Cluster Analysis and Model Comparison Using Smart Meter Data.

Load forecasting plays a crucial role in the world of smart grids. It governs many aspects of the smart grid and smart meter, such as demand response, asset management, investment, and future direction. This paper proposes time-series forecasting for short-term load prediction to unveil the load forecast benefits through different statistical and mathematical models, such as artificial neural networks, auto-regression, and ARIMA. It targets the problem of excessive computational load when dealing with time-series data. It also presents a business case that is used to analyze different clusters to find underlying factors of load consumption and predict the behavior of customers based on different parameters. On evaluating the accuracy of the prediction models, it is observed that ARIMA models with the (P, D, Q) values as (1, 1, 1) were most accurate compared to other values

Phosphoenolpyruvate carboxykinase maintains glycolysis-driven growth in Drosophila tumors

Published online: 14 September 2017Tumors frequently fail to pass on all their chromosomes correctly during cell division, and this chromosomal instability (CIN) causes irregular aneuploidy and oxidative stress in cancer cells. Our objective was to test knockdowns of metabolic enzymes in Drosophila to find interventions that could exploit the differences between normal and CIN cells to block CIN tumor growth without harming the host animal. We found that depleting by RNAi or feeding the host inhibitors against phosphoenolpyruvate carboxykinase (PEPCK) was able to block the growth of CIN tissue in a brat tumor explant model. Increasing NAD+ or oxidising cytoplasmic NADH was able to rescue the growth of PEPCK depleted tumors, suggesting a problem in clearing cytoplasmic NADH. Consistent with this, blocking the glycerol-3-phosphate shuttle blocked tumor growth, as well as lowering ROS levels. This work suggests that proliferating CIN cells are particularly vulnerable to inhibition of PEPCK, or its metabolic network, because of their compromised redox status.Rashid Hussain, Zeeshan Shaukat, Mahwish Khan, Robert Saint and Stephen L. Gregor

Chromosomal instability causes sensitivity to protein folding stress and ATP depletion

Aneuploidy -- having an unbalanced genome - is poorly tolerated at the cellular and organismal level. It gives rise to proteotoxic stress as well as a stereotypical oxidative shift which makes these cells sensitive to internal and environmental stresses. Using Drosophila as a model, we found that protein folding stress is exacerbated by redox stress that occurs in response to ongoing changes to ploidy (chromosomal instability, CIN). We also found that if de novo nucleotide synthesis is blocked, CIN cells are dependent on a high level of lysosome function to survive. Depletion of adenosine monophosphate (AMP) synthesis enzymes led to DNA damage in CIN cells, which showed elevated activity of the DNA repair enzyme activated poly(ADP ribose) polymerase (PARP). PARP activation causes depletion of its substrate, nicotinamide adenine dinucleotide (NAD+) and subsequent loss of Adenosine Tri-Phosphate (ATP), and we found that adding ATP or nicotinamide (a precursor in the synthesis of NAD+) could rescue the observed phenotypes. These findings provide ways to interpret, target and exploit aneuploidy, which has the potential to offer tumour-specific therapies.Mahwish Khan, Zeeshan Shaukat, Robert Saint and Stephen L. Gregor

Chromosomal instability triggers cell death via local signalling through the innate immune receptor Toll

Chromosomal instability (CIN) is a hallmark of cancer and has been implicated in cancer initiation, progression and the development of resistance to traditional cancer therapy. Here we identify a new property of CIN cells, showing that inducing CIN in proliferating Drosophila larval tissue leads to the activation of innate immune signalling in CIN cells. Manipulation of this immune pathway strongly affects the survival of CIN cells, primarily via JNK, which responds to both Toll and TNFα/Eiger. This pathway also activates Mmp1, which recruits hemocytes to the CIN tissue to provide local amplification of the immune response that is needed for effective elimination of CIN cells.Dawei Liu, Zeeshan Shaukat, Robert B. Saint, and Stephen L. Gregor

A Screen for selective killing of cells with chromosomal instability induced by a spindle checkpoint defect

