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Abstract: Chicory, or ‘Cichorium intybus’, is an erect perennial herb that can be used to treat a variety of diseases, including enteric sickness, diabetes, haemorrhoids, malaria, allergies, digestive issues, and more. The enzyme, called 6G-FFT, uses 1-kestose as a substrate for the synthesis of the more complex and branched fructans. To understand the residues involved in this conjugation reaction between 6G-FFT and 1-kestose, molecular docking study was performed. The amino acids ASP157, ASP33, SER32, TRP57, GLU211, ASP244, and GLU117 of the 6G-FFT protein showed a good interaction with the ligand by SP (Standard Precision) docking studies. Results for XP (Extra Precision) docking studies also suggest the amino acids THR153, GLU117, ASP244, GLU211, TRP57, ASP33 and ASP157 interact with the docking score of -10.6 Kcal/mol. Among these interacting amino acids, GLU117, ASP244, GLU211, TRP57, ASP33, and ASP157 were found to be common in both methods. This in silico study will be beneficial for further exploring conjugation reactions in Cichorium intybus.

Abstract: Breast cancer is one of the most frequent invasive malignancies in women globally and the leading cause of mortality. The HER2 target is an important therapeutic option for treating breast cancer. In the present study, efforts have been made to virtually screen the natural kinase inhibitors through molecular docking. A total of 800 HER2 protein inhibitor compounds were selected to screen out the potential inhibitors of the HER2 protein. The docking study demonstrated that these HER2 protein inhibitors confirm the strong binding interaction with HER2 protein based on the docking score, indicating that kinase inhibitors can play a major role in preventing breast cancer. Among all the inhibitors, the flavanone compound named 6-C-(3-Hydroxyisopentyl) eriodictyol, IUPAC: 2-(3, 4- dihydroxyphenyl)-5, 7-dihydroxy-6-(3-hydroxy-3-methylbutyl)- 2, 3-dihydrochromen-4-one observed to have the maximum docking score value of (-8.717), indicating the highest binding affinity with HER2 protein which might serve as the promising compound for the development of a new class of drug to combat breast cancer.

Background: Cichorium intybus is a perennial herb in the Asteraceae family that has significant ethano-medical properties and is utilized in Ayurveda and Unani therapy. The enzyme costunolide synthase contributes in the biosynthesis pathway of sesquiterpene lactones, which is thought to give the plant antimalarial action. Methods: This work uses several in-silico techniques along with docking experiments to show the structural and physiochemical characteristics of the enzyme costunolide synthase. Costunolide synthase protein interacts with lactucin and lactucopicrin with lower energy interactions of -4.99 kcal/mol for total 3 hydrogen bonds and -6.55 kcal/mol for total 2 hydrogen bonds, respectively. One domain named CYP 450 has been found which catalyzes a variety of oxidative reactions of a large number of structurally different compounds that are both endogenous and exogenous from all major domains of life. The mitochondrial cellular localization of protein was revealed with a maximum score of 1.833. Results: The phylogenetic study revealed that the enzyme costunolide synthase from Cichorium intybus has a greater resemblance to Cichorium endivia and Lactuca sativa of costunolide synthase. Molecular docking findings of sesquiterpene lactones (lactucin and lactucopicrin) with Plasmepsin II protein of P. falciparum parasites after clinical trials with sesquiterpene lactones may give the more evidences and explanations for the active involvement of lactucin and lactucopicrin as an antimalarial compound. Conclusion: This research will be used in future wet lab studies to figure out how the costunolide synthase enzyme regulates sesquiterpene lactones and to investigate additional regulatory enzyme involved in the synthesis of sesquiterpene lactones.

Traditionally, intelligence was considered to be a mental skill that primarily consisted of two narrow spheres: mathematical / logical and oral / linguistic, or IQ. Howard Gardner expanded this little idea to include many intellectuals. Later, Daniel Goleman introduced a new type of ability, emotional intelligence (EI), the ability to understand personal and others' emotions. The construction of more intelligence, as well as emotional intelligence in particular, has received a lot of attention recently, especially in terms of leadership capacity. There is some evidence that EI traits (e.g., self-awareness, self-control, motivation, public awareness, and relationship management) may be better predictors of leadership performance and success than traditional “intelligence quotient,” or IQ.

