Compensating for Large In-Plane Rotations in Natural Images

Rotation invariance has been studied in the computer vision community primarily in the context of small in-plane rotations. This is usually achieved by building invariant image features. However, the problem of achieving invariance for large rotation angles remains largely unexplored. In this work, we tackle this problem by directly compensating for large rotations, as opposed to building invariant features. This is inspired by the neuro-scientific concept of mental rotation, which humans use to compare pairs of rotated objects. Our contributions here are three-fold. First, we train a Convolutional Neural Network (CNN) to detect image rotations. We find that generic CNN architectures are not suitable for this purpose. To this end, we introduce a convolutional template layer, which learns representations for canonical 'unrotated' images. Second, we use Bayesian Optimization to quickly sift through a large number of candidate images to find the canonical 'unrotated' image. Third, we use this method to achieve robustness to large angles in an image retrieval scenario. Our method is task-agnostic, and can be used as a pre-processing step in any computer vision system.Comment: Accepted at Indian Conference on Computer Vision, Graphics and Image Processing (ICVGIP) 201

The guardians of the genome dependent tumor suppressor miRNAs network

The tumor suppressor p53 homologues, TA-p73, and p63 have been shown to function as tumor suppressors. However, how they function as tumor suppressors remains elusive. Here I present a number of models that illustrates how the TA-p73/p63 could function as tumor suppressors. Remarkably, the guardians—p53, p63, and p73—of the genome are in control of most of the known tumor suppressor miRNAs. 
TA-p73/p63 and p53, by suppressing the expression of c-Myc through TRIM32 and miR-145, they could up regulate the expression of tumor suppressor microRNAs, such as miR-15/16a, miR-29, miR-34, miR-26, let-7a/d/g, miR-30b/c/d/e, miR-146a, and a number of tumor suppressor genes. It appears that p53/TA-p73/p63-mediated repression of c-myc (and its repressed miRNA targets) inhibits tumor growth. Thus, these findings strongly suggest that p53, TA-p73 and TA-p63, by suppressing the expression of c-myc, they could increase c-myc-repressed tumor suppressor miRNAs, and thereby they could function as tumor suppressors. In addition, TA-p73/p63 and p53 appears to regulate the expression of miR-200b, c to control EMT, invasion and metastasis.

Remarkably, microRNA processing components, such as dicer, P2P-R, Ago1/2, DGCR-8, are regulated by p53, p73, and p63. By regulating the miRNA processing components, they could function as regulators of miRNA/siRNA biogenesis. Therefore, these studies suggest that the guardians of the genome p53, p73 and p63 are in control of the biogenesis of miRNAs as well. Taken together, “the guardians of the genome integrity,” p53, TA-p73 and TA-p63 are not only in control of its protein coding targets, but also non-coding tumor suppressor microRNAs and thereby they enlarge their tumor suppressor network to inhibit tumorigenesis.
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Some facts and thoughts: p73 as a tumor suppressor gene in the network of tumor suppressors

The question of whether p73 is a tumor suppressor gene, is not yet answered with full confidence. The lack of spontaneous tumor formation in p73 null mice and infrequent p73 mutations seen in a variety of cancers analyzed would straightaway negate its role as a primary tumor suppressor gene. However, accumulating evidence suggest that p73 gene and its target genes are hypermethylated in the cancer of lymphoid origin. Here I discuss some facts and thoughts that support the idea that p73 could still be a tumor suppressor gene. The tumor suppressor network in which p73 appears to be a participant involves E2F1, JunB, INK4a/p16, ARF/p19, p57kip2 and BRCA1. Knock out of each gene in E2F-1-p73-JunB-p16INK4a network of tumor suppressor proteins result in lymphoma/leukemia formation. Further, I tried to explain why lymphomas are not seen in p73 null mice and why p73 gene is not prone to frequent mutation

The TA-p73 functions as a Lung tumor suppressor by increasing the expression of miRNA, let-7