BACKGROUND: The spindle assembly checkpoint is crucial for the maintenance of a stable chromosome number. Defects in the checkpoint lead to Chromosomal INstability (CIN), which is linked to the progression of tumors with poor clinical outcomes such as drug resistance and metastasis. As CIN is not found in normal cells, it offers a cancer-specific target for therapy, which may be particularly valuable because CIN is common in advanced tumours that are resistant to conventional therapy. PRINCIPAL FINDINGS: Here we identify genes that are required for the viability of cells with a CIN phenotype. We have used RNAi knockdown of the spindle assembly checkpoint to induce CIN in Drosophila and then screened the set of kinase and phosphatase genes by RNAi knockdown to identify those that induce apoptosis only in the CIN cells. Genes identified include those involved in JNK signaling pathways and mitotic cytoskeletal regulation. CONCLUSIONS/SIGNIFICANCE: The screen demonstrates that it is feasible to selectively kill cells with CIN induced by spindle checkpoint defects. It has identified candidates that are currently being pursued as cancer therapy targets (e.g. Nek2: NIMA related kinase 2), confirming that the screen is able to identify promising drug targets of clinical significance. In addition, several other candidates were identified that have no previous connection with mitosis or apoptosis. Further screening and detailed characterization of the candidates could potentially lead to the therapies that specifically target advanced cancers that exhibit CIN.Zeeshan Shaukat, Heidi W.S. Wong, Shannon Nicolson, Robert B. Saint and Stephen L. Gregor

Autophagy regulates the survival of cells with chromosomal instability

Chromosomal instability (CIN) refers to genomic instability in which cells have gained or lost chromosomes or chromosomal fragments. A high level of CIN is common in solid tumours and is associated with cancer drug resistance and poor prognosis. The impact of CIN-induced stress and the resulting cellular responses are only just beginning to emerge. Using proliferating tissue in Drosophila as a model, we found that autophagy is activated in CIN cells and is necessary for their survival. Specifically, increasing the removal of defective mitochondria by mitophagy is able to lower levels of reactive oxygen species and the resultant cellular damage that is normally seen in CIN cells. In response to DNA damage, CIN is increased in a positive feedback loop, and we found that increasing autophagy by Tor depletion could decrease the level of CIN in proliferating cells. These findings underline the importance of autophagy control in the development of CIN tumours.Dawei Liu, Zeeshan Shaukat, Tianqi Xu, Donna Denton, Robert Saint, Stephen Gregor

Three novel F8 mutations in sporadic haemophilia A cases

Letter to the editorRashid Hussain, Noman Bin Abid, Sajjad Hussain, Zeeshan Shaukat, Mudassir Altaf, Sara Altaf, and Gulzar Niaz

Local Unit Invariance, Back-Reacting Tractors and the Cosmological Constant Problem

When physics is expressed in a way that is independent of local choices of unit systems, Riemannian geometry is replaced by conformal geometry. Moreover masses become geometric, appearing as Weyl weights of tractors (conformal multiplets of fields necessary to keep local unit invariance manifest). The relationship between these weights and masses is through the scalar curvature. As a consequence mass terms are spacetime dependent for off-shell gravitational backgrounds, but happily constant for physical, Einstein manifolds. Unfortunately this introduces a naturalness problem because the scalar curvature is proportional to the cosmological constant. By writing down tractor stress tensors (multiplets built from the standard stress tensor and its first and second derivatives), we show how back-reaction solves this naturalness problem. We also show that classical back-reaction generates an interesting potential for scalar fields. We speculate that a proper description of how physical systems couple to scale, could improve our understanding of naturalness problems caused by the disparity between the particle physics and observed, cosmological constants. We further give some ideas how an ambient description of tractor calculus could lead to a Ricci-flat/CFT correspondence which generalizes the AdS side of Maldacena's duality to a Ricci-flat space of one higher dimension.Comment: 20 pages, 2 figure

S-Alkylated/aralkylated 2-(1H-indol-3-yl-methyl)-1,3,4- oxadiazole-5-thiol derivatives. 2. Anti-bacterial, enzymeinhibitory and hemolytic activities