Background: Lactucine is related to the sesquiterpene lactone group of naturally occurring compounds and has a variety of pharmacological effects including anticancer properties found in Chicory, Wormwood, Laurus nobilis, Pyrethrum, Chamomile, etc. Lactucine has an anticancer effect which may induce apoptosis in cancerous cells and protect other cells from getting infected. Objective: In this study, Lactucine and its derivatives were screened, and performed their in-silico docking study with the proteins involved in the apoptosis-inducing effect in human leukemia cancer. Methods: The three-dimensional structure of lactucine and its derivatives were retrieved in the SDF format. Active sites of protein structures were determined by Sitemap. LigPrep module was used for geometrical refining of chemical structures of lactucine and its derivatives. The protein preparation wizard of Maestro (Schrodinger) was used for protein preparation. From the receptor-complex structure, the cocrystallized ligands were removed from the active site position of the receptor chain. All ligands were docked using default Glide settings for a grid centered on the ligand and structure. Flexible docking was performed using the extra precision (XP) feature of Glide module. The best docking poses for the lactucine and their derivatives were selected based on their docking score. The ADMET properties of lactucine 15-oxalate have been predicted by admetSAR software. Results: Proteins and ligands three-dimensional structures were retrieved from PDB and Pubchem databases, respectively. All lactucine derivatives suitably docked on the apoptosis-inducing proteins with ample Glide scores Lactucin 15-oxalate interacts with proteins which are responsible for apoptosis with a maximum of six H-bonds. Other types of interactions are also involved, like Pi-cation, Pi-Pi stacking, salt bridges, and halogen bonds. Protein CDK-4 has shown the highest number of H-bond (LYS142 salt bridges), ALA16, VAL14, ASP99, LYS35, TYR17, and ASN145) with the Lactucin 15-oxalate.. ADMET properties of lactucin 15-oxalate met with the criteria of being eligible to be a novel drug for the treatment of human leukemia cancer. The Dock score of both the Dasatinib drug and the lactucine-15-oxalate with the apoptosis-inducing protein stipulates that the selected ligand has equitable interaction with the target proteins. Conclusion: In this study, lactucine derivatives were docked with apoptosis-inducing proteins for the prediction of its anticancer effect. Lactucin15-oxalate has shown the highest binding affinity for the CDK-4 target and can be used as a lead compound for cancer treatment. Glide and Dock score for docking of lactucin 15-oxalate with CDK-4, well as the number of hydrogen bonding, is in agreement to use this ligand for study. These in-silico results are valuable to proceed with the in vitro and in vivo studies related to the anti-cancer role of lactucin 15-oxalate.

Fermi surfaces can undergo sharp transitions under smooth changes of parameters. Such transitions can have a topological character, as is the case when a higher-order singularity, one that requires cubic or higher-order terms to describe the electronic dispersion near the singularity, develops at the transition. When time-reversal and inversion symmetries are present, odd singularities can only appear in pairs within the Brillouin zone. In this case, the combination of the enhanced density of states that accompany these singularities and the nesting between the pairs of singularities leads to interaction driven instabilities. We present examples of single $n=3$ (monkey saddle) singularities when time-reversal and inversion symmetries are broken. We then turn to the question of what instabilities are possible when the singularities are isolated. For spinful electrons, we find that the inclusion of repulsive interactions destroys any isolated monkey-saddle singularity present in the noninteracting spectrum by developing Stoner or Lifshitz instabilities. In contrast, for spinless electrons and at the mean-field level, we show that an isolated monkey-saddle singularity can be stabilized in the presence of short-range repulsive interactions., 13 pages, 7 figures

Researchers discovered that diets rich in anthocyanin-rich fruits and vegetables significantly impacted gut flora. To conclude, large-scale randomized controlled clinical trials are challenging to conduct; therefore, merging data from multiple small studies may aid. A systematic review collects and analyses all research on a particular subject and design. This comprehensive review and meta-analysis examined the influence of dietary anthocyanins on Firmicutes/Bacteroide (Fir/Bac) and short-chain fatty acids (SCFAs) content. The current meta-analysis followed the guidelines of PRISMA—the preferred reporting items for systematic reviews and meta-analyses. Diets high in anthocyanins substantially reduced the Fir/Bac ratio in the assessed trials. Among three SCFAs, the highest impact was observed on acetic acid, followed by propionic acid, and then butanoic acid. The meta-analysis results also obtained sufficient heterogeneity, as indicated by I2 values. There is strong evidence that anthocyanin supplementation improves rodent gut health biomarkers (Fir/Bac and SCFAs), reducing obesity-induced gut dysbiosis, as revealed in this systematic review/meta-analysis. Anthocyanin intervention duration and dosage significantly influenced the Fir/Bac ratio and SCFA. Anthocyanin-rich diets were more effective when consumed over an extended period and at a high dosage.

