Inferring physical laws by artificial intelligence based causal models

The advances in Artificial Intelligence (AI) and Machine Learning (ML) have opened up many avenues for scientific research, and are adding new dimensions to the process of knowledge creation. However, even the most powerful and versatile of ML applications till date are primarily in the domain of analysis of associations and boil down to complex data fitting. Judea Pearl has pointed out that Artificial General Intelligence must involve interventions involving the acts of doing and imagining. Any machine assisted scientific discovery thus must include casual analysis and interventions. In this context, we propose a causal learning model of physical principles, which not only recognizes correlations but also brings out casual relationships. We use the principles of causal inference and interventions to study the cause-and-effect relationships in the context of some well-known physical phenomena. We show that this technique can not only figure out associations among data, but is also able to correctly ascertain the cause-and-effect relations amongst the variables, thereby strengthening (or weakening) our confidence in the proposed model of the underlying physical process.Comment: Latex 12 pages, 16 figure

A quantum tug of war between randomness and symmetries on homogeneous spaces

We explore the interplay between symmetry and randomness in quantum information. Adopting a geometric approach, we consider states as $H$-equivalent if related by a symmetry transformation characterized by the group $H$. We then introduce the Haar measure on the homogeneous space $\mathbb{U}/H$, characterizing true randomness for $H$-equivalent systems. While this mathematical machinery is well-studied by mathematicians, it has seen limited application in quantum information: we believe our work to be the first instance of utilizing homogeneous spaces to characterize symmetry in quantum information. This is followed by a discussion of approximations of true randomness, commencing with $t$-wise independent approximations and defining $t$-designs on $\mathbb{U}/H$ and $H$-equivalent states. Transitioning further, we explore pseudorandomness, defining pseudorandom unitaries and states within homogeneous spaces. Finally, as a practical demonstration of our findings, we study the expressibility of quantum machine learning ansatze in homogeneous spaces. Our work provides a fresh perspective on the relationship between randomness and symmetry in the quantum world.Comment: 9 + 1 pages, 3 figure

Anticancer property of Bryophyllum pinnata (Lam.) Oken. leaf on human cervical cancer cells

<p>Abstract</p> <p>Background</p> <p><it>Bryophyllum pinnata </it>(<it>B. pinnata</it>) is a common medicinal plant used in traditional medicine of India and of other countries for curing various infections, bowel diseases, healing wounds and other ailments. However, its anticancer properties are poorly defined. In view of broad spectrum therapeutic potential of <it>B. pinnata </it>we designed a study to examine anti-cancer and anti-Human Papillomavirus (HPV) activities in its leaf extracts and tried to isolate its active principle.</p> <p>Methods</p> <p>A chloroform extract derived from a bulk of botanically well-characterized pulverized <it>B</it>. <it>pinnata </it>leaves was separated using column chromatography with step- gradient of petroleum ether and ethyl acetate. Fractions were characterized for phyto-chemical compounds by TLC, HPTLC and NMR and Biological activity of the fractions were examined by MTT-based cell viability assay, Electrophoretic Mobility Shift Assay, Northern blotting and assay of apoptosis related proteins by immunoblotting in human cervical cancer cells.</p> <p>Results</p> <p>Results showed presence of growth inhibitory activity in the crude leaf extracts with IC₅₀at 552 μg/ml which resolved to fraction F4 (Petroleum Ether: Ethyl Acetate:: 50:50) and showed IC₅₀at 91 μg/ml. Investigations of anti-viral activity of the extract and its fraction revealed a specific anti-HPV activity on cervical cancer cells as evidenced by downregulation of constitutively active AP1 specific DNA binding activity and suppression of oncogenic c-Fos and c-Jun expression which was accompanied by inhibition of HPV18 transcription. In addition to inhibiting growth, fraction F4 strongly induced apoptosis as evidenced by an increased expression of the pro-apoptotic protein Bax, suppression of the anti-apoptotic molecules Bcl-2, and activation of caspase-3 and cleavage of PARP-1. Phytochemical analysis of fraction F4 by HPTLC and NMR indicated presence of activity that resembled Bryophyllin A.</p> <p>Conclusions</p> <p>Our study therefore demonstrates presence of anticancer and anti-HPV an activity in <it>B</it>. <it>pinnata </it>leaves that can be further exploited as a potential anticancer, anti-HPV therapeutic for treatment of HPV infection and cervical cancer.</p

