Monthly evapotranspiration estimation using optimal climatic parameters: efficacy of hybrid support vector regression integrated with whale optimization algorithm.

For effective planning of irrigation scheduling, water budgeting, crop simulation, and water resources management, the accurate estimation of reference evapotranspiration (ETo) is essential. In the current study, the hybrid support vector regression (SVR) coupled with Whale Optimization Algorithm (SVR-WOA) was employed to estimate the monthly ETo at Algiers and Tlemcen meteorological stations positioned in the north of Algeria under three different optimal input scenarios. Monthly climatic parameters, i.e., solar radiation (Rs), wind speed (Us), relative humidity (RH), and maximum and minimum air temperatures (Tmax and Tmin) of 14 years (2000-2013), were obtained from both stations. The accuracy of the hybrid SVR-WOA model was appraised against hybrid SVR-MVO (Multi-Verse Optimizer), and SVR-ALO (Ant Lion Optimizer) models through performance measures, i.e., mean absolute error (MAE), root-mean-square error (RMSE), index of scattering (IOS), index of agreement (IOA), Pearson correlation coefficient (PCC), Nash-Sutcliffe efficiency (NSE), and graphical interpretation (time-variation and scatter plots, radar chart, and Taylor diagram). The results showed that the SVR-WOA model performed superior to the SVR-MVO and SVR-ALO models at both stations in all scenarios. The SVR-WOA-1 model with five inputs (i.e., Tmin, Tmax, RH, Us, Rs: scenario-1) had the lowest value of MAE = 0.0658/0.0489 mm/month, RMSE = 0.0808/0.0617 mm/month, IOS = 0.0259/0.0165, and the highest value of NSE = 0.9949/0.9989, PCC = 0.9975/0.9995, and IOA = 0.9987/0.9997 for testing period at both stations, respectively. The proposed hybrid SVR-WOA model was found to be more appropriate and efficient in comparison to SVR-MVO and SVR-ALO models for estimating monthly ETo in the study region.

Gold Nanorod-Induced Effects in a Mesogenic Compound 4-(trans-4-n-Hexylcyclohexyl) isothiocyanatobenzene.

Gold nanorods (GNRs) have a capsule-like structure with different optical properties than spherical gold nanoparticles due to surface plasmon resonance. Liquid crystals (LCs) are mesogenic compounds having crystal-like orientation and liquid-like fluidity. They are important materials from a technological point of view. Both GNRs and LC compounds are anisotropic in shape and properties. Different nano entities show interesting results when dispersed in different liquid crystalline materials which are instrumental from the application point of view. In the present work, GNRs have been dispersed in nematic liquid crystalline materials, namely 4-(trans-4-n-hexylcyclohexyl) isothiocyanatobenzene (6CHBT). Calorimetric, texture, spectroscopic, and dielectric studies were carried out for a pure 6CHBT and its composites with GNRs. Different calorimetric and dielectric parameters such as transition temperature, enthalpy, heat flow, permittivity, dielectric strength, dielectric anisotropy, and relaxation frequency have been determined, and the effect of GNRs has been explored. This article gives an insight into the influence of GNRs on the morphology and anisotropic physical properties of the nematic liquid crystalline material.

Forecasting of stage-discharge in a non-perennial river using machine learning with gamma test.

Knowledge of the stage-discharge rating curve is useful in designing and planning flood warnings; thus, developing a reliable stage-discharge rating curve is a fundamental and crucial component of water resource system engineering. Since the continuous measurement is often impossible, the stage-discharge relationship is generally used in natural streams to estimate discharge. This paper aims to optimize the rating curve using a generalized reduced gradient (GRG) solver and the test the accuracy and applicability of the hybridized linear regression (LR) with other machine learning techniques, namely, linear regression-random subspace (LR-RSS), linear regression-reduced error pruning tree (LR-REPTree), linear regression-support vector machine (LR-SVM) and linear regression-M5 pruned (LR-M5P) models. An application of these hybrid models was performed and test to modeling the Gaula Barrage stage-discharge problem. For this, 12-year historical stage-discharge data were collected and analyzed. The 12-year historical daily flow data (m3/s) and stage (m) from during the monsoon season, i.e., June to October only from 03/06/2007 to 31/10/2018, were used for discharge simulation. The best suitable combination of input variables for LR, LR-RSS, LR-REPTree, LR-SVM, and LR-M5P models was identified and decided using the gamma test. GRG-based rating curve equations were found to be as effective and more accurate as conventional rating curve equations. The outcomes from GRG, LR, LR-RSS, LR-REPTree, LR-SVM, and LR-M5P models were compared to observed values of daily discharge based on Nash Sutcliffe model efficiency coefficient (NSE), Willmott Index of Agreement (d), Kling-Gupta efficiency (KGE), mean absolute error (MAE), mean bias error (MBE), relative bias in percent (RE), root mean square error (RMSE) Pearson correlation coefficient (PCC) and coefficient of determination (R2). The LR-REPTree model (combination 1: NSE = 0.993, d = 0.998, KGE = 0.987, PCC(r) = 0.997, and R2 = 0.994 and minimum value of RMSE = 0.109, MAE = 0.041, MBE = -0.010 and RE = -0.1%; combination 2; NSE = 0.941, d = 0.984, KGE = 0. 923, PCC(r) = 0. 973, and R2 = 0. 947 and minimum value of RMSE = 0. 331, MAE = 0.143, MBE = -0.089 and RE = -0.9%) performed superior to the GRG, LR, LR-RSS, LR-SVM, and LR-M5P models in all input combinations during the testing period. It was also noticed that the performance of the alone LR and its hybrid models (i.e., LR-RSS, LR-REPTree, LR-SVM, and LR-M5P) was better than the conventional stage-discharge rating curve, including the GRG method.