Colored wheat has gained enormous attention from the scientific community, but the information available on the anthocyanin biosynthetic genes is very minimal. The study involved their genome-wide identification, in silico characterization and differential expression analysis among purple, blue, black and white wheat lines. The recently released wheat genome mining putatively identified eight structural genes in the anthocyanin biosynthesis pathway with a total of 1194 isoforms. Genes showed distinct exon architecture, domain profile, regulatory elements, chromosome emplacement, tissue localization, phylogeny and synteny, indicative of their unique function. RNA sequencing of developing seeds from colored (black, blue and purple) and white wheats identified differential expressions in 97 isoforms. The F3H on group two chromosomes and F3′5′H on 1D chromosomes could be significant influencers in purple and blue color development, respectively. Apart from a role in anthocyanin biosynthesis, these putative structural genes also played an important role in light, drought, low temperature and other defense responses. The information can assist in targeted anthocyanin production in the wheat seed endosperm.

We propose that doped Weyl semimetals with four Weyl points are natural candidates to realize higher-order topological superconductors, which exhibit a fully gapped bulk while the surface hosts robust gapless chiral hinge states. We show that in such a doped Weyl semimetal, a featureless finite-range attractive interaction favors a $p+ip$ pairing symmetry. By analyzing its topological properties, we identify such a chiral pairing state as a higher-order topological superconductor, which depending on the existence of a four-fold roto-inversion symmetry $\mathsf{R}_{4z}$, is either intrinsic (meaning that the corresponding hinge states can only be removed by closing the bulk gap, rather than modifying the surface states) or extrinsic. We achieve this understanding via various methods recently developed for higher-order topology, including Wannier representability, Wannier spectrum, and defect classification approaches. For the $\mathsf{R}_{4z}$ symmetric case, we provide a complete classification of the higher-order topological superconductors. We show that such second-order topological superconductors exhibit chiral hinge modes that are robust in the absence of interaction effects but can be eliminated at the cost of introducing surface topological order., 20 pages, 14 figures

We study the dissipative dynamics of a periodically driven inhomogeneous critical lattice model in one dimension. The closed system dynamics starting from pure initial states is well-described by a driven Conformal Field Theory (CFT), which predicts the existence of both heating and non-heating phases in such systems. Heating is inhomogeneous and is manifested via the emergence of black-hole like horizons in the system. The robustness of this CFT phenomenology when considering thermal initial states and open systems remains elusive. First, we present analytical results for the Floquet CFT time evolution for thermal initial states. Moreover, using exact calculations of the time evolution of the lattice density matrix, we demonstrate that for short and intermediate times, the closed system phase diagram comprising heating and non-heating phases, persists for thermal initial states on the lattice. Secondly, in the fully open system with boundary dissipators, we show that the nontrivial spatial structure of the heating phase survives particle-conserving and non-conserving dissipations through clear signatures in mutual information and energy density evolution., SciPost Physics, 13 (5), ISSN:2542-4653

Drug discovery and optimization of lead compounds become complex when 3D structures of macromolecules are not available. The advancement in computer-aided drug designing and high-throughput virtual screening has opened new doors for significant therapeutic approaches in modern technology instead of conventional methods, which are found to be cost-effective and time-consuming. So, this carried to be striving area across the world. Because of this problem, the idea of ligand-based drug designing has thrown light on the similarity principle where similar molecules exhibit similar biological properties. The unification of these methodologies led to an expanding area in the chemical and biological data, along with the rise in the difficulty of the R&D process. Here, we discussed the methods used for pharmacophore modeling, hypothesis building and validation, and quantitative structure–activity relationship analysis.