Differentially localized survivin and STAT3 as markers of gastric cancer progression: Association with Helicobacter pylori

BackgroundLocalization and differential expression of STAT3 and survivin in cancer cells are often related to distinct cellular functions. The involvement of survivin and STAT3 in gastric cancer has been reported in separate studies but without clear understanding of their kinetics in cancer progression.MethodsWe examined intracellular distribution of STAT3 and survivin in gastric adenocarcinoma and compared it with normal and precancer tissues using immunoblotting and immunohistochemistry.ResultsAnalysis of a total of 156 gastric samples comprising 61 histologically normal, 30 precancerous tissues (comprising intestinal metaplasia and dysplasia), and 65 adenocarcinomas, collected as endoscopic biopsies from treatment naïve study participants, revealed a significant (P < .001) increase in overall protein levels. Survivin expression was detectable in both cytoplasmic (90.8%) and nuclear (87.7%) compartments in gastric adenocarcinomas lesions. Precancerous dysplastic gastric lesions exhibited a moderate survivin expression (56.7%) localized in cytoplasmic compartment. Similarly, STAT3 and pSTAT3 expression was detected at high level in gastric cancer lesions. The levels of compartmentalized expression of survivin and STAT3/pSTAT3 correlated in precancerous and adenocarcinoma lesions. Although overexpression of these proteins was found associated with the tobacco use and alcohol consumption, their expression invariably and strongly correlated with concurrent Helicobacter pylori infection. Receiver operating characteristic analysis of nuclear survivin, STAT3, and pSTAT3 in different study groups showed acceptable positive and negative predictive values with area under the curve above 0.8 (P < .001).ConclusionOverall, our results suggest that overall increase in survivin and STAT3 and their subcellular localization are key determinants of gastric cancer progression, which can be collectively used as potential disease biomarkers and therapeutic targets for gastric cancer.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144680/1/cnr21004-Supplementary_Methods_20180313.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144680/2/cnr21004-sup-0001-F1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144680/3/cnr21004_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144680/4/cnr21004.pd

Aberrant expression and constitutive activation of STAT3 in cervical carcinogenesis: implications in high-risk human papillomavirus infection

<p>Abstract</p> <p>Background</p> <p>Recent observations indicate potential role of transcription factor STAT3 in cervical cancer development but its role specifically with respect to HPV infection is not known. Present study has been designed to investigate expression and activation of STAT3 in cervical precancer and cancer in relation to HPV infection during cervical carcinogenesis. Established cervical cancer cell lines and prospectively-collected cervical precancer and cancer tissues were analyzed for the HPV positivity and evaluated for STAT3 expression and its phosphorylation by immunoblotting and immunohistochemistry whereas STAT3-specific DNA binding activity was examined by gel-shift assays.</p> <p>Results</p> <p>Analysis of 120 tissues from cervical precancer and cancer lesions or from normal cervix revealed differentially high levels of constitutively active STAT3 in cervical precancer and cancer lesions, whereas it was absent in normal controls. Similarly, a high level of constitutively active STAT3 expression was observed in HPV-positive cervical cancer cell lines when compared to that of HPV-negative cells. Expression and activity of STAT3 were found to change as a function of severity of cervical lesions from precancer to cancer. Expression of active pSTAT3 was specifically high in cervical precancer and cancer lesions found positive for HPV16. Interestingly, site-specific accumulation of STAT3 was observed in basal and suprabasal layers of HPV16-positive early precancer lesions which is indicative of possible involvement of STAT3 in establishment of HPV infection. In HPV16-positive cases, STAT3 expression and activity were distinctively higher in poorly-differentiated lesions with advanced histopathological grades.</p> <p>Conclusion</p> <p>We demonstrate that in the presence of HPV16, STAT3 is aberrantly-expressed and constitutively-activated in cervical cancer which increases as the lesion progresses thus indicating its potential role in progression of HPV16-mediated cervical carcinogenesis.</p