Selectively replicating adenoviruses targeting deregulated E2F activity are potent, systemic antitumor agents.

We have engineered a human adenovirus, ONYX-411, that selectively replicates in human tumor cells, but not normal cells, depending upon the status of their retinoblastoma tumor suppressor protein (pRB) pathway. Early and late viral gene expression as well as DNA replication were significantly reduced in a functional pRB-pathway-dependent manner, resulting in a restricted replication profile similar to that of nonreplicating adenoviruses in normal cells both in vitro and in vivo. In contrast, the viral life cycle and tumor cell killing activity of ONYX-411 was comparable to that of wild-type adenovirus following infection of human tumor cells in vitro as well as after systemic administration in tumor-bearing animals.

Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity.

ONYX-015 is an adenovirus that lacks the E1B-55K gene product for p53 degradation. Thus, ONYX-015 was conceived as an oncolytic virus that would selectively replicate in p53-defective tumor cells. Here we show that loss of E1B-55K leads to the induction, but not the activation, of p53 in ONYX-015-infected primary cells. We use a novel adenovirus mutant, ONYX-053, to demonstrate that loss of E1B-55K-mediated late viral RNA export, rather than p53 degradation, restricts ONYX-015 replication in primary cells. In contrast, we show that tumor cells that support ONYX-015 replication provide the RNA export function of E1B-55K. These data reveal that tumor cells have altered mechanisms for RNA export and resolve the controversial role of p53 in governing ONYX-015 oncolytic selectivity.

Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways.

RNA interference (RNAi) is a universal and evolutionarily conserved phenomenon of post-transcriptional gene silencing by means of sequence-specific mRNA degradation, triggered by small double-stranded RNAs. Because this mechanism can be efficiently induced in vivo by expressing target-complementary short hairpin RNA (shRNA) from non-viral and viral vectors, RNAi is attractive for functional genomics and human therapeutics. Here we systematically investigate the long-term effects of sustained high-level shRNA expression in livers of adult mice. Robust shRNA expression in all the hepatocytes after intravenous infusion was achieved with an optimized shRNA delivery vector based on duplex-DNA-containing adeno-associated virus type 8 (AAV8). An evaluation of 49 distinct AAV/shRNA vectors, unique in length and sequence and directed against six targets, showed that 36 resulted in dose-dependent liver injury, with 23 ultimately causing death. Morbidity was associated with the downregulation of liver-derived microRNAs (miRNAs), indicating possible competition of the latter with shRNAs for limiting cellular factors required for the processing of various small RNAs. In vitro and in vivo shRNA transfection studies implied that one such factor, shared by the shRNA/miRNA pathways and readily saturated, is the nuclear karyopherin exportin-5. Our findings have fundamental consequences for future RNAi-based strategies in animals and humans, because controlling intracellular shRNA expression levels will be imperative. However, the risk of oversaturating endogenous small RNA pathways can be minimized by optimizing shRNA dose and sequence, as exemplified here by our report of persistent and therapeutic RNAi against human hepatitis B virus in vivo.

The host response to adenovirus, helper-dependent adenovirus, and adeno-associated virus in mouse liver.

Understanding host responses to viral gene therapy vectors is necessary for the development of safe and efficacious in vivo gene transfer agents. We describe the use of high-density spotted complementary DNA microarrays in monitoring the in vivo host transcriptional responses in mouse liver upon administration of either a "first-generation"adenoviral (Ad) vector, a helper-dependent "gutless" adenoviral (HD) vector, or an adeno-associated viral (AAV) vector containing human factor IX (hFIX) expression cassettes. Since HD and AAV do not contain any viral genes, they allow us to assess the host response to the viral capsid and packaged nonviral DNA in whole animals. Comparison of the host response to Ad and HD helps assess the importance of leaky adenoviral gene expression. While all three vectors induced characteristic temporally sequenced programs of gene expression, the gene expression programs induced by the Ad and HD adenovirus vectors were remarkably similar, including the induction of a prominent type I interferon (IFN)-dependent cluster within 6 hours of administration. In contrast, the AAV-based vector caused far fewer alterations of host-gene expression. Our results indicate that recognition of the Ad capsid or double-stranded DNA (of nonviral origin) in the vector elicits a robust type I IFN response that is, however, not elicited by AAV-derived vector transduction.

Inhibition of hepatitis B virus in mice by RNA interference.