Proteins are very flexible biomolecules. The accurate knowledge of protein structure is very important from its functional point of view. In protein structure prediction, the three-dimensional structure of a protein is modeled from its amino acid sequence using knowledge-based approaches. Computational algorithms and tools have made significant improvements in the field of structural modeling. Protein structure prediction methods include comparative modeling (homology modeling), threading, and ab initio approach. Several tools and software have been developed for the 3D modeling of proteins. Each protein modeling methods have certain limitations that should be kept in mind while selecting a tool for structure modeling. The structural details of X-ray crystallography and nuclear magnetic resonance spectroscopy-verified protein structures guide the development of modeling software and also useful in assessing the accuracy of the protein model.

Finger millet (Eleusine coracana L.) is climate resilient minor millet of Asia and Africa with wide adaptation and unparallel nutritional profile. To date, genomic resources available in finger millet are scanty and genetic control of agronomic traits remains elusive. Here, a collection of eco-geographically diverse 186 genotypes was quantified for variation in 13 agronomic traits and reaction to blast to identify marker-trait associations (MTAs) using genotyping-by-sequencing (GBS) and genome-wide association study (GWAS). GBS generated 2977 high quality single nucleotide polymorphism (SNPs) markers and identified three subpopulations with varying admixture levels. General linear and mixed model approaches of GWAS to correct for population structure and genetic relatedness identified 132 common MTAs for agronomic traits across the years. The phenotypic variance explained by the makers varied from 4.8% (TP692389-flag leaf width) to 20% (TP714446-green fodder weight). Of these, 26 MTAs showed homology with candidate genes having role in plant growth, development and photosynthesis in the genomes of foxtail millet, rice, maize, wheat and barley. We also found 4 common MTAs for neck blast resistance, which explained 5.9-15.1% phenotypic variance. Three MTAs for neck blast resistance showed orthologues in related genera having putative functions in pathogen defense in plants. The results of this work lay a foundation for understanding the genetic architecture of agronomic traits and blast resistance in finger millet and provide a framework for genomics assisted breeding.

In the present computational study, we found that lactucin 15-oxalate a chemical component present in the cichorium intybus (chicory) has a potential apoptosis inducing effect in human leukemia cancer cell and may acts as an anticancer agent. Lactucine and its derivatives were used as ligand molecules to trace out its binding interactions with proteins involved in apoptosis and these ligands were docked with different apoptosis inducing protein such as caspases, cytochrome C, apaf-1, CDKs, etc involved in cell cycle regulation. Among lactucine derivatives, the lactucin 15-oxalate showed virtuous affinity for the apoptosis inducing protein. In addition to this, the number of the hydrogen bonding was higher with lactucin 15-oxalate as compare to other derivatives which indicates its suitability as an anticancer agent. An apoptosis inducing agent if implemented for the treatment of leukemia cancer, then it can reduce the use of multidrug dose therapy and chemotherapeutic drugs. However, different in vitro as well as clinical trials are needed for further validation of the lactucin 15-oxalate.

As exemplified by the growing interest in the quantum anomalous Hall effect, the research on topology as an organizing principle of quantum matter is greatly enriched from the interplay with magnetism. In this vein, we present a combined electrical and thermoelectrical transport study on the magnetic Weyl semimetal ${\mathrm{EuCd}}_{2}{\mathrm{As}}_{2}$. Unconventional contribution to the anomalous Hall and anomalous Nernst effects were observed both above and below the magnetic transition temperature of ${\mathrm{EuCd}}_{2}{\mathrm{As}}_{2}$, indicating the existence of significant Berry curvature. ${\mathrm{EuCd}}_{2}{\mathrm{As}}_{2}$ represents a rare case in which this unconventional transverse transport emerges both above and below the magnetic transition temperature in the same material. The transport properties evolve with temperature and field in the antiferromagnetic phase in a different manner than in the paramagnetic phase, suggesting different mechanisms to their origin. Our results indicate ${\mathrm{EuCd}}_{2}{\mathrm{As}}_{2}$ is a fertile playground for investigating the interplay between magnetism and topology, and potentially a plethora of topologically nontrivial phases rooted in this interplay.

