ethnobotanical usage, present the current pharmacological status and discuss potential bottlenecks in harnessing the proclaimed phytomedicinal worth of this prescribed Ayurvedic medicinal plant. Finally, we also look into the possible future of the drug discovery and pharmaceutical R&D efforts directed at exploring its pharma legacy.

Discovering compressing serial episodes from event sequences

Most pattern mining methods yield a large number of frequent patterns, and isolating a small relevant subset of patterns is a challenging problem of current interest. In this paper, we address this problem in the context of discovering frequent episodes from symbolic time-series data. Motivated by the Minimum Description Length principle, we formulate the problem of selecting relevant subset of patterns as one of searching for a subset of patterns that achieves best data compression. We present algorithms for discovering small sets of relevant non-redundant episodes that achieve good data compression. The algorithms employ a novel encoding scheme and use serial episodes with inter-event constraints as the patterns. We present extensive simulation studies with both synthetic and real data, comparing our method with the existing schemes such as GoKrimp and SQS. We also demonstrate the effectiveness of these algorithms on event sequences from a composable conveyor system; this system represents a new application area where use of frequent patterns for compressing the event sequence is likely to be important for decision support and control.

Sources of contention and the emerging reality concerning Qohelet's Carpe Diem advice

Abstract: When Qohelet declares “there is nothing new under the sun,” his own words are no exception. It has been known for a century now that not all of Qohelet’s material is original to his own genius, and the idea that Qohelet is directly dependent on a literary source(s) is standard fare. The hallmark example continues to be Siduri the alewife’s advice to Gilgamesh which displays remarkable correspondence with Ecclesiastes 9: 7-9. However, what may have been construed as an instance of clear literary dependency a century ago cannot be maintained in light of the data that continues to emerge from the ancient Near East. New sources have risen that contend with the Gilgamesh Epic, and there has yet to emerge a definitive victor. This paper calls into question the very idea that Qohelet was directly dependent on a literary precursor and joins with a few select voices both past and present in suggesting an alternate interpretation of the data.

Altruism with Social Roots: An Emerging Literature

Revised: 2007-01.-- Published as an article in: Revista Desarrollo y Sociedad (2006), Semestre II, pp. 245-260.