Hepatitis B virus (HBV) infection substantially increases the risk of chronic liver disease and hepatocellular carcinoma in humans. RNA interference (RNAi) of virus-specific genes has emerged as a potential antiviral mechanism. Here we show that RNAi can be applied to inhibit production of HBV replicative intermediates in cell culture and in immunocompetent and immunodeficient mice transfected with an HBV plasmid. Cotransfection with plasmids expressing short hairpin RNAs (shRNAs) homologous to HBV mRNAs induced an RNAi response. Northern and Southern analyses of mouse liver RNA and DNA showed substantially reduced levels of HBV RNAs and replicated HBV genomes upon RNAi treatment. Secreted HBV surface antigen (HBsAg) was reduced by 94.2% in cell culture and 84.5% in mouse serum, whereas immunohistochemical detection of HBV core antigen (HBcAg) revealed >99% reduction in stained hepatocytes upon RNAi treatment. Thus, RNAi effectively inhibited replication initiation in cultured cells and mammalian liver, showing that such an approach could be useful in the treatment of viral diseases.

Adeno-associated virus vectors for short hairpin RNA expression.

Five recent publications have documented the successful development and use of gene transfer vectors based on adeno-associated virus (AAV) for expressing short hairpin RNA (shRNA). In cultured mammalian cells and in whole animals, infection with these vectors was shown to result in specific, efficient, and stable knockdown of various targeted endo- or exogenous genes. Here we review this exciting approach, to trigger RNA interference in vitro and in vivo by shRNA expressed from AAV vectors, and describe the state-of-the-art technology for vector particle generation. In particular, we present a set of novel AAV vector plasmids that were specifically designed for the easy and rapid cloning of shRNA expression cassettes into AAV. The plasmids contain alternative RNA polymerase III promoters (U6, H1, or 7SK) together with a respective terminator sequence, as well as stuffer DNA to guarantee an optimal vector size for efficient packaging into AAV capsids. To provide maximum versatility and user-friendliness, the constructs were also engineered to contain a set of unique restriction enzyme recognition sites, allowing the simple and straightforward replacement of the shRNA cassette or other vector components with customized sequences. Our novel vector plasmids complement existing AAV vector technology and should help further establish AAV as a most promising alternative to using adeno- or retro-?lentiviral vectors as shRNA delivery vehicles.

Liver transduction with recombinant adeno-associated virus is primarily restricted by capsid serotype not vector genotype.

We and others have recently reported highly efficient liver gene transfer with adeno-associated virus 8 (AAV-8) pseudotypes, i.e., AAV-2 genomes packaged into AAV-8 capsids. Here we studied whether liver transduction could be further enhanced by using viral DNA packaging sequences (inverted terminal repeats [ITRs]) derived from AAV genotypes other than 2. To this end, we generated two sets of vector constructs carrying expression cassettes embedding a gfp gene or the human factor IX (hfIX) gene flanked by ITRs from AAV genotypes 1 through 6. Initial in vitro analyses of gfp vector DNA replication, encapsidation, and cell transduction revealed a surprisingly high degree of interchangeability among the six genotypes. For subsequent in vivo studies, we cross-packaged the six hfIX variants into AAV-8 and infused mice via the portal vein with doses of 5 x 10(10) to 1.8 x 10(12) particles. Notably, all vectors expressed comparably high plasma hFIX levels within a dose cohort over the following 6 months, concurrent with the finding of equivalent vector DNA copy numbers per cell. Partial hepatectomies resulted in approximately 80% drops of hFIX levels and vector DNA copy numbers in all groups, indicating genotype-independent persistence of predominantly episomal vector DNA. Southern blot analyses of total liver DNA in fact confirmed the presence of identical and mostly nonintegrated molecular vector forms for all genotypes. We conclude that, unlike serotypes, AAV genotypes are not critical for efficient hepatocyte transduction and can be freely substituted. This corroborates our current model for AAV vector persistence in the liver and provides useful information for the future design and application of recombinant AAV.

The 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3, and 9.

Adeno-associated virus serotype 8 (AAV8) is currently emerging as a powerful gene transfer vector, owing to its capability to efficiently transduce many different tissues in vivo. While this is believed to be in part due to its ability to uncoat more readily than other AAV serotypes such as AAV2, understanding all the processes behind AAV8 transduction is important for its application and optimal use in human gene therapy. Here, we provide the first report of a cellular receptor for AAV8, the 37/67-kDa laminin receptor (LamR). We document binding of LamR to AAV8 capsid proteins and intact virions in vitro and demonstrate its contribution to AAV8 transduction of cultured cells and mouse liver in vivo. We also show that LamR plays a role in transduction by three other closely related serotypes (AAV2, -3, and -9). Sequence and deletion analysis allowed us to map LamR binding to two protein subdomains predicted to be exposed on the AAV capsid exterior. Use of LamR, which is constitutively expressed in many clinically relevant tissues and is overexpressed in numerous cancers, provides a molecular explanation for AAV8's broad tissue tropism. Along with its robust transduction efficiency, our findings support the continued development of AAV8-based vectors for clinical applications in humans, especially for tumor gene therapy.