The recently introduced topological quantum chemistry (TQC) framework has provided a description of universal topological properties of all possible band insulators in all space groups based on crystalline unitary symmetries and time reversal. While this formalism filled the gap between the mathematical classification and the practical diagnosis of topological materials, an obvious limitation is that it only applies to weakly interacting systems-which can be described within band theory. It is an open question to which extent this formalism can be generalized to correlated systems that can exhibit symmetry protected topological phases which are not adiabatically connected to any band insulator. In this work we address the many facettes of this question by considering the specific example of a Hubbard diamond chain. This model features a Mott insulator, a trivial insulating phase and an obstructed atomic limit phase. Here we discuss the nature of the Mott insulator and determine the phase diagram and topology of the interacting model with infinite density matrix renormalization group calculations, variational Monte Carlo simulations and with many-body topological invariants. We then proceed by considering a generalization of the TQC formalism to Green's functions combined with the concept of topological Hamiltonian to identify the topological nature of the phases, using cluster perturbation theory to calculate the Green's functions. The results are benchmarked with the above determined phase diagram and we discuss the applicability and limitations of the approach and its possible extensions., 16 pages, 13 figures

Millets and pseudocereals are ancient domesticated food grains and continue to be staple foods for a large segment of Asian, African and Andean population. They are nutritionally superior to major cereals in terms of slow digestible carbohydrates, non-allergenic proteins, dietary fibre and micronutrients. They contain 55–75% starch, 7–15% protein, 2–5% lipid, 2–4% minerals, and 7–15% dietary fibre. The unique nutritional features of these food grains lay in the health beneficial nutraceutical contents. The nutritional and health benefits of millets and pseudocereals have been very well documented and they are recommended to minimize the intensity as well as management of non-communicable diseases such as diabetes, cardiovascular diseases, and obesity. The nutritional and health benefits of these grains have been receiving increased attention and efforts are being made to provide them to the non-traditional consumers worldwide in convenience ready-to-cook and ready-to-eat forms. In the present scenario of sedentary life style, prevention of life style related diseases and to lead healthy life, regular consumption of millets, and pseudocereals is highly desirable.

Although the food systems in developing countries have changed dramatically since the green revolution, malnutrition still remains a challenge and is now known to include the concurrent dimensions of under-nourishment and micronutrient deficiency as a serious issue in developing as well as developed countries. An average cereal protein value of 10% will give us the total cereal protein production of approximately 17 million tons annually. The accumulation of seed protein is a complicated characteristic and seed storage proteins are proteins that considerably accumulate in developing seed, whose principal role is to behave as the nitrogen, carbon, and sulfur storage reserve. These proteins are mobilized quickly during the germination of seeds and are the principal cause of nitrogen reduction to increasing plantings. In particular, the enzymatic functions of seed storage proteins are not known although proteins are structurally distinct in storage from various crops, they all have certain prevalent features. Plant storage proteins may be categorized into two categories; proteins from seed storage (SSPs) and plant storage (VSPs). SSPs are a group of proteins that accumulate in seeds at high concentrations in the late stages of seed development, whereas VSPs are protein accumulation in vegetative tissues, such as roots and tubers, based on plant species. SSPs are depleted during germination, and the subsequent amino acids are used as a food source by the growing seedlings. The most popular proteins in crops are the SSPs and the most commonly consumed plant proteins by human beings are crop proteins. Millets are considered as an enriched source of many essential amino acids derived from many quality proteins. According to World Health Organization, the proteins harboring more than 40% essential amino acids are called quality proteins and upon digestion and hydrolytic cleavage, several bioactive peptides having multiple health attributes are generated. In this chapter, we have briefly described about the proteins and peptides and their role in nutritional improvement present in millet.

We prove two Lieb-Schultz-Mattis type theorems that apply to any translationally invariant and local fermionic $d$-dimensional lattice Hamiltonian for which fermion-number conservation is broken down to the conservation of fermion parity. We show that when the internal symmetry group $G^{\,}_{f}$ is realized locally (in a repeat unit cell of the lattice) by a nontrivial projective representation, then the ground state cannot be simultaneously nondegenerate, symmetric (with respect to lattice translations and $G^{\,}_{f}$), and gapped. We also show that when the repeat unit cell hosts an odd number of Majorana degrees of freedom and the cardinality of the lattice is even, then the ground state cannot be simultaneously nondegenerate, gapped, and translation symmetric., Comment: 51 pages with 2 figures