Catalytic decomposition of 2-chlorophenol using an ultrasonicassisted Fe3O4–TiO2@MWCNT system: influence factors, pathway and mechanism study

As a reusable sonocatalyst, magnetically separable Fe3O4–TiO2@MWCNT (FMT) was synthesized by an ultrasound-assisted wet impregnation method and was evaluated in the removal of 2-chlorophenol (2CP). Physical and chemical properties of the catalyst composite materials were investigated by All catalysts were systematically characterized using Transmission Electron Microscopy (TEM), X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), X-ray Photoelectron Spectroscopy (XPS), Energy Dispersive X-Ray Analysis (EDX), Dynamic light scattering (DLS), and N2-physisorption. The efficiency and kinetics of 2CP removal by FMT-assisted sonocatalysis (FMT-US) was systematically investigated under various operational parameters i.e. pH, FMT and 2CP concentration, temperature and ultrasonic power. The results indicated that 0.4 g L-1 FMT dosage, pH 5, temperature of 35℃ as well as 50 w ultrasound power are the most favorable conditions for the degradation of the 2CP. Furthermore, both of the superoxide and hydroxyl radicals were produced in the reaction, however, superoxide radicals were assumed to be the dominating reactive species for the 2CP degradation, according to the scavenging tests and electron paramagnetic resonance tests. Moreover, the FMT catalyst exhibited a high reusability and stability in the US/FMT system during the five repetitive experiments. The intermediate products were identified by GC–MS, thereby a possible degradation pathway is proposed. The chemical oxygen demand (COD) and corresponding total organic carbon (TOC) removal efficiencies were 64.9% and 56.7%, respectively. Finally, toxicity tests showed that the toxicity of the solution increased during the first 5 min and then decreased significantly with the progress of the oxidation. The mechanisms of ultrasound irritation enhanced FMT activation were also proposed

Phylogenetic Signal Variation in the Genomes of Medicago (Fabaceae)

Genome-scale data offer the opportunity to clarify phylogenetic relationships that are difficult to resolve with few loci, but they can also identify genomic regions with evolutionary history distinct from that of the species history. We collected whole-genome sequence data from 29 taxa in the legume genus Medicago, then aligned these sequences to the Medicago truncatula reference genome to confidently identify 87 596 variable homologous sites. We used this data set to estimate phylogenetic relationships among Medicago species, to investigate the number of sites needed to provide robust phylogenetic estimates and to identify specific genomic regions supporting topologies in conflict with the genome-wide phylogeny. Our full genomic data set resolves relationships within the genus that were previously intractable. Subsampling the data reveals considerable variation in phylogenetic signal and power in smaller subsets of the data. Even when sampling 5000 sites, no random sample of the data supports a topology identical to that of the genome-wide phylogeny. Phylogenetic relationships estimated from 500-site sliding windows revealed genome regions supporting several alternative species relationships among recently diverged taxa, consistent with the expected effects of deep coalescence or introgression in the recent history of Medicago. [Medicago; phylogenomics; whole-genome resequencing.

Methylation-sensitive linking libraries enhance gene-enriched sequencing of complex genomes and map DNA methylation domains