I have previously proposed that TA-p73-depenedent tumor suppressor pathway could inhibit the development of lung adenocarcinoma. This hypothesis is strongly supported by a recent finding showing that TA-p73 specific knockout mice are prone to lung adenocarcinoma. However, the p73-dependent tumor suppressor pathway remains ill defined. It has been shown that let-7 cluster is highly expressed in normal lung. Loss of let-7 expression: a) is common in Non-small cell lung carcinoma; and b) enhances lung tumor formation, indicating that it could function as a lung tumor suppressor. Based on these facts, I hypothesized that let-7 could be a transcriptional target of p73. To confirm this hypothesis, I have analyzed the let-7 cluster promoters using TRASFAC bioinformatics software. This analysis suggests that Let-7c contains three perfect p53-RE half-sites and five nearly perfect p53RE sites. In addition, other let-7 cluster miRNAs appear to contain several p53-REs, suggesting that Let-7 miRNA cluster could be a transcriptional target of p73/p63/p53. Furthermore, negative regulators of let-7 biogenesis, such as lin-28, c-myc and DCAMKL-1, are suppressed by p53-miRs, such as let-7, miR-145, miR-34, miR-15/16, miR-103/107 and miR-221, suggesting that TA-p73/p63/p53, by suppressing the expression of lin-28, c-myc and DCAMKL-1, it could increase the expression of let-7. By increasing the expression of let-7, TA-p73 could suppress the expression of its targets, such as N/H/K-ras, HMGA2, Cyclins, MCMs, BUBs, and CDCs; thereby it could inhibit the initiation of lung tumors. Together, this study proposes for the first time the TA-p73/p63-let-7-INK4a/ARF as a lung tumor suppressor pathway

Melancholy in the Poems of Abhi (Abibullah)

Mind plays a major role in human life. The mind is susceptible to pleasure and pain and can lose itself. Mind in a minute, in its first part is characterized by reaching the peak of pleasure and the second half ends. Literature is closely related to the mind of the creator and the reader. So comparing literature with introspective psychology is essential. Psychology is divided into several categories such as social psychology, educational psychology, behavioural psychology, animal psychology, psychiatric psychology, and developmental psychology. Among these, mutant psychology is most closely associated with creationists. Depression, a part of mutant psychology, is understood as a mental illness that everyone knows. Therefore, this article seeks to compare the Maunathin Naavugal poems by Abibullah with the psychological field of depression

Tumor suppressors function as a bottleneck against cellular reprogramming into iPS cells

Generating individual specific pluoripotent stem cells from differentiated cells is essential for regenerative medicine. Here, I propose that the tumor suppressor TA-p73/p63-dependent microRNA network may inhibit self-renewal and reprogramming. It has recently been shown that C-terminal NHL domain of TRIM32, an ubiquitin ligase, binds to Argonaute 1(Ago-1, a component of RNA information silencing complex) and thereby the complex TRIM32-Ago1 promotes the efficiency of processing of microRNA-134. 
Bioinformatics analysis of TRIM32 promoter revealed five p73/p63 binding sites in the TRIM32 promoter, indicating that it could be a transcriptional target of TA-p73/p63. This data suggests a possibility that the TA-p73/p63, by increasing the expression of TRIM32, it could increase the Ago1/2 activity and thereby it could increase the processing of miR-134. 
Further, bioinformatics analysis of miR-134 suggests that it could inhibit the expression of Nanog, Sox-2, Oct4, and LRH-1. This data suggests that TA-p73/p63 could down regulate reprogramming factors Nanog, Sox-2, Oct-4, and LRH-1 through its target miR-134. Furthermore, p53/TA-p73/p63 may increase the expression of let-7, which, in turn, inhibits lin-28 expression to inhibit reprogramming. Therefore, inhibiting the expression of TA-p73/p63 will be useful in improving reprogramming efficiency. Analysis of microarray data with bioinformatics and computational biology approach revealed that p53/TA-p73/p63-microRNAs could disrupt the core-reprogramming network in ES cells and thereby they could inhibit self-renewal and reprogramming. Remarkably, miR-106 appears to increase the expression of TA-p73 by suppressing its negative regulator, Itch, indicating that by inhibiting the expression of TA-p73/p63 through anti-miR-106, one could increase the efficiency of reprogramming. This study will present molecular insights into why eliminating tumor suppressor function is indispensable for improving reprogramming efficiency. 