Purpose: To evaluate the antibacterial, enzyme-inhibitory and hemolytic activities of Salkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol  derivatives.Methods: Antibacterial activities of the compounds were evaluated using broth dilution method in 96 well plates. Enzyme inhibitory activities assays were investigated against α-glucosidase, butyrylcholinesterase (BchE) and lipoxygenase (LOX) using acarbose, eserine and baicalien as reference standards, respectively. A mixture of enzyme, test compound and the substrate was incubated and variation in absorbance noted before and after incubation. In tests for hemolytic activities, the compounds were incubated with red blood cells and variations in absorbance were used as indices their hemolytic activities.Results: The compounds were potent antibacterial agents. Five of them exhibited very good antibacterial potential similar to ciprofloxacin, and had minimum inhibitory concentrations (MIC) of at least 9.00 ± 4.12 μM against S. aureus, E.coli, and B. subtilis. One of the compounds had strong enzyme inhibitory potential against α-glucosidase, with IC50 of 17.11 ± 0.02 μg/mL which was better than that of standard acarbose (IC50 38.25 ± 0.12 μg/mL). Another compound had 1.5 % hemolytic activity. Conclusion: S-Alkylated/aralkylated 2-(1H-indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol deviratives with valuable antibacterial, anti-enzymatic and hemolytic activities have been successfully synthesized. These compounds may be useful in the development of pharmaceutical products.Keywords: 2-(1H-Indol-3-ylmethyl)-1,3,4-oxadiazole-5-thiol derivatives, Enzyme inhibition, Antibacterial activity, Hemolytic activity, Molecular dockin

Ameliorating heat stressed conditions in wheat by altering its physiological and phenotypic traits associated with varying nitrogen levels

Currently, more than half of the global nations cultivating wheat crops are facing severe consequences of climate change and its associated heat stress in terms of quantitative and qualitative yield losses. Plants exposed to heat stress need a balanced and adequate amount of mineral nutrients to counter its ill effects. Therefore, the present study was designed to investigate the potential effects of heat stress applied during the vegetative growth period (Zadoks growth scale: ZGS 5-60) on physiological and phenotypic traits of wheat (Triticum aestivum) crop subjected to variable rates of nitrogen (N). In this experiment, wheat plants of cv. ‘Punjab-2011’ were exposed to two levels of temperature i.e. heat stress (HS) and control or non-heat stress (NHS), and three N rates (N50 = 50 kg ha-1, N100= 100 kg ha-1 and N150 = 150 kg ha-1). The experiment was executed under controlled conditions in a completely randomized design (CRD) with six replications. One set of eighteen pots containing wheat seedlings was placed in a compartment of the greenhouse under heat-stressed conditions, while another set was placed in another compartment under non-heated conditions. The greenhouse compartments were equipped with a heating and cooling system to maintain desired ecological conditions. Pots in heated chamber were kept for 60 days from emergence (ZGS = 5-60), and then shifted to non-heated chamber till harvesting. The temperature in heat stress treatment was almost 2 ± 0.47 °C higher than in non-heated treatment. The results indicated that HS significantly reduced the photosynthetic rate by 42.52%, leaf photosynthetic efficiency by 56.82%, chlorophyll scores by 20.11%, relative water contents (RWC) by 12.81%, tillers by 48.21%, grain weight by 21.47% and grain yield by 68.20% relative to NHS conditions. These reductions were more prominent in plants subjected to a limited N dose rate (50 kg N ha-1). Furthermore, the results also revealed higher transpiration rate, stomatal conductance, and membrane ruptures under HS with N50 treatment.  However, N150 treatment compensated for the detrimental effects of HS on wheat plants by improving the photosynthetic rate and efficiencies, higher RWC, more stability of membrane and pigments, more tillers, and higher grain weight, and grain yield of wheat. Additionally, grain yield was negatively correlated with transpiration rate, stomatal conductance, internal CO2 concentration, and membrane leakage. In conclusion, a high dose rate of N under high temperatures during vegetative growth could alleviate the magnitude of penalties to grain yield and enhance the potential of wheat crops to withstand heat-induced detrimental effects