The spin-1/2 Heisenberg model on the pyrochlore lattice is an iconic frustrated three-dimensional spin system with a rich phase diagram. Besides hosting several ordered phases, the model is debated to possess a spin-liquid ground state when only nearest-neighbor antiferromagnetic interactions are present. Here, we contest this hypothesis with an extensive numerical investigation using both exact diagonalization and complementary variational techniques. Specifically, we employ a RVB-like many-variable Monte Carlo ansatz and convolutional neural network quantum states for (variational) calculations with up to $4\times 4^3$ and $4 \times 3^3$ spins, respectively. We demonstrate that these techniques yield consistent results, allowing for reliable extrapolations to the thermodynamic limit. Our main results are (1) the determination of the phase transition between the putative spin-liquid phase and the neighboring magnetically ordered phase and (2) a careful characterization of the ground state in terms of symmetry-breaking tendencies. We find clear indications of spontaneously broken inversion and rotational symmetry, calling the scenario of a featureless quantum spin-liquid into question. Our work showcases how many-variable variational techniques can be used to make progress in answering challenging questions about three-dimensional frustrated quantum magnets., Comment: 9 pages, 5 figures

The future of food and sustainability of the staple food crops are of utmost importance in the 21st century. Micronutrient deficiency, for example, in iron and zinc, is a common cause of human diseases. Mineral content of the staple food crops has therefore crosscutting importance for food engineering and planetary health. Finger millet, a staple food of agricultural importance worldwide, is rich in iron and zinc, and an ideal model to study the prospects of biofortified foods in times of climate change. We report here a multiomics study of the iron and zinc homeostasis in the finger millet. We identified and characterized 15 candidate genes potentially involved in iron and zinc homeostasis pathways in the finger millet. Structural and functional annotation of the candidate genes revealed a high similarity index with their respective homologs (Oryza sativa, Triticum aestivum, Zea mays, Hordeum vulgare, and Setaria italica). Transcriptome-wide expression analysis showed that genes involved in uptake and translocation of iron and zinc are highly expressed in the GP-1 genotype, while those involved in bioavailability of iron and zinc are expressed more in the GP-45 genotype of the finger millet. In conclusion, finger millet, being a stress-resilient crop, utilizes a combination of strategies in iron and zinc homeostasis pathway, which appear to play an important role in food crop acquisition of iron and zinc, despite environmentally limiting conditions. These data offer molecular insights on iron and zinc accumulation and paves the way for new strategies toward staple food crop with mineral biofortification.

We analyze the topological properties of a chiral ${p}+i{p}$ superconductor for a two-dimensional metal/semimetal with four Dirac points. Such a system has been proposed to realize second-order topological superconductivity and host corner Majorana modes. We show that with an additional $\mathsf{C}_4$ rotational symmetry, the system is in an intrinsic higher-order topological superconductor phase, and with a lower and more natural $\mathsf{C}_2$ symmetry, is in a boundary-obstructed topological superconductor phase. The boundary topological obstruction is protected by a bulk Wannier gap. However, we show that the well-known nested-Wilson loop is in general unquantized despite the particle-hole symmetry, and thus fails as a topological invariant. Instead, we show that the higher-order topology and boundary-obstructed topology can be characterized using an alternative defect classification approach, in which the corners of a finite sample is treated as a defect of a space-filling Hamiltonian. We establish "Dirac+$({p}+i{p})$" as a sufficient condition for second-order topological superconductivity., 11 pages, 6 figures

Many of the experiments in twisted bilayer graphene (TBG) differ from each other in terms of the details of their phase diagrams. Few controllable aspects aside, this discrepancy is largely believed to be arising from the presence of a varying degree of twist angle inhomogeneity across different samples. Real space maps indeed reveal TBG devices splitting into several large domains of different twist angles. Motivated by these observations, we study the quantum mechanical tunneling across a domain wall (DW) that separates two such regions. We show that the tunneling of the moir\'e particles can be understood by the formation of an effective step potential at the DW. The height of this step potential is simply a measure of the difference in twist angles. These computations lead us to identify the global transport signatures for detecting and quantifying the local twist angle variations. In particular, Using Landauer-B\"uttiker formalism we compute single-channel conductance ($dI/dV$) and Fano factor for shot noise (ratio of noise power and mean current). A zero-bias, sub-meV transport gap is observed in the conductance which scales with the height of the step potential. One of the key findings of our work is that transport in presence of twist angle inhomogeneity is "noisy", though sub-Poissonian. In particular, the differential Fano factor peaks near the van Hove energies corresponding to the domains in the sample. The location and the strength of the peak is simply a measure of the degree of twist angle inhomogeneity., Comment: 17 pages, 14 figures