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Tumor suppressors p53, p63, and p73 inhibit migrating cancer stem cells by increasing the expression of stem cell suppressing miRNAs

ZEB1/2 has been shown to suppress the expression of the tumor suppressors E-cadherin, TA-p73, INK4b, CDKN1a, and thereby promotes epithelial to mesenchymal transition, invasion, and metastasis. I have recently shown that p53-dependent miRs, such as miR-192, 215, 145, 203, 200b/c, 183, suppress the expression of ZEB1/2. Another recent study showed that ZEB1/2 suppresses the expression of miR-200b/c, miR-203, & miR-183, which in turn, inhibit the expression of stem cell factors, such as Sox-2, Klf-4, and BMI. ZEB1/2, by inhibiting the expression of stem cell factors suppressing miRs, it up regulates the expression of stem cell factors. By up regulating the stem cell factors and down regulating metastasis suppressors, ZEB1/2 promotes both metastasis and migration of cancer stem cells. p53/p63/p73, by down regulating the expression of ZEB1/2 through its target miRNAs, it could activate the expression of stem cell suppressing miRNAs, such as miR-200b/c, miR-203 & miR-183. Thereby, it could inhibit the expression of stem cell factors, such as Sox-2, Klf-4 and BMI-1(an inhibitor of INK4a/ARF). In addition, p53/p63/p73 appears to inhibit the expression of other EMT inducers, such as Snail1/2 and Twist, expression through its target miRs. Remarkably, bioinformatics analysis of stem cell factors suppressing miRNAs, miR-200, miR-183, miR-141, and miR-203, promoters revealed a number of p53/p63/p73 responsive elements, indicating that they could be direct transcriptional targets of p53/TA-p63/p73. Together, these data suggest that p53/TA-p63/p73, by suppressing the expression of ZEB1/2, Snail1/2, and Twist through its target miRs, it could inhibit migration, metastasis, and proliferation of cancer stem cells. In conclusion, the data presented here provide mechanistic insights into how TA-p63/p73 and p53 function as metastasis suppressors. 

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Curcumin Functions as a Positive Regulator of miRNA Processing & a Negative Regulator of Cancer Stem Cell Proliferation

Identifying agents that inhibit the proliferation of cancer stem cells is of great importance in cancer biology. Curcumin has been shown to function as an anti-cancer agent. One of the tumor suppressors that appear to be induced in response to curcumin treatment is p53. A recent study suggests that curcumin increases the expression of miRNAs, such as miR-22, miR-181a, b, c, miR-34, miR-103, and miR-21. Intriguingly, miR-34, 181b, c, miR-103, miR-21, and miR-24 have been identified as transcriptional targets of the tumor suppressor p53. This data suggests a possibility that curcumin, by inducing the expression of p53, it could increase the expression of these microRNAs. A number of groups have shown that c-Myc, Sox-2, Klf-4, Oct-4, Sox-2, Nanog, and Lin28 are required for reprogramming of differentiated cells into pluripotent stem cells and for cancer stem cell proliferation. Interestingly, miR-21 has recently been shown to represses stem cell factors such as Oct4, Nanog, sox2, and c-Myc, indicating that curcumin by increasing the expression of miR-21, it could inhibit cancer stem cell proliferation. In addition, curcumin induced p53 may result in increased expression of its target, miR-145. Interestingly, it has recently been shown that miR-145 suppresses the expression of c-myc, klf-4, Oct-4, and Sox-2 in human embryonic stem cells (hESCs) and thereby promotes the differentiation of hESC. This data suggests that p53-dependent miR-145 expression will result in down regulation of Oct-4, Klf-4, Sox-2, Nanog, and c-myc and inhibition of stem cell proliferation. Further, curcumin induced miR-22 appears to inhibit the expression of estrogen receptor α. Remarkably, it has recently been shown that estrogen receptor α inhibits the processing of several microRNAs, including the tumor suppressor miR-145. This data suggests that curcumin, by inhibiting the expression of estrogen receptor α. through its target miR-22, it could increase the processing of miR-145 and down regulate the expression of its target genes (Oct-4, Klf-4, Sox-2, Nanog, and c-myc). Thereby, curcumin could function as a positive regulator of miRNA processing and a negative regulator of cancer stem cell proliferation. 

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