<p>Abstract</p> <p>Background</p> <p>Many plant genomes are resistant to whole-genome assembly due to an abundance of repetitive sequence, leading to the development of gene-rich sequencing techniques. Two such techniques are hypomethylated partial restriction (HMPR) and methylation spanning linker libraries (MSLL). These libraries differ from other gene-rich datasets in having larger insert sizes, and the MSLL clones are designed to provide reads localized to "epigenetic boundaries" where methylation begins or ends.</p> <p>Results</p> <p>A large-scale study in maize generated 40,299 HMPR sequences and 80,723 MSLL sequences, including MSLL clones exceeding 100 kb. The paired end reads of MSLL and HMPR clones were shown to be effective in linking existing gene-rich sequences into scaffolds. In addition, it was shown that the MSLL clones can be used for anchoring these scaffolds to a BAC-based physical map. The MSLL end reads effectively identified epigenetic boundaries, as indicated by their preferential alignment to regions upstream and downstream from annotated genes. The ability to precisely map long stretches of fully methylated DNA sequence is a unique outcome of MSLL analysis, and was also shown to provide evidence for errors in gene identification. MSLL clones were observed to be significantly more repeat-rich in their interiors than in their end reads, confirming the correlation between methylation and retroelement content. Both MSLL and HMPR reads were found to be substantially gene-enriched, with the <it>Sal</it>I MSLL libraries being the most highly enriched (31% align to an EST contig), while the HMPR clones exhibited exceptional depletion of repetitive DNA (to ~11%). These two techniques were compared with other gene-enrichment methods, and shown to be complementary.</p> <p>Conclusion</p> <p>MSLL technology provides an unparalleled approach for mapping the epigenetic status of repetitive blocks and for identifying sequences mis-identified as genes. Although the types and natures of epigenetic boundaries are barely understood at this time, MSLL technology flags both approximate boundaries and methylated genes that deserve additional investigation. MSLL and HMPR sequences provide a valuable resource for maize genome annotation, and are a uniquely valuable complement to any plant genome sequencing project. In order to make these results fully accessible to the community, a web display was developed that shows the alignment of MSLL, HMPR, and other gene-rich sequences to the BACs; this display is continually updated with the latest ESTs and BAC sequences.</p

Role of cytokine in malignant T-cell metabolism and subsequent alternation in T-cell tumor microenvironment

T cells are an important component of adaptive immunity and T-cell-derived lymphomas are very complex due to many functional sub-types and functional elasticity of T-cells. As with other tumors, tissues specific factors are crucial in the development of T-cell lymphomas. In addition to neoplastic cells, T- cell lymphomas consist of a tumor micro-environment composed of normal cells and stroma. Numerous studies established the qualitative and quantitative differences between the tumor microenvironment and normal cell surroundings. Interaction between the various component of the tumor microenvironment is crucial since tumor cells can change the microenvironment and vice versa. In normal T-cell development, T-cells must respond to various stimulants deferentially and during these courses of adaptation. T-cells undergo various metabolic alterations. From the stage of quiescence to attention of fully active form T-cells undergoes various stage in terms of metabolic activity. Predominantly quiescent T-cells have ATP-generating metabolism while during the proliferative stage, their metabolism tilted towards the growth-promoting pathways. In addition to this, a functionally different subset of T-cells requires to activate the different metabolic pathways, and consequently, this regulation of the metabolic pathway control activation and function of T-cells. So, it is obvious that dynamic, and well-regulated metabolic pathways are important for the normal functioning of T-cells and their interaction with the microenvironment. There are various cell signaling mechanisms of metabolism are involved in this regulation and more and more studies have suggested the involvement of additional signaling in the development of the overall metabolic phenotype of T cells. These important signaling mediators include cytokines and hormones. The impact and role of these mediators especially the cytokines on the interplay between T-cell metabolism and the interaction of T-cells with their micro-environments in the context of T-cells lymphomas are discussed in this review article

Physical and Genetic Structure of the Maize Genome Reflects Its Complex Evolutionary History

Maize (Zea mays L.) is one of the most important cereal crops and a model for the study of genetics, evolution, and domestication. To better understand maize genome organization and to build a framework for genome sequencing, we constructed a sequence-ready fingerprinted contig-based physical map that covers 93.5% of the genome, of which 86.1% is aligned to the genetic map. The fingerprinted contig map contains 25,908 genic markers that enabled us to align nearly 73% of the anchored maize genome to the rice genome. The distribution pattern of expressed sequence tags correlates to that of recombination. In collinear regions, 1 kb in rice corresponds to an average of 3.2 kb in maize, yet maize has a 6-fold genome size expansion. This can be explained by the fact that most rice regions correspond to two regions in maize as a result of its recent polyploid origin. Inversions account for the majority of chromosome structural variations during subsequent maize diploidization. We also find clear evidence of ancient genome duplication predating the divergence of the progenitors of maize and rice. Reconstructing the paleoethnobotany of the maize genome indicates that the progenitors of modern maize contained ten chromosomes